Pilot study of a virtual weight management program for Duchenne muscular dystrophy.

INTRODUCTION/AIMS: Young people with Duchenne muscular dystrophy (DMD) are at increased risk of obesity. Weight management is important to families; however, several barriers exist. This pilot study aimed to investigate the feasibility and acceptability of a co-designed weight management program for DMD. METHODS: The Supporting Nutrition and Optimizing Wellbeing Program (SNOW-P) was a single-arm diet and behavior weight management intervention delivered via weekly telehealth/phone visits over 6 weeks to young people with DMD and obesity (body mass index (BMI) ≥95th percentile) and their caregivers. Using an online survey, caregivers of boys with DMD were consulted on the structure and topics delivered in SNOW-P. Primary outcomes were feasibility and acceptability; secondary outcomes were weight, physical function, and quality of life at 6- and 12-weeks follow-up. RESULTS: Of nineteen eligible participants, eight were enrolled (median age 11.4 years, range 4.9-15.8), and seven completed the program. Visit attendance was high (88%-100%); most participants reported high satisfaction and that participation was easy. Suggested changes included online and visual DMD-specific resources. At 6-weeks, median change in weight z-scores was -0.01 (IQR: -0.23, 0.17) indicating that on average, weight gain tracked as expected for age. Waist circumference measured by caregivers lacked accuracy and the completion rate of caregiver-reported secondary outcome measures (e.g., food diaries) was low. DISCUSSION: A co-designed, telehealth/phone weight management program appeared to be feasible and acceptable in a small group of boys with DMD. An adapted, hybrid telehealth and face-to-face program is recommended for efficacy testing.

Clinical practice guideline for the management of paediatric Charcot-Marie-Tooth disease.

BACKGROUND AND OBJECTIVES: Charcot-Marie-Tooth disease (CMT) is the most common inherited neuropathy and often presents during childhood. Guidelines for the optimal management of common problems experienced by individuals with CMT do not exist, for either children or adults. We formed the Paediatric CMT Best Practice Guidelines Consortium to develop evidence and consensus-based recommendations for the clinical management of children and adolescents with CMT, with the primary objective of promoting optimal, standardised care globally. METHODS: Development of this clinical practice guideline involved a series of systematic reviews covering 10 clinical questions, modified Delphi methodology involving an international panel of clinicians to generate consensus where evidence did not exist, and application of the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach to evaluate the body of literature and formulate recommendations. RESULTS: The final guideline includes three evidence-based and 31 consensus-based recommendations. They encompass the management of muscle weakness, balance and mobility impairment, sensory symptoms, muscle cramps, impaired upper limb function, respiratory impairment, maintenance of joint range of motion and non-surgical management of joint deformity. Consensus was not achieved in some management areas, reflecting differences in practice between clinicians and healthcare settings, and highlighting the need for further research. CONCLUSIONS: This clinical practice guideline provides practical and implementable guidance on the management of common clinical problems experienced by children with CMT and advocates for improved access to multidisciplinary care. Successful dissemination and implementation of these recommendations will be critical in ensuring their application across multiple healthcare settings.

Delivering multidisciplinary neuromuscular care for children via telehealth.

INTRODUCTION/AIMS: In response to coronavirus disease 2019 (COVID-19) pandemic restrictions int 2020, our face-to-face (F2F) multidisciplinary neuromuscular clinic (NMC) transitioned to widespread use of telehealth (TH). This study aimed to (1) understand parent/guardian, child, and clinician perceptions of TH; (2) examine TH-related changes in clinical activity; and (3) use these findings to inform a future model of care for the NMC. METHODS: A clinical audit was undertaken to examine clinical activity throughout 2018-2020. Online surveys were distributed to clinicians and parents of children attending the NMC via TH in 2020. A working group of clinicians created a checklist to guide a future hybrid model of TH and F2F care. RESULTS: Total clinical activity in 2020 was maintained from previous years; 62.8% of all appointments occurred via TH, and 82.3% of patients attended NMC by TH at least once. Ninety-nine parents (30.6% response rate), 52 children, and 17 clinicians (77% response rate) responded to the survey. All groups reported better interaction when F2F compared to TH. Eighty percent of parents identified advantages of TH and reported lower levels of stress. A lack of "hands-on" physical assessment was identified by parents and clinicians as a TH limitation. Most families (68.1% of parents; 58.8% of children) and all clinicians indicated a preference for a mix of TH and F2F NMC appointments in the future. DISCUSSION: This study has informed a checklist to guide future TH use in a new hybrid model of care. Further investigation is required to assess health impacts of TH use in pediatric neuromuscular care.

A pilot feasibility study of a group-delivered cancer parenting program: Enhancing Connections-Group.

OBJECTIVE: The purpose of this study was to examine the feasibility and short-term impact of a 5-session fully manualized, group-delivered cancer parenting education program to diagnosed parents or surrogate parents with a school-age child. DESIGN: Single group, pre-post-test design with intent to treat analysis. SAMPLE: A total of 16 parents completed the program who were diagnosed within 12 months with non-metastatic cancer of any type (Stages 0-III), read and wrote English, had a child 5-17 years old who knew the parent's diagnosis. METHODS: Assessments occurred at baseline and at 2 months post-baseline on standardized measures of parental depressed mood, anxiety, parenting self-efficacy, parenting quality, parenting skills and child behavioral-emotional adjustment. FINDINGS/RESULTS: The program was feasible and well accepted: 16/18 (89%) of the enrolled participants were included in the intent to treat analysis. Program staff were consistently positive and enthusiastic about the demonstrated skills they observed in group attendees during the group-delivered sessions, including the emergence of support between attendees. Outcomes on all measures improved between baseline and post-intervention; changes were statistically significant on measures of parents' anxiety, parents' self-efficacy, parents' skills, and parenting quality. CONCLUSIONS: The group-delivered Enhancing Connections cancer parenting program has potential to improve behavioral-emotional outcomes on standardized measures of skills and emotional adjustment in parents, parent-surrogates and children. Future testing is warranted. IMPLICATIONS FOR PSYCHOSOCIAL PROVIDERS: After a brief training, a fully manualized cancer parenting program can enhance parenting competencies and parent-reported child outcomes.

Assessing maternal dietary quality in early pregnancy in the programming of intrauterine fetal growth.

INTRODUCTION: It is established globally that a healthy maternal diet during pregnancy is important in programming fetal growth and development. The assessment of maternal dietary intake, however, is challenging both in clinical practice and in research studies. The aim of this study was to compare three individual dietary quality scores in early pregnancy based on European, American and World Health Organization (WHO) nutrient recommendations for the identification of suboptimal fetal growth. MATERIAL AND METHODS: Women were recruited conveniently at their first antenatal hospital visit and completed a supervised 4-day diet history. The results were dichotomized into those women meeting and those not meeting macronutrient and micronutrient recommendations from the European Food Safety Authority (EFSA), WHO and the Institute of Medicine (USA). Composite nutrient scores were derived. The relation between the three individual dietary scores in early pregnancy and subsequent birthweight and small-for-gestational-age was compared using regression analyses. RESULTS: Of the 202 women, the mean age was 32.2 (SD 5.0) years and 44.6% were nulliparas. The mean dietary quality scores were: EFSA 9.4 (SD 3.1), WHO 8.5 (SD 3.7) and USA 9.6 (SD 3.6). On multivariable regression, there was a positive relationship between the EFSA (ß = 44.7, 95% CI 17.0-72.4, P = 0.002), WHO (ß = 39.2, 95% CI 17.2-61.1, P = 0.001), and USA (ß = 40.0 95% CI 17.6-62.3, P = 0.001) score and birthweight. All 3 scores were positively associated with birthweight centiles. However, only those in the lowest quartile of the EFSA score were more likely to be small-for-gestational-age (odds ratio 2.8, 95% CI 1.1-7.4, P = 0.03). CONCLUSIONS: This study found that a dietary quality score based on European nutrient recommendations was better than other international recommendations at identifying in early pregnancy those women at risk of suboptimal fetal growth.

Development and validation of the Charcot-Marie-Tooth Disease Infant Scale.

Many genetic subtypes of Charcot-Marie-Tooth disease (CMT) show signs of symptomatic disease during the earliest years of life. This might be the ideal time to intervene before progression of clinical sequelae due to demyelination and axonal loss. In the absence of disease-specific clinical trial outcome measures for CMT during infancy and early childhood the aim of this study was to develop and validate a functional measure of disease severity, known as the Charcot-Marie-Tooth disease Infant Scale (CMTInfS). Development projects involved identification of a preliminary pool of 31 items representing the range of disability in affected patients aged 0-4 years from a systematic review of the literature, peer review by 12 expert clinicians and researchers in the field, design of a scoring algorithm and pilot testing in 22 participants. Subsequently, a series of validation projects were conducted based on 128 assessments of: 26 confirmed cases of inherited neuropathy (17 CMT1A, one CMT1B, one CMT1D, one CMT2C, one CMT2S, two CMT4C, one CMTX3, one Riboflavin Transporter Deficiency Type 2, and one unidentified mutation); seven 'at risk' cases and 95 unaffected healthy controls recruited through the NIH-funded Inherited Neuropathies Consortium. Validation projects included: Item, Factor and Rasch analysis, intra- and inter-rater reliability, discriminant ability and convergent validity with the CMT Pediatric Scale (CMTPedS) for children aged 3-4 years. Development and validation projects produced a psychometrically robust 15-item scale. Rasch analysis supported the viability of the CMTInfS as a unidimensional measure of disease severity and showed good overall model fit, no evidence of misfitting items or persons and was well targeted for affected children. The CMTInfS demonstrated high intra-rater reliability [intraclass correlation coefficient (ICC)3,1 0.999, 95% confidence interval 0.996-1.000) and inter-rater reliability (ICC2,1 0.997, 95% confidence interval 0.992-0.999). The CMTInfS was able to discriminate between the CMT group and controls (P = 0.006), and convergent validity demonstrated good agreement between CMTInfS and CMTPedS scores (r = 0.76, P = 0.01). The final version of the CMTInfS requires 20 min to administer and is a reliable and sensitive functional outcome measure for early onset CMT and related neuropathies.10.1093/brain/awy280_video1awy280media15970672819001.

Feasibility of recruitment to a behavioural smoking cessation intervention combined with ongoing online support.

The aim of this randomized controlled trial was to determine whether a behavioural intervention in pregnancy supported by online information would improve smoking cessation rates. However, due to a number of challenges, recruitment to this trial was reluctantly halted. We aimed to recruit 220 maternal smokers within 2 years and after screening 1995 women, just 22 enrolled over a 8-month period. Only three women accessed the online element of the intervention and, at follow up, no women reported quitting. We report our findings as they may inform the design and powering of future smoking cessation interventions in pregnancy.

Searching for tryptase in the RBL-2H3 mast cell model: Preparation for comparative mast cell toxicology studies with zebrafish.

Mast cells comprise a physiologically and toxicologically important cell type that is ubiquitous among species and tissues. Mast cells undergo degranulation, in which characteristic intracellular granules fuse with the plasma membrane and release many bioactive substances, such as enzymes ß-hexosaminidase and tryptase. Activity of mast cells in the toxicology model organism, zebrafish, has been monitored via tryptase release and cleavage of substrate N-α-benzoyl-dl-Arg-p-nitroanilide (BAPNA). An extensively used in vitro mast cell model for studying toxicant mechanisms is the RBL-2H3 cell line. However, instead of tryptase, granule contents such as ß-hexosaminidase have usually been employed as RBL-2H3 degranulation markers. To align RBL-2H3 cell toxicological studies to in vivo mast cell studies using zebrafish, we aimed to develop an RBL-2H3 tryptase assay. Unexpectedly, we discovered that tryptase release from RBL-2H3 cells is not detectable, using BAPNA substrate, despite optimized assay that can detect as little as 1 ng tryptase. Additional studies performed with another substrate, tosyl-Gly-Pro-Lys-pNA, and with an enzyme-linked immunosorbent assay, revealed a lack of tryptase protein released from stimulated RBL-2H3 cells. Furthermore, none of the eight rat tryptase genes (Tpsb2, Tpsab1, Tpsg1, Prss34, Gzmk, Gzma, Prss29, Prss41) is expressed in RBL-2H3 cells, even though all are found in RBL-2H3 genomic DNA and even though ß-hexosaminidase mRNA is constitutively expressed. Therefore, mast cell researchers should utilize ß-hexosaminidase or another reliable marker for RBL-2H3 degranulation studies, not tryptase. Comparative toxicity testing in RBL-2H3 cells in vitro and in zebrafish mast cells in vivo will require use of a degranulation reporter different from tryptase.

Heat Exposure and Hypohydration Exacerbate Physiological Strain During Load Carrying.

Adams, EL, Casa, DJ, Huggins, RA, DeMartini-Nolan, JK, Stearns, RL, Kennedy, RM, Bosworth, MM, DiStefano, LJ, Armstrong, LE, and Maresh, CM. Heat exposure and hypohydration exacerbate physiological strain during load carrying. J Strength Cond Res 33(3): 727-735, 2019-Heat exposure and hypohydration induce physiological and psychological strain during exercise; however, it is unknown if the separate effects of heat exposure and hypohydration are synergistic when co-occurring during loaded exercise. This study compared separate and combined effects of heat exposure and hypohydration on physiological strain, mood state, and visual vigilance during loaded exercise. Twelve men (mean ± SD; age, 20 ± 2 years; body mass, 74.0 ± 8.2 kg; maximal oxygen uptake, 57.0 ± 6.0 ml·kg·min) completed 4 trials under the following conditions: euhydrated temperate (EUT), hypohydrated temperate (HYT), euhydrated hot (EUH), and hypohydrated hot (HYH). Exercise was 90 minutes of treadmill walking (∼50% V[Combining Dot Above]O2max, 5% grade) while carrying a 45-lb rucksack. Profile of Mood States and the Scanning Visual Vigilance Test were completed before and after exercise. The separate effects of heat exposure (EUH) and hypohydration (HYT) on post-exercise rectal temperature (Tre) were similar (38.25 ± 0.63°C vs. 38.22 ± 0.29°C, respectively, p > 0.05), whereas in combination (HYH), post-exercise Tre was far greater (39.32 ± 0.43°C). Increase in Tre per 1% body mass loss (BML) for HYH (vs. EUH) was greater than HYT (vs. EUT) (0.32 vs. 0.04°C, respectively, p = 0.02); heart rate increase per 1% BML for HYH (vs. EUH) was 7 b·min compared with HYT (vs. EUT) at 3 b·min (p = 0.30). Hypohydrated hot induced greater mood disturbance (post-exercise - pre-exercise) (35 ± 21 units) compared with other conditions (EUT = 3 ± 9 units; HYT = 3 ± 16 units; EUH = 16 ± 26 units; p < 0.001). No differences occurred in visual vigilance (p > 0.05). Independently, heat exposure and hypohydration induced similar physiological strain during loaded exercise; when combined, heat exposure with hypohydration, synergistically exacerbated physiological strain and mood disturbance.

Evaluation of Serial Casting for Boys with Duchenne Muscular Dystrophy: A Case Report.

AIM: To report the effects of below-knee serial casting in two boys with Duchenne muscular dystrophy who presented with well-preserved strength and calf shortening. METHODS: Bilateral below-knee serial casts were applied over two weeks with follow-up of daily stretching and wearing of customized night splints. Outcome measures were performed at baseline, 1, 3, 6, and 12 months post-casting. These included measures of calf length, leg strength, motor function, endurance, and spatio-temporal gait parameters. RESULTS: Both boys completed serial casting with gains in muscle length. No adverse effects on strength or motor function were observed over a 12-month follow-up period.

Duration of periconceptional folic acid supplementation in women booking for antenatal care.

OBJECTIVE: To provide accurate estimates of the commencement time, duration and dosage of folic acid (FA) supplementation taken by Irish women in the periconceptional period. The study also aimed to establish the factors associated with optimal FA supplementation practices. DESIGN: Cross-sectional observational study. Women's clinical and sociodemographic details were computerised. Maternal weight and height were measured before calculating BMI. Detailed FA supplementation questionnaires were completed under the supervision of a trained researcher. SETTING: A large university maternity hospital, Republic of Ireland, January 2014-April 2016. SUBJECTS: Women (n 856) recruited at their convenience in the first trimester. RESULTS: While almost all of the women (97 %) were taking FA at enrolment, only one in four women took FA for at least 12 weeks preconceptionally (n 208). Among the 44 % of women who were supplementing with FA preconceptionally, 44 % (162/370) reported taking FA for less than the 12 weeks required to achieve optimal red-blood-cell folate levels for prevention of neural tube defects. On multivariate analysis, only planned pregnancy and nulliparity were associated with taking FA for at least 12 weeks preconceptionally. Among women who only took FA postconceptionally, almost two-thirds commenced it after day 28 of their pregnancy when the neural tube had already closed. CONCLUSIONS: As the timing of FA was suboptimal both before and after conception, we recommend that current national FA guidelines need to be reviewed.

Maternal nutrient intakes from food and drinks consumed in early pregnancy in Ireland.

Background: The aim of this observational study was to measure food, macronutrient and micronutrient intakes of women presenting for antenatal care and assess compliance with current nutritional recommendations. Methods: Women were recruited in the first trimester of pregnancy. Maternal weight and height were measured and body mass index (BMI) calculated. Body composition was measured using bioelectrical impedance analysis. Maternal energy and nutrient intakes were estimated using a validated Willett Food Frequency Questionnaire and misreporting of energy intakes (EI) determined. Results: Plausible EIs were reported in 402 women. Mean age, weight and BMI were 30.8 years, 67.1 kg and 24.6 kg/m2 respectively. Median EIs were 2111 kcal, and median protein, carbohydrate and fat intakes were 17.3, 48.1 and 36.2 g/MJ/day, respectively. More than 90% of women exceeded the recommended daily allowance for saturated fat. Nearly all of the women (99%) did not meet estimated average requirements (EAR) for vitamin D. One in three women failed to achieve a dietary folate intake of 400 µg/day. Over one in five women failed to meet the EAR for iron, and 14% failed to achieve the EAR for calcium. Conclusions: Our findings highlight concerning deficits in nutrient intakes among women and will help guide professional dietary advice to women attending for future obstetric care in Ireland.

Gait in children and adolescents with Charcot-Marie-Tooth disease: a systematic review.

Symptoms of Charcot-Marie-Tooth (CMT) disease typically arise in childhood or adolescence with gait difficulty most common. A systematic review was conducted to synthesise, review, and characterise gait in paediatric CMT. Health-related electronic databases were reviewed with search terms related to CMT and gait. Of 454 articles, 10 articles describing seven studies met eligibility criteria; samples ranged from 1 to 81, included mixed CMT sub-types and had a participant mean age of 13 years. Assessments included a variety of methods to examine only barefoot gait. Heterogeneity of gait patterns was noted. Children and adolescents with CMT walked slower, most likely due to shorter stride length. Common kinematic and kinetic abnormalities included significant foot drop during swing, reduced calf muscle power, and proximal compensatory mechanisms in the lower limb. Little data were found to inform typical functional gait characteristics or change over time. Of note, barefoot assessment does not reflect function in everyday life where footwear is commonly worn. With limited existing literature, future studies of gait in paediatric CMT need to evaluate the influence of diagnostic sub-types and disease progression; the effect of factors such as footwear and the environment; and to explore changes in gait and function throughout childhood and adolescence.

Breast-feeding and postpartum maternal weight trajectories.

OBJECTIVE: We examined whether breast-feeding, and in particular exclusive breast-feeding, was associated with maternal weight and body composition changes at 4 months postpartum independently of other maternal variables. DESIGN: Prospective longitudinal study. Women were recruited in the first trimester after an ultrasound examination confirmed an ongoing singleton pregnancy. Weight and body composition were measured using advanced bio-electrical impedance analysis at the first antenatal visit and 4 months postpartum. Detailed questionnaires were completed on breast-feeding, socio-economic status, diet and exercise in addition to routine clinical and sociodemographic details. SETTING: Large Irish university maternity hospital. SUBJECTS: Women who delivered a baby weighing ≥500 g between November 2012 and March 2014. RESULTS: At the postpartum visit, the mean weight was 70·9 (sd 14·2) kg (n 470) and the mean BMI was 25·9 (sd 5·0) kg/m2. 'Any breast-feeding' was reported by 65·1 % of women (n 306). Irish nativity (OR=0·085, P<0·001), current smoking (OR=0·385, P=0·01), relative income poverty (OR=0·421, P=0·04) and deprivation (OR=0·458, P=0·02) were negatively associated with exclusive breast-feeding. At 4 months postpartum there was no difference in maternal weight change between women who exclusively breast-fed and those who formula-fed (+2·0 v. +1·1 kg, P=0·13). Women who exclusively breast-fed had a greater increase in percentage body fat at 4 months postpartum compared with women who formula-fed (+1·0 v. -0·03 %, P=0·02), even though their dietary quality was better. Exclusive breast-feeding was not associated with postpartum maternal weight or body fat percentage change after adjusting for other maternal variables. CONCLUSIONS: There are many reasons why breast-feeding should be strongly promoted but we found no evidence to support postpartum weight management as an advantage of breast-feeding.

Antimicrobial agent triclosan is a proton ionophore uncoupler of mitochondria in living rat and human mast cells and in primary human keratinocytes.

Triclosan (TCS) is an antimicrobial used widely in hospitals and personal care products, at ~10 mm. Human skin efficiently absorbs TCS. Mast cells are ubiquitous key players both in physiological processes and in disease, including asthma, cancer and autism. We previously showed that non-cytotoxic levels of TCS inhibit degranulation, the release of histamine and other mediators, from rat basophilic leukemia mast cells (RBL-2H3), and in this study, we replicate this finding in human mast cells (HMC-1.2). Our investigation into the molecular mechanisms underlying this effect led to the discovery that TCS disrupts adenosine triphosphate (ATP) production in RBL-2H3 cells in glucose-free, galactose-containing media (95% confidence interval EC50 = 7.5-9.7 µm), without causing cytotoxicity. Using these same glucose-free conditions, 15 µm TCS dampens RBL-2H3 degranulation by 40%. The same ATP disruption was found with human HMC-1.2 cells (EC50 4.2-13.7 µm), NIH-3 T3 mouse fibroblasts (EC50 4.8-7.4 µm) and primary human keratinocytes (EC50 3.0-4.1 µm) all with no cytotoxicity. TCS increases oxygen consumption rate in RBL-2H3 cells. Known mitochondrial uncouplers (e.g., carbonyl cyanide 3-chlorophenylhydrazone) previously were found to inhibit mast cell function. TCS-methyl, which has a methyl group in place of the TCS ionizable proton, affects neither degranulation nor ATP production at non-cytotoxic doses. Thus, the effects of TCS on mast cell function are due to its proton ionophore structure. In addition, 5 µm TCS inhibits thapsigargin-stimulated degranulation of RBL-2H3 cells: further evidence that TCS disrupts mast cell signaling. Our data indicate that TCS is a mitochondrial uncoupler, and TCS may affect numerous cell types and functions via this mechanism. Copyright © 2015 John Wiley & Sons, Ltd.

Arsenic inhibits mast cell degranulation via suppression of early tyrosine phosphorylation events.

Exposure to arsenic is a global health concern. We previously documented an inhibitory effect of inorganic Arsenite on IgE-mediated degranulation of RBL-2H3 mast cells (Hutchinson et al., 2011; J. Appl. Toxicol. 31: 231-241). Mast cells are tissue-resident cells that are positioned at the host-environment interface, thereby serving vital roles in many physiological processes and disease states, in addition to their well-known roles in allergy and asthma. Upon activation, mast cells secrete several mediators from cytoplasmic granules, in degranulation. The present study is an investigation of Arsenite's molecular target(s) in the degranulation pathway. Here, we report that arsenic does not affect degranulation stimulated by either the Ca(2) (+) ionophore A23187 or thapsigargin, which both bypass early signaling events. Arsenic also does not alter degranulation initiated by another non-IgE-mediated mast cell stimulant, the G-protein activator compound 48/80. However, arsenic inhibits Ca(2) (+) influx into antigen-activated mast cells. These results indicate that the target of arsenic in the degranulation pathway is upstream of the Ca(2) (+) influx. Phospho-Syk and phospho-p85 phosphoinositide 3-kinase enzyme-linked immunosorbent assays data show that arsenic inhibits early phosphorylation events. Taken together, this evidence indicates that the mechanism underlying arsenic inhibition of mast cell degranulation occurs at the early tyrosine phosphorylation steps in the degranulation pathway. Copyright © 2016 John Wiley & Sons, Ltd.