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ENeuro Jun 2024Acetylcholine (ACh) neurons in the central nervous system are required for the coordination of neural network activity during higher brain functions, such as attention,...
Acetylcholine (ACh) neurons in the central nervous system are required for the coordination of neural network activity during higher brain functions, such as attention, learning, and memory, as well as locomotion. Disturbed cholinergic signaling has been described in many neurodevelopmental and neurodegenerative disorders. Furthermore, co-transmission of other signaling molecules, such as glutamate and GABA, with ACh has been associated with essential roles in brain function or disease. However, it is unknown when ACh neurons become cholinergic during development. Thus, understanding the timeline of how the cholinergic system develops and becomes active in the healthy brain is a crucial part of understanding brain development. To study this, we used transgenic mice to selectively label ACh neurons with tdTomato. We imaged serial sectioned brains and generated whole-brain reconstructions at different time points during pre- and postnatal development. We found three crucial time windows - two in the prenatal and one in the postnatal brain - during which most ACh neuron populations become cholinergic in the brain. We also found that cholinergic gene expression is initiated in cortical ACh interneurons, while the cerebral cortex is innervated by cholinergic projection neurons from the basal forebrain. Taken together, we show that ACh neuron populations are present and become cholinergic before postnatal day 12, which is the onset of major sensory processes, such as hearing and vision. We conclude that birth of ACh neurons and initiation of cholinergic gene expression are temporally separated during development but highly coordinated by brain anatomical structure. Acetylcholine (ACh) neurons are required for higher brain functions and locomotion. Disturbed cholinergic signaling was observed in neurodevelopmental disorders and intellectual disability. While the role of ACh release in neural circuit function is well understood, it is unknown when ACh neurons become cholinergic. We labelled ACh neurons to investigate when ACh neurons become cholinergic in the developing brain and performed reconstructions of serial sectioned brains. Here, we show that ACh neuron populations become cholinergic during three time windows pre- and postnatally. ACh neurons become cholinergic following the caudorostral direction of brain formation. In cortex and hippocampus, activation of cholinergic gene expression in ACh interneurons coincides with cholinergic innervation from the basal forebrain. We highlight that brain ACh neurons are cholinergic before P12, the onset of major sensory functions, such as hearing and vision.
PubMed: 38942474
DOI: 10.1523/ENEURO.0542-23.2024 -
The Spine Journal : Official Journal of... Jun 2024Extreme Lateral Interbody Fusion (XLIF) has been established as an effective treatment for degenerative disorders of the lumbar spine. Nevertheless, there is a potential...
BACKGROUND CONTEXT
Extreme Lateral Interbody Fusion (XLIF) has been established as an effective treatment for degenerative disorders of the lumbar spine. Nevertheless, there is a potential risk of lumbar plexus damage associated with XLIF, especially during surgeries at the L4-5 segment. Diffusion Tensor Imaging (DTI) evaluates the directional diffusion of water molecules in tissue, providing a more intricate depiction of internal tissue microstructure compared to conventional MRI techniques. The capability of DTI sequences to elucidate the three-dimensional interplay between lumbar nerve pathways and adjacent musculoskeletal structures, potentially reducing the incidence of nerve injury complications related to XLIF, remains to be established.
PURPOSE
This study evaluates the effectiveness of preoperative Diffusion Tensor Imaging (DTI) in reducing neurological complications after Extreme Lateral Interbody Fusion (XLIF) surgeries at the L4-5 level, focusing on the interaction between lumbar nerves and the psoas major muscle.
STUDY DESIGN
Retrospective case-control study.
PATIENT SAMPLE
The study included 128 patients undergoing XLIF surgery for degenerative disorders at the L4-5 segment: 68 in the traditional group and 62 in the DTI group.
OUTCOME MEASURES
The study assessed Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) scores, along with complication rates. It also documented psoas major muscle morphology and its correlation with nerve pathways.
METHODS
A retrospective analysis of 128 patients undergoing XLIF surgery for degenerative disorders at the L4-5 segment between February 2020 and August 2022 was conducted. The cohort was divided into a traditional group (68 patients) receiving pre-surgery MRI scans to identify surgical entry points at the intervertebral space midpoint (Zones II-III junction) and a DTI group (62 patients) who additionally underwent preoperative DTI to customize entry points. The study evaluated VAS and ODI scores, complication rates, psoas major muscle morphology, and its interaction with nerve pathways.
RESULTS
The traditional group uniformly chose the Zone II-III junction for entry. In contrast, the DTI group's entry points varied. Postoperative follow-up revealed significant improvements in VAS and ODI scores in both groups. However, the DTI group experienced fewer immediate postoperative complications such as thigh pain, numbness, and motor disturbances. The study also noted a ventral shift in nerve positioning in patients with elevated psoas muscles.
CONCLUSIONS
Preoperative DTI effectively maps the relationship between the psoas major muscle and lumbar nerves. Tailoring surgical entry points based on DTI results significantly reduces the risk of nerve damage in XLIF surgeries. The study underscores the importance of recognizing variability in lumbar nerve pathways due to differing psoas muscle morphologies, highlighting a higher risk of nerve injury in patients with elevated psoas muscles during XLIF procedures.
PubMed: 38942298
DOI: 10.1016/j.spinee.2024.06.017 -
The Spine Journal : Official Journal of... Jun 2024Associations between magnetic resonance imaging (MRI)-detected lumbar intervertebral disc degeneration (LDD) and LBP are often of modest magnitude. This association may...
BACKGROUND CONTEXT
Associations between magnetic resonance imaging (MRI)-detected lumbar intervertebral disc degeneration (LDD) and LBP are often of modest magnitude. This association may be larger in specific patient subgroups.
PURPOSE
To examine whether the association between LDD and LBP is modified by underlying genetic predispositions to pain.
STUDY DESIGN
Cross-sectional study in UK Biobank (UKB) and TwinsUK.
PATIENT SAMPLES
A genome-wide association study (GWAS) of the number of anatomical chronic pain locations was conducted in 347,538 UKB participants. The GWAS was used to develop a genome-wide polygenic risk score (PRS) in a holdout sample of 30,000 UKB participants. The PRS model was then used in analyses of 645 TwinsUK participants with standardized LDD MRI assessments.
OUTCOME MEASURES
Ever having had LBP associated with disability lasting ≥1 month (LBP1).
METHODS
Using the PRS as a proxy for "genetically-predicted propensity to pain", we stratified TwinsUK participants into PRS quartiles. A "basic" model examined the association between an LDD summary score (LSUM) and LBP1, adjusting for covariates. A "fully-adjusted" model also adjusted for PRS quartile and LSUM x PRS quartile interaction terms.
RESULTS
In the basic model, the odds ratio (OR) of LBP1 was 1.8 per standard deviation of LSUM (95% confidence interval [CI] 1.4 -2.3). In the fully-adjusted model, there was a statistically significant LSUM-LBP1 association in quartile 4, the highest PRS quartile (OR = 2.5 [95% CI 1.7-3.7], p=2.6×10), and in quartile 3 (OR=2.0, [95% CI 1.3-3.0]; p=0.002), with small-magnitude and/or non-significant associations in the lowest two PRS quartiles. PRS quartile was a significant effect modifier of the LSUM-LBP1 association (interaction p≤0.05).
CONCLUSIONS
Genetically-predicted propensity to pain modifies the LDD-LBP association, with the strongest association present in people with the highest genetic propensity to pain. Lumbar MRI findings may have stronger connections to LBP in specific subgroups of people.
PubMed: 38942297
DOI: 10.1016/j.spinee.2024.05.018 -
Journal of AAPOS : the Official... Jun 2024Terminal deletions of chromosome 3q are associated with a heterogenous clinical phenotype, which includes growth restriction, developmental delay, and intellectual...
Terminal deletions of chromosome 3q are associated with a heterogenous clinical phenotype, which includes growth restriction, developmental delay, and intellectual disability. However, little has been published on the ophthalmic impacts of chromosome 3q deletions. We report a 9-year-old boy with a 1.4 megabase deletion of 3q27.1q27.2 whose ocular morbidities included retinal detachment in one eye, vitreous hemorrhage in the other eye, and foveal hypoplasia in both eyes that required acute care and continuous ophthalmologic follow-up.
PubMed: 38942230
DOI: 10.1016/j.jaapos.2024.103960 -
Metabolism: Clinical and Experimental Jun 2024Metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiometabolic conditions affect populations across economic strata. Nevertheless, there are...
Disparities in metabolic dysfunction-associated steatotic liver disease and cardiometabolic conditions in low and lower middle-income countries: systematic analysis from the global burden of disease study 2019.
OBJECTIVE
Metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiometabolic conditions affect populations across economic strata. Nevertheless, there are limited epidemiological studies addressing these diseases in low (LICs) and lower-middle-income countries (lower MICs). Therefore, an analysis of the trend of MASLD and cardiometabolic conditions in these countries is necessary.
METHODS
From 2000 to 2019, jointpoint regression analysis was employed to calculate the prevalence, mortality, and disability-adjusted life years (DALYs) for cardiometabolic conditions including MASLD, type 2 diabetes mellitus (T2DM), dyslipidemia (DLP), hypertension (HTN), obesity, peripheral artery disease (PAD), atrial fibrillation and flutter (AF/AFL), ischemic heart disease (IHD), stroke, and chronic kidney disease from HTN and T2DM, in LICs and lower MICs (according to the World Bank Classification 2019) using the Global Burden of Disease 2019 data.
RESULTS
Among the eleven cardiometabolic conditions, MASLD (533.65 million), T2DM (162.96 million), and IHD (76.81 million) had the highest prevalence in LICs and Lower MICs in 2019. MASLD represented the largest proportion of global prevalence in these countries (43 %). From 2000 to 2019, mortality in LICs and lower MICs increased in all cardiometabolic conditions, with obesity-related mortality having the highest increase (+134 %). During this timeframe, there were increased age-standardized death rates (ASDR) from obesity, PAD, and AF/AFL. From all conditions, the DALYs-to-prevalence ratio was higher in LICs and lower MICs than the global average.
CONCLUSION
The burden of MASLD and cardiometabolic conditions is increasing worldwide, with LICs and lower MICs experiencing higher disability per prevalence. As these conditions are preventable, counteracting these trends requires not only the modification of ongoing actions but also the strategizing of immediate interventions.
PubMed: 38942169
DOI: 10.1016/j.metabol.2024.155958 -
Biochemical Pharmacology Jun 2024GPR56, also known as GPR56/ADGRG1, is a member of the ADGRG subgroup belonging to adhesion G protein-coupled receptors (aGPCRs). aGPCRs are the second largest subfamily... (Review)
Review
GPR56, also known as GPR56/ADGRG1, is a member of the ADGRG subgroup belonging to adhesion G protein-coupled receptors (aGPCRs). aGPCRs are the second largest subfamily of the GPCR superfamily, which is the largest family of membrane protein receptors in the human genome. Studies in recent years have demonstrated that GPR56 is integral to the normal development of the brain and functions as an important player in cortical development, suggesting that GPR56 is involved in many physiological processes. Indeed, aberrant expression of GPR56 has been implicated in multiple neurological and psychiatric disorders, including bilateral frontoparietal polymicrogyria (BFPP), depression and epilepsy. In a recent study, it was found that upregulated expression of GPR56 reduced depressive-like behaviours in an animal model of depression, indicating that GPR56 plays an important role in the antidepressant response. Given the link of GPR56 with the antidepressant response, the function of GPR56 has become a focus of research. Although GPR56 may be a potential target for the development of antidepressants, the underlying molecular mechanisms remain largely unknown. Therefore, in this review, we will summarize the latest findings of GPR56 function in neurological and psychiatric disorders (depression, epilepsy, autism, and BFPP) and emphasize the mechanisms of GPR56 in activation and signalling in those conditions. After reviewing several studies, attributing to its significant biological functions and exceptionally long extracellular N-terminus that interacts with multiple ligands, we draw a conclusion that GPR56 may serve as an important drug target for neuropsychological diseases.
PubMed: 38942087
DOI: 10.1016/j.bcp.2024.116395 -
The Lancet. Global Health Jun 2024Insufficient physical activity increases the risk of non-communicable diseases, poor physical and cognitive function, weight gain, and mental ill-health. Global...
National, regional, and global trends in insufficient physical activity among adults from 2000 to 2022: a pooled analysis of 507 population-based surveys with 5·7 million participants.
BACKGROUND
Insufficient physical activity increases the risk of non-communicable diseases, poor physical and cognitive function, weight gain, and mental ill-health. Global prevalence of adult insufficient physical activity was last published for 2016, with limited trend data. We aimed to estimate the prevalence of insufficient physical activity for 197 countries and territories, from 2000 to 2022.
METHODS
We collated physical activity reported by adults (aged ≥18 years) in population-based surveys. Insufficient physical activity was defined as not doing 150 minutes of moderate-intensity activity, 75 minutes of vigorous-intensity activity, or an equivalent combination per week. We used a Bayesian hierarchical model to compute estimates of insufficient physical activity by country or territory, year, age, and sex. We assessed whether countries or territories, regions, and the world would meet the global target of a 15% relative reduction of the prevalence of insufficient physical activity by 2030 if 2010-22 trends continue.
FINDINGS
We included 507 surveys across 163 countries and territories. The global age-standardised prevalence of insufficient physical activity was 31·3% (95% uncertainty interval 28·6-34·0) in 2022, an increase from 23·4% (21·1-26·0) in 2000 and 26·4% (24·8-27·9) in 2010. Prevalence was increasing in 103 (52%) of 197 countries and territories and six (67%) of nine regions, and was declining in the remainder. Prevalence was 5 percentage points higher among female (33·8% [29·9-37·7]) than male (28·7% [25·0-32·6]) individuals. Insufficient physical activity increased in people aged 60 years and older in all regions and both sexes, but age patterns differed for those younger than 60 years. If 2010-22 trends continue, the global target of a 15% relative reduction between 2010 and 2030 will not be met (posterior probability <0·01); however, two regions, Oceania and sub-Saharan Africa, were on track with considerable uncertainty (posterior probabilities 0·70-0·74).
INTERPRETATION
Concerted multi-sectoral efforts to reduce insufficient physical activity levels are needed to meet the 2030 target. Physical activity promotion should not exacerbate sex, age, or geographical inequalities.
FUNDING
Ministry of Public Health, Qatar, and World Health Organization.
TRANSLATIONS
For the Spanish and Portuguese translations of the abstract see Supplementary Materials section.
PubMed: 38942042
DOI: 10.1016/S2214-109X(24)00150-5 -
Epilepsy & Behavior : E&B Jun 2024It has been determined that quality of life in epilepsy is closely related to the perceived disability experienced by individuals with the diagnosis. However, this...
It has been determined that quality of life in epilepsy is closely related to the perceived disability experienced by individuals with the diagnosis. However, this measure is seldom considered in healthcare processes. The objective of the present study is to establish the psychometric properties of the Perceived Disability Questionnaire in individuals diagnosed with epilepsy within a Latin American context. A cross-sectional, analytical study was conducted involving 325 participants, aged 12 years and older (M 40.42 years), individuals diagnosed with epilepsy in Colombia. The main psychometric properties of the instrument were explored to account for its factorial validity and reliability. The Perceived Disability Questionnaire exhibits high reliability (α = 0.878) and the three subscales comprising the final version of the questionnaire (Dissatisfaction, Pessimism, and Self-Disdain) explain 45.393 % of the total variance in relation to beliefs of disability associated with the diagnosis of epilepsy; the questionnaire significantly correlates with the Quality of Life in Epilepsy Inventory (QOLIE-10). Adequate psychometric properties of the instrument are found, which allows for its proposal as a tool in epilepsy care processes within the Colombian context.
PubMed: 38941952
DOI: 10.1016/j.yebeh.2024.109915 -
Seizure Jun 2024The purpose of this study was to describe intellectual disability and its association with epilepsy and brain imaging, in a population-based group of children with...
PURPOSE
The purpose of this study was to describe intellectual disability and its association with epilepsy and brain imaging, in a population-based group of children with hemiplegic (unilateral) cerebral palsy, previously investigated and published in 2020.
MATERIALS AND METHODS
Forty-seven children of school age in northern Stockholm, fulfilling the Surveillance of Cerebral Palsy in Europe-criteria of hemiplegic (unilateral spastic) cerebral palsy, were invited to participate in the study. Twenty-one children consented to participate. A WISC (Wechsler Intelligence Scale for Children)-test was performed by an experienced psychologist.
RESULTS
In the study population of twenty-one children, 57 % (n 12) displayed uneven cognitive profiles, 38 % (n 8) intellectual disability and 62 % (n 13) had a normal IQ. 43 % (n 9) developed epilepsy. Children with extensive brain lesions had more severe intellectual disability.
CONCLUSIONS
In this study intellectual disability and/or epilepsy were associated with the type and extent of the underlying brain lesion. Intellectual disability and uneven cognitive profiles were common. We therefore recommend individual cognitive assessment to ensure an optimal school start.
PubMed: 38941801
DOI: 10.1016/j.seizure.2024.06.012 -
Asian Journal of Psychiatry Jun 2024Compared to the West, suicide prevention in the Southeast Asian (SEA) region is challenging due to resource constraints, a relatively greater contribution of social...
Compared to the West, suicide prevention in the Southeast Asian (SEA) region is challenging due to resource constraints, a relatively greater contribution of social compared to psychological factors, and low levels of general awareness coupled with high stigma around suicide and mental illness. Collaboration and knowledge sharing are essential to circumvent these challenges. The Partnerships for Life (PfL) initiative of the International Association of Suicide Prevention aims to enhance knowledge sharing, foster collaboration between nations, and support the development and implementation of evidence-informed approaches to suicide prevention. In February 2024, the SEA region of the PfL conducted the first regional workshop on suicide prevention, in which representatives from 10 out of 12 SEA nations participated. In this paper, we outline the key priorities, challenges, strengths, and opportunities for suicide prevention in the region with a view to inform resource-effective suicide prevention strategies that have optimal utility and uptake.
PubMed: 38941709
DOI: 10.1016/j.ajp.2024.104126