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Purpose: Social support is a known facilitator of exercise for people with disability. A qualitative approach was used to understand current social support practices in community gyms for young adults with disability., Methods: Embedded within a larger project "Getting Young adult Moving - Supporting Participation and Access to Recreation Centres" (GYM-SPARC), semi-structured interviews were completed with 25 gym staff, representing 29 community gym facilities across Victoria, Australia. Data were analysed using inductive thematic analysis., Results: Social support types and availability varied across community gyms. Social support practices included orientation, supervision, specialist input, logistical support, motivation, peer support and social activities. These were provided as "standard" supports available to all members, "inclusion" supports specific to people with disabilities, or "external" supports provided by external services but operating within the gym facility. Two themes described how social supports were implemented: (i) stages of participation - "getting in the door, getting started and ongoing participation," and (ii) influencing factors - "people, partnerships and policy.", Conclusion: Social support practices are seldom implemented by community gyms to facilitate young adults with disability to "get in the door." Improving partnerships between gyms, rehabilitation, health and disability services may support the transition into community gym exercise.IMPLICATIONS FOR REHABILITATIONUnderstanding current social support practices enables rehabilitation clinicians and the recreation sector to identify gaps and opportunities to promote gym participation for young adults with disability.Social supports for young adults with a disability are implemented variably across participation phases and driven by people, partnership, and policy factors.Currently, a gap exists in the provision of social support to facilitate young adults with disability "getting in the door" of community gyms.An opportunity exists for rehabilitation clinicians (such as physiotherapists) and community gyms to collaborate and facilitate the transition into community-based gym exercise for young adults with disability.

Background: Implementing scientific knowledge in clinical practice is a challenge. In this context, the effective dissemination of scientific findings is of utmost importance., Objective: The aim of this study was to develop a Practice Brief in Portuguese, Spanish and English based on a previously published Clinical Practice Guideline to promote safe and effective exercise for children and young people with Charcot-Marie-Tooth disease and related neuropathies (CMT)., Methods: The Practice Brief was developed by eight health professionals from Brazil and Australia with English, Portuguese, and Spanish translations. The target audience chosen were the medical and allied health professionals involved in the rehabilitation of paediatric CMT. The content was based on the world first "Clinical Practice Guideline for the management of paediatric Charcot-Marie-Tooth disease" [1]. The layout of the Practice Brief was designed according to the criteria for the development of educational materials. The disclosure plan for the Practice Brief involves its publication on University and Hospital websites, www.ClinicalOutcomeMeasures.org and through social media platforms such as ResearchGate, Instagram, Facebook and Twitter, as well as in print format for CMT patient care centres., Results: The English, Portuguese and Spanish versions of the Practice Brief is organised into six sections about assessment, exercise and physical rehabilitation, of which one is focused on progressive resistance exercises for the foot dorsiflexor muscles., Conclusion: We developed a Practice Brief in three languages (English, Portuguese and Spanish), synthesising the main recommendations for exercise and related rehabilitative therapies for paediatric CMT from a published clinical guideline., Competing Interests: Conflict of interest statement The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Colorectal cancer (CRC) screening services in Ireland were cancelled or postponed for periods during the COVID-19 pandemic. The aim of this study was to assess the impact of screening colonoscopy delays after a positive FIT on clinical and histopathological outcomes due to these restrictions., Methods: Participants in the Irish National Bowel Screening Programme with a positive Immunochemical Faecal Test (FIT) during the COVID-19 pandemic (March 2020-December 2021) were included. Patients were categorised into attended for a colonoscopy <3 months and attended for colonoscopy ≥3-17 months post positive FIT. Chi-Square Test of independence was performed using WinPepi., Results: 3227 individuals had a complete index colonoscopy <3 months and 262 attended colonoscopy from ≥3 to 17 months post positive FIT. Of the clients whose colonoscopy was between ≥3-17 months from positive FIT, the median wait time was 3 months. There was no significant difference found between the two groups for CRC (5.8 % vs 5.0 %, p=0.544) or for the proportion of cancer stage I, stage II and unknown (33.7 %, 40.6 %, 25.7 %, p=0.411). There was no difference in the proportions of adenomas (57.8 % vs 58.4 %, p=0.849) and the proportion of advanced adenomas (7.7 % vs 10.7 %, p=0.077) detected between the two groups. A similar proportion of polyps were detected in individuals whose index colonoscopies were postponed <3 months from positive FIT (66.9 % vs 66 %, p=0.786)., Conclusion: A median delay of 3 months in screening colonoscopies after a positive FIT does not adversely impact clinical or histopathological outcomes. There was no significant difference in cancer staging, advanced adenomas or polyps detected between those who attended colonoscopies <3 months and ≥3-17 months post positive FIT. COVID-19 related disruptions to the normal functioning of the Irish bowel screening programme did not compromise our key objectives of advanced adenoma and cancer detection., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Identify and prioritise strategies to optimise physical activity participation in the community gym setting for young adults with cerebral palsy., Methods: An e-Delphi method was implemented over three rounds with four stakeholder groups (young adults with cerebral palsy, their families, gym staff or exercise professionals, and health professionals). Strategies for change were identified by the stakeholders in round 1. In rounds 2 and 3, strategies for change were rated on the importance for implementation using a 7-point Likert scale (1 being lowest importance, 7 being highest). The consensus was achieved if ≥70% of participants identified a strategy as high importance., Results: Seventy participants (20 young adults 10 family members, 21 health professionals, and 19 exercise professionals) identified 83 strategies for improving gym participation. Of these, 44 strategies met the consensus criteria. The highest priority strategies related to changing the physical environment, addressing cost barriers, gym staff training, and developing partnerships between sectors., Conclusions: Addressing physical accessibility, cost of attendance and the skills of gym staff were agreed upon by the stakeholder groups as priority areas for future resource allocation and research translation. Clinicians and community leisure facilities must work with consumers to implement strategies in their local contexts.

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., (© 2024 The Authors. Muscle & Nerve published by Wiley Periodicals LLC.)

Background: ATL1102 is a 2'MOE gapmer antisense oligonucleotide to the CD49d alpha subunit of VLA-4, inhibiting expression of CD49d on lymphocytes, reducing survival, activation and migration to sites of inflammation. Children with DMD have dystrophin deficient muscles susceptible to contraction induced injury, which triggers the immune system, exacerbating muscle damage. CD49d is a biomarker of disease severity in DMD, with increased numbers of high CD49d expressing T cells correlating with more severe and progressive weakess, despite corticosteroid treatment., Methods: This Phase 2 open label study assessed the safety, efficacy and pharmacokinetic profile of ATL1102 administered as 25 mg weekly by subcutaneous injection for 24 weeks in 9 non-ambulatory boys with DMD aged 10-18 years. The main objective was to assess safety and tolerability of ATL1102. Secondary objectives included the effect of ATL1102 on lymphocyte numbers in the blood, functional changes in upper limb function as assessed by Performance of Upper Limb test (PUL 2.0) and upper limb strength using MyoGrip and MyoPinch compared to baseline., Results: Eight out of nine participants were on a stable dose of corticosteroids. ATL1102 was generally safe and well tolerated. No serious adverse events were reported. There were no participant withdrawals from the study. The most commonly reported adverse events were injection site erythema and skin discoloration. There was no statistically significant change in lymphocyte count from baseline to week 8, 12 or 24 of dosing however, the CD3+CD49d+ T lymphocytes were statistically significantly higher at week 28 compared to week 24, four weeks past the last dose (mean change 0.40x109/L 95%CI 0.05, 0.74; p = 0.030). Functional muscle strength, as measured by the PUL2.0, EK2 and Myoset grip and pinch measures, and MRI fat fraction of the forearm muscles were stable throughout the trial period., Conclusion: ATL1102, a novel antisense drug being developed for the treatment of inflammation that exacerbates muscle fibre damage in DMD, appears to be safe and well tolerated in non-ambulant boys with DMD. The apparent stabilisation observed on multiple muscle disease progression parameters assessed over the study duration support the continued development of ATL1102 for the treatment of DMD., Trial Registration: Clinical Trial Registration. Australian New Zealand Clinical Trials Registry Number: ACTRN12618000970246., Competing Interests: The ATL1102 in DMD clinical trial was funded in its entirety by the commercial sponsor Antisense Therapeutics Ltd. Antisense Therapeutics Ltd is a publicly traded company, listed on the Australian ASX. At the time of the trial, authors Ms Desem and Dr Tachas were employees of the sponsor and so received payment for services from the sponsor as employees. Ms. Desem and Dr Tachas hold an equity interest in the sponsor. Dr Tachas and Ms Desem along with other sponsor employees and sub-contracted specialists were involved in the study design and data analysis. Ms Desem has since left the company and no longer is employed by the sponsor. Authors Dr Woodcock and Dr Ryan were at the time of the trial employees of the Royal Children’s Hospital and Murdoch Children’s Research Institute and are not affiliated with the sponsor in any way and have not received any direct personal payment or honoraria from the sponsors, nor do they or their family members hold a financial interest or stock in the sponsor company. Dr Woodcock is still an employee of the above institutions, but Dr Ryan has since left the employment to take up public office as a Member of the Australian Parliament. Dr Woodcock and Dr Ryan were involved in the trial design as unpaid consultants. Dr Woodcock has received honoraria for work performed including educational activities and attendance at advisory board meetings from pharmaceutical companies Biogen, Novartis, Roche and Avidity and an educational travel bursary to attend an international conference in 2016 from Biogen. Dr Woodcock has received grants for research work from FSHD Global Research Foundation, FSHD Society and Fulcrum Therapeutics. Dr Woodcock has been principal investigator on a number of industry-sponsored clinical trials. None of these disclosures affected the work Dr Woodcock performed on this clinical trial. Dr Ryan has received honoraria for work performed including educational activities and attendance at advisory board meetings from pharmaceutical companies Biogen, Novartis, Roche. Dr Ryan has been principal investigator on a number of industry-sponsored clinical trials. None of these disclosures affected the work Dr Ryan performed on this clinical trial. Dr Yiu has received advisory board honoraria from Biogen and Roche, and has received research support from Biogen, Roche, Pfizer and PTC therapeutics unrelated to the content of this manuscript. Dr Yiu has been principal investigator on a number of industry-sponsored clinical trials. None of these disclosures affected the work Dr Yiu performed on this clinical trial. Prof. Delatycki has received grant awards from NHMRC and is principal investigator in industry sponsored clinical trials including trials sponsored by Rearta and PTC. As this was a clinical trial, publication was always planned from trial inception. No employees of the sponsor were involved in the data collection, although Ms Desem did liaise closely with the MCRI/RCH site staff and Clinical Trial Organisation throughout the trial. As the study statistician, author Dr Button was paid a consultancy fee for his services from the trial sponsor commercial company Antisense Therapeutics Ltd. Authors Dr Houweling, Dr Coles and Dr Tiong were recipients of a grant to perform the MDX studies. This grant was paid by the sponsor Antisense Therapeutics Ltd. None of the other authors received any payment from the sponsor to conduct this study. All other authors had input into writing or revising this manuscript. The authors confirm that the involvement of employees of the sponsor Antisense Therapeutics Ltd in the trial design, data analysis and decision to publish this data does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Woodcock et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The U.S. DoD has identified firearm suicide prevention as a key operational priority. One vital approach to addressing firearm suicides is through promoting lethal means safety, which involves the voluntary use of secure storage for personally owned firearms and/or temporarily moving firearms out of the home during risk periods. Despite promising approaches to lethal means safety, critical gaps remain in research, programming, and communication among and across scientists, DoD programmatic leaders, front-line commanders, and service members. To address these gaps, the first-ever national "Firearm Suicide Prevention in the Military: Messaging and Interventions Summit" was convened in June 2022, bringing together DoD personnel and researchers with expertise in firearm suicide prevention and lethal means safety. The Summit identified 10 recommendations to enhance firearm suicide prevention messaging and interventions in the U.S. military, including (1) repeal or amend prohibitions on questioning service members about personal firearms; (2) develop, examine, and use common language for firearm injury prevention; (3) implement a universal approach to training on comprehensive firearm injury prevention; (4) encourage leadership across disciplines and levels; (5) aim for broad culture change; (6) support innovative research; (7) consider various outcome measures; (8) promote "cultural competence" for better communication; (9) reduce territorialism; and (10) develop creative partnerships. Ultimately, these recommendations can facilitate productive partnerships with a shared goal: to develop, test, and implement strategies that standardize lethal means safety and reduce firearm suicides and other firearm injuries or harm among service members., (© The Association of Military Surgeons of the United States 2022. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

People with disability report social support facilitates participation in physical activity. A scoping review explored social support strategies used to facilitate exercise participation for people with disability (aged ≥ 15 years) in community gym settings. Seven electronic databases were searched. Studies were screened for eligibility based on title and abstract followed by full-text review. Data were analysed using content analysis and narrative synthesis. Forty-two articles reporting data from 35 studies were included. Eight types of social support were identified: supervision ( n = 30), peer support ( n = 21), specialist support ( n = 19), orientation ( n = 15), education ( n = 7), logistical support ( n = 6), motivational support ( n = 5) and organised social activities ( n = 4). Direct supervision was typically provided 1:1 or in small groups by staff experienced working with people with disability. Peer support typically involved support from exercise group participants or a peer mentor. Specialist support was usually provided by a health or exercise professional either directly to people with disability or to the people providing support to them (e.g., trainer). Orientation to the gym environment, equipment and exercise program was usually provided over 1 or 2 sessions. Gym staff may use these strategies to guide the implementation of social supports within their facilities to promote social connectedness and participation for people with disability.

Aim: Few studies have characterised the relationship between disease and gait function in children and young people with rare neuromuscular disorders (NMDs). This study aimed to describe the relationship between disease and gait in a large paediatric cohort from a neuromuscular outpatient clinic., Methods: A prospective, cross-sectional study of gait in independently ambulant children and young people aged 4-21 years with a clinical or genetically confirmed NMD. Participants traversed an electronic walkway barefoot and in footwear at self-selected and fast pace. Analysis of disease included a typically developing (TD) reference group., Results: A sample of 113 participants with NMD, mean age 9.5 years (SD 3.1), 28% female, grouped into nine diagnostic subgroups. Eighty percent reported limitations to functional mobility. Children with NMD walked slower, with a shorter and wider step compared to a TD reference group, with moderate to large effect sizes for each of these gait parameters indicative of the clinical significance of these gait deviations. Children with Duchenne muscular dystrophy (DMD) walked slowest with a markedly wide gait pattern. Footwear had little overall effect on gait in children with NMDs. All children could accelerate over short distances., Conclusions: Gait, notably speed, step length, and width are clinically significant biomarkers of disease in paediatric NMDs, affording objective functional measures in clinical settings and research.Implications for rehabilitationGait should be considered a functional biomarker of disease in children and young people with neuromuscular disorders (NMDs).Comparison of gait in a paediatric neuromuscular cohort indicates that children with Duchenne muscular dystrophy (DMD) walk slowest with a shorter step length and a wider step width which increases with age and disease progression.Measurement of gait speed is a simple, pragmatic tool to monitor disease progression in the outpatient clinical environment and relates to everyday function.In clinical research, gait can be measured as a functional outcome to demonstrate change from disease-modifying interventions and treatments in NMDs.

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., (© 2022 The Authors. Muscle & Nerve published by Wiley Periodicals LLC.)

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., Competing Interests: Competing interests: MES has received consulting fees or honoraria from Inflectis Bioscience, Passage Biosci and Mitochondria in Motion, Temple University and Albert Einstein Medical College, and is the Chair of the CMT and Related Disorders (CMTR) Consortium of the Peripheral Nerve Society. SR has been employed at the Janssen Pharmaceutical Companies of Johnson & Johnson since January 2021 and has restricted stock options. Her contributions to the paper were made prior to her current employment. IM is a board member of the CMTR Consortium of the Peripheral Nerve Society. CES is a voluntary advisory board member of the CMT Association. EMY, PB, JBa, SKB, NB, KdV, TE, MAF, RSF, JH, RAK, GAN, MaMR, KR, SWY, MPM, MoMR and JBu report no competing interests., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To evaluate feasibility of scaling up a 12-week community-based exercise program ( FitSkills ) in which young people with disability exercise with a student mentor., Method: Within a stepped wedge cluster randomised trial, seven domains of feasibility were assessed: demand, implementation, acceptability, practicality, adaptation, integration, and expansion., Results: Of the 163 participants with disability (61 females; 20.8 ± 5 y) and 226 mentors who enrolled, 123 participants and mentors completed FitSkills . Population demand was estimated at 9% of members of participating organisations. Most participants (76%) completed the twice-weekly program within 12 weeks, attending 79% of sessions (mean 18.9 ± 4.7). Key program elements valued by participants were the mentor, tailored exercise, and regular program schedule. Majority (87%) of mentors were recruited from physiotherapy, occupational therapy, and exercise science courses. Positives for participants were perceived benefits and organisational support, and for mentors, understanding disability. Communication and scheduling were burdens. Three serious and 28 non-serious adverse events occurred. Adaptations (additional screening, risk analysis, extra mentor support, or in-person consultation) enabled 29 young people with complexity to participate. The number of trial sites was expanded to 11 to accommodate participants., Conclusions: Scaling-up FitSkills is feasible, but with caveats related to communication, scheduling, and efficiency of recruitment.IMPLICATIONS FOR REHABILITATIONKey elements valued by participants as part of the successful scale-up of a community-based exercise program ( FitSkills ) across a large metropolitan city included a peer-mentor, tailored exercise, and organisational support structure. FitSkills can be adapted to include young people with complex disability with additional supports including screening, risk analysis, and professional support for the peer-mentor.The benefits of FitSkills , including social connectedness for young people with a disability and normalisation of disability for mentors, outweigh the burdens of participation.Communication with program organisers and scheduling logistics between the young person, their family/carers and peer mentors are important factors to manage for the successful implementation of FitSkills .

Purpose: We explored the effects of standardized calf massage in ambulant boys with Duchenne muscular dystrophy (DMD) using a prospective study design., Materials and Methods: Twenty boys completed two study visits, 1 week apart. At both visits, each leg received a 10-min calf massage (intervention) and a 10-min control rest period (placebo) in randomized order. Muscle length of calf and hamstrings and gastrocnemius stiffness were measured by a blinded assessor before and after intervention and placebo. Measures of gait function (timed 10-m walk/run and spatio-temporal gait parameters); gastrocnemius muscle ultrasound findings; participant perception of leg pain, stiffness and effort of walking and general psychological well-being were also collected., Results: Consistent significant small increases in muscle length of soleus, gastrocnemius and hamstrings were recorded post-massage, and gastrocnemius stiffness decreased. Small changes in gastrocnemius and soleus length only were also recorded following the control rest period. Gait function and general well-being remained stable throughout. Measurement across both study visits suggested that gains in muscle length may be cumulative with repeated massage., Conclusions: Calf massage is safe and associated with benefits to muscle length and stiffness for ambulant boys with DMD.Implications for RehabilitationIn a small sample of boys with Duchenne muscular dystrophy, calf massage was found to be safe, well-tolerated and associated with increased muscle length and decreased stiffness.The use of massage may assist in managing muscle length in boys with Duchenne muscular dystrophy.

Competing Interests: Competing interests: None declared.

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.

Background: There is limited evidence that plasma homocysteine (Hcy) is increased in women with adverse pregnancy outcomes, such as low birth weight (LBW). Objective: We examined the relationship between maternal Hcy at the first prenatal visit and birth weight. Study design: In a prospective observational study, women were recruited during their first prenatal visit after sonographic confirmation of gestational age. Along with the standard tests, blood was also taken for the measurement of maternal serum and red blood cell (RBC) folate, vitamin B12, and Hcy. In addition to collecting standard clinical and sociodemographic details, a detailed questionnaire on vitamin supplementation was completed under supervision. Birth outcomes were collected immediately after delivery. Results: Of 498 women recruited, 213 (42.8%) were nulliparous, 97 (19.4%) were obese, 64 (12.9%) selfreported as current smokers, and 489 (98.2%) were taking folic acid (FA) supplements at presentation. The mean (SD) birth weight was 3426.3 g (600.7), 14.0% of infants were small for gestational age, and 7.4% were large for gestational age. Mean (SD) plasma Hcy was 7.1 (2.1) µmol/l. On multiple linear regression, higher plasma Hcy was associated with selfreported smoking ( p  = .009), relative income poverty ( p  = .037) and Irish nativity ( p  = .009). There was no relationship between maternal plasma Hcy and birth weight centile, either overall or when analyzed separately for either smokers ( r  = 0.0001, p  = .98) and nonsmokers ( r  = -0.007, p  = .097). Plasma Hcy was correlated negatively with serum folate, RBC folate, and serum vitamin B12. There was no association between maternal Hcy and the duration of FA supplementation in weeks ( r  = -0.08, p  = .083) or between maternal Hcy and gestational age at phlebotomy ( r  = -0.54, p  = .35). Conclusions: In this well-characterized cohort of women in early pregnancy, there was no correlation between maternal plasma Hcy and birth weight. However, higher Hcy was associated with maternal smoking and social deprivation which may explain the association reported previously between an increased Hcy and LBW.RationaleThis study was conducted to investigate the relationship between maternal homocysteine in early pregnancy and infant birth weight. Increased plasma homocysteine in early pregnancy was not associated with a lower birth weight. However, there was a positive correlation between increasing plasma homocysteine and maternal smoking and social disadvantage which are risk factors for lower birth weight. This study highlights the importance of correcting for confounding variables, such as smoking and social disadvantage, when evaluating the relationship maternal nutritional biomarkers and intrauterine fetal development. Rationale This study was conducted to investigate the relationship between maternal homocysteine in early pregnancy and infant birth weight. Increased plasma homocysteine in early pregnancy was not associated with a lower birth weight. However, there was a positive correlation between increasing plasma homocysteine and maternal smoking and social disadvantage which are risk factors for lower birth weight. This study highlights the importance of correcting for confounding variables, such as smoking and social disadvantage, when evaluating the relationship maternal nutritional biomarkers and intrauterine fetal development.

Purpose: This quality improvement project aimed to assess the elements of the current workflow process that meets requirements for transitions of care from a family medicine inpatient to outpatient service following the Transitional Care Management (TCM) program developed by the Centers for Medicare & Medicaid Services. The purpose of the study was to assess the current family medicine workflow and determine whether the current process meets the criteria for billing and calculate the potential loss of reimbursement., Methods: Interviews with key personnel, review of practice policies, and a retrospective chart review were performed for clinic patients discharged from the inpatient to outpatient family medicine service., Results: A total of 37 patients met inclusion criteria for the chart review. Of these, 8% of patients seen at the outpatient clinic met all criteria for TCM. Potential reimbursement for those who met TCM criteria was $293.14 USD; the estimated potential TCM reimbursement for patients not meeting criteria was $1997.76 USD., Conclusion: Standardized, team-based TCM services have shown to decrease readmission rates for high-risk patient populations. Results from this project identified processes in place at the family medicine practice to facilitate the development of a standardized transitional care service which could meet both TCM and best practice models.

Competing Interests: Competing interests: None declared.

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 (β = 44.7, 95% CI 17.0-72.4, P = 0.002), WHO (β = 39.2, 95% CI 17.2-61.1, P = 0.001), and USA (β = 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., (© 2019 Nordic Federation of Societies of Obstetrics and Gynecology.)

Background: Weakness is the primary impairment in paediatric neuromuscular diseases, impacting gait and gait-related functional activities in ambulant children affected by these rare and often degenerative diseases. Gait speed is an indicator of health and disability, yet gait is a complex, multi-faceted activity. Using the International Classification of Function, Health and Disability (ICF) model, assessment of gait and functional ambulation should consider the impairments, activity limitations and participation restrictions due to disease, and factors related to the environment and the individual person., Methods: This narrative review involved a literature search of databases including Medline, Embase and Pubmed from 1946 to October 2019. Inclusion criteria included assessments of gait, endurance and ambulatory function in paediatric (0-18 years) neuromuscular diseases., Results: Fifty-two papers were identified reporting assessments of gait speed, timed function, endurance and ambulatory capacity, gait-related balance and qualitative descriptive assessments of gait function and effect of disease on gait and gait-related activities. Gait speed is an indicator of disability and children with neuromuscular disease walk slower than typically developing peers. Increasing disease severity and age were associated with slower walking in children with Duchenne muscular dystrophy and Charcot-Marie-Tooth disease. The six-minute walk test is used widely as a test of endurance and ambulatory capacity; six-minute walk distance was substantially reduced across all paediatric neuromuscular diseases. Endurance and ambulatory capacity was more limited in children with spinal muscular atrophy type 3, congenital muscular dystrophy and older boys with Duchenne muscular dystrophy. Only a few papers considered normalisation of gait parameters accounting for the effect on gait of height in heterogeneous groups of children and linear growth in longitudinal studies. Balance related to gait was considered in five papers, mainly in children with Charcot-Marie-Tooth disease. There was limited investigation of factors including distance requirements and terrain in children's typical environments and personal factors related to self-perception of disease effect on gait and gait-related function., Conclusion: Assessments of gait and functional ambulation are important considerations in documenting disease progression and treatment efficacy in the clinical setting; and in clinical trials of disease-modifying agents and physiotherapeutic interventions in paediatric neuromuscular diseases. There is a need for expert consensus on core gait and functional ambulation assessments for use in clinical and research settings.

Competing Interests: Competing interests: None declared.

Type I CRISPR-Cas systems are the most abundant adaptive immune systems in bacteria and archaea 1,2 . Target interference relies on a multi-subunit, RNA-guided complex called Cascade 3,4 , which recruits a trans-acting helicase-nuclease, Cas3, for target degradation 5-7 . Type I systems have rarely been used for eukaryotic genome engineering applications owing to the relative difficulty of heterologous expression of the multicomponent Cascade complex. Here, we fuse Cascade to the dimerization-dependent, non-specific FokI nuclease domain 8-11 and achieve RNA-guided gene editing in multiple human cell lines with high specificity and efficiencies of up to ~50%. FokI-Cascade can be reconstituted via an optimized two-component expression system encoding the CRISPR-associated (Cas) proteins on a single polycistronic vector and the guide RNA (gRNA) on a separate plasmid. Expression of the full Cascade-Cas3 complex in human cells resulted in targeted deletions of up to ~200 kb in length. Our work demonstrates that highly abundant, previously untapped type I CRISPR-Cas systems can be harnessed for genome engineering applications in eukaryotic cells.

The deliberate practice framework was forwarded to account for the characteristics and developmental experiences of individuals who have acquired exceptional performance in any domain. This framework proposed that experts undergo an extensive acquisition period involving the accumulation of thousands of hours of deliberate practice while overcoming various constraints that serve as functional barriers to the achievement of expertise. Although the deliberate practice framework has been examined in the context of a range of domains, disability sport remains relatively unstudied. The purpose of this study was, therefore, to examine expert disability sport athletes to determine how well their experiences and characteristics were captured by the deliberate practice framework. Quad rugby players were asked to complete a two-part survey to report their recall of the amount of time spent in individual and team practice activities, quad rugby related activities, and daily life activities at the start of their careers and every 2 years since. These activities were then rated with respect to relevance to improving performance, effort and concentration required, and enjoyment of participation. Findings revealed that quad rugby athletes engaged in similar amounts of practice throughout their career to those observed in superior performers across domains, including musicians and expert performers in the able-bodied sport domain (e.g., M = 8,309 h at 9-10 year career mark). Contrary to the original deliberate practice framework and some of the subsequent examinations in sport, disability sport athletes did not rate the most relevant and effortful activities as either low or high on enjoyment. The unique constraints imposed on disabled athletes may reduce the likelihood that clear differences will emerge when considering affective responses such as enjoyment.

Background: Disability related to the progressive and degenerative neuropathies known collectively as Charcot-Marie-Tooth disease (CMT) affects gait and function, increasing with age and influencing physical activity in adults with CMT. The relationship between CMT-related disability, ambulatory function and physical activity in children and adolescents with CMT is unknown., Method: A cross-sectional case-controlled study of physical activity in 50 children with CMT and age- and gender-matched typically developing (TD) controls [mean age 12.5 (SD 3.9) years]. A 7-day recall questionnaire assessed physical activity; CMT-related disability and gait-related function were measured to explore factors associated with physical activity., Results: Children with CMT were less active than TD controls (estimated weekly moderate to vigorous physical activity CMT 283.6 (SD 211.6) minutes, TD 315.8 (SD 204.0) minutes; p < 0.001). The children with CMT had moderate disability [CMT Pediatric Scale mean score 17 (SD 8) /44] and reduced ambulatory capacity in a six-minute walk test [CMT 507.7 (SD 137.3) metres, TD 643.3 (74.6) metres; p < 0.001]. Physical activity correlated with greater disability (ρ = -0.56, p < 0.001) and normalised six-minute walk distance (ρ = 0.74, p < 0.001)., Conclusions: CMT-related disability affects physical activity and gait-related function in children and adolescents with CMT compared to TD peers. Reduced physical activity adversely affects function across the timespan of childhood and adolescence into adulthood in people with CMT., Competing Interests: The authors have declared that no competing interests exist.

Objective: To prospectively study falls in children and adolescents with Charcot-Marie-Tooth disease (CMT)., Design: Prospective cohort study., Setting: Neuromuscular outpatient clinic of a tertiary paediatric hospital., Patients: Sixty children and adolescents ('children') aged 4-18 years, 30 with CMT and 30 typically developing (TD)., Main Outcome Measures: Falls rate over 6 months and falls characteristics questionnaire., Results: Twenty-two children with CMT reported falling at least once in 6 months compared with eight TD children (CMT 2819 (0-1915), TD 31 (0-6) total falls (range)). Detailed falls characteristics were collected from 242 individual falls (CMT 216, TD 26). Injurious falls were reported by 19 children with CMT (74 falls) compared with 2 TD children (3 falls), with cuts, grazes and bruising most common. No fractures were sustained and no child required hospitalisation. However, 12 injuries from falls in children with CMT required management by a healthcare provider, versus none in TD children. Tripping was the most common mechanism of falls in both groups. Age was the strongest predictor of falls (ρ=-0.53, p=0.006) with all children (CMT and TD) aged <7 years falling. Balance was the strongest impairment-related predictor of falls (ρ=-0.47, p=0.02). The conservative estimate of risk of falls in children and adolescents with CMT was 33 times higher than their TD peers (incidence rate ratio=32.8, 95% CI 10.2 to 106.0)., Conclusions: Children and adolescents with CMT fall more often than TD peers and sustain more injuries when they fall., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Maternal nutrition may influence intrauterine fetal development. To date, the relationship between contemporary European dietary guidelines and fetal growth has not been examined., Aims: To develop a novel Periconceptual Nutrition Score (PENS) to assess maternal dietary quality in early pregnancy and examine its relationship with fetal growth., Study Design: Women were recruited conveniently at their first clinic visit and completed a supervised four day retrospective diet history. The PENS was developed using European Food Safety Authority recommended dietary intakes for pregnancy. The relationship between PENS and fetal growth was examined., Subjects: Women with a singleton pregnancy., Outcome Measures: Birthweight, small for gestational age (SGA), neonatal head circumference., Results and Conclusions: Of the 202 women, the mean age was 32.2 ± 5.0 years and 44.6% were nulliparas. The mean PENS was 9.4 ± 3.1. On multivariable regression, there was a positive relationship between the PENS and birthweight (beta = 45.3, 95%CI 14.8-75.9, P = 0.002) and neonatal head circumference (beta = 0.12, 95%CI 0.01-0.23, P = 0.03). Compared with the lowest PENS quartile, the mean birthweight was increased in the highest quartile (Mean difference 328 g, P = 0.02). The incidence of SGA was 16.4% (n = 10/61) in the lowest PENS quartile compared to 6.5% (n = 9/139) in the top three quartiles (P = 0.03). Thus, higher maternal dietary quality was associated with increased intrauterine fetal growth. The PENS is potentially useful in identifying those women before or during pregnancy who may benefit from dietary interventions that may optimise fetal growth. It may also be useful in tracking maternal dietary quality during pregnancy., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background and Aims: While many women quit smoking spontaneously before or during early pregnancy, information is limited about maternal smoking as pregnancy advances. This study examined the smoking behaviour of women throughout pregnancy and immediately after delivery., Methods: Women on the postnatal ward were consented for BCO testing and after completing this under supervision, they were asked to complete an accompanying questionnaire on smoking behaviour (unsupervised)., Results: In this small pilot study, we found BCO testing in an inpatient environment, not surprisingly, was ineffective in identifying current smokers. As reported in other studies, we found that few women quit smoking after the time of the first antenatal visit., Conclusions: This suggests that postnatal smoking cessation interventions should receive greater attention. We recommend that all women who identify themselves as current smokers at the first antenatal visit should complete a short questionnaire postnatally and should be offered support to quit smoking or maintain cessation after they bring their baby home.

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.

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 β-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 β-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 β-hexosaminidase mRNA is constitutively expressed. Therefore, mast cell researchers should utilize β-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., (© 2018 John Wiley & Sons, Ltd.)

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.

Objectives: The aim of this study was to examine the implications of increased maternal Breath Carbon Monoxide (BCO) levels at the first antenatal visit for subsequent birthweight (BW) and neonatal outcomes., Study Design: Secondary analysis of a prospective, observational study. Pregnant women aged ≥18years who understood English were recruited (n=250). However, only women who delivered a normally formed baby weighing ≥500g were analysed (n=234). At the first antenatal visit, a research questionnaire was completed and a BCO test was performed. Obstetric and neonatal data computerised by midwives at the first antenatal visit and updated after delivery were also analysed., Results: Results from the receiver operating characteristic (ROC) curve indicated the highest combined sensitivity and specificity for smoking was observed at a BCO cut-off level of 3ppm (sensitivity 85%, specificity 90%). Of the 234 women, 53 (22.6%) had a BCO ≥3ppm but only 36 (15.4%) disclosed smoking to the midwife on routine questioning. A further 23 (9.8%) were classified as non-disclosers based on a research questionnaire and/or a BCO measurement ≥3ppm. No relationship was found between the self-reported number of cigarettes daily in early pregnancy and BW (r=0.05, p=0.78). However, an inverse relationship was found between maternal BCO levels and BW (r=-0.31, p<0.001). BCO levels ≥3ppm in early pregnancy were associated with an increased risk of emergency caesarean section, low birth weight, BW <25th centile, fetal distress and having two or more adverse pregnancy events (all p<0.05). Smoking non-disclosers had babies with decreased BWs (-400.1g, 95% CI 141.1-659.0g, p<0.001), and higher rates of BW <25th centile (56.5% versus 25.3%, p<0.001), small-for-gestational-age (21.7% versus 9.1%, p<0.001) and fetal distress (39.1% versus 16.0%, p<0.01) compared to non-smokers Non-disclosers at the first antenatal visit also had a 22% higher rate of having two or more adverse pregnancy events (p<0.05)., Conclusion: The results showed that an increased BCO level was associated with a lower BW and increased risk of adverse pregnancy and neonatal outcomes. This strengthens the case for universal BCO screening at the first antenatal visit. A high BCO reading should be an indication for referral to stop smoking services referral and close fetal surveillance., (Copyright © 2018 Elsevier B.V. All rights reserved.)

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&#95;video1awy280media15970672819001.

Objectives: This study evaluated breath carbon monoxide (BCO) testing in identifying maternal smokers as well as the difference between disclosers and non-disclosers of smoking status. We also investigated if other extrinsic factors affected the women's BCO levels in pregnancy., Design: A prospective observational study., Setting: A university obstetric hospital in an urban setting in Ireland., Participants: Women (n=250) and their partners (n=54) were recruited at their first antenatal visit. Women <18 years and those who did not understand English were excluded. A booking history, including recording of smoking status, was collected by midwives. Following this, women were recruited and completed a detailed research questionnaire on smoking and extrinsic/environmental BCO sources. A BCO test was performed on both the woman and her partner., Primary and Secondary Outcome Measures: The number of self-reported smokers and those that were positive on the BCO test. The characteristics of women who disclosed and did not disclose smoking status. The effect of extrinsic factors on the BCO test results., Results: Based on the receiver-operating characteristic curve, a BCO cut-off point of ≥3 ppm was the optimal level to identify ongoing smoking. At booking history, 15% of women reported as current smokers. Based on BCO levels ≥3 ppm combined with self-reported smoking in the research questionnaire, the rate increased to 25%. Non-disclosers had similar characteristics to non-smokers. No extrinsic factors affected maternal BCO levels., Conclusions: Based on self-report and BCO levels, a quarter of women presenting for antenatal care continued to smoke, but only 60% reported their smoking to midwives. BCO measurement is an inexpensive, practical method of improving identification of maternal smoking, and it was not effected by extrinsic sources of BCO. Improved identification means more smokers can be supported to stop smoking in early pregnancy potentially improving the short-term and long-term health of both mother and child., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Using detailed dietary and supplement questionnaires in early pregnancy, we compared the dietary intakes of micronutrients and macronutrients at the first prenatal visit of women who reported continuing to smoke during pregnancy with the intakes of women who were non-smokers., Design: Cross-sectional study conducted between June 2014 and March 2016., Setting: Stand-alone tertiary maternity hospital in an urban setting with approximately 8000 deliveries per year., Participants: Women were recruited at their convenience after sonographic confirmation of an ongoing singleton pregnancy (n=502). Detailed dietary and supplement information was available for 398 women. Women <18 years and those who did not speak English fluently were excluded., Primary and Secondary Outcome Measures: The differences in dietary micronutrients and macronutrients and maternal folate levels between women who continued to smoke in pregnancy compared with non-smokers., Results: Of the 502 women, the mean age was 30.5 (SD 5.6) years, 42.5% were nulliparas, 19.2% were obese and 398 (79.3%) completed the questionnaire satisfactorily. In the 50 (12.6%) current smokers, the micronutrients magnesium, iron, carotene and copper were lower (all p<0.005) whereas sodium and chloride were higher compared with the 348 (87.4%) non-smokers. Smokers reported lower intakes of dietary total folate (p=0.006) compared with non-smokers (i.e., dietary folate equivalents; intake from natural and fortified dietary sources) (p=0.005). Smokers also reported lower intakes of fibre than non-smokers (13.1 g (IQR 7.7) vs 16.3 g (IQR 8.5), p<0.001). The dietary intakes of former smokers compared favourably with non-smokers., Conclusions: We found that women who continue to smoke during pregnancy have serious dietary inadequacies which could potentially aggravate fetal growth restriction associated with direct toxicity from cigarettes. This provides a further reason to promote smoking cessation interventions in pregnancy, and highlights the need for dietary and supplementation interventions in women who continue to smoke., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY. Published by BMJ.)

Objective: Children with Charcot-Marie-Tooth disease (CMT) report problems with gait and footwear. We evaluated differences in spatio-temporal gait variables and gait variability between children with CMT and typically developing (TD) children, and investigated the effect of footwear upon gait., Method: A cross-sectional study of 30 children with CMT and 30 age- and gender-matched TD children aged 4-18 years. Gait was assessed at self-selected speed on an electronic walkway while barefoot and in two types of the child's own footwear; optimal (e.g., athletic-type runners) and suboptimal (e.g., flip-flops)., Results: Children with CMT walked more slowly (mean (SD) -13.81 (3.61) cm/s), with shorter steps (-6.28 (1.37) cm), wider base of support (+2.47 (0.66) cm; all p < 0.001) and greater base of support variability (0.48 (0.15) cm, p = 0.002) compared to TD children. Gait was faster in optimal footwear than suboptimal (-7.55 (1.31) cm/s) and barefoot (-7.42 (1.07) cm/sec; both p < 0.001) in the combined group of children. Gait in suboptimal footwear was more variable compared to barefoot and optimal footwear. Greater base of support variability and reduced balance was moderately correlated for both groups (CMT and TD)., Conclusion: Gait is slower with shorter, wider steps and greater base of support variability in children with CMT. Poor balance is associated with greater base of support gait variability. Suboptimal footwear negatively affects gait in all children (CMT and TD), which has clinical implications for children and adolescents with CMT who have weaker feet and ankles, and poor balance., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: Valproic acid (VPA) and its derivatives are highly protein bound with free fraction increasing with dose and serum concentration. Consensus guidelines regarding dose adjustment for hypoalbuminemia are not available., Methods: A literature search was performed using PubMed to identify articles with the following key terms: "valproate," "valproic acid," "protein binding," "albumin," and "hypoalbuminemia." We report our findings as well as 5 cases involving pharmacokinetic impact of hypoalbuminemia on valproate., Results: A previously published model for normalizing VPA serum concentration for hypoalbuminemia in patients with epilepsy was compared to results for 5 cases (4 female, 1 male) in which VPA was used for psychiatric illness. Only 1 of the cases had free serum concentrations in the range that would be expected with the model. Free concentrations ranged from 22% to 83% with no clear relationship to other factors (weight, age, serum creatinine, or dose). Female patients with similar albumin had higher free fractions than the 1 male patient., Discussion: Due to the variability in pharmacokinetic impact of hypoalbuminemia, it is important to monitor patients closely for signs of VPA toxicity in cases involving altered albumin levels. It would be prudent to use free serum VPA concentrations when patients experience fluctuations in albumin or have unexpected response to medication., Competing Interests: Disclosures: The authors have no conflicts of interest to disclose. No financial support was received for this article.

Introduction: The nerve sonographic features of Dejerine-Sottas disease (DSD) have not previously been described., Methods: This exploratory cross-sectional, matched, case-control study investigated differences in nerve cross-sectional area (CSA) in children with DSD compared to healthy controls and children with Charcot-Marie-Tooth disease type 1A (CMT1A). CSA of the median, ulnar, tibial, and sural nerves was measured by peripheral nerve ultrasound. The mean difference in CSA between children with DSD, controls, and CMT1A was determined individually and within each group., Results: Five children with DSD and five age- and sex-matched controls were enrolled. Data from five age-matched children with CMT1A was also included. Group comparison showed no mean difference in nerve CSA between children with DSD and controls. Individual analysis of each DSD patient with their matched control indicated an increase in nerve CSA in three of the five children. The largest increase was observed in a child with a heterozygous PMP22 point mutation (nerve CSA fivefold larger than a control and twofold larger than a child with CMT1A). Nerve CSA was moderately increased in two children-one with a heterozygous mutation in MPZ and the other of unknown genetic etiology., Conclusions: Changes in nerve CSA on ultrasonography in children with DSD differ according to the underlying genetic etiology, confirming the variation in underlying pathobiologic processes and downstream morphological abnormalities of DSD subtypes. Nerve ultrasound may assist in the clinical phenotyping of DSD and act as an adjunct to known distinctive clinical and neurophysiologic findings of DSD subtypes. Larger studies in DSD cohorts are required to confirm these findings.

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.

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., (© The Author 2016. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com)

Children and adolescents with Charcot-Marie-Tooth disease (CMT) report problems with gait. Little is known about gait changes over time in children with this degenerative disease. This prospective longitudinal study investigated change in spatio-temporal gait parameters and functional ambulation. Two assessments were conducted 12 months apart. Assessments included: barefoot gait on an electronic walkway; functional ambulation with a six minute walk test and the Functional Mobility Scale; and disease severity with the CMT Pediatric Scale. Gait and strength data were normalised to body anthropometrics. Twenty-seven children (mean age 12.2, SD 3.7 years) with various CMT subtypes (CMT1A 52%) were evaluated. Over 12 months, normalised variables of gait speed, stride length and six minute walk distance significantly decreased. The CMT Pediatric Scale increased 0.7 points, indicating marginal but not significant worsening of disease; notably calf strength decreased significantly over 12 months. Baseline maximum ankle dorsiflexion angle, gastrocnemius and hamstrings length, and calf strength correlated with decline in gait speed, with maximum ankle dorsiflexion angle as the strongest predictor. Deterioration over one year in normalised variables of gait speed, stride length and distance walked in six minutes are indicators of functional decline and disease progression in children and adolescents with CMT., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The dentate gyrus of the hippocampus is a site of adult neurogenesis, and is also known to contain one of the highest concentrations of labile brain zinc (Zn), thought to aid in learning and memory by supporting neurogenesis. At the same time, it is known that unbound Zn, when present at excessive levels, decreases the formation of new neurons. Since mast cells contain Zn transporters capable of moving this essential element across their plasma membrane, as well as Zn-rich granules that are dispelled upon secretion, we reasoned that mast cells contribute to Zn homeostasis in this area of the brain, as they are found in greatest numbers in and around the dentate gyrus. This line of evidence was tested by comparing Timm-stained hippocampal sections of mast cell-deficient C57BL/6-Kit W-sh/W-sh (Sash -/- ) mice to those of mast cell-containing wild type (Sash +/+ ) animals. Mast cell deficient mice were found to have significantly increased Timm-positive staining as compared to controls, reflecting an increase in labile or bioactive Zn in this region. As we observed no change in total brain Zn (protein-bound plus unbound Zn), these increases indicate that mast cells may serve to bind what would otherwise be excessive or deleterious levels of labile Zn, or that they are able to recruit metallothionein proteins. Because elevated levels of labile Zn are observed in the brains of patients with neurodegenerative diseases such as Alzheimer's, the potential contribution of mast cells to these diseases remains a compelling one. Overall, these data support a role for mast cells in either establishing or maintaining Zn homeostasis in the brain in the service of health, while Zn dysregulation has the potential to reduce learning, memory, and ultimately organismal survival., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Background/purpose: In pediatric cases of ingested foreign bodies, gastrointestinal foreign bodies (GIFB) have distinct factors contributing to longer and more costly hospitalizations., Methods: Patients admitted with ingested foreign bodies were identified in the Kids' Inpatient Database (1997-2009)., Results: Overall, 7480 cases were identified. Patients were most commonly <5years of age (44%), male (54%), and Caucasian (57%). A total of 2506 procedures were performed, GI surgical procedures (57%) most frequently, followed by GI endoscopy (24%), esophagoscopy (11%), and bronchoscopy - in cases of inhaled objects (9%). On multivariate analysis, length of stay increased when cases were associated with intestinal obstruction (OR=1.7), esophageal perforation (OR=40.0), intestinal perforation (OR=4.4), exploratory laparotomy (OR=1.9), and gastric (OR=2.9), small bowel (OR=1.5), or colon surgery (OR=2.5), all p<0.02. Higher total charges (TC) were associated with intestinal obstruction (OR=2.0), endoscopy of esophagus (OR=1.8), stomach (OR=2.1), or colon (OR=3.3), and exploratory laparotomy (OR=3.6) or surgery of stomach (OR=5.6), small bowel (OR=6.4), or colon (OR=3.4), all p<0.001., Conclusions: Surgical or endoscopic procedures are performed in approximately one third of GIFB cases. Associated psychiatric disorder or self-inflicted injury is seen in more than 20% of GIFB patients. Resource utilization is determined heavily by associated diagnoses and treatment procedures., (Copyright © 2016 Elsevier Inc. All rights reserved.)

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.

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., (© 2016 Peripheral Nerve Society.)

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., (Copyright © 2016 John Wiley & Sons, Ltd.)

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., (Copyright © 2015 John Wiley & Sons, Ltd.)