Ethical, legal, and policy challenges in field-based neuroimaging research using emerging portable MRI technologies: guidance for investigators and for oversight.

Researchers are rapidly developing and deploying highly portable MRI technology to conduct field-based research. The new technology will widen access to include new investigators in remote and unconventional settings and will facilitate greater inclusion of rural, economically disadvantaged, and historically underrepresented populations. To address the ethical, legal, and societal issues raised by highly accessible and portable MRI, an interdisciplinary Working Group (WG) engaged in a multi-year structured process of analysis and consensus building, informed by empirical research on the perspectives of experts and the general public. This article presents the WG's consensus recommendations. These recommendations address technology quality control, design and oversight of research, including safety of research participants and others in the scanning environment, engagement of diverse participants, therapeutic misconception, use of artificial intelligence algorithms to acquire and analyze MRI data, data privacy and security, return of results and managing incidental findings, and research participant data access and control.

Central autonomic network dysfunction and plasma Alzheimer's disease biomarkers in older adults.

BACKGROUND: Higher order regulation of autonomic function is maintained by the coordinated activity of specific cortical and subcortical brain regions, collectively referred to as the central autonomic network (CAN). Autonomic changes are frequently observed in Alzheimer's disease (AD) and dementia, but no studies to date have investigated whether plasma AD biomarkers are associated with CAN functional connectivity changes in at risk older adults. METHODS: Independently living older adults (N = 122) without major neurological or psychiatric disorder were recruited from the community. Participants underwent resting-state brain fMRI and a CAN network derived from a voxel-based meta-analysis was applied for overall, sympathetic, and parasympathetic CAN connectivity using the CONN Functional Toolbox. Sensorimotor network connectivity was studied as a negative control. Plasma levels of amyloid (Aß42, Aß40), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) were assessed using digital immunoassay. The relationship between plasma AD biomarkers and within-network functional connectivity was studied using multiple linear regression adjusted for demographic covariates and Apolipoprotein E (APOE) genotype. Interactive effects with APOE4 carrier status were also assessed. RESULTS: All autonomic networks were positively associated with Aß42/40 ratio and remained so after adjustment for age, sex, and APOE4 carrier status. Overall and parasympathetic networks were negatively associated with GFAP. The relationship between the parasympathetic CAN and GFAP was moderated by APOE4 carrier status, wherein APOE4 carriers with low parasympathetic CAN connectivity displayed the highest plasma GFAP concentrations (B = 910.00, P = .004). Sensorimotor connectivity was not associated with any plasma AD biomarkers, as expected. CONCLUSION: The present study findings suggest that CAN function is associated with plasma AD biomarker levels. Specifically, lower CAN functional connectivity is associated with decreased plasma Aß42/40, indicative of cerebral amyloidosis, and increased plasma GFAP in APOE4 carriers at risk for AD. These findings could suggest higher order autonomic and parasympathetic dysfunction in very early-stage AD, which may have clinical implications.

Short-term blood pressure variability and brain functional network connectivity in older adults.

Background: Blood pressure variability is increasingly linked with cerebrovascular disease and Alzheimer's disease, independent of mean blood pressure levels. Elevated blood pressure variability is also associated with attenuated cerebrovascular reactivity, which may have implications for functional hyperemia underpinning brain network connectivity. It remains unclear whether blood pressure variability is related to functional network connectivity. We examined relationships between beat-to-beat blood pressure variability and functional connectivity in brain networks vulnerable to aging and Alzheimer's disease. Methods: 53 community-dwelling older adults (mean [SD] age = 69.9 [7.5] years, 62.3% female) without history of dementia or clinical stroke underwent continuous blood pressure monitoring and resting state fMRI scan. Blood pressure variability was calculated as variability independent of mean. Functional connectivity was determined by resting state fMRI for several brain networks: default, salience, dorsal attention, fronto-parietal, and language. Multiple linear regression examined relationships between short-term blood pressure variability and functional network connectivity. Results: Elevated short-term blood pressure variability was associated with lower functional connectivity in the default network (systolic: standardized ß = -0.30 [95% CI -0.59, -0.01], p = .04). There were no significant associations between blood pressure variability and connectivity in other functional networks or between mean blood pressure and functional connectivity in any network. Discussion: Older adults with elevated short-term blood pressure variability exhibit lower resting state functional connectivity in the default network. Findings support the role of blood pressure variability in neurovascular dysfunction and Alzheimer's disease. Blood pressure variability may represent an understudied early vascular risk factor for neurovascular dysfunction relevant to Alzheimer's disease, with potential therapeutic implications.

Risk factors for in-hospital acquisition of carbapenem-resistant Enterobacterales in patients with severe burns.

BACKGROUND: Although patients with severe burns are prone to severe infections with antibiotic-resistant bacteria and inevitably have some risk factors for carbapenem-resistant Enterobacterales (CRE) acquisition, risk factors for CRE infection or colonization in these patients have not been investigated. AIM: To identify the independent risk factors for CRE acquisition in patients with severe burns. METHODS: Patients admitted to the burn intensive care unit (BICU) for acute burn care were categorized based on culture results during BICU care into the CRE group and non-CRE group, which included the carbapenem-susceptible Enterobacterales (CSE) and control groups. Clinical and microbiological factors were compared between the CRE and non-CRE groups, and between the CRE and CSE groups to identify independent risk factors for in-hospital CRE acquisition. FINDINGS: Among the included 489 patients, 101 (20.7%) and 388 (79.3%) patients were classified in the CRE and non-CRE groups, respectively. The non-CRE group included 91 (18.6%) and 297 (60.7%) patients in the CSE and control groups, respectively. In multivariate analysis between the CRE and non-CRE groups, exposure to other CRE-acquired patients (P = 0.018), abbreviated burn severity index score ≥9 (P = 0.012), and mechanical ventilation (P < 0.001) were associated with CRE acquisition. In multivariate analysis between the CRE and CSE groups, exposure to other CRE-acquired patients was associated with CRE acquisition (P = 0.048). CONCLUSION: Considering the limitation of controlling the burn severity in hospitalized patients, enhanced infection control measures for preventing in-hospital CRE transmission among patients with severe burns should be emphasized.

Mitral valve prolapse: arrhythmic risk during pregnancy and postpartum.

BACKGROUND AND AIMS: Arrhythmic mitral valve prolapse (AMVP) is linked to life-threatening ventricular arrhythmias (VAs), and young women are considered at high risk. Cases of AMVP in women with malignant VA during pregnancy have emerged, but the arrhythmic risk during pregnancy is unknown. The authors aimed to describe features of women with high-risk AMVP who developed malignant VA during the perinatal period and to assess if pregnancy and the postpartum period were associated with a higher risk of malignant VA. METHODS: This retrospective international multi-centre case series included high-risk women with AMVP who experienced malignant VA and at least one pregnancy. Malignant VA included ventricular fibrillation, sustained ventricular tachycardia, or appropriate shock from an implantable cardioverter defibrillator. The authors compared the incidence of malignant VA in non-pregnant periods and perinatal period; the latter defined as occurring during pregnancy and within 6 months after delivery. RESULTS: The authors included 18 women with AMVP from 11 centres. During 7.5 (interquartile range 5.8-16.6) years of follow-up, 37 malignant VAs occurred, of which 18 were pregnancy related occurring in 13 (72%) unique patients. Pregnancy and 6 months after delivery showed increased incidence rate of malignant VA compared to the non-pregnancy period (univariate incidence rate ratio 2.66, 95% confidence interval 1.23-5.76). CONCLUSIONS: The perinatal period could impose increased risk of malignant VA in women with high-risk AMVP. The data may provide general guidance for pre-conception counselling and for nuanced shared decision-making between patients and clinicians.

Procrastination, depressive symptomatology, and loneliness in later life.

OBJECTIVES: Procrastination is an almost universal behaviour and yet little research to date has focused on procrastination among older adults. The purpose of this study was to explore the potential association between age and procrastination, and the potential mediating roles of depressive symptomatology and loneliness. METHOD: Structural equation modelling was applied to data from 1309 participants (aged 29-92) from two waves United States Health and Retirement Study (2016-2020). Within the model, sex, education, marital status, and job status were added as covariates. RESULTS: There was no statistically significant direct effect between age and procrastination (ß = 0.06, p = 0.106). However, an indirect effect was present via depressive symptomatology (ß = -0.40, p < 0.001). No mediating effect of loneliness was observed (ß = - 0.01, p = 0.371). Subsequent analysis revealed that the symptoms, fatigue, loneliness, and lack of motivation significantly predicted procrastination. CONCLUSION: While age was not directly associated with procrastination, increasing age was associated with a decreased likelihood of depressive symptomatology, which was in turn associated with an increased likelihood of procrastination. Such findings indicates that age demonstrates no association with procrastination because of the suppressing effect of depressive symptomatology.

2023 Cardiac Society of Australia and New Zealand Expert Position Statement on Catheter and Surgical Ablation for Atrial Fibrillation.

Catheter ablation for atrial fibrillation (AF) has increased exponentially in many developed countries, including Australia and New Zealand. This Expert Position Statement on Catheter and Surgical Ablation for Atrial Fibrillation from the Cardiac Society of Australia and New Zealand (CSANZ) recognises healthcare factors, expertise and expenditure relevant to the Australian and New Zealand healthcare environments including considerations of potential implications for First Nations Peoples. The statement is cognisant of international advice but tailored to local conditions and populations, and is intended to be used by electrophysiologists, cardiologists and general physicians across all disciplines caring for patients with AF. They are also intended to provide guidance to healthcare facilities seeking to establish or maintain catheter ablation for AF.

Temporal association between atrial fibrillation and ischemic stroke: Systematic review and meta-analysis.

BACKGROUND: Paroxysmal atrial fibrillation (PAF) is strongly associated with ischemic stroke. Continuous cardiac implantable electronic devices (CIEDs) can assess PAF episodes over prolonged periods. Studies that attempted to find a temporal association between PAF and ischemic stroke were inconclusive. Thus, we performed a systematic review and meta-analysis to assess this relationship. AIMS: This study aimed to assess the temporal association between AF episodes and stroke within 30 days of the arrhythmic episode. The secondary outcome is a temporal association within a 90-day period. SUMMARY OF REVIEW: A total of 2804 studies that discussed the temporal relationship between PAF and ischemic stroke were screened, and 7 studies were included in the meta-analysis. Among the 4041 patients included in these studies, there were 138 patients with device detected PAF episodes and stroke. Four studies used a 30-day window for temporality and the pooled odds ratio (OR) showed a significant association (OR 4.11 (95% CI 1.03-16.40)). The three studies reporting on AF and stroke within a 90-day window did not find a significant temporal relationship (OR 0.43 (95% CI 0.13-1.41)). Finally, the pooled result of those seven studies did not show a significant association (OR 1.51 (95% CI 0.44-5.17)). CONCLUSION: This meta-analysis supports a temporal relationship between PAF and ischemic stroke within a 30-day window. Establishing this relationship is important for individualized risk prediction and targeted anticoagulation treatment. DATA ACCESS STATEMENT: The data will be made available upon reasonable request.

[Proactively embracing the challenges of multimorbidity].

With rapid socio-economic development and the acceleration of population aging, the average life span of human beings has increased significantly. Individuals suffering from the co-existence of multiple diseases (multimorbidity) have become a new normal in public health and posed severe challenge to human health. Multimorbidity significantly reduces the quality of life, increases disability and mortality risks, complicates disease treatment and care and increases burden of the healthcare system with higher costs. This commentary discusses the definition of multimorbidity and common public misconceptions, then assesses its profound impact on overall public health, socio-economic development and healthcare system. We also proposes the potential strategies to meet the challenges posed by multimorbidity. The main aim is to raise awareness of multimorbidity, advocate proactive responses to improve public health and build a healthy society through the development of prevention and treatment systems and promote precision prevention and treatment for multimorbidity.

A practical approach to uveitis screening in children with juvenile idiopathic arthritis.

BACKGROUND: Juvenile idiopathic arthritis (JIA)-associated uveitis typically presents as a silent chronic anterior uveitis and can lead to blindness. Adherence to current screening guidelines is hampered by complex protocols which rely on the knowledge of specific JIA characteristics. The Multinational Interdisciplinary Working Group for Uveitis in Childhood identified the need to simplify screening to enable local eye care professionals (ECPs), who carry the main burden, to screen children with JIA appropriately and with confidence. METHODS: A consensus meeting took place in January 2023 in Barcelona, Spain, with an expert panel of 10 paediatric rheumatologists and 5 ophthalmologists with expertise in paediatric uveitis. A summary of the current evidence for JIA screening was presented. A nominal group technique was used to reach consensus. RESULTS: The need for a practical but safe approach that allows early uveitis detection was identified by the panel. Three screening recommendations were proposed and approved by the voting members. They represent a standardised approach to JIA screening taking into account the patient's age at the onset of JIA to determine the screening interval until adulthood. CONCLUSION: By removing the need for the knowledge of JIA categories, antinuclear antibody positivity or treatment status, the recommendations can be more easily implemented by local ECP, where limited information is available. It would improve the standard of care on the local level significantly. The proposed protocol is less tailored to the individual than the 'gold standard' ones it references and does not aim to substitute those where they are being used with confidence.

Digital quantification of the MMSE interlocking pentagon areas: a three-stage algorithm.

The Mini-Mental State Examination (MMSE) is a widely employed screening tool for the severity of cognitive impairment. Among the MMSE items, the pentagon copying test (PCT) requires participants to accurately replicate a sample of two interlocking pentagons. While the PCT is traditionally scored on a binary scale, there have been limited developments of granular scoring scale to assess task performance. In this paper, we present a novel three-stage algorithm, called Quantification of Interlocking Pentagons (QIP) which quantifies PCT performance by computing the areas of individual pentagons and their intersection areas, and a balance ratio between the areas of the two individual pentagons. The three stages of the QIP algorithm include: (1) detection of line segments, (2) unraveling of the interlocking pentagons, and (3) quantification of areas. A set of 497 PCTs from 84 participants including their baseline and follow-up PCTs from the Rush Memory and Aging Project was selected blinded about their cognitive and clinical status. Analysis of the quantified data revealed a significant inverse relationship between age and balance ratio (beta = - 0.49, p = 0.0033), indicating that older age was associated with a smaller balance ratio. In addition, balance ratio was associated with perceptual speed (r = 0.71, p = 0.0135), vascular risk factors (beta = - 3.96, p = 0.0269), and medical conditions (beta = - 2.78, p = 0.0389). The QIP algorithm can serve as a useful tool for enhancing the scoring of performance in the PCT.

Spontaneous rupture of the right aortic sinus resulting in a sterile aorto-atrial fistula in a pet rabbit (Oryctolagus cuniculus).

Aortocardiac fistula is a broad term used to describe defects between the aorta and other cardiac chambers that can occur in humans and animals. A 1.5-year-old, 1.7 kg, male castrated Holland lop rabbit (Oryctolagus cuniculus) was presented for a two-week history of a heart murmur with corresponding cardiomegaly on radiographs. Physical examination confirmed a grade-V/VI continuous heart murmur on the right sternal border with a regular rhythm and a gallop sound. Echocardiography revealed an aortic-to-right-atrial fistula causing severe left-sided volume overload. Based on the echocardiographic findings, rupture of the right aortic sinus was suspected. Due to the poor prognosis, euthanasia was elected. On necropsy, a fistula was found connecting the right aortic sinus with the right atrium, without evidence of an inflammatory response nor evidence of an infectious etiology. The sudden onset of a heart murmur supported acquired fistulation from a ruptured aortic sinus (also known as the sinus of Valsalva), though a congenital malformation could not be completely excluded.

Organization of an ascending circuit that conveys flight motor state in Drosophila.

Natural behaviors are a coordinated symphony of motor acts that drive reafferent (self-induced) sensory activation. Individual sensors cannot disambiguate exafferent (externally induced) from reafferent sources. Nevertheless, animals readily differentiate between these sources of sensory signals to carry out adaptive behaviors through corollary discharge circuits (CDCs), which provide predictive motor signals from motor pathways to sensory processing and other motor pathways. Yet, how CDCs comprehensively integrate into the nervous system remains unexplored. Here, we use connectomics, neuroanatomical, physiological, and behavioral approaches to resolve the network architecture of two pairs of ascending histaminergic neurons (AHNs) in Drosophila, which function as a predictive CDC in other insects. Both AHN pairs receive input primarily from a partially overlapping population of descending neurons, especially from DNg02, which controls wing motor output. Using Ca2+ imaging and behavioral recordings, we show that AHN activation is correlated to flight behavior and precedes wing motion. Optogenetic activation of DNg02 is sufficient to activate AHNs, indicating that AHNs are activated by descending commands in advance of behavior and not as a consequence of sensory input. Downstream, each AHN pair targets predominantly non-overlapping networks, including those that process visual, auditory, and mechanosensory information, as well as networks controlling wing, haltere, and leg sensorimotor control. These results support the conclusion that the AHNs provide a predictive motor signal about wing motor state to mostly non-overlapping sensory and motor networks. Future work will determine how AHN signaling is driven by other descending neurons and interpreted by AHN downstream targets to maintain adaptive sensorimotor performance.

Subjective Age Moderates the Relationship Between Global Cognition and Susceptibility to Scams.

This study examined the interactive effect of subjective age on the relationship between global cognition and susceptibility to scams. Sixty-five participants underwent an assessment of global cognition (Mini Mental State Examination; MMSE), reported their perceived age (i.e., subjective age), and responded to a self-report questionnaire assessing scam susceptibility. A main effect of global cognition on scam susceptibility was found (p = .028); there was no main effect of subjective age (p = .819). An interaction between global cognition and subjective age was found (p = .016). Examination of conditional effects demonstrated that the relationship between cognition and scam susceptibility was not significant amongst those with subjective ages below one standard deviation of the mean, but was significant for those whose subjective ages fell around or above the mean. Findings suggest that individuals with older subjective ages may be particularly vulnerable to the negative effects of lower cognition on scam susceptibility.

Society for Cardiovascular Magnetic Resonance 2022 Cases of SCMR case series.

"Cases of SCMR" is a case series on the SCMR website (https://www.scmr.org) for the purpose of education. The cases reflect the clinical presentation, and the use of cardiovascular magnetic resonance (CMR) in the diagnosis and management of cardiovascular disease. The 2022 digital collection of cases are presented in this manuscript.

Predictors of standardized in-service examination performance and residency outcomes in a graduate periodontics program.

PURPOSE/OBJECTIVES: The objectives of this study were to assess the influence of learner- and education-related factors on standardized in-service examination performance and determine whether in-service examination scores predict residency outcomes. METHODS: American Academy of Periodontology (AAP) In-service Examination (AIE) scores from 10 periodontics residency classes at a single center were recorded and compared against a panel of learner- and education-related variables using multiple linear regression models. Defined residency outcome measures were analyzed against AIE scores using binomial logistic regression. RESULTS: No evaluated learner- or education-related variable was a statistically significant predictor of AIE score in this study sample. Likewise, AIE score was not a statistically significant predictor of any assessed residency outcome. CONCLUSIONS: The AAP has performed a tremendous service to periodontics residents and programs by marshaling the leadership and expertise necessary to offer a professionally constructed assessment instrument. However, in the current study, no relationship could be identified between AIE score and any outcome, including first-attempt board certification. The AAP In-service Committee appears well situated to provide additional leadership focusing on exam implementation, which may enhance AIE value in competency decision making.

Incidence and progression of atrial fibrillation in patients with and without heart failure using mineralocorticoid receptor antagonists: a meta-analysis.

BACKGROUND: Mineralocorticoid receptor antagonists (MRAs) have emerged as potential therapy to target the underlying arrhythmogenic substrate in atrial fibrillation (AF). Nevertheless, there have been inconsistent results on the impact of MRAs on AF. OBJECTIVE: We sought to evaluate the effect of MRAs on AF incidence and progression in patients with and without heart failure. METHODS: Electronic databases were searched up to September, 2022 for randomized controlled trials (RCTs) that evaluated MRA use and reported AF outcomes. Primary outcome was a composite of new-onset or recurrent AF. Safety outcomes included hyperkalemia and gynecomastia risks. A random-effects meta-analysis estimated pooled odds ratios (OR) and 95% confidence intervals (CI). RESULTS: 12 RCTs, comprising 11,419 patients treated with various MRAs were included [5960 (52%) on MRA]. On follow-up (6-39 months), 714 (5.5%) patients developed AF. MRA therapy was associated with a 32% reduction in the risk of new-onset or recurrent AF [OR 0.68 (95% CI 0.51-0.92), I2 = 40%]. On subgroup analysis, the greatest benefit magnitude was demonstrated in reducing AF recurrence [OR 0.50 (95% CI 0.30-0.83)] and among patients with left ventricular dysfunction [OR 0.59 (95% CI 0.40-0.85)]. Gynecomastia, but not hyperkalemia, was associated with MRA use. Meta-regression analysis demonstrated that therapy duration was a significant interaction factor driving the effect size (Pinteraction = 0.013). CONCLUSION: MRA use is associated with a reduction in AF risk, especially AF progression. A prominent effect is seen in patients with heart failure, further augmented by therapy duration. Prospective trials are warranted to evaluate MRA use as upstream therapy for preventing this common arrhythmia.