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BMC Pediatrics Jun 2024Menkes disease (MD) is a rare, inherited, multisystemic copper metabolism disorder. Classical Menkes disease is characterized by low serum copper and ceruloplasmin... (Review)
Review
BACKGROUND
Menkes disease (MD) is a rare, inherited, multisystemic copper metabolism disorder. Classical Menkes disease is characterized by low serum copper and ceruloplasmin concentrations, leading to multiple abnormalities in the whole-body, especially in connective tissue and central nervous system. However, serum copper and ceruloplasmin levels are not reliable diagnostic biomarkers due to the low concentrations in healthy newborns either. The featured imaging manifestations play an important role in diagnosing Menkes disease. To our knowledge, there are few reports on the systemic imaging manifestations of Menkes disease.
CASE PRESENTATION
A 4-month-old male patient presented with recurrent seizures. He had cognitive, intellectual, growth, gross motor, precision movement, and language developmental lags. The patient's hemoglobin and serum ceruloplasmin level were low. On MRI, increased intracranial vascular tortuosity, cerebral and cerebellar atrophy, white matter changes, and basal ganglia abnormalities were observed. Plain radiograph revealed wormian bones, rib flaring, metaphyseal spurring, and periosteal reactions in the long bones of the limbs. A pathogenic variant in ATP7A gene was identified in the patient, so he was confirmed the diagnosis of Menkes disease. His symptoms did not improve despite symptomatic and supportive treatment during his hospitalization. Unfortunately, the infant died 3 months after leaving hospital.
CONCLUSION
A comprehensive and intuitive understanding of the disease's imaging manifestations can help clinicians to identify the disease and avoid delays in care.
Topics: Humans; Menkes Kinky Hair Syndrome; Male; Infant; Magnetic Resonance Imaging; Brain; Whole Body Imaging; Bone and Bones
PubMed: 38926644
DOI: 10.1186/s12887-024-04885-x -
BMJ Paediatrics Open Jun 2024Early identification of suspected developmental delays (SDDs) is crucial for planning early interventions. This study aimed to determine the prevalence of SDDs and the...
BACKGROUND
Early identification of suspected developmental delays (SDDs) is crucial for planning early interventions. This study aimed to determine the prevalence of SDDs and the associated determinants in children aged 12 months in the northeast of Iran, using the Age and Stage Questionnaire-3 (ASQ-3) as the evaluative tool.
METHODS
This study conducted an analytical cross-sectional design to investigate all children who had completed the ASQ-3 screening form at 12 months of age within the time frame of 2016-2023 in the northeast of Iran. The necessary data were extracted from the electronic health record database associated with Mashhad University of Medical Sciences. To examine the factors associated with SDDs within each domain of the ASQ-3, a multiple logistic regression model was employed, and the results were presented using ORs along with 95% CIs.
RESULTS
Over 7 years, 236 476 children (96.74%) underwent routine ASQ-3 screening at 12 months. After excluding certain cases, 226 076 children (95.60%) were included. Among them, 51 593 children (22.82%) had a score below -1 SD, indicating SDD prevalence in at least one domain. The social-personal domain had the highest prevalence with 22 980 children (10.16%), while the gross motor domain had the lowest with 5650 children (2.50%). Logistic regression analysis identified strong predictors of SDDs, including hospitalisation at birth (OR=1.85, 95% CI:1.69 to 2.02), prematurity (OR=1.56, 95% CI: 1.37 to 1.79), urbanisation (OR=1.51, 95% CI: 1.45 to 1.57), boys (OR=1.36, 95% CI: 1.31 to 1.40) and lack of exclusive breast feeding until 6 months (OR=1.30, 95% CI: 1.25 to 1.34).
CONCLUSION
The prevalence of SDDs highlights the urgency for prompt action, while considering contributing factors. Policymakers can address modifiable risk factors associated with SDDs, including urbanisation risks, support programmes for immigrant families and the importance of exclusive breast feeding until 6 months. Additionally, it is recommended establishing gender-specific local standard cut-off points for the ASQ.
Topics: Humans; Iran; Developmental Disabilities; Male; Female; Cross-Sectional Studies; Prevalence; Infant; Risk Factors; Surveys and Questionnaires; Logistic Models
PubMed: 38925677
DOI: 10.1136/bmjpo-2023-002393 -
Early Human Development Jun 2024The low attendance of families in child developmental follow-up programs for at-risk preterm children is a challenge in Brazil.
INTRODUCTION
The low attendance of families in child developmental follow-up programs for at-risk preterm children is a challenge in Brazil.
OBJECTIVE
This study evaluates the feasibility of implementing a developmental follow-up program for Brazilian preterm infants in a hybrid format.
METHODS
This is an observational, prospective cohort study, involving preterm infants. Longitudinal developmental test results, the participation frequency in the program, and the number of referrals to early intervention programs were used to assess feasibility. The General Movements (GMs) assessment, Alberta Infant Motor Scale (AIMS) and, Survey of Wellbeing of Young Children (SWYC) Milestones were administered via telehealth. The Bayley-III was administered in-person.
RESULTS
Thirty-four preterm infants attended the follow-up until 12 months of corrected age and 18 (52.9 %) concluded all follow-up assessments. Twenty-six (76.5 %) attended all assessments via telehealth, and 26 (76.5 %) attended the in-person assessment. Eighteen (52.9 %) infants showed at least one altered result in development tests. Infants exhibiting abnormal results in the GMs assessment, motor developmental delay according to the AIMS, or developmental delay based on Balley-III were promptly referred to early intervention services.
CONCLUSION
This study demonstrated high participation rate and low dropout in a developmental follow-up program employing a hybrid format. The substantial number of identified infants with developmental delay emphasizes the importance of timely detection of motor delays to referral to early intervention services.
PubMed: 38924944
DOI: 10.1016/j.earlhumdev.2024.106069 -
American Journal of Medical Genetics.... Jun 2024Haploinsufficiency of FOXP1 gene is responsible for a neurodevelopmental disorder presenting with intellectual disability (ID), autism spectrum disorder (ASD),...
Haploinsufficiency of FOXP1 gene is responsible for a neurodevelopmental disorder presenting with intellectual disability (ID), autism spectrum disorder (ASD), hypotonia, mild dysmorphic features, and multiple congenital anomalies. Joint contractures are not listed as a major feature of FOXP1-related disorder. We report five unrelated individuals, each harboring likely gene disruptive de novo FOXP1 variants or whole gene microdeletion, who showed multiple joint contractures affecting at least two proximal and/or distal joints. Consistent with the phenotype of FOXP1-related disorder, all five patients showed developmental delay with moderate-to-severe speech delay, ID, ASD, and facial dysmorphic features. FOXP1 is implicated in neuronal differentiation and in organizing motor axon projections, thus providing a potential developmental basis for the joint contractures. The combination of joint contractures and neurodevelopmental disorders supports the clinical suspicion of FOXP1-related phenotype.
PubMed: 38924631
DOI: 10.1002/ajmg.a.63713 -
Annals of the New York Academy of... Jun 2024Considerable debate exists about the interplay between auditory and motor speech systems. Some argue for common neural mechanisms, whereas others assert that there are...
Considerable debate exists about the interplay between auditory and motor speech systems. Some argue for common neural mechanisms, whereas others assert that there are few shared resources. In four experiments, we tested the hypothesis that priming the speech motor system by repeating syllable pairs aloud improves subsequent syllable discrimination in noise compared with a priming discrimination task involving same-different judgments via button presses. Our results consistently showed that participants who engaged in syllable repetition performed better in syllable discrimination in noise than those who engaged in the priming discrimination task. This gain in accuracy was observed for primed and new syllable pairs, highlighting increased sensitivity to phonological details. The benefits were comparable whether the priming tasks involved auditory or visual presentation. Inserting a 1-h delay between the priming tasks and the syllable-in-noise task, the benefits persisted but were confined to primed syllable pairs. Finally, we demonstrated the effectiveness of this approach in older adults. Our findings substantiate the existence of a speech production-perception relationship. They also have clinical relevance as they raise the possibility of production-based interventions to improve speech perception ability. This would be particularly relevant for older adults who often encounter difficulties in perceiving speech in noise.
PubMed: 38924165
DOI: 10.1111/nyas.15179 -
Molecular Neurobiology Jun 2024Evidence suggests that long non-coding RNAs (lncRNAs) play a significant role in autism. Herein, we explored the functional role and possible molecular mechanisms of...
Evidence suggests that long non-coding RNAs (lncRNAs) play a significant role in autism. Herein, we explored the functional role and possible molecular mechanisms of NEAT1 in valproic acid (VPA)-induced autism spectrum disorder (ASD). A VPA-induced ASD rat model was constructed, and a series of behavioral tests were performed to examine motor coordination and learning-memory abilities. qRT-PCR and western blot assays were used to evaluate target gene expression levels. Loss-and-gain-of-function assays were conducted to explore the functional role of NEAT1 in ASD development. Furthermore, a combination of mechanistic experiments and bioinformatic tools was used to assess the relationship and regulatory role of the NEAT1-YY1-UBE3A axis in ASD cellular processes. Results showed that VPA exposure induced autism-like developmental delays and behavioral abnormalities in the VPA-induced ASD rat model. We found that NEAT1 was elevated in rat hippocampal tissues after VPA exposure. NEAT1 promoted VPA-induced autism-like behaviors and mitigated apoptosis, oxidative stress, and inflammation in VPA-induced ASD rats. Notably, NEAT1 knockdown improved autism-related behaviors and ameliorated hippocampal neuronal damage. Mechanistically, it was observed that NEAT1 recruited the transcription factor YY1 to regulate UBE3A expression. Additionally, in vitro experiments further confirmed that NEAT1 knockdown mitigated hippocampal neuronal damage, oxidative stress, and inflammation through the YY1/UBE3A axis. In conclusion, our study demonstrates that NEAT1 is highly expressed in ASD, and its inhibition prominently suppresses hippocampal neuronal injury and oxidative stress through the YY1/UBE3A axis, thereby alleviating ASD development. This provides a new direction for ASD-targeted therapy.
PubMed: 38922486
DOI: 10.1007/s12035-024-04309-y -
GeroScience Jun 2024Empagliflozin is currently known to decrease blood glucose levels, delay renal failure, and reduce the risk of cardiovascular death and all-cause mortality in patients...
Empagliflozin is currently known to decrease blood glucose levels, delay renal failure, and reduce the risk of cardiovascular death and all-cause mortality in patients with type 2 diabetes with cardiovascular disease. However, the effects of empagliflozin on the lifespan and health of naturally aged organisms are unclear. This study was designed to investigate the impacts and potential mechanisms of empagliflozin on lifespan and liver senescence in naturally aged mice. Our study revealed that empagliflozin improved survival and health in naturally aged mice. Empagliflozin extended the median survival of male mice by 5.9%. Meanwhile, empagliflozin improved learning memory and motor balance, decreased body weight, and downregulated the hepatic protein expression of P21, P16, α-SMA, and COL1A1. Empagliflozin modulates the structure of the intestinal flora, increasing the relative abundance of Lachnospiraceae, Ruminococcaceae, Lactobacillus, Blautia, and Muribaculaceae and decreasing the relative abundance of Erysipelotrichaceae, Turicibacter, and Dubosiella in naturally aged mice. Further exploration discovered that empagliflozin increased the concentration of SCFAs, decreased the levels of the inflammatory factors TNF-α, IL-6, and CXCL9, and regulated the PI3K/AKT/P21 and AMPK/SIRT1/NF-κB pathways, which may represent the underlying mechanisms involved in these beneficial hepatic effects. Taken together, the above results indicated that empagliflozin intervention could be considered a potential strategy for extending lifespan and slowing liver senescence in naturally aged mice.
PubMed: 38922380
DOI: 10.1007/s11357-024-01250-9 -
Sports (Basel, Switzerland) May 2024Reaction time (RT) is a widely used measure for testing physical performance in motor tasks. This study focused on assessing the processing speed in athletes....
Reaction time (RT) is a widely used measure for testing physical performance in motor tasks. This study focused on assessing the processing speed in athletes. Twenty-five healthy volunteers were assigned to the control (n = 16) or athletes groups (n = 9). They were evaluated during motor reaction tasks based on visual stimuli and three difficulty conditions. Physiological measures were obtained from motion capture and electromyography recordings of several muscles. Two RT phases, decision-making (DMK) and electromechanical delay (EMD), were used to analyze the processing speed. The results show significant RT differences between groups. The athletes were ~30% faster compared to the control group. Despite the fact that all participants were right-handed, RT did not show any differences between hands performances in any group. However, DMK time revealed significant differences between the hands. Controls showed a longer DMK time for the right-hand election, ~20% more than the left, while athletes showed no such disparity. These findings reveal that quantifying the decision-making component of reaction time is crucial to assessing processing speed in sport. This approach could facilitate the monitoring of adaptations in both motor-cognitive and neuromuscular processes. The theoretical implications presented in this study offer perspectives on handedness research.
PubMed: 38921845
DOI: 10.3390/sports12060151 -
Cureus May 2024TUBG1, a tubulin gene, plays an important role in neurodevelopment. Here we describe a case of a novel TUGB1 mutation (NM_001070.4:c.821C>T) (p.Thr274Ile). This patient...
TUBG1, a tubulin gene, plays an important role in neurodevelopment. Here we describe a case of a novel TUGB1 mutation (NM_001070.4:c.821C>T) (p.Thr274Ile). This patient presented similarly to previous cases with features including microcephaly, epilepsy, and speech and motor delay. Unique characteristics were also present such as trigonocephaly, tethered frenulum, scoliosis, nystagmus, and a concurrent FBXW7 mutation. This case expands our breadth of knowledge on TUBG1 genotypic and phenotypic variation. However, further work is needed to fully understand this rare mutation and the associations between TUBG1 and FBXW7 mutations.
PubMed: 38919239
DOI: 10.7759/cureus.61132 -
Advances in Experimental Medicine and... 2024Temporal information processing in the range of a few hundred milliseconds to seconds involves the cerebellum and basal ganglia. In this chapter, we present recent... (Review)
Review
Temporal information processing in the range of a few hundred milliseconds to seconds involves the cerebellum and basal ganglia. In this chapter, we present recent studies on nonhuman primates. In the studies presented in the first half of the chapter, monkeys were trained to make eye movements when a certain amount of time had elapsed since the onset of the visual cue (time production task). The animals had to report time lapses ranging from several hundred milliseconds to a few seconds based on the color of the fixation point. In this task, the saccade latency varied with the time length to be measured and showed stochastic variability from one trial to the other. Trial-to-trial variability under the same conditions correlated well with pupil diameter and the preparatory activity in the deep cerebellar nuclei and the motor thalamus. Inactivation of these brain regions delayed saccades when asked to report subsecond intervals. These results suggest that the internal state, which changes with each trial, may cause fluctuations in cerebellar neuronal activity, thereby producing variations in self-timing. When measuring different time intervals, the preparatory activity in the cerebellum always begins approximately 500 ms before movements, regardless of the length of the time interval being measured. However, the preparatory activity in the striatum persists throughout the mandatory delay period, which can be up to 2 s, with different rate of increasing activity. Furthermore, in the striatum, the visual response and low-frequency oscillatory activity immediately before time measurement were altered by the length of the intended time interval. These results indicate that the state of the network, including the striatum, changes with the intended timing, which lead to different time courses of preparatory activity. Thus, the basal ganglia appear to be responsible for measuring time in the range of several hundred milliseconds to seconds, whereas the cerebellum is responsible for regulating self-timing variability in the subsecond range. The second half of this chapter presents studies related to periodic timing. During eye movements synchronized with alternating targets at regular intervals, different neurons in the cerebellar nuclei exhibit activity related to movement timing, predicted stimulus timing, and the temporal error of synchronization. Among these, the activity associated with target appearance is particularly enhanced during synchronized movements and may represent an internal model of the temporal structure of stimulus sequence. We also considered neural mechanism underlying the perception of periodic timing in the absence of movement. During perception of rhythm, we predict the timing of the next stimulus and focus our attention on that moment. In the missing oddball paradigm, the subjects had to detect the omission of a regularly repeated stimulus. When employed in humans, the results show that the fastest temporal limit for predicting each stimulus timing is about 0.25 s (4 Hz). In monkeys performing this task, neurons in the cerebellar nuclei, striatum, and motor thalamus exhibit periodic activity, with different time courses depending on the brain region. Since electrical stimulation or inactivation of recording sites changes the reaction time to stimulus omission, these neuronal activities must be involved in periodic temporal processing. Future research is needed to elucidate the mechanism of rhythm perception, which appears to be processed by both cortico-cerebellar and cortico-basal ganglia pathways.
Topics: Animals; Cerebellum; Basal Ganglia; Time Perception; Saccades; Time Factors; Humans
PubMed: 38918348
DOI: 10.1007/978-3-031-60183-5_6