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Analysing the effect of early acetazolamide administration on patients with a high risk of permanent cerebrospinal fluid leakage.
In this study, we examined the role of early acetazolamide administration in reducing the risk of cerebrospinal fluid (CSF) leakage in patients with a high risk of permanent CSF leakage. In a randomised clinical trial, 57 patients with a high risk of permanent CSF leakage (rhinorrhea, otorrhea, pneumatocele or imaging-based evidence of severe skull-base fracture) were analysed. In the experimental group, acetazolamide, at 25 mg/kg/day, was started in the first 48 hours after admission. In the control group, acetazolamide was administered after the first 48 hours at the same dose administered to the patients in the experimental group. The following factors were compared between the two groups: duration of CSF leakage, duration of hospital stay, incidence of meningitis, need for surgical intervention and need for lumbar puncture (LP) and lumbar drainage (LD). All of the patients in the experimental group stopped having CSF leakage less than 14 days after the first day of admission, but 6 out of 21 patients (22%) in the control group continued having CSF leakage after 14 days of admission, which was a significant difference (P=0.01). This study showed that early acetazolamide administration can prevent CSF leakage in patients with a high risk of permanent CSF leak.
A 12-year epidemiologic study on primary spinal cord tumors in Isfahan, Iran.
BACKGROUND: Although primary spinal cord tumors (PSCTs) comprise a minority of primary central nervous system tumors, they often impose a great deal of morbidity on their victims. Few epidemiologic studies have addressed PSCTs in Iran. MATERIALS AND METHODS: We analyzed the demographic/clinical features of all primary intraspinal tumors (with a specific focus on primary intradural spinal cord tumors) identified between 1992 and 2004 in three of the major related hospitals in Isfahan, Iran. We also tracked the malignant cases until 2012. RESULTS: 102 patients with primary intraspinal tumors were found; 82 tumors were Intradural (36 intramedullary and 46 extramedullary) and 20 extradural. The principal intradural histological subtypes were nerve sheath tumor (33%), ependymoma (22%), astrocytoma (16%), and meningioma (15%). 20 (19%) of the tumors were malignant. Local pain (43%) and motor disabilities (36%) were the most common first-presenting symptoms in the patients. Male-to-female ratio was significant only in ependymoma (male:female ratio = 3.6, P < 0.05). The mean age in meningioma (57 years, standard error [SE]: 15.7) was significantly higher than other types (one-way ANOVA, P < 0.05). CONCLUSION: Our results reflect analogous frequency of distribution for PSCTs compared with most of the previous counterpart studies worldwide. The only notable exception was the comparatively fewer frequency of spinal cord meningioma in our study.
Neurotransmitter modulation of human facial emotion recognition
Human facial emotion recognition (FER) is an evolutionarily preserved process that influences affiliative behaviours, approach/avoidance and fight-or-flight responses in the face of detecting threat cues, thus enhancing adaptation and survival in social groups. Here, we provide a narrative literature review on how human FER is modulated by neurotransmitters and pharmacological agents, classifying the documented effects by central neurotransmitter systems. Synthesising the findings from studies involving functional neuroimaging and FER tasks, we highlight several emerging themes; for example, noradrenaline promotes an overall positive bias in FER, while serotonin, dopamine and gamma-aminobutyric acid modulate emotions relating to self-preservation. Finally, other neurotransmitters including the cholinergic and glutamatergic systems are responsible for rather non-specific pro-cognitive effects in FER. With the ongoing accumulation of evidence further characterising the individual contributions of each neurotransmitter system, we argue that a sensible next step would be the integration of experimental neuropharmacology with computational models to infer further insights into the temporal dynamics of different neurotransmitter systems modulating FER.
Hypothalamic volume, sleep, and APOE genotype in cognitively healthy adults
INTRODUCTION: Sleep dysfunction in those at higher risk of dementia may be associated with early structural changes to the hypothalamus. METHODS: We used multivariate regression to analyze self-reported sleep (Pittsburgh Sleep Quality Index [PSQI]) from cognitively healthy participants in the PREVENT Dementia and Alzheimer's and Families (ALFA) studies (n = 1939), stratified by apolipoprotein E (APOE) genotype as homozygotes, heterozygotes, and non-carriers. FreeSurfer was used to extract hypothalamic subunit volumes from T1-weighted magnetic resonance images. RESULTS: APOE ε4 homozygotes had a larger anterior–superior hypothalamus compared to heterozygotes and non-carriers, an effect which was driven by younger people in the cohort. APOE ε4 carriers had a higher PSQI global score after age 55, and smaller anterior–superior and tubular–superior subunits were associated with more sleep disturbances. Sleep duration and efficiency worsened with age, but only in participants with a small anterior–inferior hypothalamus. DISCUSSION: This suggests that aging and APOE ε4 are associated with hypothalamic changes, highlighting mechanisms linking sleep dysfunction to dementia. Highlights: Apolipoprotein E (APOE) ε4 homozygotes ha a larger anterior–superior hypothalamus. APOE ε4 carriers have worse sleep, but only after age 55. Worse sleep in APOE ε4 carriers was associated with smaller hypothalamic subunits. Higher age was associated with worse sleep in people with a small hypothalamus.
Pain in women: bridging the gender pain gap.
Bridging the gender pain gap requires collaborative efforts that address female-specific biological and psychosocial dimensions of pain through evidence-based, compassionate and empathy-driven approaches.
Glucagon-Like Peptide 1 Receptor Agonists and Mental Health: A Systematic Review and Meta-Analysis.
IMPORTANCE: People with obesity and diabetes have poorer psychiatric and cognitive outcomes and lower quality of life (QOL) compared with those without. Glucagon-like peptide 1 receptor agonists (GLP1-RAs) are treatments for diabetes and obesity that may also influence psychiatric outcomes. OBJECTIVE: To conduct a meta-analysis of randomized placebo-controlled trials to evaluate psychiatric, cognitive, and QOL outcomes with GLP1-RA treatment. DATA SOURCES: MEDLINE, Embase, PsycINFO, and CENTRAL databases were searched from inception through June 24, 2024. STUDY SELECTION: Double-blind placebo-controlled trials comparing GLP1-RA to placebo in adults with overweight/obesity and/or diabetes, reporting on psychiatric, cognition, or QOL outcomes, were included. DATA EXTRACTION AND SYNTHESIS: Data extraction was performed in parallel by 2 reviewers. Random-effects meta-analysis was performed. Effect size measures were log risk ratios (log[RR]) and standardized mean differences (Hedges g). The quality of studies was appraised using the Cochrane risk-of-bias tool (RoB2). Certainty of evidence was assessed via GRADEpro. MAIN OUTCOMES AND MEASURES: Main outcomes were risk of psychiatric adverse events (serious and nonserious) and change in mental health symptom severity, health-related quality of life, and cognition. RESULTS: Eighty randomized clinical trials involving 107 860 patients were included in the meta-analysis. The mean (SD) age of participants across studies in the meta-analysis was 60.1 (7.1) years; 43 251 were female (40.1%) and 64 608 male (59.9%). GLP1-RA treatment was not associated with a significant difference in risk of serious psychiatric adverse events (log[RR] = -0.02; 95% CI, -0.20 to 0.17; P = .87) and nonserious psychiatric adverse events (log[RR] = -0.03; 95% CI, -0.21 to 0.16], P = .76), or depressive symptom change (g = 0.02; 95% CI, -0.51 to 0.55; P = .94), compared with placebo. GLP1-RA treatment was associated with improvements in restrained eating (g = 0.35; 95% CI, 0.13 to 0.57; P = .002) and emotional eating behavior (g = 0.32; 95% CI, 0.11 to 0.54; P = .003) and in mental health-related QOL (g = 0.15; 95% CI, 0.07 to 0.22; P
Nurse-delivered sleep restriction therapy to improve insomnia disorder in primary care: the HABIT RCT.
BACKGROUND: Insomnia is a prevalent and distressing sleep disorder. Multicomponent cognitive-behavioural therapy is the recommended first-line treatment, but access remains extremely limited, particularly in primary care where insomnia is managed. One principal component of cognitive-behavioural therapy is a behavioural treatment called sleep restriction therapy, which could potentially be delivered as a brief single-component intervention by generalists in primary care. OBJECTIVES: The primary objective of the Health-professional Administered Brief Insomnia Therapy trial was to establish whether nurse-delivered sleep restriction therapy in primary care improves insomnia relative to sleep hygiene. Secondary objectives were to establish whether nurse-delivered sleep restriction therapy was cost-effective, and to undertake a process evaluation to understand intervention delivery, fidelity and acceptability. DESIGN: Pragmatic, multicentre, individually randomised, parallel-group, superiority trial with embedded process evaluation. SETTING: National Health Service general practice in three regions of England. PARTICIPANTS: Adults aged ≥ 18 years with insomnia disorder were randomised using a validated web-based randomisation programme. INTERVENTIONS: Participants in the intervention group were offered a brief four-session nurse-delivered behavioural treatment involving two in-person sessions and two by phone. Participants were supported to follow a prescribed sleep schedule with the aim of restricting and standardising time in bed. Participants were also provided with a sleep hygiene leaflet. The control group received the same sleep hygiene leaflet by e-mail or post. There was no restriction on usual care. MAIN OUTCOME MEASURES: Outcomes were assessed at 3, 6 and 12 months. Participants were included in the primary analysis if they contributed at least one post-randomisation outcome. The primary end point was self-reported insomnia severity with the Insomnia Severity Index at 6 months. Secondary outcomes were health-related and sleep-related quality of life, depressive symptoms, work productivity and activity impairment, self-reported and actigraphy-defined sleep, and hypnotic medication use. Cost-effectiveness was evaluated using the incremental cost per quality-adjusted life-year. For the process evaluation, semistructured interviews were carried out with participants, nurses and practice managers or general practitioners. Due to the nature of the intervention, both participants and nurses were aware of group allocation. RESULTS: We recruited 642 participants (n = 321 for sleep restriction therapy; n = 321 for sleep hygiene) between 29 August 2018 and 23 March 2020. Five hundred and eighty participants (90.3%) provided data at a minimum of one follow-up time point; 257 (80.1%) participants in the sleep restriction therapy arm and 291 (90.7%) participants in the sleep hygiene arm provided primary outcome data at 6 months. The estimated adjusted mean difference on the Insomnia Severity Index was -3.05 (95% confidence interval -3.83 to -2.28; p
Sleep and motor learning in stroke (SMiLES): a longitudinal study investigating sleep-dependent consolidation of motor sequence learning in the context of recovery after stroke.
INTRODUCTION: There is growing evidence that sleep is disrupted after stroke, with worse sleep relating to poorer motor outcomes. It is also widely acknowledged that consolidation of motor learning, a critical component of poststroke recovery, is sleep-dependent. However, whether the relationship between disrupted sleep and poor outcomes after stroke is related to direct interference of sleep-dependent motor consolidation processes, is currently unknown. Therefore, the aim of the present study is to understand whether measures of motor consolidation mediate the relationship between sleep and clinical motor outcomes post stroke. METHODS AND ANALYSIS: We will conduct a longitudinal observational study of up to 150 participants diagnosed with stroke affecting the upper limb. Participants will be recruited and assessed within 7 days of their stroke and followed up at approximately 1 and 6 months. The primary objective of the study is to determine whether sleep in the subacute phase of recovery explains the variability in upper limb motor outcomes after stroke (over and above predicted recovery potential from the Predict Recovery Potential algorithm) and whether this relationship is dependent on consolidation of motor learning. We will also test whether motor consolidation mediates the relationship between sleep and whole-body clinical motor outcomes, whether motor consolidation is associated with specific electrophysiological sleep signals and sleep alterations during subacute recovery. ETHICS AND DISSEMINATION: This trial has received both Health Research Authority, Health and Care Research Wales and National Research Ethics Service approval (IRAS: 304135; REC: 22/LO/0353). The results of this trial will help to enhance our understanding of the role of sleep in recovery of motor function after stroke and will be disseminated via presentations at scientific conferences, peer-reviewed publication, public engagement events, stakeholder organisations and other forms of media where appropriate. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT05746260, registered on 27 February 2023.
Neurofeedback modulation of insula activity via MEG-based brain-machine interface: a double-blind randomized controlled crossover trial.
Insula activity has often been linked to pain perception, making it a potential target for therapeutic neuromodulation strategies such as neurofeedback. However, it is not known whether insula activity is under cognitive control and, if so, whether this activity is consequently causally related to pain. Here, we conducted a double-blind randomized controlled crossover trial to test the modulation of insula activity and pain thresholds using neurofeedback training. Nineteen healthy subjects underwent neurofeedback training for upmodulation and downmodulation of right insula activity using our magnetoencephalography (MEG)-based brain-machine interface. We observed significant differences in insula activity between the upmodulation and downmodulation training sessions. Furthermore, resting-state insula activity significantly decreased following downmodulation training compared to following upmodulation training. Compared with upmodulation training, downmodulation training was also associated with increased pain thresholds, albeit with no significant interaction effect. These findings show that humans can cognitively modulate insula activity as a potential route to develop therapeutic MEG neurofeedback systems for clinical testing. However, the present findings do not provide direct evidence of a causal link between modulation of insula activity and changes in pain thresholds.
Effects of 28-day simvastatin administration on emotional processing, reward learning, working memory, and salivary cortisol in healthy participants at-risk for depression: OxSTEP, an online experimental medicine trial.
BACKGROUND: Statins are among the most prescribed medications worldwide. Both beneficial (e.g. antidepressant and pro-cognitive) and adverse (e.g. depressogenic and cognitive-impairing) mental health outcomes have been described in clinical studies. The underlying neuropsychological mechanisms, whether positive or negative, are, however, not established. Clarifying such activities has implications for the safe prescribing and repurposing potential of these drugs, especially in people with depression. METHODS: In this double-blind, randomized, placebo-controlled experimental medicine study, we investigated the effects of simvastatin on emotional processing, reward learning, working memory, and waking salivary cortisol (WSC) in 101 people at-risk for depression due to reported high loneliness scores (mean 7.3 ± 1.2 on the UCLA scale). This trial was largely conducted during periods of social distancing due to the COVID-19 pandemic (July 2021-February 2023), and we employed a fully remote design within a UK-wide sample. RESULTS: High retention rates, minimal outlier data, and typical main effects of task condition (e.g. emotion) were seen in all cognitive tasks, indicating this approach was comparable to in-person testing. After 28 days, we found no statistically significant differences (F's 0.20) for any of the measures of emotional processing, reward learning, working memory, and WSC. CONCLUSIONS: Study results do not substantiate concerns regarding adverse neuropsychiatric events due to statins and support the safety of their prescribing in at-risk populations. Although other unmeasured cognitive processes may be involved, our null findings are also in line with more recent clinical evidence suggesting statins do not show antidepressant or pro-cognitive efficacy.
Pain management in preterm infants with necrotizing enterocolitis: an international expert consensus statement
Abstract Necrotizing enterocolitis (NEC) is probably the most painful intestinal disease affecting infants born preterm. NEC is known to cause highly severe and prolonged pain that has been associated with adverse short- and long-term effects. However, research on pain management in infants with NEC is scarce. This is likely due to its low incidence and very acute occurrence. As a result, the optimal pain management for these vulnerable infants remains unknown, and analgesic therapy practices are highly variable. Therefore, we aimed to establish expert-based consensus recommendations on pain management for NEC. Experts of the European Society for Paediatric Research (ESPR) Special Interest Groups on Neonatal pain and NEC were invited to participate in two consensus meetings. Prior to the first hybrid consensus meeting, an online survey provided input for potential recommendations. During the consensus meetings, experts shared clinical expertise and voted on recommendations. An expert consensus statement, comprising nine recommendations on optimal pain assessment and pain treatment in infants with NEC, was developed. Expert recommendations included regular pain assessments with a neonatal pain scale with additional assessments on indication and pre-emptive administration of analgesic therapy (e.g., paracetamol and an opioid) in infants with NEC stage ≥ II. Conclusion: This expert consensus statement provides clinical recommendations essential for any healthcare professional caring for premature infants with NEC. The recommended guidance this statement provides on pain management strategies is key to preventing and reducing pain in this vulnerable population. What is Known: • Necrotizing enterocolitis (NEC) is a very painful disease, making effective pain management essential.• Current pain management practices for infants with NEC are highly variable. What is New: • This expert consensus statement provides recommendations on optimal pain assessment and pain treatment in infants with NEC.• These clinical recommendations may help better prevent pain in these vulnerable infants.
Human decisions about when to act originate within a basal forebrain-nigral circuit.
Decisions about when to act are critical for survival in humans as in animals, but how a desire is translated into the decision that an action is worth taking at any particular point in time is incompletely understood. Here we show that a simple model developed to explain when animals decide it is worth taking an action also explains a significant portion of the variance in timing observed when humans take voluntary actions. The model focuses on the current environment's potential for reward, the timing of the individual's own recent actions, and the outcomes of those actions. We show, by using ultrahigh-field MRI scanning, that in addition to anterior cingulate cortex within medial frontal cortex, a group of subcortical structures including striatum, substantia nigra, basal forebrain (BF), pedunculopontine nucleus (PPN), and habenula (HB) encode trial-by-trial variation in action time. Further analysis of the activity patterns found in each area together with psychophysiological interaction analysis and structural equation modeling suggested a model in which BF integrates contextual information that will influence the decision about when to act and communicates this information, in parallel with PPN and HB influences, to nigrostriatal circuits. It is then in the nigrostriatal circuit that action initiation per se begins.
Ultra-high temporal resolution 4D angiography using arterial spin labeling with subspace reconstruction.
PURPOSE: To achieve ultra-high temporal resolution non-contrast 4D angiography with improved spatiotemporal fidelity. METHODS: Continuous data acquisition using 3D golden-angle sampling following an arterial spin labeling preparation allows for flexibly reconstructing 4D dynamic angiograms at arbitrary temporal resolutions. However, k-space data is often temporally "binned" before image reconstruction, negatively affecting spatiotemporal fidelity and limiting temporal resolution. In this work, a subspace was extracted by linearly compressing a dictionary constructed from simulated curves of an angiographic kinetic model. The subspace was used to represent and reconstruct the voxelwise signal timecourse at the same temporal resolution as the data acquisition without temporal binning. Physiological parameters were estimated from the resulting images using a Bayesian fitting approach. A group of eight healthy subjects were scanned and the in vivo results reconstructed by different methods were compared. Because of the difficulty of obtaining ground truth 4D angiograms with ultra-high temporal resolution, the in vivo results were cross-validated with numerical simulations. RESULTS: The proposed method enables 4D time-resolved angiography with much higher temporal resolution (14.7 ms) than previously reported (˜50 ms) while maintaining high spatial resolution (1.1 mm isotropic). Blood flow dynamics were depicted in greater detail, thin vessel visibility was improved, and the estimated physiological parameters also exhibited more realistic spatial patterns with the proposed method. CONCLUSION: Incorporating a subspace compressed kinetic model into the reconstruction of 4D ASL angiograms notably improved the temporal resolution and spatiotemporal fidelity, which was subsequently beneficial for accurate physiological modeling.