Aim: The absence of dystrophin in patients with Duchenne Muscular Dystrophy (DMD) causes muscle fiber necrosis and fibrosis and eventually muscle weakness and contractures. This study aimed to investigate the timing and extent of lower limb contracture development and to examine how contractures, muscle strength, and kinematic (e.g., limb position or joint movement) deviations relate to longitudinal changes in gait spatiotemporal parameters. Methods: Seventy-five ambulatory boys with DMD participated in this prospective longitudinal study of contractures, isometric muscle strength, and gait analysis. Nonlinear mixed modeling (NLMIXED) exponential growth curve models were developed to investigate the effects of contractures, muscle strength, and kinematic deviations on longitudinal changes in gait spatiotemporal parameters. Results: Ankle plantar flexion contractures were present as early as 4 years of age. Hip flexion contractures, assessed by the Thomas test, and knee flexion contractures, assessed by knee extension in supine, developed around 13 years of age and did not exceed ten degrees. Over time, gait speed, stride length, and cadence decreased. Statistically significant covariates for gait speed included hip flexor contracture (limitation in hip extension), hip extensor and ankle plantar flexor strength, and pelvic tilt Gait Variable Score (GVS). Plantar flexor strength was a significant covariate for stride length, while pelvic obliquity GVS significantly correlated with cadence. Conclusion: Subtle changes in hip extensor and ankle plantar flexor strength, along with pelvic range of motion during gait, are indicators of DMD disease progression. Gait analysis, including easily accessible measures of gait speed and normalized stride length, may provide a more sensitive indicator of DMD disease progression than manual assessments of contractures and muscle strength.

As early as 23,000 years ago, we as a human society cultivated the land by growing proto weeds: Poa (Snir et al. , 2015). Although it is not known if that practice was any more sustainable than current farming and crop production practices with respect to biodiversity, preserving soils and the environment, and feeding all of us, it is important to note the evidence in this book of practices that embrace and are improving sustainability in the present (Buitink and Leprince, 2022). In Advances in Seed Science and Technology for More Sustainable Crop Production , Buitink and Leprince have collected the works of notable authors to establish a higher understanding of seed quality, germination and dormancy, not to mention how seeds for both crop plants and weeds behave when in the soil or stored for future use.

BACKGROUND:Duchenne Muscular Dystrophy (DMD) is an X-linked muscle disorder caused by a mutation or deletion in the dystrophin gene. In boys with DMD, muscle weakness progresses in a proximal to distal pattern, leading to gait abnormalities at all joints, in all planes of motion. Longitudinal studies are imperative to quantify changes in gait function due to DMD and are of particular importance when examining the efficacy of treatment interventions. RESEARCH QUESTION:The purpose of this study was to examine the sensitivity of the Gait Deviation Index (GDI) and Movement Analysis Profile (Gait Profile Score (GPS) and Gait Variable Score (GVS)) to quantify the longitudinal ambulatory decline in boys with DMD. A secondary aim was to quantify the effect of corticosteroid (CS) treatment. METHODS:The gait patterns of 75 boys were assessed longitudinally, 11 were steroid naïve (SN), and 64 received CS treatment. Joint kinematics were collected using either a VICON 612 or a Motion Analysis Corporation 3-D system. Representative trials were used to compute the GDI, GPS and the nine GVS for each boy for each visit. RESULTS:At baseline, GVS for the boys with DMD revealed abnormalities in all lower extremity joints and in all planes of movement compared to TD peers. GDI and GPS indices verified that the overall quality of gait in boys with DMD decreases at a significant rate with age. Boys who were steroid naïve changed at a rate 3 times greater than boys on CS in coronal plane hip motion. SIGNIFICANCE:The gait indices of GDI and GPS are able to identify changes in the quality of gait patterns in boys with DMD. Although boys on steroids had greater gait deviations than boys who were SN at baseline, the rate of decline in gait quality was slower in boys on CS.

ISO Technical Committee 34 “Food Products”/Subcommittee 16 “Horizontal methods for molecular biomarker analysis” works to ensure that standardized biomolecular testing and laboratory criteria are reproducible and technically sound reducing potentialdisputes between exporting and importing nations and increasing predictability in world trade. Harmonized, easy to handle methods of analysis with defined patterns and known nomenclatures bring more customers to the market. TC 34/SC 16 has increased international stakeholders’ participation in standardizing biomarker testing, improved the quality and relevance of these standards and continues to increase transparency in international markets, particularly for food authenticity, varietal identification and genetically engineered (GMO) products. ISO standards have been adopted by Codex Alimentarius and many governments throughout the world. The International Organization for Standardization (ISO.org) was formed in 1946. It is an independent, nongovernmental voluntary consensus standard body based in Geneva, Switzerland with a membership of 165 national standards bodies. The US ISO member is the American National Standards Institute (ANSI.org) a consortium of US standardization organizations. ISO TC 34/SC 16 was created in 2008. There are 45 participating countries. Contributing organizations in liaison with TC 34/SC 16 include AOAC International, Cereals and Grains Association, the European Commission, the International Seed Testing Association, the US Pharmacopeia, the European Plant Protection Organization and the International Plant Protection Convention. The scope of TC 34/SC 16 is, "Standardization of biomolecular testing methods applied to foods, feeds, seeds and other propagules of food and feed crops." The US delegation responsible for developing the US position for standards development in food authenticity and allergen detection is called the US Technical Advisory Group (TAG). It was delegated to the American Oil Chemist’s Society (AOCS.org) by ANSI. AOCS also hosts the TC 34/SC 16 international secretariat.

Background: Orthopedic treatment of flexed-knee gait consists of hamstring lengthening along with surgery at other levels. Transfer of the semitendinosus (hamstring transfer) was introduced to avoid increase of anterior pelvic tilt as well as reduce risk of recurrence. Methods: We retrospectively assessed children with spastic cerebral palsy and flexed-knee gait pre-operatively, 1 year post-operatively, and at a minimum of 7 years post-operatively. Results: The 39 patients were a mean 9.4 ± 3.4 years at the time of surgery, 20 subjects underwent hamstring transfer, and 19 subjects had hamstring lengthening with mean follow-up 9.1 years. Passive range of motion improved initially, but regressed at long term. Dynamic minimum knee flexion in stance decreased in both groups at the first post-operative study, and was maintained at final follow-up in 64-67% of patients. There was a small increase in anterior pelvic tilt at the 1-year follow-up which subsequently decreased to less than pre-operative in the hamstring lengthening group but remained mildly increased (5°) in the hamstring transfer group at final follow-up. Success in correcting stance knee flexion of the entire group was 69% of the Gross Motor Function Classification System grades I and II and 60% of the Gross Motor Function Classification System grade III subjects. Gait profile Score and sagittal knee Gait Variable Score both showed clinically important improvement after surgery and was mostly maintained long term for both groups. Lateral hamstring lengthening was beneficial in more severe patients, with minimal risk of adverse effects. Conclusion: Hamstring surgery as part of single event multi-level surgery (SEMLS) is effective in correcting flexed-knee gait in 60%–70% of patients with minimal effect on anterior pelvic tilt. There was no added advantage to hamstring transfer. Biceps Femoris lengthening may be beneficial and without significant additional risk. Level of evidence: level III.

Harmonized, easy to handle methods of analysis with defined patterns and known nomenclatures bring more customers to the market. The International Organization for Standardization (ISO.org) was formed in 1946. It is an independent, non-governmental voluntary consensus standard body based in Geneva, Switzerland with a membership of 165 national standards bodies. The US ISO member is the American National Standards Institute (ANSI.org), a consortium of US standardization organizations. There are 45 participating countries. The US delegation responsible for developing the US position for standards development in agricultural molecular biomarker analysis was delegated to the American Oil Chemist’s Society (AOCS.org) by ANSI. The AOCS US TAG also hosts the TC 34/SC 16 international secretariat. TC 34/SC 16 has published 31 standards with another 6 under development. The six under development are: ISO/AWI 5354 Molecular biomarkers of agricultural fibers. Screening of genetically modified organisms (GMOs) in cotton and textiles; ISO/DIS 16577 Molecular biomarker analysis. Vocabulary for molecular biomarker analytical methods in agriculture and food production; ISO/CD 16578 Molecular biomarker analysis. Requirements for microarray detection of specific nucleic acid sequences; ISO/DTS 20224-8 Molecular biomarker analysis. Detection of animal-derived materials in foodstuffs and feedstuffs by real-time PCR Part 8: Turkey DNA detection method; ISO/DTS 20224-9; Molecular biomarker analysis. Detection of animal-derived materials in foodstuffs and feedstuffs by real-time PCR. Part 9: Goose DNA detection method and ISO/FDIS 22942-1 Molecular biomarker analysis. Isothermal polymerase chain reaction (isoPCR) methods. Part 1: General requirements. We will discuss details and publication of these new standards.

BACKGROUND:Duchenne muscular dystrophy (DMD) is an X-linked recessive genetic disorder, that is characterized by progressive muscle degeneration and loss of ambulation between 7-13 years of age. Novel pharmacological agents targeting the genetic defects and disease mechanisms are becoming available; however, corticosteroid (CS) therapy remains the standard of care.OBJECTIVE:The purpose of this longitudinal study was to elucidate the effect of CS therapy on the rate of muscle strength and gross motor skill decline in boys with DMD and assess the sensitivity of selected outcome measures.METHODS:Eighty-four ambulatory boys with DMD (49-180 months), 70 on CS, 14 corticosteroid naïve (NCS), participated in this 8-year multi-site study. Outcomes included; isokinetic dynamometry, the Standing (STD) and Walking/Running/jumping (WRJ) dimensions of the Gross Motor Function Measure (GMFM), and Timed Function Tests (TFTs). Nonlinear mixed modeling procedures determined the rate of change with age and the influence of steroids.RESULTS:Despite CS therapy the rate of decline in strength with age was significant in all muscle groups assessed. CS therapy significantly slowed decline in knee extensor strength, as the NCS group declined at 3x the rate of the CS group. Concurrently, WRJ skills declined in the NCS group at twice the rate of the CS group. 4-stair climb and 10 meter walk/run performance was superior in the boys on CS therapy.CONCLUSION:CS therapy slowed the rate of muscle strength decline and afforded longer retention of select gross motor skills in boys on CS compared to boys who were NCS. Isokinetic dynamometry, Walk/Run/Jump skills, and select TFTs may prove informative in assessing the efficacy of new therapeutics in ambulatory boys with DMD.

Commentary The article by Liyanarachi et al. represents a significant effort to assess the range of ankle motion in a large cross-sectional cohort of children from 5 to 15 years of age, as well as the contribution of the gastrocnemius to restriction of dorsiflexion according to the Silfverskiöld test. The investigators found that ankle dorsiflexion decreased with increasing age between 5 and 15 years and concluded that “a majority [approximately 55%] had a tight gastrocnemius when the ankle dorsiflexion threshold was set at <5°” with knee extension. This statement is misleading because, if 55% of children fell in this range, then this represents a normal finding rather than “tightness.” Furthermore, this represents more than gastrocnemius tightness as measurements reflect the contribution of the soleus as well as the gastrocnemius. One might think that the assessment of ankle motion would be a simple and straightforward measure, but, of course, it is far from simple: First, the landmarks for measurement must be clearly defined. For the leg, these landmarks should include the axis from the head of the fibula to the lateral malleolus, and for the foot, they should include the lateral border of the foot along the fifth metatarsal1. Next, the subtalar joint must be firmly held in neutral throughout the measurements. The use of 2 examiners, as was done here, is essential but often is unachievable in the usual clinical setting. The most difficult issue is standardization of the amount of force used to dorsiflex the foot. In adults, there is some variation in calf muscle mass, but in growing children there will be marked changes in the length of tibial and foot segments as well as increasing triceps surae muscle mass, requiring a greater dorsiflexion force to achieve maximum dorsiflexion. There are a variety of devices in addition to the ones cited in the paper, including handheld dynamometers and other measuring devices, but there are no standards to guide what level of force to use for each age group in order to normalize the measurements, and stabilization of the subtalar joint may be difficult when using these devices with a footplate2,3. In addition, although the investigators demonstrated high intra-rater reliability in each age group, the repeat measurements were done immediately one after the other; as such, this assessment is biased. Moreover, there was no assessment of inter-rater reliability. I do not see the value of the static footprint measure for assessing triceps surae contracture; however, dynamic pedobarography would be a very valuable measure as it enables one to document the presence of heel strike, first rocker, and the progression of ankle rockers throughout stance phase and thereby assess the functionally relevant influence of triceps surae tightness. The big question is: how do we use this information, and how do we improve standards? In patients with toe-walking, the presence of contracture is used to help decide whether to use bracing or casting as a primary intervention, or surgery if there is substantial contracture. In addition, assessment of increasing dorsiflexion range is used as a measure of the success of any intervention, so a uniform measure of assessment is important. When a subject is asked to do a runner’s stretch, leaning forward into a wall, the level of dorsiflexion achieved is substantially greater than can be achieved with manual manipulation. So perhaps measurement using this maneuver in both knee extension and flexion may produce more reliable measurements. The most important functional measures of ankle motion are maximum dorsiflexion in stance phase of gait and ankle power at push-off as measured by 3-dimensional gait analysis because normalization of these parameters is what we strive for. Although these measurements require an expensive and complex gait laboratory and do not provide information regarding full range of motion, they do reflect adequate range and strength. Finally, the “normal” dorsiflexion reported here is substantially less than most standards of 15° with knee extension and 20° with knee flexion1,4. Presumably, this is due to due to a difference in the amount of force applied to achieve maximum dorsiflexion. This study helps us to recognize the difficulty in establishing a reliable standard for this measure and the importance of striving for consistency when assessing ankle motion and the outcomes of our clinical interventions in this area.

BACKGROUND:In boys with DMD, muscle weakness progresses in a proximal to distal pattern, leading to compensatory gait strategies, including hyperlordosis and equinus, that increase energy cost and accelerate the loss of walking capacity.RESEARCH QUESTION:The purpose of this study was to determine the changes in the energy cost of walking that occur with disease progression and to determine the optimal normalization scheme for the longitudinal assessment of the energy cost of walking in boys with DMD.METHODS:Energy cost was assessed with the COSMED K4b2. Three normalization schemes were examined: gross energy cost (EC), net non-dimensional oxygen cost (NNcost) and speed-matched control energy cost (SMC-EC). Nonlinear mixed modeling procedures determined the rate of change with age. Linear regression was used to asses the relationship between each normalization scheme and age and body height.RESULTS:74 boys with DMD were assessed for the energy cost of walking. Velocity decreased at a significant rate (-.00245/month, p = .03) across time; (Fig. 2), while gross EC (.003248/month, p = 0.0026), NNcost (.006155/month, p < 0.0001) and SMC-EC (.001690/month, p = 0.03) all increased significantly. Age and height were significantly associated with NNcost and SMC-EC. The sensitivity of NNcost and SMC-EC to age over time were similar, while SMC-EC was less sensitive to changes in height over time than NNcost.SIGNIFICANCE:In contrast to able-bodied peers, boys with DMD decrease their velocity while all walking energy cost measures increased over time. Both SMC-EC and NNcost proved appropriate normalization schemes for boys with DMD. Compared to gross EC, both NNcost and SMC-EC were less sensitive to changes in age over time, while SMC-EC was less sensitive to changes in height than NNcost. Therefore, both NNCost and SMC-EC are suggested normalization schemes for the longitudinal assessment of energy cost in boys with DMD.

Purpose Pharmacologic doses of corticosteroid (CS) have been shown to ameliorate the progression of Duchenne muscular dystrophy (DMD) preserving strength, pulmonary function and ambulation as well as reducing the incidence of scoliosis. However, there are serious side effects of CS, which may impact dose tolerance. The purpose of this study was to compare the magnitude of positive CS effects on patients in our clinic to those reported in the literature. Methods We retrospectively reviewed medical records and radiographs of 142 DMD patients who were seen between 1st January 1991 and 31st December 2017. Results In total, 101 boys met study inclusion criteria. Of these 32 were steroid naïve, 37 took the recommended dose (standard of care, SOC) of Prednisone or Deflazacort, and 32 took a lower dose (LD). Following initiation of CS, both treatment groups showed an increase in weight velocity and decrease in linear growth velocity. Although there was a trend to later loss of ambulation (LOA) in the SOC group relative to the naïve group by one year, this was not significant, however, a small subgroup of boys on Deflazacort showed a 3.4 year later LOA than the naïve group. The incidence of scoliosis was reduced from 69% in the naïve, to 41% in the LD and 47% in the SOC group. Conclusions Although there was a reduction in the incidence of scoliosis, it was not as robust as seen elsewhere. Many published studies have inadequate data on scoliosis probably due to the lack of inclusion of orthopaedists in the study group. Level of evidence IV

Orthopedic care is an important aspect of the overall management of patients with Duchenne muscular dystrophy (DMD). In addition to progressive muscle weakness and loss of function, patients may develop joint contractures, scoliosis, and osteoporosis, causing fractures; all of these necessitate intervention by a multidisciplinary team including an orthopedic surgeon as well as rehabilitation specialists such as physio- and occupational therapists. The causes of these musculoskeletal complications are multifactorial and are related to primary effects on the muscles from the disease itself, secondary effects from weak muscles, and the related side effects of treatments, such as glucocorticoid use that affect bone strength. The musculoskeletal manifestations of DMD change over time as the disease progresses, and therefore, musculoskeletal management needs change throughout the life span of an individual with DMD. In this review, we target pediatricians, neurologists, orthopedic surgeons, rehabilitation physicians, anesthesiologists, and other individuals involved in the management of patients with DMD by providing specific recommendations to guide clinical practice related to orthopedic issues and surgical management in this setting.

In 2010, Care Considerations for Duchenne Muscular Dystrophy, sponsored by the Centers for Disease Control and Prevention, was published in Lancet Neurology, and in 2018, these guidelines were updated. Since the publication of the first set of guidelines, survival of individuals with Duchenne muscular dystrophy has increased. With contemporary medical management, survival often extends into the fourth decade of life and beyond. Effective transition of respiratory care from pediatric to adult medicine is vital to optimize patient safety, prognosis, and quality of life. With genetic and other emerging drug therapies in development, standardization of care is necessary to accurately assess treatment effects in clinical trials. This revision of respiratory recommendations preserves a fundamental strength of the original guidelines: namely, reliance on a limited number of respiratory tests to guide patient assessment and management. A progressive therapeutic strategy is presented that includes lung volume recruitment, assisted coughing, and assisted ventilation (initially nocturnally, with the subsequent addition of daytime ventilation for progressive respiratory failure). This revision also stresses the need for serial monitoring of respiratory muscle strength to characterize an individual's respiratory phenotype of severity as well as provide baseline assessments for clinical trials. Clinical controversies and emerging areas are included.

ABSTRACTIntroductionNatural history studies for Duchenne muscular dystrophy (DMD) have not included measures of community ambulation.MethodsStep activity (SA) monitors quantified community ambulation in 42 boys (ages 4–16 years) with DMD with serial enrollment up to 5 years by using a repeated‐measures mixed model. Additionally, data were compared with 10‐meter walk/run (10mWR) speed to determine validity and sensitivity.ResultsThere were significant declines in average strides/day and percent strides at moderate, high and pediatric high rates as a function of age (P < 0.05). Significant correlations for 10mWR versus high and low stride rates were found at baseline (P < 0.05). SA outcomes were sensitive to change over 1 year, but the direction and parameter differed by age group (younger vs. older). Changes in strides/day and percentages of high frequency and low frequency strides correlated significantly with changes in 10mWR speed (P < 0.05).DiscussionCommunity ambulation data provide valid and sensitive real‐world measures that may inform clinical trials. Muscle Nerve 57: 401–406, 2018

Duchenne muscular dystrophy (DMD) is an X-linked genetic neuromuscular disorder characterized by progressive proximal to distal muscle weakness. The success of randomized clinical trials for novel therapeutics depends on outcome measurements that are sensitive to change. As the development of motor skills may lead to functional improvements in young boys with DMD, their inclusion may potentially confound clinical trials. Three-dimensional gait analysis is an under-utilized approach that can quantify joint moments and powers, which reflect functional muscle strength. In this study, gait kinetics, kinematics, spatial-temporal parameters, and timed functional tests were quantified over a one-year period for 21 boys between 4 and 8 years old who were enrolled in a multisite natural history study. At baseline, hip moments and powers were inadequate. Between the two visits, 12 boys began a corticosteroid regimen (mean duration 10.8 ± 2.4 months) while 9 boys remained steroid-naïve. Significant between-group differences favoring steroid use were found for primary kinetic outcomes (peak hip extensor moments (p = .007), duration of hip extensor moments (p = .007), peak hip power generation (p = .028)), and spatial-temporal parameters (walking speed (p = .016) and cadence (p = .021)). Significant between-group differences were not found for kinematics or timed functional tests with the exception of the 10 m walk test (p = .03), which improves in typically developing children within this age range. These results indicate that hip joint kinetics can be used to identify weakness in young boys with DMD and are sensitive to corticosteroid intervention. Inclusion of gait analysis may enhance detection of a treatment effect in clinical trials particularly for young boys with more preserved muscle function.

The aim of this study was to determine whether prednisone and deflazacort play a different role in child behavior and perceived health related psychosocial quality of life in ambulant boys with Duchenne Muscular Dystrophy. As part of a prospective natural-history study, parents of sixty-seven ambulant boys with DMD (27 taking prednisone, 15 taking deflazacort, 25 were steroid naïve) completed the Child Behavior Checklist (CBCL) for assessment of behavioral, emotional and social problems and both parents and boys with DMD completed the PedsQL™4.0 generic core scale short form. Boys with DMD had higher rates of general behavioral problems than age-matched peers. No significant differences were found among the groups for any of the CBCL syndrome scales raw scores, including internalizing and externalizing behaviors; however, on average boys taking deflazacort demonstrated more withdrawn behaviors than those taking prednisone, while on average the boys taking prednisone demonstrated more aggressive behaviors than boys taking deflazacort. Age, internalizing and externalizing behaviors accounted for 39 and 48% of the variance in psychosocial quality of life for both parents and boys with DMD, respectively. Overall, the use of steroids was not associated with more behavioral problems in boys with DMD. As behavior played a significant role in psychosocial quality of life, comprehensive assessment and treatment of behavioral problems is crucial in this population.