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Summary: This study evaluates serum creatine kinase isoenzyme activity in children with osteogenesis imperfecta to determine its usefulness as a biochemical marker during treatment with bisphosphonate. The changes of creatine kinase (CK) isoenzyme activity during and after discontinuation therapy were observed. These results could be useful in addressing over-treatment risk prevention. Introduction: The brain isoenzyme of creatine kinase (CKbb) is highly expressed in mature osteoclasts during osteoclastogenesis, thus plays an important role in bone resorption. We previously identified high serum CKbb levels in 18 children with osteogenesis imperfect (OI) type 1 treated for 1 year with bisphosphonate (neridronate). In the present study, serum CK isoenzymes were evaluated in the same children with continuous versus discontinued neridronate treatment over a further 2-year follow-up period. Methods: This study included 18 children with OI type 1, 12 with continued (group A) and 6 with ceased (group B) neridronate treatment. Auxological data, serum biochemical markers of bone metabolism, bone mineral density z-score, and serum total CK and isoenzyme activities were determined in both groups. Results: Serum CKbb was progressively and significantly increased in group A ( p < 0.004) but rapidly decreased to undetectable levels in group B. In both groups, the cardiac muscle creatine kinase isoenzyme (CKmb) showed a marked decrease, while serum C-terminal telopeptide (CTx) levels were almost unchanged. Conclusions: This study provides evidence of the cumulative effect of neridronate administration in increasing serum CKbb levels and the reversible effect after its discontinuation. This approach could be employed for verifying the usefulness of serum CKbb as a biochemical marker in patients receiving prolonged bisphosphonate treatment. Moreover, the decreased serum CKmb levels suggest a systemic effect of these drugs. [ABSTRACT FROM AUTHOR]

A correction to the article "Serum creatine kinase isoenzymes in children with osteogenesis imperfecta" is presented.

Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Ehlers-Danlos syndromes are a heterogeneous group of Heritable Connective Tissue Disorders characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. Among the different types, the hypermobile Ehlers-Danlos syndrome is the most frequent and includes generalized joint hypermobility as the major diagnostic criterion. Joint hypermobility in hypermobile Ehlers-Danlos syndrome is often associated with pain that does not always allow the use of effective pain-reducing treatments. Patients with hEDS constantly describe their pain in detail. Eighty-nine patients with hEDS diagnoses were recruited and evaluated. They were asked to describe their pain in writing. The texts were examined through Linguistic Inquiry and Word Count. Correlational analyses were conducted between pain perception and language. A comparison of high/low pain perception and the quality of metaphors was carried out. The results showed that language quality varies depending on how much pain is perceived. The greater the pain is perceived, the lesser the positive effects and the greater the negative effects and dehumanizing metaphors are being used. Moreover, a greater pain seems to be related to a verbal experience of greater isolation and less self-care. In conclusion, the use of metaphors is a useful tool for examining illness experience and may help clinicians in the rehabilitation program.

Filamin C is a protein specifically expressed in myocytes and cardiomyocytes and is involved in several biological functions, including sarcomere contractile activity, signaling, cellular adhesion, and repair. FLNC variants are associated with different disorders ranging from striated muscle (myofibrillar distal or proximal) myopathy to cardiomyopathies (CMPs) (restrictive, hypertrophic, and dilated), or both. The outcome depends on functional consequences of the detected variants, which result either in FLNC haploinsufficiency or in an aberrant protein, the latter affecting sarcomere structure leading to protein aggregates. Cardiac manifestations of filaminopathies are most often described as adult onset CMPs and limited reports are available in children or on other cardiac spectrums (congenital heart defects-CHDs, or arrhythmias). Here we report on 13 variants in 14 children (2.8%) out of 500 pediatric patients with early-onset different cardiac features ranging from CMP to arrhythmias and CHDs. In one patient, we identified a deletion encompassing FLNC detected by microarray, which was overlooked by next generation sequencing. We established a potential genotype-phenotype correlation of the p.Ala1186Val variant in severe and early-onset restrictive cardiomyopathy (RCM) associated with a limb-girdle defect (two new patients in addition to the five reported in the literature). Moreover, in three patients (21%), we identified a relatively frequent finding of long QT syndrome (LQTS) associated with RCM (n = 2) and a hypertrabeculated left ventricle (n = 1). RCM and LQTS in children might represent a specific red flag for FLNC variants. Further studies are warranted in pediatric cohorts to delineate potential expanding phenotypes related to FLNC .

Physical and mechanical properties of continuous carbon or glass fiber reinforced endodontic posts are relevant to increase the retention and resistance of the tooth-restoration system. Hollow posts have been recently designed for delivering the luting cement through the post hole, thus enhancing the post-dentin interface by reducing the risk of air bubbles formation. Methods: Three type of endodontic posts, a carbon fiber hollow post, a glass fiber hollow post and a compact glass fiber post were investigated. Mechanical properties of these posts were assessed through bending tests. Teeth were subjected to fatigue cycling and the strength of restored teeth was detected through static tests. Failure modes were investigated through optical and scanning electron microscopy. Results show that composite posts increase the mechanical stability by more than 100% compared to premolars restored with particulate composite. Carbon fiber posts retain the highest strength (1467 N ± 304 N) among the investigated post and core restoration, but an unfavorable type of fracture has been observed, preventing the tooth re-treatment. Instead, more compliant posts (i.e., glass fiber reinforced composite, providing a strength of 1336 N ± 221 N), show a favorable mode of fracture that allows the re-treatment of teeth in the case that failure occurs. Glass fiber hollow posts show a good trade-off between strength and a favorable type of fracture.

Cardiomyopathy (CMP) is a rare disease in the pediatric population, with a high risk of morbidity and mortality. The genetic etiology of CMPs in children is extremely heterogenous. These two factors play a major role in the difficulties of establishing standard diagnostic and therapeutic protocols. Isolated CMP in children is a frequent finding, mainly caused by sarcomeric gene variants with a detection rate that can reach up to 50% of analyzed cohorts. Complex multisystemic forms of pediatric CMP are even more heterogenous. Few studies in literature take into consideration this topic as the main core since it represents a rarity (systemic CMP) within a rarity (pediatric population CMP). Identifying etiology in this cohort is essential for understanding prognosis, risk stratification, eligibility to heart transplantation and/or mechanical-assisted procedures, preventing multiorgan complications, and relatives' recurrence risk calculation. The previous points represent a cornerstone in patients' empowerment and personalized medical care approach. The aim of this work is to propose a new approach for an algorithm in the setting of the diagnostic framework of systemic pediatric CMP. On the other hand, during the literature review, we noticed a relatively common etiologic pattern in some forms of complex/multisystem CMP. In other words, certain syndromes such as Danon, Vici, Alström, Barth, and Myhre syndrome share a common pathway of directly or indirectly defective "autophagy" process, which appears to be a possible initiating/triggering factor for CMPs. This conjoint aspect could be important for possible prognostic/therapeutic implications in this category of patients. However, multicentric studies detailed functional and experimental models are needed prior to deriving conclusions.

The genetic background of congenital heart diseases (CHDs) is extremely complex, heterogenous, and still majorly to be determined. CHDs can be sporadic or familial. In this article we discuss in detail the phenotypic spectrum of selected genes including MYH7, GATA4, NKX2-5, TBX5, and TBX20. Our goal is to offer the clinician a general overview of the clinical spectrum of the analyzed topics that are traditionally known as causative for CHDs but we underline in this review the possible progressive functional (cardiomyopathy) and electric aspects (arrhythmias) caused by the genetic background., Competing Interests: Financial conflicts of interest and funding The authors declare no conflict of interest, and funding was not obtained for producing the article., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Monosomy 1p36 syndrome is now considered the most common terminal deletion syndrome, with an estimated incidence of 1 in 5000. Cardiac involvement is well described in the literature mainly in terms of congenital heart defects (CHDs) and cardiomyopathies (CMPs). Few data in the literature describe the potential progressive nature of aortic dilatation (root and ascending aorta) in 1p36 deletion syndrome. SKI harboured in the deleted region might play a predisposing factor for this aspect., Methods: we reviewed the aortic aspect both in the literature and in our cohort, where major attention to the aortic abnormalities was given through dedicated echocardiographic measurements even in previously screened individuals., Results: aortic involvement in 1p36 deletion syndrome was described in the literature three times within the CHD context. We observed three additional patients from our cohort (three out of nine patients) with aortic dilatation. All patients with dilated aorta had SKI haploinsufficiency within the deleted region., Conclusions: at long-term outcome and with a growing population of this rare disease, this association (1p36 deletion and aortic dilatation) might represent a major concern especially in terms of risk stratification and the potential need for specific management (conservative pharmacologic and eventually surgical) whenever indicated. The present study suggests the need for detailed multicentric studies and indication to periodic echocardiographic screening in addition to baseline tests, especially in individuals with deletions harbouring SKI .

Neuromuscular disorders (NMDs) are highly heterogenous from both an etiological and clinical point of view. Their signs and symptoms are often multisystemic, with frequent cardiac involvement. In fact, childhood onset forms can predispose a person to various progressive cardiac abnormalities including cardiomyopathies (CMPs), valvulopathies, atrioventricular conduction defects (AVCD), supraventricular tachycardia (SVT) and ventricular arrhythmias (VA). In this review, we selected and described five specific NMDs: Friedreich's Ataxia (FRDA), congenital and childhood forms of Myotonic Dystrophy type 1 (DM1), Kearns Sayre Syndrome (KSS), Ryanodine receptor type 1-related myopathies ( RYR1 -RM) and Laminopathies. These changes are widely investigated in adults but less researched in children. We focused on these specific topics due their relative frequency and their potential unexpected cardiac manifestations in children. Moreover these conditions present different inheritance patterns and mechanisms of action. We decided not to discuss Duchenne and Becker muscular dystrophies due to extensive work regarding the cardiac aspects in children. For each described NMD, we focused on the possible cardiac manifestations such as different types of CMPs (dilated-DCM, hypertrophic-HCM, restrictive-RCM or left ventricular non compaction-LVNC), structural heart abnormalities (including valvulopathies), and progressive heart rhythm changes (AVCD, SVT, VA). We describe the current management strategies for these conditions. We underline the importance, especially for children, of a serial multidisciplinary personalized approach and the need for periodic surveillance by a dedicated heart team. This is largely due to the fact that in children, the diagnosis of certain NMDs might be overlooked and the cardiac aspect can provide signs of their presence even prior to overt neurological diagnosis.

Objective: To conduct a systematic review and meta-analysis to assess if the presence of an endodontic post may increase the fracture resistance of endodontically-treated maxillary premolars directly restored with composite., Methods: A comprehensive systematic literature search according to the PRISMA statement was conducted to assess in vitro studies including endodontically-treated maxillary premolars, restored with different type of posts supporting direct composite reconstructions. Two groups of meta-analyses were performed using fixed effects model and additional Trial Sequential Analysis (TSA) was carried out. Moreover, risk of bias was conducted and quality of evidence for any performed meta-analysis was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE)., Results: Twenty-four articles met the inclusion criteria and 13 studies also underwent quantitative evaluation. Fracture resistance of endodontically-treated premolars restored with fiber posts was significantly less than sound teeth (p value: < 0.00001), however endodontically-treated premolars with a fiber post provided an increase in fracture resistance when compared to equivalent teeth restored without post (p value: 0.003). TSA revealed high power of both meta-analyses. Moderate risk of bias was reported in 23/24 studies; only 1 study showed high risk of bias. GRADE system showed moderate strength of evidence due to the presence of a study with high risk of bias and to wide confidence intervals., Significance: Within the limitation of the present systematic review and meta-analysis, it can be concluded that endodontically-treated maxillary premolars restored with a fiber post and direct composite restoration demonstrated increased fracture resistance when compared to equivalent teeth without post., (Copyright © 2021 The Academy of Dental Materials. Published by Elsevier Inc. All rights reserved.)

Background : The aim of this study was to investigate cuspal deflection caused by material shrinkage and temperature rise occurring in the pulp chamber during photopolymerization. The aim of this study was also to investigate the effect of flowable and packable bulk-fill composites on cuspal deflection occurring in mesio-occlusal-distal (MOD) cavities restored through the bulk-fill or through the incremental layering technique. Additionally, mechanical and thermal properties of bulk-fill composites were considered. Methods : Two bulk-fill composites (high-viscosity and low-viscosity), largely differing in material composition, were used. These composites were characterized through linear shrinkage and compressive test. Cuspal deformation during restoration of mesio-occlusal-distal cavities of human premolars was evaluated using both the bulk-fill and the incremental layering techniques. Temperature rise was measured through thermocouples placed 1 mm below the cavity floor. Results : Shrinkage of the flowable composite was significantly higher ( p < 0.05) than that of packable composite, while mechanical properties were significantly lower ( p < 0.05). For cusp distance variation, no significant difference was observed in cavities restored through both restorative techniques, while temperature rise values spanned from 8.2 °C to 11.9 °C. Conclusions : No significant difference in cusp deflection between the two composites was observed according to both the restorative techniques. This result can be ascribed to the Young's modulus suggesting that the packable composite is stiffer, while the flowable composite is more compliant, thus balancing the cusp distance variation. The light curing modality of 1000 mW/cm 2 for 20 s can be considered thermally safe for the pulp chamber.

Idiopathic scoliosis is the most common form of spinal deformity in children. However, secondary causes of scoliosis, such as ganglioneuroma, should be always considered to avoid wrong diagnosis, and further investigations are required when there are atypical signs. We report a case of ganglioneuroma misdiagnosed as idiopathic scoliosis and review the literature to identify the red flags useful for physicians during the evaluation of a child with scoliosis. On the basis of both clinical and radiographic criteria that emerged from this study, we propose an algorithm that could help in the differential diagnosis, suggesting when to perform an MRI.

Background: Creatine kinase (Ck) catalyzes the reversible transfer of high-energy phosphate groups between adenosine triphosphate and phosphocreatine. The brain isoform (Ckbb) is greatly induced in mature osteoclasts, playing an important role in bone-resorbing function during osteoclastogenesis. High Ckbb serum level has been found in patients with osteopetrosis and in patients with bisphosphonate (BP)-induced osteopetrosis. BPs are considered the treatment of choice for children with osteogenesis imperfecta (OI), acting as potent inhibitors of bone resorption by suppressing the activity of osteoclasts., Methods: We determined total serum Ck and isoform activity in 18 prepubertal children with type I OI, before and during treatment with the BP neridronate infusions., Results: Basal serum Ckbb levels were slightly elevated with respect to controls (mean ± SD = 3.0 ± 2.7 vs. 2.0 ± 2.2) and progressively increased after neridronate treatment (t0 vs. t4: mean ± SD = 3.0 ± 2.7 to 10.8 ± 8.1), with significant increment after first, second, and fourth infusions (P < 0.01). An inverse correlation was found between serum Ckbb and serum CTx at basal level., Conclusion: Our results support previous observations that increased serum Ckbb reflects failure of osteoclasts or, at least, suppression of osteoclasts. Upon considering that BPs are long acting, this information could be useful to prevent the risk of overtreatment after long-term BP exposure in pediatric patients with OI.

Cardiovascular involvement is relatively rare in osteogenesis imperfecta and has a predilection for left-sided cardiac valves. We report a 5 years old female child affected by osteogenesis imperfecta type I in which an asymptomatic mild form of Ebstein's anomaly, a congenital tricuspid malformation, was diagnosed during routinely investigation. The association of these two relatively rare entities could provide new insight to better understand the pathogenesis of cardiac involvement in osteogenesis imperfecta.