Frontiers in congenital disorders of glycosylation consortium, a cross-sectional study report at year 5 of 280 individuals in the natural history cohort.

OBJECTIVE: Our report describes clinical, genetic, and biochemical features of participants with a molecularly confirmed congenital disorder of glycosylation (CDG) enrolled in the Frontiers in Congenital Disorders of Glycosylation (FCDGC) Natural History cohort at year 5 of the study. METHODS: We enrolled individuals with a known or suspected CDG into the FCDGC Natural History Study, a multicenter prospective and retrospective natural history study of all genetic causes of CDG. We conducted a cross-sectional analysis of baseline study visit data from participants with confirmed CDG who were consented into the FCDGC Natural History Study (5U54NS115198) from October 2019 to November 2023. RESULTS: Three hundred thirty-three subjects consented to the FCDGC Natural History Study. Of these, 280 unique individuals had genetic data available that was consistent with a diagnosis of CDG. These 280 individuals were enrolled into the study between October 8, 2019 and November 29, 2023. One hundred forty-one (50.4%) were female, and 139 (49.6%) were male. Mean and median age at enrollment was 10.1 and 6.5 years, respectively, with a range of 0.22 to 71.4 years. The cohort encompassed individuals with disorders of N-linked protein glycosylation (57%), glycosylphosphatidylinositol anchor disorder (GPI anchor) (15%), disorders of Golgi homeostasis, trafficking and transport (12%), dolichol metabolism disorders (5%), disorders of multiple pathways (6%), and other (5%). The most frequent presenting symptom(s) leading to diagnosis were developmental delay/disability (77%), followed by hypotonia (56%) and feeding difficulties (42%). Mean and median time between first related symptom and diagnosis was 2.7 and 0.8 years, respectively. One hundred percent of individuals in our cohort had developmental differences/disabilities at the time of their baseline visit, followed by 97% with neurologic involvement, 91% with gastrointestinal (GI)/liver involvement, and 88% with musculoskeletal involvement. Severity of disease in individuals was scored on the Nijmegen Progression CDG Rating Scale (NPCRS) with 27% of scores categorized as mild, 44% moderate, and 29% severe. Of the individuals with N-linked protein glycosylation defects, 83% of those with data showed a type 1 pattern on carbohydrate deficient transferrin (CDT) analysis including 82/84 individuals with PMM2-CDG, 6% a type 2 pattern, 1% both type 1 and type 2 pattern and 10% a normal or nonspecific pattern. One hundred percent of individuals with Golgi homeostasis and trafficking defects with data showed a type 2 pattern on CDT analysis, while Golgi transport defect showed a type II pattern 73% of the time, a type 1 pattern for 7%, and 20% had a normal or nonspecific pattern. Most of the variants documented were classified as pathogenic or likely pathogenic using ACMG criteria. For the majority of the variants, the predicted molecular consequence was missense followed by nonsense and splice site, and the majority of the diagnoses are inherited in an autosomal recessive pattern but with disorders of all major nuclear inheritance included. DISCUSSION: The FCDGC Natural History Study serves as an important resource to build future research studies, improve clinical care, and prepare for clinical trial readiness. Herein is the first overview of CDG participants of the FCDGC Natural History Study.

Neurobehavioral outcomes of neonatal asymptomatic congenital cytomegalovirus infection at 12-months.

BACKGROUND: Congenital cytomegalovirus (cCMV) is the most common congenital viral infection in the United States. Symptomatic infections can cause severe hearing loss and neurological disability, although ~ 90% of cCMV infections are asymptomatic at birth. Despite its prevalence, the long-term neurobehavioral risks of asymptomatic cCMV infections are not fully understood. The objective of this work was to evaluate for potential long-term neurobehavioral sequelae in infants with asymptomatic cCMV. METHODS: Infants with cCMV were identified from a universal newborn cCMV screening study in a metropolitan area in the midwestern United States. Asymptomatic infants with cCMV were enrolled in a longitudinal neurodevelopmental study (N = 29). Age- and sex-matched healthy control infants (N = 193) were identified from the Baby Connectome Project (BCP), a longitudinal study of brain and behavioral development. The BCP sample supplemented an additional group of healthy control infants (N = 30), recruited from the same participant registry as the BCP specifically for comparison with infants with asymptomatic cCMV. Neurobehavioral assessments and parent questionnaires, including the Mullen Scales of Early Learning, the Repetitive Behavior Scales for Early Childhood (RBS-EC), and the Infant Toddler Social Emotional Assessment (ITSEA) were administered at 12 months of age. Neurobehavioral scores were compared between infants with asymptomatic cCMV and all identified healthy control infants. RESULTS: Infants with asymptomatic cCMV performed equivalently compared to healthy control infants on the neurobehavioral measures tested at 12 months of age. CONCLUSIONS: These results indicate that at 12 months of age, infants with asymptomatic cCMV are not statistically different from controls in a number of neurobehavioral domains. Although follow-up is ongoing, these observations provide reassurance about neurobehavioral outcomes for infants with asymptomatic cCMV and inform the ongoing discussion around universal screening. Additional follow-up will be necessary to understand the longer-term outcomes of these children.

The Family Meal Model: Influences on Family Mealtime Participation.

The family meal affords benefits such as positive nutritional habits, trust building, connecting, parent modeling, and teaching. During the school-aged years, families can support children's development of health behaviors and family routines. This interdisciplinary study examined families' experiences of mealtimes and the factors that support or hinder mealtime participation. Grounded theory methods guided data collection and analysis. Semi-structured interviews were conducted with 21 families with at least one school-aged child (n = 68). Interviews were audio recorded and transcribed. Researchers coded and categorized data, identified themes, and generated a model. Families defined family mealtime as all family members being together at the kitchen or dining room table eating a meal. Families enjoyed being together, conversing, and connecting through family mealtime participation. The Family Meal Model proposes relationships between factors that support or hinder a family's mealtime participation. Discussion includes support for a broadened role of occupational therapy in promoting family occupation through family meals.

Periodic Refresher Emails for Emergency Department Mass Casualty Incident Plans.

Audience and Type of Curriculum: This mass casualty incident (MCI) curriculum is intended for use as refresher content in the months between more formal education, such as hands-on MCI training and drills. The target audience for each topic varies, but the majority of them apply to all disciplines such as direct patient care roles (emergency room technicians, nurses, paramedics, advanced practice practitioners, resident physicians, attending physicians, etc.) and emergency department clerks/coordinators. Topics intended for only one or more discipline are labeled as such. See curriculum chart or email schedule (Appendix AI) for details. Length of Curriculum: This curriculum is intended for use as weekly refresher emails spanning up to a 30-week period. Introduction: There have been an increasing number of mass casualty events occurring throughout the country in recent years, many of which involve penetrating trauma. Education surrounding response to an MCI is broad and has many complex and ever-changing aspects that require staff to be updated on the most current information. Educational Goals: This curriculum is intended to maintain a knowledge base of MCI processes to mitigate degradation of necessary knowledge between hands-on MCI training. Educational Methods: The educational strategies used in this curriculum include short weekly refresher emails and optional external links for further reading. Research Methods: This content was evaluated for efficacy by administering electronic knowledge tests at baseline, mid-way (at 16 weeks), and at the end of the curriculum (32 weeks) via email. Additionally, brief content questions were asked in person while staff members were on shift throughout the entire study period, and a post-study survey was administered in order to obtain staff opinions on email length and training processes in general. Results: Scores for the knowledge tests were slightly higher at the end of the 32 weeks compared to baseline. Subjective feedback was positive overall at the end of the testing period. Discussion: Training and maintaining knowledge of roles and concepts of mass casualty incidents is vital since such events will never happen when expected. Short refresher emails allow educators to use spaced repetition and interleaving methods which have been shown to be a helpful adjunct to maintain knowledge, skills, and attitudes learned in more formal training.1,2. Topics: Mass casualty incident, emergency department, decontamination, blast injury, media relations, biological agents, reprocessing, crisis standard of care, SALT (Sort, Assess, Lifesaving Interventions, Treatment/Transport) triage, personal protective equipment, disaster carts, airways, passive security, family reunification.

How did the television get in the child's bedroom? Analysis of family interviews.

OBJECTIVE: Although recent research has shown associations between a television in the bedroom of children (BTV) and obesity, medical and negative societal consequences, the family decision making process supporting or opposing BTV is not yet understood. A qualitative research approach elicited rich, decision making experiences of families. METHODS: Structured family interviews (n=21) in spring 2011 in Oklahoma City captured direct quotations about family beliefs and practices related to BTV. Systematic constant comparative methods of grounded theory guided identification of patterns and themes across families to develop a model of family decision making for BTV. RESULTS: Nine themes represented family decision making processes for BTV. Supporting themes included "I didn't even think about it" and "benefit to me." Opposing themes included: "watch a lot more TV and get less sleep," "bedroom door would probably be closed a lot," "everyone knows it rots your brain," and "what the heck are they watching." CONCLUSIONS: Development of a conceptual model represented the basis for decisions opposing BTV in child concerns for development and missed opportunities while decisions supporting BTV reflected its use as a parenting tool. The emerged model could be useful in guiding strategies to modify family routines and address active and passive parenting strategies that negatively affect child health.

Blood lactate and hormonal responses to prototype flywheel ergometer workouts.

The purpose of the study was to compare blood lactate and hormonal responses with flywheel ergometer (FERG) leg presses for preliminary assessment of workouts best suited for future in-flight resistance exercise. Comprised of 10 repetition sets, the workouts entailed 3 sets of concentric and eccentric (CE3) actions, or concentric-only actions done for 3 (CO3) or 6 (CO6) sets. Methods employed included assessment of blood lactate concentrations ([BLa-]) before and 5 minutes postexercise. Venous blood was also collected before and at 1 and 30 minutes postexercise to assess growth hormone, testosterone, cortisol concentrations ([GH], [T], [C]) and [T/C] ratios. [BLa-] were compared with 2 (time) x 3 (workout) analysis of variance. Hormones were assessed with 2 (gender) x 3 (time) x 3 (workout) analysis of covariances. Results showed [BLa-] had a time effect. Growth hormone concentration showed gender x workout, gender x time, and workout x time interactions, whereas [T] had a 3-way interaction. [C] had gender, time, and workout effects. [T/C] yielded a gender x time interaction. It was concluded that, because CO6 and CE3 yielded similar anabolic hormonal data but the latter had a lower [C] 30 minutes postexercise, CE3 served as the best workout. Although the FERG was originally designed for microgravity, the effort put forth by current subjects was like that for workouts aimed at greater athletic performance and conditioning. Practical applications suggest that eccentric actions should be used for FERG workouts geared toward muscle mass and strength improvement.

Impact of acceleration on blood lactate values derived from high-speed resistance exercise.

Acceleration, or an increase in the rate of movement, is integral to success in many sports. Improvements in acceleration often entail workouts done at intensities that elicit higher blood lactate concentrations (BLa). The purpose of the study is to assess the impact of acceleration on BLa. Methods required subjects (n = 45) to perform 4 workouts that each involved two 1-minute sets of hip- and knee-extension repetitions on an inertial exercise trainer (Impulse Training Systems, Newnan, Georgia). Subjects performed 2 workouts comprised solely of phasic or tonic repetitions; their sequence was randomized to prevent an order effect. Before and 5 minutes after exercise, subjects' BLa were assessed with a calibrated analyzer (Sports Resource Group, Hawthorne, New York). Post and delta (post-pre) BLa both served as criterion measures for multivariate analysis. Average and peak acceleration values, derived from both phasic and tonic workouts, served as predictor variables. Results showed statistical significance (p < 0.05; R = 0.2534) and yielded the following prediction equation from phasic workouts: delta BLa = 1.40 + 1.116 (average acceleration set 1)--0.011 (peak acceleration set 1)--0.634 (average acceleration set 2) + 0.005 (peak acceleration set 2). Conclusions suggest delta BLa variance, which represents the increase of the metabolite incurred from workouts, is most easily explained by average acceleration values, which describes the mean increase in the rate of movement from phasic workouts. To improve an athlete's tolerance for acceleration-induced BLa increases, workouts should be tailored with respect to the muscles involved and the duration of exercise bouts of their chosen sport.

Growth hormone levels after flywheel ergometer exercise: correlation with independent variables.

INTRODUCTION: In-flight muscle mass and strength losses are likely exacerbated by low growth hormone (GH) concentrations. Factors associated with exercise may foretell resultant GH levels and thereby help blunt future mass and strength losses. METHODS: To assess the ability of variables to predict GH variance from resistive exercise done on a flywheel ergometer (FE) designed for in-flight exercise, subjects (N=17) performed three types of workouts on the device. With a randomized design, subjects performed the workouts with the intent to determine if changes in post-exercise GH concentrations are impacted by contractile mode and workload. Body mass, blood lactate (BLa-) concentrations, and peak angular velocity (PAV), average power (AP), and total work (TW) from workouts attempted to predict GH variance. Pre-exercise blood draws, and at 1 and 30 min after workouts, were used to determine GH concentrations. BLa- levels were measured before workouts and at 5 min post-exercise. Delta (8, post-pre) and 30-min post-workout GH levels served as criterion variables. RESULTS: Multivariate regression with an alpha < or = 0.05 yielded the following significant prediction equation: deltaGH = 13.64 - 0.014 (body mass) - 0.607 (post-exercise BLa-) + 0.659 (deltaBLa-) - 0.624(PAV) + 0.653(TW) + 0.147(AP). DISCUSSION: Univariate correlations show body mass, deltaBLa-, and TW were the best predictors of deltaGH variance. Future research should also attempt to identify additional variables that account for the unexplained GH variance from FE workouts.

Performance evaluation of a high-speed inertial exercise trainer.

A high-speed, low-resistance inertial exercise trainer (IET, Impulse Training Systems, Newnan, Ga) is increasingly employed in rehabilitative and athletic performance settings. Repetitions on an IET are done through a large range of motion because multijoint movements occur over more than one plane of motion, with no limitation on velocities or accelerations attained. The current study purpose is to assess data reproducibility from an instrumented IET through multiple test-retest measures. Data collection methods required the IET left and right halves to be fitted with a TLL-2K force transducer (Transducer Techniques, Temecula, Calif) on one of its pulleys, and an infrared position sensor (Model CX3-AP-1A, automationdirect.com) located midway on the underside of each track. Signals passed through DI-158U signal conditioners (DATAQ Instruments, Akron, Ohio) and were measured with a four-channel analog data acquisition card at 4000 Hz. To assess data reproducibility, college-age subjects (n = 45) performed four IET workouts that were spaced 1 week apart. Workouts entailed two 60-second sets of repetitive knee- and hip-extensor muscle actions as subjects were instructed to exert maximal voluntary effort. Results from multiple test-retest measures show that the IET elicited reproducible intra- and interworkout data despite the unique challenge of multiplanar and multijoint exercise done over a large range of motion. We conclude that future studies in which IET performance measurement is required may choose to instrument the device with current methodology. Current practical applications include making IET data easier to comprehend for the coaches, athletes, and health care providers who use the device.