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Journal of Inherited Metabolic Disease Jun 2024Cerebrotendinous xanthomatosis is a rare and treatable metabolic disorder related to the accumulation of cholestanol. This disorder is primarily associated with motor...
Cerebrotendinous xanthomatosis is a rare and treatable metabolic disorder related to the accumulation of cholestanol. This disorder is primarily associated with motor and cognitive impairments, although the latter has not been extensively characterized. The objectives of this work were to define the cognitive profile found in cerebrotendinous xanthomatosis patients, investigate the progression of cognitive impairment over time, and search for radio-clinical correlations. Through a multicentric chart review study, we collected cognitive and radiological data from nine children and eighteen adults with genetically proven cerebrotendinous xanthomatosis. We performed a volumetric and morphological analysis of the brain magnetic resonance imaging. In our cohort, 44% (4/9) of children and 78% (14/18) of adults exhibited cognitive impairment that can be severe. The study revealed a significant impairment in various cognitive domains, specifically executive, attentional, language, and visuo-spatial. Among adults, 16% (3/18) developed dementia after age 50. These three patients had delayed chenodeoxycholic acid treatment and important cerebral atrophy. Besides these three cases of late-onset cognitive decline, Mini-Mental State Evaluation was generally stable, suggesting cognitive impairment due to a neurodevelopmental disorder and persisting in adulthood. Cognitive impairment was less common in children, possibly related to early chenodeoxycholic acid treatment in our cohort. The severity of magnetic resonance imaging abnormalities did not predict cognitive impairment in patients. Overall, in cerebrotendinous xanthomatosis, cognitive impairment can be severe and mainly neurodevelopmental. Early chenodeoxycholic acid treatment might be associated with a reduced risk of cognitive decline.
PubMed: 38897600
DOI: 10.1002/jimd.12765 -
The Science of the Total Environment Jun 2024Ammonia (NH), which is a precursor of secondary particulate matter (PM), can be produced through three-way catalyst (TWC) side reactions in light-duty gasoline vehicles...
Ammonia (NH), which is a precursor of secondary particulate matter (PM), can be produced through three-way catalyst (TWC) side reactions in light-duty gasoline vehicles (LDGVs), posing a threat to human health and air quality. To explore ammonia emission characteristics, 8 LDGVs and 1 hybrid electric light-duty vehicle (HEV) with various mileages traveled were analyzed with a chassis dynamometer system during regulation driving cycles. The emission factors of the adopted China VI in-use LDGVs were 7.04 ± 2.61 mg/km under cold-start conditions and 4.94 ± 1.69 mg/km under hot-start conditions. With increasing mileage traveled, the total ammonia emissions increased, and the difference between the cold/hot-start results decreased. The emissions of in-use LDGVs with bi-fuel engines were analyzed, and more ammonia was generated in the compressed natural gas (CNG) mode through the hydrocarbon (HC) reforming reaction. The relationship between the emissions of ammonia and conventional pollutants was established. During the initial cold-start phase, a delay in ammonia formation was observed, and the ammonia emissions conformed with the CO and HC emissions after exhaust heating. Vehicle specific power (VSP) analysis revealed that the interval of highest ammonia emissions corresponded to acceleration events at high speeds. For the HEV, the transition from motor to engine drive conditions contributed to ammonia emission occurrence because of the more pronounced cold-start events. The use of HEV technology could introduce additional uncertainties in controlling urban ammonia emissions. Detailed analysis of emission characteristics could provide data support for future research on ammonia emission standards and control strategies for LDGVs.
PubMed: 38897474
DOI: 10.1016/j.scitotenv.2024.173967 -
Nutritional Neuroscience Jun 2024Vitamin D is involved in several processes related to the development of neuronal and non-neuronal cells. There is a possible link between maternal vitamin D status in...
AIM
Vitamin D is involved in several processes related to the development of neuronal and non-neuronal cells. There is a possible link between maternal vitamin D status in pregnancy and delayed neurocognitive development in the offspring. The aim of the study was to explore the association of maternal and cord blood vitamin D levels with infants' neurodevelopment at 6 and 9 months of age.
METHODOLOGY
A cohort study was conducted in western Rajasthan, India. Maternal and cord blood samples were collected at the time of delivery. Serum 25(OH)-vitamin D levels were measured in both. Infant neurodevelopment was assessed at 6 and 9 months of age in six domains namely cognitive, receptive language, expressive language, fine motor, gross motor and social-emotional using the Bayley Scale of Infant Development- III (BSID-III).
RESULTS
A total of 175 mother-child pairs were enrolled. Among the mothers taking part in this study, 7.3% had deficient and 59.09% had insufficient levels of serum 25(OH) vitamin D during the third trimester of their pregnancy. Maternal and cord blood serum 25-OH vitamin D levels were 18.86 ± 8.53 ng/mL and 17.39 ± 8.87 ng/mL, respectively, and there was a significant correlation (r = 0.9778, = 0.000) between levels of vitamin D. Based on the repeated measures ANOVA, post hoc Tukey's HSD test, maternal vitamin D levels had a significant relationship ( = 0.047) to the cognitive development of infants at 6 months of age. Furthermore, cord serum vitamin D levels showed a significant association ( = 0.023 and = 0.010) with the social-emotional development of the infant at the age of 6 and 9 months.
CONCLUSION
Maternal and cord serum 25-OH vitamin D deficiency was significantly associated with the cognitive and social-emotional development of infants.
PubMed: 38896552
DOI: 10.1080/1028415X.2024.2366649 -
Synapse (New York, N.Y.) Jul 2024The goal of this report is to explore how K2P channels modulate axonal excitability by using the crayfish ventral superficial flexor preparation. This preparation allows...
The goal of this report is to explore how K2P channels modulate axonal excitability by using the crayfish ventral superficial flexor preparation. This preparation allows for simultaneous recording of motor nerve extracellular action potentials (eAP) and intracellular excitatory junctional potential (EJP) from a muscle fiber. Previous pharmacological studies have demonstrated the presence of K2P-like channels in crayfish. Fluoxetine (50 µM) was used to block K2P channels in this study. The blocker caused a gradual decline, and eventually complete block, of motor axon action potentials. At an intermediate stage of the block, when the peak-to-peak amplitude of eAP decreased to ∼60%-80% of the control value, the amplitude of the initial positive component of eAP declined at a faster rate than that of the negative peak representing sodium influx. Furthermore, the second positive peak following this sodium influx, which corresponds to the after-hyperpolarizing phase of intracellularly recorded action potentials (iAP), became larger during the intermediate stage of eAP block. Finally, EJP recorded simultaneously with eAP showed no change in amplitude, but did show a significant increase in synaptic delay. These changes in eAP shape and EJP delay are interpreted as the consequence of depolarized resting membrane potential after K2P channel block. In addition to providing insights to possible functions of K2P channels in unmyelinated axons, results presented here also serve as an example of how changes in eAP shape contain information that can be used to infer alterations in intracellular events. This type of eAP-iAP cross-inference is valuable for gaining mechanistic insights here and may also be applicable to other model systems.
Topics: Animals; Astacoidea; Fluoxetine; Action Potentials; Motor Neurons; Axons
PubMed: 38896000
DOI: 10.1002/syn.22304 -
Frontiers in Pharmacology 2024Patients with mutations that alter the function of the sodium channel present with a range of clinical features, including mild to severe seizures, developmental delay,...
Patients with mutations that alter the function of the sodium channel present with a range of clinical features, including mild to severe seizures, developmental delay, intellectual disability, autism, feeding dysfunction, motor impairment, and hypotonia. In an effort to identify compounds that could be potentially beneficial in associated epilepsy, Atkin et al. conducted an screen which resulted in the identification of 90 compounds that effectively reduced sodium influx into the cells expressing the human R1872Q mutation. The top compounds that emerged from this screen included amitriptyline, carvedilol, and nilvadipine. In the current study, we evaluated the ability of these three compounds to increase resistance to 6 Hz or pentylenetetrazole (PTZ)-induced seizures in wild-type CF1 mice and in a mouse line expressing the human R1620L mutation. We also evaluated the effects of fenfluramine administration, which was recently associated with a 60%-90% decrease in seizure frequency in three patients with -associated epilepsy. While amitriptyline, carvedilol, and fenfluramine provided robust protection against induced seizures in CF1 mice, only carvedilol was able to significantly increase resistance to 6 Hz- and PTZ-induced seizures in RL/+ mutants. These results provide support for further evaluation of carvedilol as a potential treatment for patients with mutations.
PubMed: 38895634
DOI: 10.3389/fphar.2024.1397225 -
Korean Journal of Anesthesiology Jun 2024Elderly patients with femoral neck fractures, particularly those with severe comorbidities or living in regions with limited medical resources, may experience delays in...
BACKGROUND
Elderly patients with femoral neck fractures, particularly those with severe comorbidities or living in regions with limited medical resources, may experience delays in surgical treatment. Although the benefits of preoperative rehabilitation (prehabilitation) in hip arthroplasty have been reported, pain management remains a challenge. The pericapsular nerve group (PENG) block, known for its exceptional analgesic effect and motor function preservation, may be a promising intervention during prehabilitation in these patients.
CASE
We enrolled ten patients with Garden classification 3-4 femoral neck fractures scheduled for hip arthroplasty. After receiving a PENG block with 20 ml of 0.375% ropivacaine, all patients underwent initial prehabilitation sessions comprising 9 mobility levels, ranging from bed-sitting to walking. One patient was excluded due to experiencing high blood pressure during prehabilitation. Six of the nine remaining patients (66.7%) were successfully transferred from bed to wheelchair.
CONCLUSIONS
The PENG block enhanced prehabilitation for patients with femoral neck fractures undergoing hip arthroplasty.
PubMed: 38894684
DOI: 10.4097/kja.24232 -
Journal of Neuropathology and... Jun 2024Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder due to deletion or mutation of survival motor neuron 1 (SMN1) gene. Although survival...
Revealing the potential role of hsa-miR-663a in modulating the PI3K-Akt signaling pathway via miRNA microarray in spinal muscular atrophy patient fibroblast-derived iPSCs.
Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder due to deletion or mutation of survival motor neuron 1 (SMN1) gene. Although survival motor neuron 2 (SMN2) gene is still present in SMA patients, the production of full-length survival motor neuron (SMN) protein is insufficient owing to missing or mutated SMN1. No current disease-modifying therapies can cure SMA. The aim of this study was to explore microRNA (miRNA)-based therapies that may serve as a potential target for therapeutic intervention in delaying SMA progression or as treatment. The study screened for potentially dysregulated miRNAs in SMA fibroblast-derived iPSCs using miRNA microarray. Results from the miRNA microarray were validated using quantitative reverse transcription polymerase chain reaction. Bioinformatics analysis using various databases was performed to predict the potential putative gene targeted by hsa-miR-663a. The findings showed differential expression of hsa-miR-663a in SMA patients in relation to a healthy control. Bioinformatics analysis identified GNG7, IGF2, and TNN genes that were targeted by hsa-miR-663a to be involved in the PI3K-AKT pathway, which may be associated with disease progression in SMA. Thus, this study suggests the potential role of hsa-miR-663a as therapeutic target for the treatment of SMA patients in the near future.
PubMed: 38894621
DOI: 10.1093/jnen/nlae065 -
Clinical Genetics Jun 2024Ionotropic glutamate receptors (iGluRs), specifically α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs), play a crucial role in orchestrating...
Ionotropic glutamate receptors (iGluRs), specifically α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs), play a crucial role in orchestrating excitatory neurotransmission in the brain. AMPARs are intricate assemblies of subunits encoded by four paralogous genes: GRIA1-4. Functional studies have established that rare GRIA variants can alter AMPAR currents leading to a loss- or gain-of-function. Patients affected by rare heterozygous GRIA variants tend to have family specific variants and only few recurrent variants have been reported. We deep-phenotyped a cohort comprising eight unrelated children and adults, harboring a recurrent and well-established disease-causing GRIA1 variant (NM_001114183.1: c.1906G>A, p.(Ala636Thr)). Recurrent symptoms included motor and/or language delay, mild-severe intellectual disability, behavioral and psychiatric comorbidities, hypotonia and epilepsy. We also report challenges in social skills, autonomy, living and work situation, and occupational levels. Furthermore, we compared their clinical manifestations in relation to those documented in patients presenting with rare heterozygous variants at analogous positions within paralogous genes. This study provides unprecedented details on the neurodevelopmental outcomes, cognitive abilities, seizure profiles, and behavioral abnormalities associated with p.(Ala636Thr) refining and broadening the clinical phenotype.
PubMed: 38890806
DOI: 10.1111/cge.14577 -
Scientific Reports Jun 2024Neurodevelopmental disorders (NDD) in offspring are associated with a complex combination of pre-and postnatal factors. This study uses machine learning and population...
Neurodevelopmental disorders (NDD) in offspring are associated with a complex combination of pre-and postnatal factors. This study uses machine learning and population data to evaluate the association between prepregnancy or perinatal risk factors and the NDD of offspring. Population-based retrospective cohort data were obtained from Korea National Health Insurance Service claims data for 209,424 singleton offspring and their mothers who gave birth for the first time in 2007. The dependent variables were motor development disorder (MDD), cognitive development disorder (CDD) and combined overall neurodevelopmental disorder (NDD) from offspring. Seventeen independent variables from 2002 to 2007 were included. Random forest variable importance and Shapley Additive Explanation (SHAP) values were calculated to analyze the directions of its associations with the predictors. The random forest with oversampling registered much higher areas under the receiver-operating-characteristic curves than the logistic regression of interaction and non-linearity terms, 79% versus 50% (MDD), 82% versus 52% (CDD) and 74% versus 50% (NDD). Based on random forest variable importance, low socioeconomic status and age at birth were highly ranked. In SHAP values, there was a positive association between NDD and pre- or perinatal outcomes, especially, fetal male sex with growth restriction associated the development of NDD in offspring.
Topics: Humans; Female; Risk Factors; Machine Learning; Male; Pregnancy; Neurodevelopmental Disorders; Adult; Republic of Korea; Retrospective Studies; Infant, Newborn; Child, Preschool; Child
PubMed: 38886474
DOI: 10.1038/s41598-024-64590-8 -
IEEE Transactions on Neural Systems and... 2024The loss of sensitivity of the upper limb due to neurological injuries severely limits the ability to manipulate objects, hindering personal independence. Non-invasive...
The loss of sensitivity of the upper limb due to neurological injuries severely limits the ability to manipulate objects, hindering personal independence. Non-invasive augmented sensory feedback techniques are used to promote neural plasticity hence to restore the grasping function. This work presents a wearable device for restoring sensorimotor hand functions based on Discrete Event-driven Sensory Control policy. It consists of an instrumented glove that, relying on piezoelectric sensors, delivers short-lasting vibrotactile stimuli synchronously with the relevant mechanical events (i.e., contact and release) of the manipulation. We first performed a feasibility study on healthy participants (20) that showed overall good performances of the device, with touch-event detection accuracy of 96.2% and a response delay of 22 ms. Later, we pilot tested it on two participants with limited sensorimotor functions. When using the device, they improved their hand motor coordination while performing tests for hand motor coordination assessment (i.e., pick and place test, pick and lift test). In particular, they exhibited more coordinated temporal correlations between grip force and load force profiles and enhanced performances when transferring objects, quantitatively proving the effectiveness of the device.
Topics: Humans; Feedback, Sensory; Male; Hand; Hand Strength; Adult; Female; Healthy Volunteers; Young Adult; Wearable Electronic Devices; Feasibility Studies; Psychomotor Performance; Touch; Vibration; Equipment Design; Pilot Projects
PubMed: 38885098
DOI: 10.1109/TNSRE.2024.3415709