Regulatory elements in (7q21.3) locus contribute to genetic control of coronal nonsyndromic craniosynostosis and bone density-related traits.

Purpose: The etiopathogenesis of coronal nonsyndromic craniosynostosis (cNCS), a congenital condition defined by premature fusion of 1 or both coronal sutures, remains largely unknown.

Methods: We conducted the largest genome-wide association study of cNCS followed by replication, fine mapping, and functional validation of the most significant region using zebrafish animal model.

Results: Genome-wide association study identified 6 independent genome-wide-significant risk alleles, 4 on chromosome 7q21.

Tremor Suppression Using Functional Electrical Stimulation.

Parkinson's disease (PD) and essential tremor are two major causes of pathological tremor among people over 60 years old. Due to the side effects and complications of traditional tremor management methods such as medication and deep brain surgery, non invasive tremor suppression methods have become more popular in recent years. Functional electrical stimulation (FES) is one of the methods used to reduce tremor in several studies.

Real-world data are not always big data: the case for primary data collection on medication use in pregnancy in the context of birth defects research.

Many examples of the use of real-world data in the area of pharmacoepidemiology include "big data," such as insurance claims, medical records, or hospital discharge databases. However, "big" is not always better, particularly when studying outcomes with narrow windows of etiologic relevance. Birth defects are such an outcome, for which specificity of exposure timing is critical.

Insights From the Transition to Competency-Based Medical Education in Neurology Programs.

Canadian neurology residency programs recently transitioned to Competency-Based Medical Education (CBME). Iterative evaluation is required to optimize CBME implementation. This study aimed to examine the variability and challenges in uptake of CBME in neurology residency programs and identify its benefits and pitfalls.

A milder form of molybdenum cofactor deficiency type A presenting as Leigh's syndrome-like phenotype highlighting the secondary mitochondrial dysfunction: a case report.

Background: Molybdenum cofactor deficiency (MoCD) (OMIM 252150) is an autosomal-recessive disorder caused by mutations in four genes involved in the molybdenum cofactor (MOCO) biosynthesis pathway.

Objectives: We report a milder phenotype in a patient with gene mutation who presented with a Leigh-like presentation.

Case Report: We present the case of a 10-year-old boy who was symptomatic at the age of 5 months with sudden onset of dyskinesia, nystagmus, and extrapyramidal signs following a febrile illness.

Rare variants in increase risk for isolated hypoplastic left heart syndrome.

Hypoplastic left heart syndrome (HLHS) is a severe congenital heart defect (CHD) characterized by hypoplasia of the left ventricle and aorta along with stenosis or atresia of the aortic and mitral valves. HLHS represents only ∼4%-8% of all CHDs but accounts for ∼25% of deaths. HLHS is an isolated defect (i.

Clinical milestones as triggers for palliative care intervention in progressive Supranuclear palsy and multiple system atrophy.

not required for reviews.

Exome-wide assessment of isolated biliary atresia: A report from the National Birth Defects Prevention Study using child-parent trios and a case-control design to identify novel rare variants.

The etiology of biliary atresia (BA) is unknown, but recent studies suggest a role for rare protein-altering variants (PAVs). Exome sequencing data from the National Birth Defects Prevention Study on 54 child-parent trios, one child-mother duo, and 1513 parents of children with other birth defects were analyzed. Most (91%) cases were isolated BA.

Predictive language comprehension in Parkinson's disease.

Verb and action knowledge deficits are reported in persons with Parkinson's disease (PD), even in the absence of dementia or mild cognitive impairment. However, the impact of these deficits on combinatorial semantic processing is less well understood. Following on previous verb and action knowledge findings, we tested the hypothesis that PD impairs the ability to integrate event-based thematic fit information during online sentence processing.

Using Deep Learning for Task and Tremor Type Classification in People with Parkinson's Disease.

Hand tremor is one of the dominating symptoms of Parkinson's disease (PD), which significantly limits activities of daily living. Along with medications, wearable devices have been proposed to suppress tremor. However, suppressing tremor without interfering with voluntary motion remains challenging and improvements are needed.

Real-Time Performance Assessment of High-Order Tremor Estimators Used in a Wearable Tremor Suppression Device.

The side effects and complications of traditional treatments for treating pathological tremor have led to a growing research interest in wearable tremor suppression devices (WTSDs) as an alternative approach. Similar to how the human brain coordinates the function of the human system, a tremor estimator determines how a WTSD functions. Although many tremor estimation algorithms have been developed and validated, whether they can be implemented on a cost-effective embedded system has not been studied; furthermore, their effectiveness on tremor signals with multiple harmonics has not been investigated.

Preliminary Assessment of the Safety of a Fault-Tolerant Control-based Wearable Tremor Suppression Glove.

The advent of wearable tremor suppression de-vices (WTSDs) has provided a promising alternative approach for parkinsonian tremor management, especially for individuals whose tremors are not managed by conventional treatment options. Currently, research in WTSDs has shown successful results with a tremor suppression ratio of up to 99 %; however, the user safety of WTSDs has not been properly considered, especially in the occurrence of unexpected events, such as faults and disturbances. In this study, a fault-tolerant control system was developed and integrated into the control system of a WTSD for the first time.

The Case for Medicine-Pediatrics Training in the U.S. Military.

Residency programs in the combined specialty of Internal Medicine-Pediatrics (Med-Peds) are not offered in the military graduate medical education system despite existing in the civilian sector for over 50 years. This residency consists of 4 years of training and results in the development of board-certified internists and pediatricians who can care for patients from infancy to death. This versatility, combined with an emphasis on the transition from childhood to adulthood, would be valuable to the Military Health System.

Triggers for Referral to Specialized Palliative Care in Advanced Neurologic and Neurosurgical Conditions: A Systematic Review.

Background And Objectives: To systematically review the literature for the most suitable trigger criteria for referral to specialist palliative care services in life-limiting and life-threatening neurologic and neurosurgical conditions.

Methods: Literature searches were conducted in Ovid MEDLINE and EMBASE (1990-December 2020). To be included, studies must have trigger/referral criteria clearly outlined, a ≥75% nononcology neurosciences population, and consensus or guidelines documents regarding palliative neurosciences or trigger/referral criteria.

Exome sequencing identifies genetic variants in anophthalmia and microphthalmia.

Anophthalmia and microphthalmia (A/M) are rare birth defects affecting up to 2 per 10,000 live births. These conditions are manifested by the absence of an eye or reduced eye volumes within the orbit leading to vision loss. Although clinical case series suggest a strong genetic component in A/M, few systematic investigations have been conducted on potential genetic contributions owing to low population prevalence.

Survey-based identification of design requirements and constraints for a wearable tremor suppression device.

Introduction: Parkinsonian tremor has severely impacted the lives of 65% of individuals with Parkinson's disease, and nearly 25% do not respond to traditional treatments. Although wearable tremor suppression devices (WTSDs) have become a promising alternative approach, this technology is still in the early stages of development, and no studies have reported the stakeholders' opinions on this technology and their desired design requirements.

Methods: An online survey was distributed to affected Canadians and Canadian movement disorder specialists (MDS) to acquire information on demographics, the current state of treatments, opinions on the WTSDs, and the desired design requirements of future WTSDs.

A genome-wide association study of obstructive heart defects among participants in the National Birth Defects Prevention Study.

Obstructive heart defects (OHDs) share common structural lesions in arteries and cardiac valves, accounting for ~25% of all congenital heart defects. OHDs are highly heritable, resulting from interplay among maternal exposures, genetic susceptibilities, and epigenetic phenomena. A genome-wide association study was conducted in National Birth Defects Prevention Study participants (N  = 3978; N  = 2507), investigating the genetic architecture of OHDs using transmission/disequilibrium tests (TDT) in complete case-parental trios (N  = 440; N  = 275) and case-control analyses separately in infants (N  = 1635; N  = 990) and mothers (case status defined by infant; N  = 1703; N  = 1078).

Exome sequencing identifies variants in infants with sacral agenesis.

Background: Sacral agenesis (SA) consists of partial or complete absence of the caudal end of the spine and often presents with additional birth defects. Several studies have examined gene variants for syndromic forms of SA, but only one has examined exomes of children with non-syndromic SA.

Methods: Using buccal cell specimens from families of children with non-syndromic SA, exomes of 28 child-parent trios (eight with and 20 without a maternal diagnosis of pregestational diabetes) and two child-father duos (neither with diagnosis of maternal pregestational diabetes) were exome sequenced.

Exome sequencing of child-parent trios with bladder exstrophy: Findings in 26 children.

Bladder exstrophy (BE) is a rare, lower ventral midline defect with the bladder and part of the urethra exposed. The etiology of BE is unknown but thought to be influenced by genetic variation with more recent studies suggesting a role for rare variants. As such, we conducted paired-end exome sequencing in 26 child/mother/father trios.

Neuropathology of Perry Syndrome: Evidence of Medullary and Hypothalamic Involvement.

Background: Perry syndrome is a rare genetic parkinsonian disorder with TAR DNA binding protein 43 (TDP-43) pathology clinically presenting with parkinsonism, neuropsychiatric features, weight loss, and central hypoventilation. As respiratory complications are often the cause of death, studies likely show the early stage of the neurodegenerative process. Because of the rarity of this condition, few studies exist, and each case provides insight into pathological findings in this neurodegenerative condition.

Real-Time Voluntary Motion Prediction and Parkinson's Tremor Reduction Using Deep Neural Networks.

Wearable tremor suppression devices (WTSD) have been considered as a viable solution to manage parkinsonian tremor. WTSDs showed their ability to improve the quality of life of individuals suffering from parkinsonian tremor, by helping them to perform activities of daily living (ADL). Since parkinsonian tremor has been shown to be nonstationary, nonlinear, and stochastic in nature, the performance of the tremor models used by WTSDs is affected by their inability to adapt to the nonlinear behaviour of tremor.

Design and Preliminary Performance Assessment of a Wearable Tremor Suppression Glove.

Objective: Approximately 25% of individualsliving with parkinsonian tremor do not respond to traditional treatments. Wearable tremor suppression devices (WTSD) provide an alternative approach, however, tremor in the fingers has not been given as much attention as tremor in the elbow and the wrist. Therefore, the objective of this study is to design a wearable tremor suppression glove that can suppress tremor simultaneously, but independently, in multiple hand joints without restricting the user's voluntary motion.

Paternal genetic variants and risk of obstructive heart defects: A parent-of-origin approach.

Previous research on risk factors for obstructive heart defects (OHDs) focused on maternal and infant genetic variants, prenatal environmental exposures, and their potential interaction effects. Less is known about the role of paternal genetic variants or environmental exposures and risk of OHDs. We examined parent-of-origin effects in transmission of alleles in the folate, homocysteine, or transsulfuration pathway genes on OHD occurrence in offspring.