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Management of lymphadenitis due to non-tuberculous mycobacterial infection in children
Purpose: Non-tuberculous mycobacterial (NTM) infection is an important cause of cervico-facial lymph node enlargement in young children. The optimal treatment is thought to be early complete excision without chemotherapy. We compared management of patients referred to our centre to this "gold standard" and determined clinical outcomes by type of primary surgical intervention (complete excision vs. incomplete excision). Methods: Retrospective study of management and clinical outcomes of all children (<12 years) with NTM lymphadenitis referred to a single UK centre between May 1998 and May 2008. Results: We identified 43 children. Median time from onset of swelling to operation was 6 weeks. Management was: no operation (n = 1, 2 %), complete excision (n = 20, 47 %), incision and drainage (n = 17, 40 %) and fine needle aspirate (n = 5, 12 %). Children not treated by primary complete excision were more likely to have: reoperation (91 vs. 30 %; χ 2 = 16.48; p < 0.0001); persistent lymphadenitis (77 vs. 30 %; χ 2 = 9.45; p = 0.002); sinus formation (26 vs. 5 %; χ2 = 3.74; p = 0.05). Conclusion: Failure to undertake primary complete excision leads to further morbidity. A high index of suspicion is required for timely appropriate management to avoid unnecessary morbidity and further intervention. © Springer-Verlag 2012.
Incidence, risk factors, management, and outcomes of stroke in pregnancy
To estimate the incidence of antenatal stroke in the United Kingdom and to describe risk factors associated with stroke during pregnancy, management, and outcomes. A population-based (nationwide) cohort and nested case-control study was conducted using the UK Obstetric Surveillance System between October 2007 and March 2010. We investigated the potential factors associated with antenatal stroke using a logistic regression analysis to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Thirty cases of antenatal stroke were reported giving an estimated incidence of 1.5 cases per 100,000 women delivering (95% CI 1.0-2.1). The incidences of nonhemorrhagic and hemorrhagic stroke were 0.9 (95% CI 0.5-1.3) and 0.6 (95% CI 0.3-1.0) per 100,000 women delivering. Factors associated with increased risk of antenatal stroke were history of migraine (adjusted OR 8.5, 95% CI 1.5-62.1), gestational diabetes (adjusted OR 26.8, 95% CI 3.2-∞), and preeclampsia or eclampsia (adjusted OR 7.7, 95% CI 1.3-55.7). There was wide variation in the use of pharmacologic, surgical, and organized stroke unit care. There were six stroke-related maternal deaths giving a case-fatality rate of 20% of all strokes, 50% of hemorrhagic strokes, and a mortality rate of 0.3 (95% CI 0.1-0.6) per 100,000 women delivering. The risk of a stroke during pregnancy is low; however, the poor outcomes in terms of morbidity and mortality and variations in care highlight the importance of such women receiving specialist stroke care. Clinicians should be aware of an association with a history of migraine, gestational diabetes, and preeclampsia or eclampsia. II. © 2012 Lippincott Williams & Wilkins, Inc.
Catechol-O-methyltransferase activity does not influence emotional processing in men
Background: Catechol-O-methyltransferase (COMT) regulates cortical dopaminergic transmission and prefrontal-dependent cognitive function. However, its role in other cognitive processes, including emotional processing, is relatively unexplored. We therefore investigated the separate and interactive influences of COMT inhibition and Val158Met (rs4680) genotype on performance on an emotional test battery. Methods: We recruited 74 healthy men homozygous for the functional COMT Val158Met polymorphism. Volunteers were administered either a single 200 mg dose of the brain-penetrant COMT inhibitor tolcapone or placebo in a double-blind, randomised manner. Emotional processing was assessed using the emotional test battery, and mood was rated using visual analogue scales and the Profile of Mood States (POMS) questionnaire across the test day. Results: There were no main or interactive effects of Val158Met genotype or tolcapone on any of the emotional processing measures or mood ratings. Conclusions: Our findings suggest that, at least in healthy adult men, COMT has little or no effect on emotional processing or mood. These findings contrast with several neuroimaging studies that suggest that COMT modulates neural activity during emotional processing. Thus, further studies are required to understand how COMT impacts on the relationship between behavioural output and neural activity during emotional processing. Nevertheless, our data suggest that novel COMT inhibitors under development for treating cognitive dysfunction are unlikely to have acute off target effects on emotional behaviours.
Centering inclusivity in the design of online conferences—An OHBM–Open Science perspective
Abstract As the global health crisis unfolded, many academic conferences moved online in 2020. This move has been hailed as a positive step towards inclusivity in its attenuation of economic, physical, and legal barriers and effectively enabled many individuals from groups that have traditionally been underrepresented to join and participate. A number of studies have outlined how moving online made it possible to gather a more global community and has increased opportunities for individuals with various constraints, e.g., caregiving responsibilities. Yet, the mere existence of online conferences is no guarantee that everyone can attend and participate meaningfully. In fact, many elements of an online conference are still significant barriers to truly diverse participation: the tools used can be inaccessible for some individuals; the scheduling choices can favour some geographical locations; the set-up of the conference can provide more visibility to well-established researchers and reduce opportunities for early-career researchers. While acknowledging the benefits of an online setting, especially for individuals who have traditionally been underrepresented or excluded, we recognize that fostering social justice requires inclusivity to actively be centered in every aspect of online conference design. Here, we draw from the literature and from our own experiences to identify practices that purposefully encourage a diverse community to attend, participate in, and lead online conferences. Reflecting on how to design more inclusive online events is especially important as multiple scientific organizations have announced that they will continue offering an online version of their event when in-person conferences can resume.
Fronto-parietal involvement in chronic stroke motor performance when corticospinal tract integrity is compromised.
BACKGROUND: Preserved integrity of the corticospinal tract (CST) is a marker of good upper-limb behavior and recovery following stroke. However, there is less understanding of neural mechanisms that might help facilitate upper-limb motor recovery in stroke survivors with extensive CST damage. OBJECTIVE: The purpose of this study was to investigate resting state functional connectivity in chronic stroke survivors with different levels of CST damage and to explore neural correlates of greater upper-limb motor performance in stroke survivors with compromised ipsilesional CST integrity. METHODS: Thirty chronic stroke survivors (24 males, aged 64.7 ± 10.8 years) participated in this study. Three experimental sessions were conducted to: 1) obtain anatomical (T1, T2) structural (diffusion) and functional (resting state) MRI sequences, 2) determine CST integrity with transcranial magnetic stimulation (TMS) and conduct assessments of upper-limb behavior, and 3) reconfirm CST integrity status. Participants were divided into groups according to the extent of CST damage. Those in the extensive CST damage group did not show TMS evoked responses and had significantly lower ipsilesional fractional anisotropy. RESULTS: Of the 30 chronic stroke survivors, 12 were categorized as having extensive CST damage. Stroke survivors with extensive CST damage had weaker functional connectivity in the ipsilesional sensorimotor network and greater functional connectivity in the ipsilesional fronto-parietal network compared to those with preserved CST integrity. For participants with extensive CST damage, improved motor performance was associated with greater functional connectivity of the ipsilesional fronto-parietal network and higher fractional anisotropy of the ipsilesional rostral superior longitudinal fasciculus. CONCLUSIONS: Stroke survivors with extensive CST damage have greater resting state functional connectivity of an ipsilesional fronto-parietal network that appears to be a behaviorally relevant neural mechanism that improves upper-limb motor performance.
Identification and disruption of a neural mechanism for accumulating prospective metacognitive information prior to decision-making.
More than one type of probability must be considered when making decisions. It is as necessary to know one's chance of performing choices correctly as it is to know the chances that desired outcomes will follow choices. We refer to these two choice contingencies as internal and external probability. Neural activity across many frontal and parietal areas reflected internal and external probabilities in a similar manner during decision-making. However, neural recording and manipulation approaches suggest that one area, the anterior lateral prefrontal cortex (alPFC), is highly specialized for making prospective, metacognitive judgments on the basis of internal probability; it is essential for knowing which decisions to tackle, given its assessment of how well they will be performed. Its activity predicted prospective metacognitive judgments, and individual variation in activity predicted individual variation in metacognitive judgments. Its disruption altered metacognitive judgments, leading participants to tackle perceptual decisions they were likely to fail.
Can MRI measure myelin? Systematic review, qualitative assessment, and meta-analysis of studies validating microstructural imaging with myelin histology.
Recent years have seen an increased understanding of the importance of myelination in healthy brain function and neuropsychiatric diseases. Non-invasive microstructural magnetic resonance imaging (MRI) holds the potential to expand and translate these insights to basic and clinical human research, but the sensitivity and specificity of different MR markers to myelination is a subject of debate. To consolidate current knowledge on the topic, we perform a systematic review and meta-analysis of studies that validate microstructural imaging by combining it with myelin histology. We find meta-analytic evidence for correlations between various myelin histology metrics and markers from different MRI modalities, including fractional anisotropy, radial diffusivity, macromolecular pool, magnetization transfer ratio, susceptibility and longitudinal relaxation rate, but not mean diffusivity. Meta-analytic correlation effect sizes range widely, between R2 = 0.26 and R2 = 0.82. However, formal comparisons between MRI-based myelin markers are limited by methodological variability, inconsistent reporting and potential for publication bias, thus preventing the establishment of a single most sensitive strategy to measure myelin with MRI. To facilitate further progress, we provide a detailed characterisation of the evaluated studies as an online resource. We also share a set of 12 recommendations for future studies validating putative MR-based myelin markers and deploying them in vivo in humans.
FAST-IT: Find A Simple Test — In TIA (transient ischaemic attack): a prospective cohort study to develop a multivariable prediction model for diagnosis of TIA through proteomic discovery and candidate lipid mass spectrometry, neuroimaging and machine learning—study protocol
IntroductionTransient ischaemic attack (TIA) may be a warning sign of stroke and difficult to differentiate from minor stroke and TIA-mimics. Urgent evaluation and diagnosis is important as treating TIA early can prevent subsequent strokes. Recent improvements in mass spectrometer technology allow quantification of hundreds of plasma proteins and lipids, yielding large datasets that would benefit from different approaches including machine learning. Using plasma protein, lipid and radiological biomarkers, our study will develop predictive algorithms to distinguish TIA from minor stroke (positive control) and TIA-mimics (negative control). Analysis including machine learning employs more sophisticated modelling, allowing non-linear interactions, adapting to datasets and enabling development of multiple specialised test-panels for identification and differentiation.Methods and analysisPatients attending the Emergency Department, Stroke Ward or TIA Clinic at the Royal Adelaide Hospital with TIA, minor stroke or TIA-like symptoms will be recruited consecutively by staff-alert for this prospective cohort study. Advanced neuroimaging will be performed for each participant, with images assessed independently by up to three expert neurologists. Venous blood samples will be collected within 48 hours of symptom onset. Plasma proteomic and lipid analysis will use advanced mass spectrometry (MS) techniques. Principal component analysis and hierarchical cluster analysis will be performed using MS software. Output files will be analysed for relative biomarker quantitative differences between the three groups. Differences will be assessed by linear regression, one-way analysis of variance, Kruskal-Wallis H-test, χ2 test or Fisher’s exact test. Machine learning methods will also be applied including deep learning using neural networks.Ethics and disseminationPatients will provide written informed consent to participate in this grant-funded study. The Central Adelaide Local Health Network Human Research Ethics Committee approved this study (HREC/18/CALHN/384; R20180618). Findings will be disseminated through peer-reviewed publication and conferences; data will be managed according to our Data Management Plan (DMP2020-00062).
Differential effects of early or late exposure to prenatal maternal immune activation on mouse embryonic neurodevelopment.
SignificancePrenatal exposure to maternal infection increases the risk of developing mental health disorders, such as schizophrenia and autism spectrum disorder. Exposure to maternal immune activation has been associated with a number of neuroanatomical deficits in adolescent and adult offspring, with differing effects based on the gestational timing of infection. However, little is known about how the embryo brain is affected. We show, using whole-brain MRI, that maternal immune activation significantly affects brain anatomy. When the exposure occurs early in pregnancy, volume reductions are mainly observed, while the opposite is true for exposure later in pregnancy. Furthermore, we identify alterations to the density of certain classes of neurons and glia, which have been associated with stress and inflammation in the brain.
Shared and Distinct Patterns of Functional Connectivity to Emotional Faces in Autism Spectrum Disorder and Attention-Deficit/Hyperactivity Disorder Children
Impairments in emotional face processing are demonstrated by individuals with neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), which is associated with altered emotion processing networks. Despite accumulating evidence of high rates of diagnostic overlap and shared symptoms between ASD and ADHD, functional connectivity underpinning emotion processing across these two neurodevelopmental disorders, compared to typical developing peers, has rarely been examined. The current study used magnetoencephalography to investigate whole-brain functional connectivity during the presentation of happy and angry faces in 258 children (5–19 years), including ASD, ADHD and typically developing (TD) groups to determine possible differences in emotion processing. Data-driven clustering was also applied to determine whether the patterns of connectivity differed among diagnostic groups. We found reduced functional connectivity in the beta band in ASD compared to TD, and a further reduction in the ADHD group compared to the ASD and the TD groups, across emotions. A group-by-emotion interaction in the gamma frequency band was also observed. Greater connectivity to happy compared to angry faces was found in the ADHD and TD groups, while the opposite pattern was seen in ASD. Data-driven subgrouping identified two distinct subgroups: NDD-dominant and TD-dominant; these subgroups demonstrated emotion- and frequency-specific differences in connectivity. Atypicalities in specific brain networks were strongly correlated with the severity of diagnosis-specific symptoms. Functional connectivity strength in the beta network was negatively correlated with difficulties in attention; in the gamma network, functional connectivity strength to happy faces was positively correlated with adaptive behavioural functioning, but in contrast, negatively correlated to angry faces. Our findings establish atypical frequency- and emotion-specific patterns of functional connectivity between NDD and TD children. Data-driven clustering further highlights a high degree of comorbidity and symptom overlap between the ASD and ADHD children.
Multiple-mouse magnetic resonance imaging with cryogenic radiofrequency probes for evaluation of brain development.
Multiple-mouse magnetic resonance imaging (MRI) increases scan throughput by imaging several mice simultaneously in the same magnet bore, enabling multiple images to be obtained in the same time as a single scan. This increase in throughput enables larger studies than otherwise feasible and is particularly advantageous in longitudinal study designs where frequent imaging time points result in high demand for MRI resources. Cryogenically-cooled radiofrequency probes (CryoProbes) have been demonstrated to have significant signal-to-noise ratio benefits over comparable room temperature coils for in vivo mouse imaging. In this work, we demonstrate implementation of a multiple-mouse MRI system using CryoProbes, achieved by mounting four such coils in a 30-cm, 7-Tesla magnet bore. The approach is demonstrated for longitudinal quantification of brain structure from infancy to early adulthood in a mouse model of Sanfilippo syndrome (mucopolysaccharidosis type III), generated by knockout of the Hgsnat gene. We find that Hgsnat-/- mice have regionally increased growth rates compared to Hgsnat+/+ mice in a number of brain regions, notably including the ventricles, amygdala and superior colliculus. A strong sex dependence was also noted, with the lateral ventricle volume growing at an accelerated rate in males, but several structures in the brain parenchyma growing faster in females. This approach is broadly applicable to other mouse models of human disease and the increased throughput may be particularly beneficial in studying mouse models of neurodevelopmental disorders.
Correction: Brain mapping across 16 autism mouse models reveals a spectrum of functional connectivity subtypes (Molecular Psychiatry, (2021), 26, 12, (7610-7620), 10.1038/s41380-021-01245-4)
Table 1 lacks important phenotypic information regarding the Syn2 mouse line (Syn2), and also reports a set of wrong references. We apologies for this oversight, which was due to misalignment of text and table referencing software. The original article has been corrected.