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The American Journal of Managed Care Jun 2023Amyotrophic lateral sclerosis (ALS), or Lou Gehrig disease, is a progressive, always-fatal neuromuscular disease characterized by motor neuron degeneration in the brain...
Amyotrophic lateral sclerosis (ALS), or Lou Gehrig disease, is a progressive, always-fatal neuromuscular disease characterized by motor neuron degeneration in the brain and spinal cord. As upper and lower motor neurons fail, inability to transmit messages to the muscles causes muscle stiffness, atrophy, and wasting. The incidence of this incurable disease is increasing in the United States, and its prognosis is grim. On average, patients survive about 3 to 5 years from symptom onset. Until recently, few risk factors were known, but some are newly emerging. About 10% of cases are related to genetic variants. Patients who develop ALS often experience diagnostic delays (10-16 months on average), and its heterogeneity contributes to that delay. Diagnosis is based primarily on clinical signs and symptoms and exclusion of other causes of motor neuron dysfunction. Reliable, accessible biomarkers are needed to aid early ALS diagnosis, differentiate from ALS-mimicking diseases, predict survival, and monitor disease progression and treatment response. Misdiagnosing ALS can have devastating consequences, including unnecessary emotional burden, delayed and/or inappropriate treatment, and undue financial burden. The grim prognosis and sure progression to death creates considerable burden and reduces quality of life for patients and caregivers.
Topics: Humans; Amyotrophic Lateral Sclerosis; Delayed Diagnosis; Quality of Life; Brain; Risk Factors
PubMed: 37433091
DOI: 10.37765/ajmc.2023.89390 -
Cold Spring Harbor Molecular Case... Dec 2023Rare genetic conditions are challenging for the primary care provider to manage without proper guidelines. This clinical review is designed to assist the pediatrician,...
Rare genetic conditions are challenging for the primary care provider to manage without proper guidelines. This clinical review is designed to assist the pediatrician, family physician, or internist in the primary care setting to manage the complexities of 16p11.2 deletion syndrome. A multidisciplinary medical home with the primary care provider leading the care and armed with up-to-date guidelines will prove most helpful to the rare genetic patient population. A special focus on technology to fill gaps in deficits, review of case studies on novel medical treatments, and involvement with the educational system for advocacy with an emphasis on celebrating diversity will serve the rare genetic syndrome population well.
Topics: Child; Humans; Adolescent; Chromosome Deletion; Chromosome Disorders; Autistic Disorder; Intellectual Disability; Chromosomes, Human, Pair 16
PubMed: 38050025
DOI: 10.1101/mcs.a006316 -
Cureus Oct 2023Background Preterm births are a significant concern worldwide due to their association with both short- and long-term morbidity. Modern neonatal intensive care...
Background Preterm births are a significant concern worldwide due to their association with both short- and long-term morbidity. Modern neonatal intensive care techniques have improved the survival of infants born at the brink of viability. However, there remain significant challenges concerning their neurodevelopment. A considerable proportion of very low birth weight infants exhibit significant motor deficits such as cerebral palsy or cognitive, behavioral, or attention disabilities. The consequences of these impairments, particularly given their life-long nature, can be severe for the affected individuals, families, and public health resources. Consequently, timely neurodevelopmental assessment is critical in recognizing delayed development and selecting infants for neurodevelopmental stimulation. This study aimed to estimate the neurodevelopment of preterm infants, identify influencing factors, detect at-risk groups, and refer/recommend early intervention when developmental delays are observed. Methodology This prospective, observational, hospital-based study done in the department of pediatrics, Gujarat Medical Education and Research Society (GMERS) Medical College and Hospital, Gotri, Vadodara, Gujrat, India included inborn and outborn preterm neonates admitted to the Neonatal Intensive Care Unit (NICU) or the Sick Newborn Care Unit from their first day of life. The study period was from October 2020 to January 2021, and only neonates with an uncomplicated clinical course were included. Newborns were enrolled in a high-risk clinic, and follow-up appointments were scheduled at three, six, nine, and 12 months of corrected gestational age (CGA). We used the Baroda Developmental Screening Tool (BDST) to calculate the developmental quotient (DQ) at each appointment. This assessment involved parental interviews, observation of developmental milestones, and simple test demonstrations. The gathered DQ data at different ages were analyzed and compared across groups. Results Of 100 preterms enrolled, 62 preterms were followed up until 12 months of CGA. Thirteen patients out of the 62 (approximately one-fifth) preterm neonates exhibited developmental delays at one year of CGA, most of whom were early preterm infants. Twenty-six patients (approximately two-fifths) were delayed at three months of CGA, and thus 13 patients (half) showed catch-up growth and development. There was no statistically significant difference between the neurodevelopment of female and male infants. However, infants born to mothers with better socioeconomic status and higher education showed improved neurodevelopment. Conclusions Our study findings suggest that preterm infants discharged from the NICU exhibit poor neurodevelopmental outcomes, especially those born early preterm. This pattern indicates an inverse relationship between neurodevelopmental delay and the maturity of the neonate. Maternal education and socioeconomic status positively impacted the neurodevelopment of preterm NICU graduates. Thus, regular follow-up (at least once every three months), early detection by a screening scale like the BDST and intervention significantly improved neurodevelopmental outcomes.
PubMed: 38022026
DOI: 10.7759/cureus.47775 -
Pediatric Research Feb 2024This meta-analysis aimed to identify the near- and long-term neurodevelopmental prognoses of preterm or low birth weight (LBW) infants with different severities of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This meta-analysis aimed to identify the near- and long-term neurodevelopmental prognoses of preterm or low birth weight (LBW) infants with different severities of intraventricular hemorrhage (IVH).
METHODS
Four databases were searched for observational studies that were qualified using the Newcastle-Ottawa Scale.
RESULTS
37 studies involving 32,370 children were included. Compared to children without IVH, children with mild IVH had higher incidences of neurodevelopmental impairment (NDI), cerebral palsy (CP), motor/cognitive delay, hearing impairment and visual impairment, as well as lower scores of the mental development index (MDI) and psychomotor development (PDI). Moreover, compared to mild IVH, severe IVH increased susceptibilities of children to NDI, motor delay, CP, hearing impairment and visual impairment, with worse performances in MDI, PDI, motor score and IQ. Mild IVH was not associated with seizures or epilepsy.
CONCLUSIONS
Adverse neurodevelopmental outcomes positively associated with the occurrence and severity of IVH in preterm or LBW infants, providing evidence for counseling and further decisions regarding early therapeutic interventions.
IMPACT
Adverse neurodevelopmental outcomes later in life were closely associated with the occurrence and severity of IVH in preterm or LBW infants. Our results highlight the importance to make prediction of the neurodevelopmental outcomes of children born preterm or LBW with a history of IVH, which will guide affected parents when their children need clinical interventions to reach the full potential. We emphasize the importance of identifying specific developmental delays that may exist in children with IVH, providing detailed information for the development of comprehensive intervention measures.
Topics: Infant, Newborn; Infant; Child; Humans; Infant, Premature; Infant, Premature, Diseases; Infant, Low Birth Weight; Cerebral Hemorrhage; Cerebral Palsy; Hearing Loss; Vision Disorders
PubMed: 37935882
DOI: 10.1038/s41390-023-02877-8 -
PNAS Nexus Aug 2023The cellular cytoskeleton relies on diverse populations of motors, filaments, and binding proteins acting in concert to enable nonequilibrium processes ranging from...
The cellular cytoskeleton relies on diverse populations of motors, filaments, and binding proteins acting in concert to enable nonequilibrium processes ranging from mitosis to chemotaxis. The cytoskeleton's versatile reconfigurability, programmed by interactions between its constituents, makes it a foundational active matter platform. However, current active matter endeavors are limited largely to single force-generating components acting on a single substrate-far from the composite cytoskeleton in cells. Here, we engineer actin-microtubule (MT) composites, driven by kinesin and myosin motors and tuned by crosslinkers, to ballistically restructure and flow with speeds that span three orders of magnitude depending on the composite formulation and time relative to the onset of motor activity. Differential dynamic microscopy analyses reveal that kinesin and myosin compete to delay the onset of acceleration and suppress discrete restructuring events, while passive crosslinking of either actin or MTs has an opposite effect. Our minimal advection-diffusion model and spatial correlation analyses correlate these dynamics to structure, with motor antagonism suppressing reconfiguration and demixing, while crosslinking enhances clustering. Despite the rich formulation space and emergent formulation-dependent structures, the nonequilibrium dynamics across all composites and timescales can be organized into three classes-slow isotropic reorientation, fast directional flow, and multimode restructuring. Moreover, our mathematical model demonstrates that diverse structural motifs can arise simply from the interplay between motor-driven advection and frictional drag. These general features of our platform facilitate applicability to other active matter systems and shed light on diverse ways that cytoskeletal components can cooperate or compete to enable wide-ranging cellular processes.
PubMed: 37575673
DOI: 10.1093/pnasnexus/pgad245 -
Nursing Open Aug 2023The objective was to identify if family social exclusion is associated with child motor and social development delay in Southeastern Brazil.
AIM
The objective was to identify if family social exclusion is associated with child motor and social development delay in Southeastern Brazil.
DESIGN
A cross-sectional study was conducted using data from a sample of 348 children under 3 years, proportional to the number of children registered in the primary care centres of the municipality.
METHODS
Child development was measured using the "Developmental Surveillance Instrument" which was developed by the Ministry of Health in Brazil and is used for public health nurses and clinicians in their practice. An index was used to evaluate social exclusion.
RESULTS
The prevalence of child motor and socioemotional developmental delay was 27.6% and 17.2%, respectively. Children in the most social excluded group were more likely to have delayed motor development (OR = 3.4; 95% CI = 1.14; 10.55) and socioemotional developmental delay (OR = 3.9; 95% CI = 1.05; 9.02) than children in the least social excluded group.
Topics: Humans; Child; Child, Preschool; Cross-Sectional Studies; Developmental Disabilities; Child Development; Social Isolation; Social Group
PubMed: 37229522
DOI: 10.1002/nop2.1736 -
Sensors (Basel, Switzerland) Sep 2022(1) Background: The purpose of this study was to evaluate the analysis of measurements of bioelectric signals obtained from electromyographic sensors. A system that...
(1) Background: The purpose of this study was to evaluate the analysis of measurements of bioelectric signals obtained from electromyographic sensors. A system that controls the speed and direction of rotation of a brushless DC motor (BLDC) was developed; (2) Methods: The system was designed and constructed for the acquisition and processing of differential muscle signals. Basic information for the development of the EMG signal processing system was also provided. A controller system implementing the algorithm necessary to control the speed and direction of rotation of the drive rotor was proposed; (3) Results: Using two muscle groups (biceps brachii and triceps), it was possible to control the direction and speed of rotation of the drive unit. The control system changed the rotational speed of the brushless motor with a delay of about 0.5 s in relation to the registered EMG signal amplitude change; (4) Conclusions: The prepared system meets all the design assumptions. In addition, it is scalable and allows users to adjust the signal level. Our designed system can be implemented for rehabilitation, and in exoskeletons or prostheses.
Topics: Arm; Electricity; Electromyography; Exoskeleton Device; Muscle, Skeletal; Signal Processing, Computer-Assisted
PubMed: 36146180
DOI: 10.3390/s22186829 -
Behavioural Pharmacology Aug 2014Delay discounting describes the subjective devaluation of a reward when it is delayed. In animals, the adjusting-delay (AD) and increasing-delay (ID) tasks often are...
Delay discounting describes the subjective devaluation of a reward when it is delayed. In animals, the adjusting-delay (AD) and increasing-delay (ID) tasks often are used to assess individual differences in, and drug effects on, delay discounting. No study to date, however, has compared systematically the measures of discounting produced in these tasks. The current study examined the correlation between measures of delay discounting derived from AD and ID procedures. Twenty rats completed 30 sessions under each task (order counterbalanced across rats). Quantitative measures of delay discounting produced by the two tasks were positively correlated, suggesting that the AD and ID tasks measure the same underlying facet of impulsive choice (i.e. individual or conjoint sensitivities to reward delay and magnitude). The measures derived from either task, however, depended on the sequences in which the tasks were experienced. That is, pre-exposure to one task decreased discounting of delayed rewards in the second task. Consistent with other published findings, exposure to delayed consequences during the initial discounting assessment might explain this effect. Despite the observed correlation between ID and AD indifference delays, we suggest that the ID procedure might be a more appropriate procedure for pharmacological studies.
Topics: Animals; Conditioning, Operant; Delay Discounting; Male; Motor Activity; Neuropsychological Tests; Rats, Long-Evans; Regression Analysis; Time Factors
PubMed: 24978484
DOI: 10.1097/FBP.0000000000000055 -
ENeuro Aug 2022Behavioral interactions with moving objects are challenged by response latencies within the sensory and motor nervous systems. In vision, the combined latency from...
Behavioral interactions with moving objects are challenged by response latencies within the sensory and motor nervous systems. In vision, the combined latency from phototransduction and synaptic transmission from the retina to central visual areas amounts to 50-100 ms, depending on stimulus conditions. Time required for generating appropriate motor output adds to this latency and further compounds the behavioral delay. Neuronal adaptations that help counter sensory latency within the retina have been demonstrated in some species, but how general these specializations are, and where in the circuitry they originate, remains unclear. To address this, we studied the timing of object motion-evoked responses at multiple signaling stages within the mouse retina using two-photon fluorescence calcium and glutamate imaging, targeted whole-cell electrophysiology, and computational modeling. We found that both ON and OFF-type ganglion cells, as well as the bipolar cells that innervate them, temporally advance the position encoding of a moving object and so help counter the inherent signaling delay in the retina. Model simulations show that this predictive capability is a direct consequence of the spatial extent of the cells' linear visual receptive field, with no apparent specialized circuits that help predict beyond it.Signal transduction and synaptic transmission within sensory signaling pathways costs time. Not a lot of time, just tens to a few hundred milliseconds depending on the sensory system, but enough to challenge fast behavioral interactions under dynamic stimulus conditions, like catching a moving fly. To counter neuronal delays, nervous systems of many species use anticipatory mechanisms. One such mechanism in the mammalian visual system helps predict the future position of a moving target through a process called phase advancing. Here we ask for functionally diverse neuron populations in the mouse retina how common is phase advancing and demonstrate that it is common and generated at multiple signaling stages.
PubMed: 35995559
DOI: 10.1523/ENEURO.0270-22.2022 -
Translational Psychiatry Nov 2021Reward sensitivity has been suggested as one of the central pathophysiological mechanisms in Tourette disorder. However, the subjective valuation of a reward by...
Reward sensitivity has been suggested as one of the central pathophysiological mechanisms in Tourette disorder. However, the subjective valuation of a reward by introduction of delay has received little attention in Tourette disorder, even though it has been suggested as a trans-diagnostic feature of numerous neuropsychiatric disorders. We aimed to assess delay discounting in Tourette disorder and to identify its brain functional correlates. We evaluated delayed discounting and its brain functional correlates in a large group of 54 Tourette disorder patients and 31 healthy controls using a data-driven approach. We identified a subgroup of 29 patients with steeper reward discounting, characterised by a higher burden of impulse-control disorders and a higher level of general impulsivity compared to patients with normal behavioural performance or to controls. Reward discounting was underpinned by resting-state activity of a network comprising the orbito-frontal, cingulate, pre-supplementary motor area, temporal and insular cortices, as well as ventral striatum and hippocampus. Within this network, (i) lower connectivity of pre-supplementary motor area with ventral striatum predicted a higher impulsivity and a steeper reward discounting and (ii) a greater connectivity of pre-supplementary motor area with anterior insular cortex predicted steeper reward discounting and more severe tics. Overall, our results highlight the heterogeneity of the delayed reward processing in Tourette disorder, with steeper reward discounting being a marker of burden in impulsivity and impulse control disorders, and the pre-supplementary motor area being a hub region for the delay discounting, impulsivity and tic severity.
Topics: Delay Discounting; Humans; Impulsive Behavior; Insular Cortex; Magnetic Resonance Imaging; Reward; Tourette Syndrome
PubMed: 34732691
DOI: 10.1038/s41398-021-01691-2