Skeletal Deficiency Research Articles

Aesthetic Outcome of Isolated Advancement Genioplasty With and Without Submental Liposuction in the Treatment of Skeletal Chin Deficiency in Double Chin Patients (A Randomized Controlled Clinical Trial).

This study was conducted to evaluate the effect of submental liposuction with advancement genioplasty versus advancement genioplasty alone on esthetics in double chin patients. Twenty-six patients with deficient chin were included in the study. The patients were distributed into 2 groups: submental fat liposuction in conjunction with advancement genioplasty group as intervention one and advancement genioplasty alone as a control group. Preoperative and postoperative computed tomography was performed for all patients. With the help of various software, diagnosis, virtual planning, and evaluation were done. Patient satisfaction was evaluated by a Face-Q questionnaire. The study was conducted on 26 patients with deficient chin, 88.9% were females and 11.1% were males. The mean age of cases was (25.5±3.5y), clinically all cases went uneventful, and there were no statistically significant differences regarding soft tissue relapse between the study and control groups. All patients showed statistically significant increases in scores of satisfaction with the chin, psychological well-being, and social well-being scales. Submental fat liposuction can be a good intervention choice in mild-moderate chin deficient cases when added to an advanced genioplasty procedure.

Growth deficiency in a mouse model of Kabuki syndrome 2 bears mechanistic similarities to Kabuki syndrome 1.

Growth deficiency is a characteristic feature of both Kabuki syndrome 1 (KS1) and Kabuki syndrome 2 (KS2), Mendelian disorders of the epigenetic machinery with similar phenotypes but distinct genetic etiologies. We previously described skeletal growth deficiency in a mouse model of KS1 and further established that a Kmt2d-/- chondrocyte model of KS1 exhibits precocious differentiation. Here we characterized growth deficiency in a mouse model of KS2, Kdm6atm1d/+. We show that Kdm6atm1d/+ mice have decreased femur and tibia length compared to controls and exhibit abnormalities in cortical and trabecular bone structure. Kdm6atm1d/+ growth plates are also shorter, due to decreases in hypertrophic chondrocyte size and hypertrophic zone height. Given these disturbances in the growth plate, we generated Kdm6a-/- chondrogenic cell lines. Similar to our prior in vitro model of KS1, we found that Kdm6a-/- cells undergo premature, enhanced differentiation towards chondrocytes compared to Kdm6a+/+ controls. RNA-seq showed that Kdm6a-/- cells have a distinct transcriptomic profile that indicates dysregulation of cartilage development. Finally, we performed RNA-seq simultaneously on Kmt2d-/-, Kdm6a-/-, and control lines at Days 7 and 14 of differentiation. This revealed surprising resemblance in gene expression between Kmt2d-/- and Kdm6a-/- at both time points and indicates that the similarity in phenotype between KS1 and KS2 also exists at the transcriptional level.

Skeletal Muscle SIRT3 Deficiency Contributes to Pulmonary Vascular Remodeling in Pulmonary Hypertension Due to Heart Failure With Preserved Ejection Fraction.

Pulmonary hypertension (PH) is a major complication linked to adverse outcomes in heart failure with preserved ejection fraction (HFpEF), yet no specific therapies exist for PH associated with HFpEF (PH-HFpEF). We have recently reported on the role of skeletal muscle SIRT3 (sirtuin-3) in modulation of PH-HFpEF, suggesting a novel endocrine signaling pathway for skeletal muscle modulation of pulmonary vascular remodeling. Using skeletal muscle-specific Sirt3 knockout mice (Sirt3skm-/-) and mass spectrometry-based comparative secretome analysis, we attempted to define the processes by which skeletal muscle SIRT3 defects affect pulmonary vascular health in PH-HFpEF. Sirt3skm-/- mice exhibited reduced pulmonary vascular density accompanied by pulmonary vascular proliferative remodeling and elevated pulmonary pressures. Comparative analysis of secretome by mass spectrometry revealed elevated secretion levels of LOXL2 (lysyl oxidase homolog 2) in SIRT3-deficient skeletal muscle cells. Elevated circulation and protein expression levels of LOXL2 were also observed in plasma and skeletal muscle of Sirt3skm-/- mice, a rat model of PH-HFpEF, and humans with PH-HFpEF. In addition, expression levels of CNPY2 (canopy fibroblast growth factor signaling regulator 2), a known proliferative and angiogenic factor, were increased in pulmonary artery endothelial cells and pulmonary artery smooth muscle cells of Sirt3skm-/- mice and animal models of PH-HFpEF. CNPY2 levels were also higher in pulmonary artery smooth muscle cells of subjects with obesity compared with nonobese subjects. Moreover, treatment with recombinant LOXL2 protein promoted pulmonary artery endothelial cell migration/proliferation and pulmonary artery smooth muscle cell proliferation through regulation of CNPY2-p53 signaling. Last, skeletal muscle-specific Loxl2 deletion decreased pulmonary artery endothelial cell and pulmonary artery smooth muscle cell expression of CNPY2 and improved pulmonary pressures in mice with high-fat diet-induced PH-HFpEF. This study demonstrates a systemic pathogenic impact of skeletal muscle SIRT3 deficiency in remote pulmonary vascular remodeling and PH-HFpEF. This study suggests a new endocrine signaling axis that links skeletal muscle health and SIRT3 deficiency to remote CNPY2 regulation in the pulmonary vasculature through myokine LOXL2. Our data also identify skeletal muscle SIRT3, myokine LOXL2, and CNPY2 as potential targets for the treatment of PH-HFpEF.

Apical expansion of calvarial osteoblasts and suture patency is dependent on fibronectin cues.

The skull roof, or calvaria, is comprised of interlocking plates of bones that encase the brain. Separating these bones are fibrous sutures that permit growth. Currently, we do not understand the instructions for directional growth of the calvaria, a process which is error-prone and can lead to skeletal deficiencies or premature suture fusion (craniosynostosis, CS). Here, we identify graded expression of fibronectin (FN1) in the mouse embryonic cranial mesenchyme (CM) that precedes the apical expansion of calvaria. Conditional deletion of Fn1 or Wasl leads to diminished frontal bone expansion by altering cell shape and focal actin enrichment, respectively, suggesting defective migration of calvarial progenitors. Interestingly, Fn1 mutants have premature fusion of coronal sutures. Consistently, syndromic forms of CS in humans exhibit dysregulated FN1 expression, and we also find FN1 expression altered in a mouse CS model of Apert syndrome. These data support a model of FN1 as a directional substrate for calvarial osteoblast migration that may be a common mechanism underlying many cranial disorders of disparate genetic etiologies.

The Complexity of Skeletal Transverse Dimension: From Diagnosis, Management, and Treatment Strategies to the Application of Collaborative Cross (CC) Mouse Model.

This study investigates the significance of skeletal transverse dimension (STD) in orthodontic therapy and its impact on occlusal relationships. The primary goal is to enhance understanding and promote the integration of transverse skeletal diagnostics into routine orthodontic assessments. To achieve this aim, the study employs a comprehensive approach, utilizing model analysis, clinical assessments, radiographic measurements, and occlusograms. The initial step involves a meticulous assessment of deficiencies in the maxilla, mainly focusing on transverse dimension issues. Various successful diagnostic methods are employed to ascertain the type and presence of these deficiencies. Furthermore, the study compares surgically assisted maxillary expansion (SARME) and orthopedic maxillary expansion (OME) in addressing skeletal transverse issues. Stability assessments and efficacy analyses are conducted to provide valuable insights into the superiority of SARME over OME. The findings reveal that proper evaluation of STD is crucial in orthodontic diagnosis, as overlooking transverse dimension issues can lead to complications such as increased masticatory muscle activity, occlusal interferences, and an elevated risk of gingival recession. Surgically assisted maxillary expansion emerges as a more stable solution than orthopedic methods. In conclusion, incorporating skeletal transverse diagnostics into routine orthodontic assessments is imperative for achieving optimal occlusal relationships and minimizing negative consequences on dentition, periodontium, and joints. The study emphasizes the significance of accurate three-dimensional assessments and recommends the consideration of SARME over OME for addressing skeletal transverse deficiencies. Finally, the Collaborative Cross (CC) mouse model is also a novel mouse model for studying complex traits. Exploring the Collaborative Cross mouse model opens avenues for future research, promising further insights into transverse skeletal issues in orthodontics.

Not So Rare: Diseases Based on Mutant Proteins Controlling Endoplasmic Reticulum-Mitochondria Contact (MERC) Tethering.

Mitochondria-endoplasmic reticulum contacts (MERCs), also called endoplasmic reticulum (ER)-mitochondria contact sites (ERMCS), are the membrane domains, where these two organelles exchange lipids, Ca2+ ions, and reactive oxygen species. This crosstalk is a major determinant of cell metabolism, since it allows the ER to control mitochondrial oxidative phosphorylation and the Krebs cycle, while conversely, it allows the mitochondria to provide sufficient ATP to control ER proteostasis. MERC metabolic signaling is under the control of tethers and a multitude of regulatory proteins. Many of these proteins have recently been discovered to give rise to rare diseases if their genes are mutated. Surprisingly, these diseases share important hallmarks and cause neurological defects, sometimes paired with, or replaced by skeletal muscle deficiency. Typical symptoms include developmental delay, intellectual disability, facial dysmorphism and ophthalmologic defects. Seizures, epilepsy, deafness, ataxia, or peripheral neuropathy can also occur upon mutation of a MERC protein. Given that most MERC tethers and regulatory proteins have secondary functions, some MERC protein-based diseases do not fit into this categorization. Typically, however, the proteins affected in those diseases have dominant functions unrelated to their roles in MERCs tethering or their regulation. We are discussing avenues to pharmacologically target genetic diseases leading to MERC defects, based on our novel insight that MERC defects lead to common characteristics in rare diseases. These shared characteristics of MERCs disorders raise the hope that they may allow for similar treatment options.

Balancing beauty and science: a review of facial implant materials in craniofacial surgery.

Facial reconstruction and augmentation, integral in facial plastic surgery, address defects related to trauma, tumors infections, and congenital skeletal deficiencies. Aesthetic considerations, including age-related facial changes, involve volume loss and diminished projection, often associated with predictable changes in the facial skeleton. Autologous, allogeneic, and alloplastic implants are used to address these concerns. Autologous materials such as bone, cartilage, and fat, while longstanding options, have limitations, including unpredictability and resorption rates. Alloplastic materials, including metals, polymers, and ceramics, offer alternatives. Metals like titanium are biocompatible and used primarily in fracture fixation. Polymers, such as silicone and polyethylene, are widely used, with silicone presenting migration, bony resorption, and visibility issues. Polyethylene, particularly porous polyethylene (MedPor), was reported to have one of the lowest infection rates while it becomes incorporated into the host. Polyether-ether-ketone (PEEK) exhibits mechanical strength and compatibility with imaging modalities, with custom PEEK implants providing stable results. Acrylic materials, like poly-methylmethacrylate (PMMA), offer strength and is thus mostly used in the case of cranioplasty. Bioceramics, notably hydroxyapatite (HaP), offer osteoconductive and inductive properties, and HaP granules demonstrate stable volume retention in facial aesthetic augmentation. Combining HaP with other materials, such as PLA, may enhance mechanical stability. 3D bioprinting with HaP-based bioinks presents a promising avenue for customizable and biocompatible implants. In conclusion, various materials have been used for craniofacial augmentation, but none have definitively demonstrated superiority. Larger randomized controlled trials are essential to evaluate short- and long-term complications comprehensively, potentially revolutionizing facial balancing surgery.

Nutritional considerations for people living with a Fontan circulation: a narrative review.

The population of people living with a Fontan circulation are highly heterogenous, including both children and adults, who have complex health issues and comorbidities associated with their unique physiology throughout life. Research focused on nutritional considerations and interventions in the Fontan population is extremely limited beyond childhood. This review article discusses the current literature examining nutritional considerations in the setting of Fontan physiology and provides an overview of the available evidence to support nutritional management strategies and future research directions. Protein-losing enteropathy, growth deficits, bone mineral loss, and malabsorption are well-recognised nutritional concerns within this population, but increased adiposity, altered glucose metabolism, and skeletal muscle deficiency are also more recently identified issues. Emergencing evidence suggets that abnormal body composition is associated with poor circulatory function and health outcomes. Many nutrition-related issues, including the impact of congenital heart disease on nutritional status, factors contributing to altered body composition and comorbidities, as well as the role of the microbiome and metabolomics, remain poodly understood.

PIEZO1 loss-of-function compound heterozygous mutations in the rare congenital human disorder Prune Belly Syndrome

Prune belly syndrome (PBS), also known as Eagle-Barret syndrome, is a rare, multi-system congenital myopathy primarily affecting males. Phenotypically, PBS cases manifest three cardinal pathological features: urinary tract dilation with poorly contractile smooth muscle, wrinkled flaccid ventral abdominal wall with skeletal muscle deficiency, and intra-abdominal undescended testes. Genetically, PBS is poorly understood. After performing whole exome sequencing in PBS patients, we identify one compound heterozygous variant in the PIEZO1 gene. PIEZO1 is a cation-selective channel activated by various mechanical forces and widely expressed throughout the lower urinary tract. Here we conduct an extensive functional analysis of the PIEZO1 PBS variants that reveal loss-of-function characteristics in the pressure-induced normalized open probability (NPo) of the channel, while no change is observed in single-channel currents. Furthermore, Yoda1, a PIEZO1 activator, can rescue the NPo defect of the PBS mutant channels. Thus, PIEZO1 mutations may be causal for PBS and the in vitro cellular pathophysiological phenotype could be rescued by the small molecule, Yoda1. Activation of PIEZO1 might provide a promising means of treating PBS and other related bladder dysfunctional states.

Photographic analysis of orofacial soft tissue alterations related to rapid maxillary expansion in pediatric patients.

Maxillary transverse deficiency is widely recognized as one of the most common skeletal issues in orthodontics, and rapid maxillary expansion (RME) is commonly employed as a treatment method. This study aimed to investigate the impact of RME on the soft tissues of the orofacial region in pediatric patients. The study included two groups: an experimental group comprising 30 patients (16 females and 14 males) with maxillary skeletal transverse deficiency who required rapid maxillary expansion (RME), and a control group consisting of patients (10 females and 10 males) who did not require RME or orthodontic treatment. Frontal and profile photographs were taken before and after RME for both groups. Frontal photographs were used to obtain 12 linear measurements, while profile photographs were used to perform 2 linear and 2 angular measurements using the "protractor" and "pixel ruler" software. Burstone-Legan, Steiner and Rickett's analyses were performed to determine the locations of the upper and lower lips. Student t-test, paired samples t-test and Mann-Whitney U test were used to evaluate the data. In the experimental group, there was a statistically significant increase in nose width and intercommissural distance at the end of the treatment (p < 0.05). Similarly, both the experimental and control groups showed a statistically significant increase in the dorsum of nose length at T2 compared to the initial measurement (p < 0.05). Furthermore, the male participants in the experimental group exhibited a statistically significantly higher increase in nose length and dorsum of the nose during the T1 and T2 periods compared to the female participants in the experimental group (p < 0.05). RME may lead to changes in soft tissues in pediatric patients and was observed to be gender-specific. However, these changes were not clinically noticeable, and long-term follow-up studies are needed to determine the long-term effects of these changes.

Randomized clinical trial of surgically assisted rapid maxillary expansion with two and three segments for nasal breathing.

To evaluate surgically assisted rapid maxillary expansion (SARME), with osteotomies separating the maxilla into two segments (SARME-2S) and three segments (SARME-3S), on obstruction symptoms and nasal cavity dimensions in patients with maxillary transverse skeletal deficiency (MTSD). Sixteen patients with MTSD of 7mm or above were evaluated in each group, for a total of 32 patients. All patients were evaluated pre- and postoperatively up to 10months after the expander activations. The minimum cross-sectional area (MCA) and the volume of the nasal cavities were identified by acoustic rhinometry. The Nasal Obstruction Symptom Evaluation (NOSE) scale questionnaire was applied. The palate surface area (PSA) was measured, via digitized maxillary models, as a criterion for comparison with the other variables studied. There was no difference between the groups (p = 0.370) and was verified a significant increase in PSA postoperatively. MCA showed a small increase without statistical significance, and together with the volume of the nasal cavities remained constant during the study. NOSE scale scores decreased significantly in the postoperative periods, implying a decrease in nasal obstruction symptoms in both groups. SARME with two and three segments show similar results, and both may improve nasal obstruction symptoms when present in patients with MTSD. SARME, regardless of the chosen surgical technique, should follow the recommendation to correct just the MTSD. While an improvement in nasal breathing is expected, this must be understood as likely, but not certain.

Ketone ester administration improves glycemia in obese mice.

During periods of prolonged fasting/starvation, the liver generates ketones [i.e., β-hydroxybutyrate (βOHB)] that primarily serve as alternative substrates for ATP production. Previous studies have demonstrated that elevations in skeletal muscle ketone oxidation contribute to obesity-related hyperglycemia, whereas inhibition of succinyl CoA:3-ketoacid CoA transferase (SCOT), the rate-limiting enzyme of ketone oxidation, can alleviate obesity-related hyperglycemia. As circulating ketone levels are a key determinant of ketone oxidation rates, we tested the hypothesis that increases in circulating ketone levels would worsen glucose homeostasis secondary to increases in muscle ketone oxidation. Accordingly, male C57BL/6J mice were subjected to high-fat diet-induced obesity, whereas their lean counterparts received a standard chow diet. Lean and obese mice were orally administered either a ketone ester (KE) or placebo, followed by a glucose tolerance test. In tandem, we conducted isolated islet perifusion experiments to quantify insulin secretion in response to ketones. We observed that exogenous KE administration robustly increases circulating βOHB levels, which was associated with an improvement in glucose tolerance only in obese mice. These observations were independent of muscle ketone oxidation, as they were replicated in mice with a skeletal muscle-specific SCOT deficiency. Furthermore, the R-isomer of βOHB produced greater increases in perifusion insulin levels versus the S-isomer in isolated islets from obese mice. Taken together, acute elevations in circulating ketones promote glucose-lowering in obesity. Given that only the R-isomer of βOHB is oxidized, further studies are warranted to delineate the precise role of β-cell ketone oxidation in regulating insulin secretion.NEW & NOTEWORTHY It has been demonstrated that increased skeletal muscle ketone metabolism contributes to obesity-related hyperglycemia. Since increases in ketone supply are key determinants of organ ketone oxidation rates, we determined whether acute elevations in circulating ketones following administration of an oral ketone ester may worsen glucose homeostasis in lean or obese mice. Our work demonstrates the opposite, as acute elevations in circulating ketones improved glucose tolerance in obese mice.

Delayed skeletal development and IGF-1 deficiency in a mouse model of lysinuric protein intolerance.

SLC7A7 deficiency, or lysinuric protein intolerance (LPI), causes loss of function of the y+LAT1 transporter critical for efflux of arginine, lysine and ornithine in certain cells. LPI is characterized by urea cycle dysfunction, renal disease, immune dysregulation, growth failure, delayed bone age, and osteoporosis. We previously reported that Slc7a7 knockout mice (C57BL/6 x 129/SvEv F2) recapitulate LPI phenotypes, including growth failure. Our main objective was to characterize the skeletal phenotype in these mice. Compared to wild type littermates, juvenile Slc7a7 knockout mice demonstrated 70% lower body weights, 87% lower plasma IGF-1 concentrations, and delayed skeletal development. Because poor survival prevents evaluation of mature knockout mice, we generated a conditional Slc7a7 deletion in mature osteoblasts or mesenchymal cells of the osteo-chondroprogenitor lineage, butno differences in bone architecture were observed. Overall, global Slc7a7 deficiency caused growth failure with low plasma IGF-1 concentrations and delayed skeletal development, but Slc7a7 deficiency in the osteoblastic lineage was not a major contributor to these phenotypes. Future studies utilizing additional tissue-specific Slc7a7 knockout models may help dissect cell autonomous and non-cell autonomous mechanisms underlying phenotypes in LPI.

Loss of NOR-1 represses muscle metabolism through mTORC1-mediated signaling and mitochondrial gene expression in C2C12 myotubes.

Gene expression of the NR4A nuclear orphan receptor NOR-1 is reduced in obesity and in human skeletal muscle during disuse. It has been well established that NOR-1 is highly responsive to both aerobic and resistance exercise and NOR-1 overexpression is coincident with a plethora of metabolic benefits. However, it is unclear whether loss of NOR-1 contributes to inappropriate metabolic signaling in skeletal muscle that could lead to insulin resistance. The purpose of this study was to elucidate the impact of NOR-1 deficiency on C2C12 metabolic signaling. Changes in gene expression after siRNA-mediated NOR-1 knockdown in C2C12 myotubes were determined by qPCR and bioinformatic analysis of RNA-Seq data. Our RNA-Seq data identified several metabolic targets regulated by NOR-1 and implicates NOR-1 as a modulator of mTORC1 signaling via Akt-independent mechanisms. Furthermore, pathway analysis revealed NOR-1 knockdown perturbs the insulin resistance and insulin sensitivity pathways. Taken together, these data suggest skeletal muscle NOR-1 deficiency may contribute to altered metabolic signaling that is consistent with metabolic disease. We postulate that strategies that improve NOR-1 may be important to offset the negative impact that inactivity, obesity, and type 2 diabetes have on mitochondria and muscle metabolism.

Precision of Proximal Segment Repositioning Using Digitally Planned Custom Made guide in Sagittal Split Ramus Osteotomy

Background: Orthognathic surgery is widely used surgical procedure. The most common used orthognathic surgical procedure is bilateral sagittal split osteotomy (BSSO) that is used for managing skeletal mandibular excess, deficiency or asymmetry. Objective: To correct functional and aesthetic problems. Patients and Methods: A total of (12 patients) 24 condyles have been included in our study all with cl II malocclusion, open bites and asymmetry, both genders males and females, their age ranges between18 to 40 years, all the cases had preoperative and postoperative CT scans. Results: By comparing pre and post operative CT scans regarding condylar positions for both groups. The results revealed that there was less movement of condylar head in group with device and direction of movement was more favorable. Conclusion: This study showed that the Digitally Planned Custom Made guide was useful in repositioning condyles with minimal movement post operatively and more favorable direction of movement. Keywords: Orthognathic surgery, condyles, CADCAM guides, sagittal split ramus osteotomy, proximal segment

Precision of Proximal Segment Repositioning Using Digitally Planned Custom Made guide in Sagittal Split Ramus Osteotomy

Background: Orthognathic surgery is widely used surgical procedure. The most common used orthognathic surgical procedure is bilateral sagittal split osteotomy (BSSO) that is used for managing skeletal mandibular excess, deficiency or asymmetry.&#x0D; Objective: To correct functional and aesthetic problems.&#x0D; Patients and Methods: A total of (12 patients) 24 condyles have been included in our study all with cl II malocclusion, open bites and asymmetry, both genders males and females, their age ranges between18 to 40 years, all the cases had preoperative and postoperative CT scans.&#x0D; Results: By comparing pre and post operative CT scans regarding condylar positions for both groups. The results revealed that there was less movement of condylar head in group with device and direction of movement was more favorable.&#x0D; Conclusion: This study showed that the Digitally Planned Custom Made guide was useful in repositioning condyles with minimal movement post operatively and more favorable direction of movement.

Sarcopenia as a Predictive Factor for Recurrence of Hepatocellular Carcinoma Following Radiofrequency Ablation.

Sarcopenia is a skeletal muscle mass deficiency and a potential prognostic factor for the recurrence of hepatocellular carcinoma (HCC). To determine whether sarcopenia correlates with the recurrence rate of HCC after curative radiofrequency ablation (RFA) in early and very early HCC. We retrospectively reviewed 669 HCC patients who underwent their first curative RFA at Siriraj hospital from 2011 to 2020. Fifty-six patients who were diagnosed with HCC by triple-phase CT scan and had complete response on follow-up CT were included. All patients underwent skeletal muscle index (SMI) assessment at level L3 vertebra and sarcopenia was defined by the cut-off values of 52.4 cm2/m2 for men and 38.5 cm2/m2 for women. We compared patients with and without sarcopenia. Time to recurrence was evaluated by the Kaplan-Meier method. Univariate and multivariate Cox regression analysis was performed. Sarcopenia was present in 37 of 56 patients (66.1%). There was no significant difference between groups except body mass index (BMI) (P<0.001) and serum alanine aminotransferase (ALT) (P=0.035). There was a promising result indicating the difference of time to recurrence between each group (P=0.046) and potential association of sarcopenia with HCC recurrence (HR=2.06; P=0.052). The Child-Pugh score and tumor number were independent risk factors for HCC recurrence (HR=2.04; P=0.005 and HR=2.68; P=0.017, respectively). Sarcopenia is a potential prognostic factor for recurrence of HCC in Thai patients who underwent RFA. A larger study is required to properly confirm this association.

The unsolved problem of radial longitudinal dysplasia: how can we reliably prevent recurrence, preserve growth and optimize function?

Congenital radial longitudinal dysplasia remains an 'unsolved problem' in hand surgery. The challenges presented by the skeletal deficiency of the distal radius and soft tissue dysplasia of the severe radial longitudinal deficiency have been addressed by a number of techniques that aim to stabilize the position of the hand relative to the forearm and optimize forearm growth and hand function. Analysis of hand function and position in these children is difficult because of the abnormal 'wrist' mechanics, and the published results of the techniques used to date often lack a standardized approach and importantly the perception of function from the patient's perspective. The existing data is reviewed and compared with the results of cohorts from two major congenital upper limb centres. Soft tissue distraction prior to radialization or centralization may offer benefit in ulnar growth and forearm length but there is a need for further research into the long-term functional outcomes of the various techniques available to determine the optimal choice for these children.Level of evidence: V.

Clinical advances in maxillary skeletal expansion and introduction of a new MARPE concept.

Transverse maxillary deficiency, typically characterized by the clinical manifestations of unilateral or bilateral crossbite, is a common orthodontic discrepancy. The primary goal of maxillary expansion should be to obtain a nearly maximum width increase in the basal bone of the constricted maxilla and to avoid the dental expansion of the anchor teeth. The introduction of miniscrew anchorage-supported rapid maxillary expansion (MARPE) devices has helped increase the feasibility of obtaining nonsurgical transverse correction in late adolescents and young adults with optimum orthopedic effects. However, the success rate of MARPE shows a negative correlation with age. Although MARPE offers an effective method for correcting a transverse skeletal deficiency, given the appliance cost and increased risk for complications, it could present challenges for adult patients and practitioners in daily practice. In this article, current advances in maxillary skeletal expansion are summarized, and a new MARPE concept is introduced. The new MARPE design offers several advantages to other existing methods: (1) it can be installed directly to the patient in the clinical setting with no additional laboratory waiting times. (2) It is purely a bone-borne appliance. (3) The appliance is designed to be placed in the thickest part of the anterior palate to maximize the cortical and trabecular bone support. (4) Allows for bicortical placement of the miniscrews with no perforations in the nasal floor. Finally, (5) offers an esthetic and minimalistic approach to maxillary skeletal expansion in late adolescent and adult patients.

Skeletal Muscle CSE Deficiency Leads to Insulin Resistance in Mice.

Cystathionine-γ-lyase (CSE) is expressed in various tissues and generates H2S via an alternative desulfuration reaction. We sought to explore the functions of skeletal muscle CSE using skeletal muscle conditional knockout CSE (MCSEKO) mice. It was found that body weight, muscle morphology, and exercise capacity were not altered in MCSEKO mice compared with littermate wild-type mice. RNA-seq-based transcriptome analysis showed that 275 genes were differentially regulated in skeletal muscle and multiple signaling pathways including insulin signaling and mTOR, PI3K-AKT, and cGMP-PKG signaling pathways were enriched in MCSEKO mice. The intraperitoneal glucose tolerance test and insulin tolerance test showed that glucose tolerance and insulin sensitivity were reduced in MCSEKO mice. Glucose transporter 4 (GLU4) and PKG-1 expression levels and insulin receptor substrate-1(IRS1)/PI3K/Akt signaling pathway were downregulated whilst the mTOR/S6K/S6 pathway was enhanced in MCSEKO mice. These effects were reversed by the H2S supplement. Aerobic treadmill training significantly promoted glucose tolerance and insulin sensitivity and improved GLU4 and PKG-1 levels, promoted IRS1/PI3K/Akt signaling and suppressed mTOR/S6K/S6 signaling pathway in MCSEKO mice. Our data suggest that skeletal muscle CSE/H2S signaling is critical for the maintenance of insulin sensitivity, which is associated with maintaining the balance in PKG, PI3K/Akt, and mTOR/S6K/S6 signaling pathways in skeletal muscle.