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Turkish Journal of Medical Sciences 2023Hypoxic ischemic encephalopathy (HIE) is one of the common causes of mortality and morbidity in newborns. Despite therapeutic hypothermia, an important treatment with...
BACKGROUND/AIM
Hypoxic ischemic encephalopathy (HIE) is one of the common causes of mortality and morbidity in newborns. Despite therapeutic hypothermia, an important treatment with proven efficacy, the morbidity and mortality rates remain high. The aim of this study was to neurodevelopmentally evaluate patients who underwent therapeutic hypothermia.
MATERIAL AND METHOD
Included herein were patients who underwent hypothermia between 2018 and 2020. Their medical files were reviewed retrospectively, and their demographic and clinical information was recorded. Patients whose contact information was available were called to the developmental pediatrics outpatient clinic for a neurodevelopmental evaluation. The Bayley Scales of Infant and Toddler Development 3rd Edition (Bayley-III) was used as the evaluation tool. Laboratory values and clinical parameters of the patients were further analyzed.
RESULTS
It was found that 42 patients underwent hypothermia in 3 years, of whom 14 (33.3%) had died. Of the 28 patients who were discharged, 20 children could be reached, and a neurodevelopmental evaluation was performed. Developmental delay in the cognitive area was detected in 11 (55%) patients, delay in the language area was found in 9 (45%) patients, and delay in the motor area was found in 11 (55%) patients. The correlation and regression analysis results determined that the time to start cooling was the most effective common factor in all 3 fields of scoring.
CONCLUSION
The time to start cooling is related to the neurodevelopmental outcomes of patients with HIE. The earlier cooling is started, the better the neurodevelopmental results. Despite therapeutic hypothermia, the neurodevelopmental development of infants may be adversely affected. These patients should be followed-up neurodevelopmentally for a long time.
Topics: Humans; Hypoxia-Ischemia, Brain; Hypothermia, Induced; Male; Female; Infant, Newborn; Retrospective Studies; Neurodevelopmental Disorders; Infant; Child, Preschool; Developmental Disabilities
PubMed: 38813516
DOI: 10.55730/1300-0144.5748 -
Turkish Journal of Medical Sciences 2023Williams-Beuren syndrome (WBS) is a rare genetic disorder with delays in language and cognitive development, but, with increased awareness of clinical features and a...
BACKGROUND/AIM
Williams-Beuren syndrome (WBS) is a rare genetic disorder with delays in language and cognitive development, but, with increased awareness of clinical features and a reliable diagnostic test, WBS is becoming more widely recognized in childhood. Adaptive behavior skills and/or maladaptive behavior are important for the prognosis of individuals with WBS. The aim of this study was to investigate the clinical and developmental characteristics of patients with WBS and further increase awareness about it by evaluating the adaptive skills and maladaptive behaviors of the patients.
MATERIALS AND METHODS
The data of WBS patients followed-up at the Developmental Behavioral Pediatrics Unit were reviewed. Patient data on perinatal and postnatal history, developmental stages, physical and neurological examination findings were collected. The International Guide for Monitoring Child Development (GMCD) was administered to each child. In addition, semistructured interviews were conducted with the parents using the Vineland Adaptive Behavior Scales, Second edition (Vineland-II).
RESULTS
A total of 12 patients diagnosed with WBS via detection of the 7q11.23 deletion, of whom 6 were girls, were retrospectively reviewed. The mean age at the time of review was 54.6 ± 32.5 months. The mean age at first presentation to the Developmental Behavioral Pediatrics Outpatient Clinic was 15 ± 11.5 months. In the first developmental evaluation using the GMCD, there was a delay in fine and gross motor domains in 6 patients, in the language domains in 4 patients, and in all of the domains in 2 patients. Findings with Vineland-II showed socialization and communication domains as strengths, but the daily living skills and motor skills domains were weaknesses. In terms of maladaptive behavior, the patients tended to frequently have behavioral problems, neurodevelopmental disease, anxiety disorders, eating problems, and sleeping problems.
CONCLUSION
This retrospective review of 12 patients indicated a general delay in overall development, and confirmed impairment in both adaptive and maladaptive functioning in WBS.
Topics: Humans; Williams Syndrome; Female; Child, Preschool; Male; Infant; Retrospective Studies; Adaptation, Psychological; Child; Child Development
PubMed: 38812996
DOI: 10.55730/1300-0144.5701 -
Frontiers in Neuroscience 2024The human's upright standing is a complex control process that is not yet fully understood. Postural control models can provide insights into the body's internal control...
The human's upright standing is a complex control process that is not yet fully understood. Postural control models can provide insights into the body's internal control processes of balance behavior. Using physiologically plausible models can also help explaining pathophysiological motion behavior. In this paper, we introduce a neuromusculoskeletal postural control model using sensor feedback consisting of somatosensory, vestibular and visual information. The sagittal plane model was restricted to effectively six degrees of freedom and consisted of nine muscles per leg. Physiologically plausible neural delays were considered for balance control. We applied forward dynamic simulations and a single shooting approach to generate healthy reactive balance behavior during quiet and perturbed upright standing. Control parameters were optimized to minimize muscle effort. We showed that our model is capable of fulfilling the applied tasks successfully. We observed joint angles and ranges of motion in physiologically plausible ranges and comparable to experimental data. This model represents the starting point for subsequent simulations of pathophysiological postural control behavior.
PubMed: 38812972
DOI: 10.3389/fnins.2024.1393749 -
Neurophotonics Apr 2024People with Parkinson's disease (PD) experience changes in fine motor skills, which is viewed as one of the hallmark signs of this disease. Due to its non-invasive...
Parkinson's disease patients show delayed hemodynamic changes in primary motor cortex in fine motor tasks and decreased resting-state interhemispheric functional connectivity: a functional near-infrared spectroscopy study.
SIGNIFICANCE
People with Parkinson's disease (PD) experience changes in fine motor skills, which is viewed as one of the hallmark signs of this disease. Due to its non-invasive nature and portability, functional near-infrared spectroscopy (fNIRS) is a promising tool for assessing changes related to fine motor skills.
AIM
We aim to compare activation patterns in the primary motor cortex using fNIRS, comparing volunteers with PD and sex- and age-matched control participants during a fine motor task and walking. Moreover, inter and intrahemispheric functional connectivity (FC) was investigated during the resting state.
APPROACH
We used fNIRS to measure the hemodynamic changes in the primary motor cortex elicited by a finger-tapping task in 20 PD patients and 20 controls matched for age, sex, education, and body mass index. In addition, a two-minute walking task was carried out. Resting-state FC was also assessed.
RESULTS
Patients with PD showed delayed hypoactivation in the motor cortex during the fine motor task with the dominant hand and delayed hyperactivation with the non-dominant hand. The findings also revealed significant correlations among various measures of hemodynamic activity in the motor cortex using fNIRS and different cognitive and clinical variables. There were no significant differences between patients with PD and controls during the walking task. However, there were significant differences in interhemispheric connectivity between PD patients and control participants, with a statistically significant decrease in PD patients compared with control participants.
CONCLUSIONS
Decreased interhemispheric FC and delayed activity in the primary motor cortex elicited by a fine motor task may one day serve as one of the many potential neuroimaging biomarkers for diagnosing PD.
PubMed: 38812966
DOI: 10.1117/1.NPh.11.2.025004 -
Frontiers in Human Neuroscience 2024Parkinson's disease (PD) generally progresses slowly, but it is controversial whether delaying treatment accelerates the progression.
BACKGROUND
Parkinson's disease (PD) generally progresses slowly, but it is controversial whether delaying treatment accelerates the progression.
OBJECTIVE
Determine the correlation between the time of dopaminergic replacement treatment initiation and the severity of clinical symptoms in PD, including motor and non-motor symptoms.
METHODS
PD patients were divided between 155 people who were diagnosed and 165 PD patients receiving dopamine replacement therapy. Basic patient characteristics included gender, age, age at onset, disease duration, and the time of dopaminergic replacement treatment initiation. We used MDS-UPDRS scores to evaluate the severity of motor symptoms and we also used the scale to assess the severity of non-motor symptoms such as cognition, mood, sleep, and quality of life.
RESULTS
The mean time between symptom onset and the initiation of drug treatment was 31.0 (22.5) months. After adjusting for age, sex, age at onset, and disease duration, we found that the MDS-Unified Parkinson's Disease Rating Scale (UPDRS)-III score increased faster in the group with a similar disease duration (F = 8.7, = 0.0034) than the treatment group. The cumulative incidence of progression to H-Y score 3 in de novo PD group over disease duration was 39.7% in 50months and 92.2% in 100 months, while in treated group such cumulative incidence was 15.5% in 50 months, 51.4% in 100 months and 81.5% in 150 months. The cumulative incidence of patients in the PD group was higher than that in the treated group ( = 0.001), suggesting that untreated patients were more likely to progress to the advanced stages. Symptoms onset, the time between symptom onset and treatment initiation, age, sex, and disease duration explained 28.95% of the total variation in the MDS-UPDRS-III score for motor symptoms. In drug-naïve patients, the time between symptom onset and treatment initiation explained 20.1% of the total variation in the MDS-UPDRS-III score for motor symptoms ( = 6.15, < 0.001).
CONCLUSIONS
These data in our study showed that early dopaminergic replacement treatment have played a positive role in PD patients, while dopaminergic replacement delayed treatment might be detrimental to motor symptoms and non-motor state of PD patient. Recognizing early stage symptoms of PD and early diagnosis are of great significance to treatment.
PubMed: 38807633
DOI: 10.3389/fnhum.2024.1325324 -
PLoS Neglected Tropical Diseases May 2024Congenital toxoplasmosis is a treatable, preventable disease, but untreated causes death, prematurity, loss of sight, cognition and motor function, and substantial costs...
BACKGROUND
Congenital toxoplasmosis is a treatable, preventable disease, but untreated causes death, prematurity, loss of sight, cognition and motor function, and substantial costs worldwide.
OBJECTIVES
We asked whether high performance of an Immunochromatographic-test (ICT) could enable accurate, rapid diagnosis/treatment, establishing new, improved care-paradigms at point-of-care and clinical laboratory.
METHODS
Data were obtained in 12 studies/analyses addressing: 1-feasibility/efficacy; 2-false-positives; 3-acceptability; 4-pink/black-line/all studies; 5-time/cost; 6-Quick-Information/Limit-of-detection; 7, 8-acute;-chronic; 9-epidemiology; 10-ADBio; 11,12-Commentary/Cases/Chronology.
FINDINGS
ICT was compared with gold-standard or predicate-tests. Overall, ICT performance for 1093 blood/4967 sera was 99.2%/97.5% sensitive and 99.0%/99.7% specific. However, in clinical trial, FDA-cleared-predicate tests initially caused practical, costly problems due to false-positive-IgM results. For 58 persons, 3/43 seronegative and 2/15 chronically infected persons had false positive IgM predicate tests. This caused substantial anxiety, concerns, and required costly, delayed confirmation in reference centers. Absence of false positive ICT results contributes to solutions: Lyon and Paris France and USA Reference laboratories frequently receive sera with erroneously positive local laboratory IgM results impeding patient care. Therefore, thirty-two such sera referred to Lyon's Reference laboratory were ICT-tested. We collated these with other earlier/ongoing results: 132 of 137 USA or French persons had false-positive local laboratory IgM results identified correctly as negative by ICT. Five false positive ICT results in Tunisia and Marseille, France, emphasize need to confirm positive ICT results with Sabin-Feldman-Dye-test or western blot. Separate studies demonstrated high performance in detecting acute infections, meeting FDA, CLIA, WHO REASSURED, CEMark criteria and patient and physician satisfaction with monthly-gestational-ICT-screening.
CONCLUSIONS/SIGNIFICANCE
This novel paradigm using ICT identifies likely false positives or raises suspicion that a result is truly positive, rapidly needing prompt follow up and treatment. Thus, ICT enables well-accepted gestational screening programs that facilitate rapid treatment saving lives, sight, cognition and motor function. This reduces anxiety, delays, work, and cost at point-of-care and clinical laboratories.
TRIAL REGISTRATION
NCT04474132, https://clinicaltrials.gov/study/NCT04474132 ClinicalTrials.gov.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Antibodies, Protozoan; False Positive Reactions; Immunoglobulin M; Prenatal Diagnosis; Sensitivity and Specificity; Toxoplasma; Toxoplasmosis, Congenital
PubMed: 38805559
DOI: 10.1371/journal.pntd.0011335 -
Scientific Reports May 2024Amyotrophic lateral sclerosis (ALS) selectively affects motor neurons. SOD1 is the first causative gene to be identified for ALS and accounts for at least 20% of the...
Amyotrophic lateral sclerosis (ALS) selectively affects motor neurons. SOD1 is the first causative gene to be identified for ALS and accounts for at least 20% of the familial (fALS) and up to 4% of sporadic (sALS) cases globally with some geographical variability. The destabilisation of the SOD1 dimer is a key driving force in fALS and sALS. Protein aggregation resulting from the destabilised SOD1 is arrested by the clinical drug ebselen and its analogues (MR6-8-2 and MR6-26-2) by redeeming the stability of the SOD1 dimer. The in vitro target engagement of these compounds is demonstrated using the bimolecular fluorescence complementation assay with protein-ligand binding directly visualised by co-crystallography in G93A SOD1. MR6-26-2 offers neuroprotection slowing disease onset of SOD1 mice by approximately 15 days. It also protected neuromuscular junction from muscle denervation in SOD1 mice clearly indicating functional improvement.
Topics: Superoxide Dismutase-1; Animals; Organoselenium Compounds; Amyotrophic Lateral Sclerosis; Isoindoles; Mice; Azoles; Humans; Mice, Transgenic; Disease Models, Animal; Neuroprotective Agents
PubMed: 38802492
DOI: 10.1038/s41598-024-62903-5 -
BioRxiv : the Preprint Server For... May 2024Though hierarchy is commonly invoked in descriptions of motor cortical function, its presence and manifestation in firing patterns remain poorly resolved. Here we use...
Though hierarchy is commonly invoked in descriptions of motor cortical function, its presence and manifestation in firing patterns remain poorly resolved. Here we use optogenetic inactivation to demonstrate that short-latency influence between forelimb premotor and primary motor cortices is asymmetric during reaching in mice, demonstrating a partial hierarchy between the endogenous activity in each region. Multi-region recordings revealed that some activity is captured by similar but delayed patterns where either region's activity leads, with premotor activity leading more. Yet firing in each region is dominated by patterns shared between regions and is equally predictive of firing in the other region at the single-neuron level. In dual-region network models fit to data, regions differed in their dependence on across-region input, rather than the amount of such input they received. Our results indicate that motor cortical hierarchy, while present, may not be exposed when inferring interactions between populations from firing patterns alone.
PubMed: 38798685
DOI: 10.1101/2023.09.23.559136