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Introduction: Histological data on muscle fiber size and proportion in (very) young typically developing (TD) children is not well documented and data on capillarization and satellite cell content are also lacking. Aims: This study investigated the microscopic properties of the medial gastrocnemius muscle in growing TD children, grouped according to age and gender to provide normal reference values in healthy children. Methods: Microbiopsies of the medial gastrocnemius (MG) muscle were collected in 46 TD boys and girls aged 2-10 years subdivided into 4 age groups (2-4, 4-6, 6-8 and 8-10 years). Sections were immunostained to assess fiber type cross-sectional area (fCSA) and proportion, the number of satellite cells (SC), capillary to fiber ratio (C/F), capillary density for type I and II fiber (CFD), capillary domain, capillary-to-fiber perimeter exchange index (CFPE) and heterogeneity index. fCSA was normalized to fibula length 2 and the coefficient of variation (CV) was calculated to reflect fCSA intrasubject variability. Results: Absolute fCSA of all fibers increased with age (r = 0.72, p < 0.001) but more in boys (+112%, p < 0.05) than in girls (+48%, p > 0.05) Normalized fCSA, CV and fiber proportion did not differ between age groups and gender. C/F was strongly correlated with age in boys (r = 0.83, p < 0.001), and to a lesser extent in girls (r = 0.37, p = 0.115), while other capillary parameters as well as the number of SC remained stable with increasing age in boys and girls. Discussion: This study provides reference values of histological measures in MG according to age in normally growing boys and girls. These data may be used as a reference to determine disease impact and efficacy of therapeutic approach on the muscle., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Andries, Deschrevel, Maes, De Beukelaer, Corvelyn, Staut, De Houwer, Costamagna, Nijs, Metsemakers, Nijs, Hens, De Wachter, Prinsen, Desloovere, Van Campenhout and Gayan-Ramirez.)

CRISPR-Cas are prokaryotic adaptive immune systems. Cas nucleases generally use CRISPR-derived RNA guides to specifically bind and cleave DNA or RNA targets. Here, we describe the experimental characterization of a bacterial CRISPR effector protein Cas12m representing subtype V-M. Despite being less than half the size of Cas12a, Cas12m catalyzes auto-processing of a crRNA guide, recognizes a 5'-TTN' protospacer-adjacent motif (PAM), and stably binds a guide-complementary double-stranded DNA (dsDNA). Cas12m has a RuvC domain with a non-canonical catalytic site and accordingly is incapable of guide-dependent cleavage of target nucleic acids. Despite lacking target cleavage activity, the high binding affinity of Cas12m to dsDNA targets allows for interference as demonstrated by its ability to protect bacteria against invading plasmids through silencing invader transcription and/or replication. Based on these molecular features, we repurposed Cas12m by fusing it to a cytidine deaminase that resulted in base editing within a distinct window., Competing Interests: Declaration of interests Two patent applications have been filed related to this work, with J.v.d.O., P.M., W.Y.W., and S.C.A.C. as inventors. J.v.d.O. is founder and scientific adviser of NTrans Technologies and adviser of Scope Biosciences and Hudson River Biotechnology. W.X.Y. and D.A.S. are employees and shareholders of Arbor Biotechnologies, Inc. C.L.B. is a co-founder and member of the scientific advisory board for Locus Biosciences and is a member of the scientific advisory board for Benson Hill. C.L.B. has submitted patent applications on CRISPR technologies unrelated to this work., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Hereditary spastic paraplegia (HSP) is a neurological, genetic disorder that predominantly presents with lower limb spasticity and muscle weakness. Pediatric pure HSP types with infancy or childhood symptom onset resemble in clinical presentation to children with bilateral spastic cerebral palsy (SCP). Hence, treatment approaches in these patient groups are analogous. Altered muscle characteristics, including reduced medial gastrocnemius (MG) muscle growth and hyperreflexia have been quantified in children with SCP, using 3D-freehand ultrasound (3DfUS) and instrumented assessments of hyperreflexia, respectively. However, these muscle data have not yet been studied in children with HSP. Therefore, we aimed to explore these MG muscle characteristics in HSP and to test the hypothesis that these data differ from those of children with SCP and typically developing (TD) children. A total of 41 children were retrospectively enrolled including (1) nine children with HSP (ages of 9-17 years with gross motor function levels I and II), (2) 17 age-and severity-matched SCP children, and (3) 15 age-matched typically developing children (TD). Clinically, children with HSP showed significantly increased presence and severity of ankle clonus compared with SCP ( p = 0.009). Compared with TD, both HSP and SCP had significantly smaller MG muscle volume normalized to body mass ( p ≤ 0.001). Hyperreflexia did not significantly differ between the HSP and SCP group. In addition to the observed pathological muscle activity for both the low-velocity and the change in high-velocity and low-velocity stretches in the two groups, children with HSP tended to present higher muscle activity in response to increased stretch velocity compared with those with SCP. This exploratory study is the first to reveal MG muscle volume deficits in children with HSP. Moreover, high-velocity-dependent hyperreflexia and ankle clonus is observed in children with HSP. Instrumented impairment assessments suggested similar altered MG muscle characteristics in pure HSP type with pediatric onset compared to bilateral SCP. This finding needs to be confirmed in larger sample sizes. Hence, the study results might indicate analogous treatment approaches in these two patient groups., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 De Beukelaer, Bar-On, Hanssen, Peeters, Prinsen, Ortibus, Desloovere and Van Campenhout.)

Purpose: By means of a case series we wanted to describe and correlate the clinical and imaging features of bone marrow oedema syndrome (BMOS) of the foot and ankle in children., Methods: A retrospective data study was performed on patients born on or after 01 January 2001 who underwent multiple MRI scans of the foot and ankle for pain symptoms. Six patients who presented with increased signal intensity on T2-weighted MR imaging without any underlying causes or concomitant pathology were included., Results: All patients, three boys and three girls with a mean age of 11 years (8 to 14), displayed patchy areas of increased signal intensity on T2-weighted and turbo inversion recovery magnitude (TIRM) images. On average, six tarsal bones were involved (4 to 8). In all patients, treatment consisted of rest and/or protected weight-bearing. The mean time for symptoms to improve during treatment was 6 months (1 to 16). The mean duration of treatment was nine months (3 to 16). In all patients clinical and imaging symptoms were strongly correlated and regressed in time., Conclusion: BMOS as a pathological entity should be considered in paediatric patients with foot and ankle pain without a clear underlying cause, and characteristic T2-weighted and TIRM signal intensity increase on MRI images. As BMOS is transient and self-limiting, conservative treatment is advised while the oedema regresses. An early diagnosis of this pathology could prevent unnecessary diagnostic investigations and invasive treatments., Level of Evidence: IV., (Copyright © 2020, The author(s).)

Cerebral palsy (CP), the single largest cause of childhood physical disability, is characterized firstly by a lesion in the immature brain, and secondly by musculoskeletal problems that progress with age. Previous research reported altered muscle properties, such as reduced volume and satellite cell (SC) numbers and hypertrophic extracellular matrix compared to typically developing (TD) children (>10 years). Unfortunately, data on younger CP patients are scarce and studies on SCs and other muscle stem cells in CP are insufficient or lacking. Therefore, it remains difficult to understand the early onset and trajectory of altered muscle properties in growing CP children. Because muscle stem cells are responsible for postnatal growth, repair and remodeling, multiple adult stem cell populations from young CP children could play a role in altered muscle development. To this end, new methods for studying muscle samples of young children, valid to delineate the features and to elucidate the regenerative potential of muscle tissue, are necessary. Using minimal invasive muscle microbiopsy, which was applied in young subjects under general anaesthesia for the first time, we aimed to isolate and characterize muscle stem cell-derived progenitors of TD children and patients with CP. Data of 15 CP patients, 3-9 years old, and 5 aged-matched TD children were reported. The muscle microbiopsy technique was tolerated well in all participants. Through the explant technique, we provided muscle stem cell-derived progenitors from the Medial Gastrocnemius. Via fluorescent activated cell sorting, using surface markers CD56, ALP, and PDGFRa, we obtained SC-derived progenitors, mesoangioblasts and fibro-adipogenic progenitors, respectively. Adipogenic, skeletal, and smooth muscle differentiation assays confirmed the cell identity and ability to give rise to different cell types after appropriate stimuli. Myogenic differentiation in CP SC-derived progenitors showed enhanced fusion index and altered myotube formation based on MYOSIN HEAVY CHAIN expression, as well as disorganization of nuclear spreading, which were not observed in TD myotubes. In conclusion, the microbiopsy technique allows more focused muscle research in young CP patients. Current results show altered differentiation abilities of muscle stem cell-derived progenitors and support the hypothesis of their involvement in CP-altered muscle growth., (Copyright © 2020 Corvelyn, De Beukelaer, Duelen, Deschrevel, Van Campenhout, Prinsen, Gayan-Ramirez, Maes, Weide, Desloovere, Sampaolesi and Costamagna.)

Objective: Giving in to food temptations is typically labeled as self-regulation failure. However, when indulgence stems from self-licensing processes, that is, relying on reasons to justify diet deviations, these instances might actually promote successful goal striving. This research aimed to theoretically define and test under what conditions self-licensing would be considered functional (e.g., when it ultimately serves the long-term goal of weight control) and dysfunctional (e.g., when it threatens successful goal striving)., Method: First, a pool of items reflecting functional and dysfunctional ways of self-licensing was tested and representative items were selected (Study 1; N = 194). Next, their classification was corroborated by examining the associations with indices of (un)successful dietary regulation (Study 2; N = 147). Finally, it was tested whether (dys)functional self-licensing predicted unhealthy snack intake, by means of participants keeping an unhealthy snack diary (Study 3; N = 54)., Results: The theorized distinction was confirmed, and the obtained correlational patterns supported the proposed (dys)functionality of the two types of self-licensing. Importantly, results showed that dysfunctional self-licensing predicted higher snack intake, whereas functional self-licensing predicted lower snack intake., Conclusion: The present studies provide evidence for the existence of two types of self-licensing, and thereby contribute to theoretical development., (© 2018 Wiley Periodicals, Inc.)

Objective: Research on self-licensing, i.e. employing justifications to give into temptation, largely consists of studies examining dichotomous food choices (healthy vs. unhealthy), while evidence for its effects on how much (unhealthy) food is consumed remains scarce. The present studies aimed to demonstrate self-licensing effects on caloric consumption in both lab (Study 1 & 2) and field setting (Study 3)., Design: In all studies, female student samples were recruited. They either received a justification cue (license condition) or not (control condition), after which they could eat freely from unhealthy snacks (Study 1, N = 85 and Study 2, N = 95) or choose a snack for direct consumption at a take-out lunch place (Study 3, N = 110)., Main Outcome Measures: Caloric value of consumed snacks (Study 1 and 2) and chosen snack (Study 3)., Results: In all studies, caloric consumption was higher in the license condition compared to the control condition: Participants ate more of the provided unhealthy snacks (Study 1 and 2) and chose a snack of higher caloric value (Study 3)., Conclusions: The present research corroborates self-licensing as an important factor in the consumption of unhealthy foods by employing more ecologically valid outcomes.

Self-licensing, employing reasons to justify indulgence, may help resolve the conflict between immediate temptations and long-term goals in favor of the former. It was hypothesized that this conflict-resolving potential of self-licensing may benefit self-regulation over time. With a momentary assessment design, we examined how self-licensing affects self-regulatory ability and the capacity to deal with subsequent self-regulatory conflicts. One hundred thirty-six female participants filled out surveys eight times per day for one week. Food temptation strength, conflict, resistance, and enactment were assessed, as well as license opportunity and perceived self-regulatory ability. When self-licensing opportunity was high (vs. low), a weaker association between temptation strength and conflict was observed. High license opportunity was associated with higher perceived self-regulatory ability for instances of low degrees of temptation enactment and predicted better handling of subsequent conflict after high degrees of prior temptation enactment. These results suggest that self-licensing can support self-regulation after initial failure.

Background: Emotional eating (i.e., overeating in response to negative affect) is a commonly accepted explanation for eating behaviors that are not in line with personal eating-norms. However, the empirical evidence for a causal link between self-reported emotional eating and overeating is mixed. The present study tested an alternative hypothesis stating that high emotional eating scores are indicative of a susceptibility to use negative affect as a confabulated, post-hoc reason to explain overeating., Methods: Female students (N = 46) participated in a 'taste-test' and came back to the lab a day later to receive feedback that they either ate too much (norm-violation condition) or an acceptable amount of food (control condition), whereafter emotional eating was assessed. Negative affect was measured several times throughout the study., Results: In the norm-violation condition, participants with high emotional eating scores retrospectively rated their affect prior to eating as more negative than participants with low emotional eating scores. In the control condition, no effect of emotional score on affect ratings was found., Discussion: For some individuals emotional eating scores may represent a tendency to retrospectively attribute overeating to negative affect. This could explain the lack of consistent findings for a link between self-reported emotional eating and overeating., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Previous studies have mainly examined the immediate effects of self-licensing on self-regulation failure. The present vignette studies examined what happens when a second self-regulation dilemma is encountered., Methods: In Studies 1 (N = 52) and 2 (N = 166), participants read a vignette in which the protagonist chooses to buy a treat while being on a diet, which was preceded by a license (License condition) or not (Control condition). The self-reported likelihood of indulging again when a second dilemma was presented in the same situation served as the dependent variable. Study 2 included measures of self-regulatory ability (motivation and self-efficacy) and also presented the dilemma in a new situation., Results: Study 1 showed that participants were more likely to indulge again after an initial indulgent choice with a license. This was replicated in Study 2, which also showed that self-licensing had no effect on goal re-engagement in a new situation. A marginally significant positive effect of self-licensing was found for self-efficacy., Conclusions: The results obtained suggest that self-licensing negatively affects goal re-engagement in the same situation, but not in a new situation. Whether self-licensing maintains or increases feelings of self-efficacy needs to be validated in future studies., (© 2016 The International Association of Applied Psychology.)

Objective: The present studies examined the role of environmental cues in steering people's dietary decisions in response to food temptations. Based on the notion that people show a tendency to conform to eating standards derived from the eating behavior of others, it was hypothesized that communication of other people's dietary decisions through environmental cues affect whether and what people eat., Methods: Conformity to environmental cues about food intake was assessed in a local bakery (Study 1, N=144) and a lab setting (Study 2, N=65). Participants were unobtrusively presented with a bowl of individually wrapped chocolates. The presence of empty wrappers was manipulated, to indicate whether others who had been in the same situation had or had not eaten. Conformity to environmental cues about food choice was assessed in Study 3 (N=90). Participants were required to choose between a healthy and an unhealthy snack. Food wrappers indicated whether previous participants had chosen the healthy or the unhealthy snack., Results: As expected, participants were more likely to take chocolates in the presence of an environmental cue that others did too. Also, participants were more likely to choose a snack that was consistent with the choice of others., Conclusions: Together, these findings support our main hypothesis that environmental cues steer people's decisions concerning food intake and food choice. Moreover, the results suggest that only small changes in the environment may support healthy eating behavior., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Purpose: The Dutch national policy regarding alcohol and youth relies on retailers' willingness to refuse to sell alcohol to underage customers. This study examined unobtrusively whether supermarkets and liquor stores do indeed comply with the legal age restrictions for alcohol sales., Methods: A research protocol was developed based on the methodology of mystery shopping. Using the protocol, 150 supermarkets and 75 liquor stores were visited by 15-year-old adolescents who tried to buy soft alcoholic beverages (legal age, 16 years), and 75 liquor stores were visited by 17-year-old adolescents who tried to buy strong alcoholic beverages (legal age, 18)., Results: Of all 300 buying attempts, 86% were successful. In supermarkets, 88% of all attempts succeeded. In liquor stores, a difference was found between the purchase of strong alcohol by 17-year-olds (89%) and the purchase of soft alcoholic beverages by 15-year-olds (77%). In only 71 of all visits, mystery shoppers were asked for an ID. In 39% of these cases, they were still able to buy alcohol. Female adolescents were more successful in buying alcohol than male adolescents., Conclusions: The results show that supermarkets and liquor stores generally fail to see the need for extra care when young customers try to buy alcohol. Legal age restrictions without enforcement and facilitation clearly do not suffice to protect adolescents from early exposure to alcohol.