Research Priorities for Childhood Apraxia of Speech: A Long View.

This article introduces the Special Issue: Selected Papers From the 2022 Apraxia Kids Research Symposium. The field of childhood apraxia of speech (CAS) has developed significantly in the past 15 years, with key improvements in understanding of basic biology including genetics, neuroscience, and computational modelling; development of diagnostic tools and methods; diversity of evidence-based interventions with increasingly rigorous experimental designs; and understanding of impacts beyond impairment-level measures. Papers in this special issue not only review and synthesize the some of the substantial progress to date but also present novel findings addressing critical research gaps and adding to the overall body of knowledge.

Pharmacological TRPC6 inhibition improves survival and muscle function in mice with Duchenne muscular dystrophy.

Gene mutations causing loss of dystrophin result in the severe muscle disease known as Duchenne muscular dystrophy (DMD). Despite efforts at genetic repair, DMD therapy remains largely palliative. Loss of dystrophin destabilizes the sarcolemmal membrane, inducing mechanosensitive cation channels to increase calcium entry and promote cell damage and, eventually, muscle dysfunction.

An Investigation of Developmental Coordination Disorder Characteristics in Children With Childhood Apraxia of Speech.

Purpose: Children with childhood apraxia of speech (CAS) evidence a high rate of co-occurring fine and gross motor deficits. This clinical focus article reports a preliminary investigation of characteristics of developmental coordination disorder (DCD), a neurodevelopmental disorder categorized by poor motor proficiency and functional limitations, in this population.

Method: Children with CAS underwent a comprehensive motor evaluation using the Movement Assessment Battery for Children-Second Edition, the Developmental Coordination Disorder Questionnaire, and a developmental history questionnaire to determine if they met criteria for a DCD diagnosis as specified in the (DSM-5).

3D-printed oxygen-releasing scaffolds improve bone regeneration in mice.

Low oxygen (O) diffusion into large tissue engineered scaffolds hinders the therapeutic efficacy of transplanted cells. To overcome this, we previously studied hollow, hyperbarically-loaded microtanks (μtanks) to serve as O reservoirs. To adapt these for bone regeneration, we fabricated biodegradable μtanks from polyvinyl alcohol and poly (lactic-co-glycolic acid) and embedded them to form 3D-printed, porous poly-ε-caprolactone (PCL)-μtank scaffolds.

Development of nation-wide reference intervals using an indirect method and harmonized assays.

Objectives: For many years, clinical laboratories have either verified or estimated reference intervals (RI) for laboratory tests. Those calculations have largely been performed by direct sampling analysis of ostensibly healthy individuals or by post-analysis biochemical screening. Recently however, indirect calculations have come to the forefront as an IFCC endorsed method by using normal and abnormal patient data.

Cardiopulmonary Arrest and Resuscitation in the Prone Patient: An Adult Simulation Case for Internal Medicine Residents.

Introduction: Acute respiratory distress syndrome (ARDS) is present in approximately 10% of ICU admissions and is associated with great morbidity and mortality. Prone ventilation has been shown to improve refractory hypoxemia and mortality in patients with ARDS.

Methods: In this simulation, a 70-year-old male had been transferred to the ICU for ARDS and was undergoing scheduled prone ventilation as part of his care when he experienced a cardiopulmonary arrest secondary to a tension pneumothorax.

Dual Effects of Lipid Metabolism on Osteoblast Function.

The skeleton is a dynamic and metabolically active organ with the capacity to influence whole body metabolism. This newly recognized function has propagated interest in the connection between bone health and metabolic dysfunction. Osteoblasts, the specialized mesenchymal cells responsible for the production of bone matrix and mineralization, rely on multiple fuel sources.

Online Pro-Tobacco Marketing Exposure Is Associated With Dual Tobacco Product Use Among Underage US Students.

Purpose: To understand the effect of pro-tobacco marketing on electronic cigarette and combustible cigarette dual use among US middle and high school students under 18 years of age.

Design: Data were derived from the 2018 National Youth Tobacco Survey, an annual self-administered school-based cross-sectional survey.

Setting: The survey was administered in public and private middle and high schools across the United States.

L-Plastin deficiency produces increased trabecular bone due to attenuation of sealing ring formation and osteoclast dysfunction.

Bone resorption requires the formation of complex, actin-rich cytoskeletal structures. During the early phase of sealing ring formation by osteoclasts, L-plastin regulates actin-bundling to form the nascent sealing zones (NSZ). Here, we show that L-plastin knockout mice produce osteoclasts that are deficient in the formation of NSZs, are hyporesorptive, and make superficial resorption pits in vitro.

The role of osteoblasts in energy homeostasis.

Osteoblasts are specialized mesenchymal cells that synthesize bone matrix and coordinate the mineralization of the skeleton. These cells work in harmony with osteoclasts, which resorb bone, in a continuous cycle that occurs throughout life. The unique function of osteoblasts requires substantial amounts of energy production, particularly during states of new bone formation and remodelling.

Retrospective video analysis of the early speech sound development of infants and toddlers later diagnosed with lateralisation errors.

Although lateralisation errors (LEs) are a common speech sound disorder, no studies have examined their early development. The purpose of this exploratory small-scale investigation was to compare the early (birth-24 months) speech sound development between children later diagnosed with LEs and typically developing children. This was a between-group case-controlled design with six monolingual English-speaking participants.

Connexin43 enhances Wnt and PGE2-dependent activation of β-catenin in osteoblasts.

Connexin43 is an important modulator of many signaling pathways in bone. β-Catenin, a key regulator of the osteoblast differentiation and function, is among the pathways downstream of connexin43-dependent intercellular communication. There are striking overlaps between the functions of these two proteins in bone cells.

Connexin43 regulates osteoprotegerin expression via ERK1/2 -dependent recruitment of Sp1.

In bone, connexin43 expression in cells of the osteoblast lineage plays an important role in restraining osteoclastogenesis and bone resorption. While there is a consensus around the notion that the anti-osteoclastogenic factor, osteoprotegerin, is a driver of this effect, how connexin43 regulates osteoprotegerin gene expression is unclear. Here, we show that loss of connexin43 decreased osteoprotegerin gene expression and reduced ERK1/2 activation.

Effect of patellar luxation on radiographic measurements of tibial plateau angle in small-breed dogs.

OBJECTIVE To determine whether medial patellar luxation would affect radiographic tibial plateau angle (TPA) measurements in small-breed dogs. DESIGN Prospective cross-sectional study. ANIMALS 15 small-breed dogs (25 stifle joints) with grade 2 or 3 medial patellar luxation (5 dogs with unilateral luxation and 10 dogs with bilateral luxation).

Regulation of Osteoblast Metabolism by Wnt Signaling.

Wnt/β-catenin signaling plays a critical role in the achievement of peak bone mass, affecting the commitment of mesenchymal progenitors to the osteoblast lineage and the anabolic capacity of osteoblasts depositing bone matrix. Recent studies suggest that this evolutionarily-conserved, developmental pathway exerts its anabolic effects in part by coordinating osteoblast activity with intermediary metabolism. These findings are compatible with the cloning of the gene encoding the low-density lipoprotein related receptor-5 (LRP5) Wnt co-receptor from a diabetes-susceptibility locus and the now well-established linkage between Wnt signaling and metabolism.

Diminished Canonical β-Catenin Signaling During Osteoblast Differentiation Contributes to Osteopenia in Progeria.

Patients with Hutchinson-Gilford progeria syndrome (HGPS) have low bone mass and an atypical skeletal geometry that manifests in a high risk of fractures. Using both in vitro and in vivo models of HGPS, we demonstrate that defects in the canonical WNT/β-catenin pathway, seemingly at the level of the efficiency of nuclear import of β-catenin, impair osteoblast differentiation and that restoring β-catenin activity rescues osteoblast differentiation and significantly improves bone mass. Specifically, we show that HGPS patient-derived iPSCs display defects in osteoblast differentiation, characterized by a decreased alkaline phosphatase activity and mineralizing capacity.

Effect of Implementing a Bundled-Payment Program for Heart Failure at a Safety-Net Community Hospital.

Safety net community hospitals face unique challenges when entering risk-based contracts. The financial viability of such programs in these settings has not been well studied. This study analyzed a bundled-payment program for congestive heart failure at one such facility.

Connexin43 and the Intercellular Signaling Network Regulating Skeletal Remodeling.

Purpose Of The Review: This review highlights recent developments into how intercellular communication through connexin43 facilitates bone modeling and remodeling.

Recent Findings: Connexin43 is required for both skeletal development and maintenance, particularly in cortical bone, where it carries out multiple functions, including preventing osteoclastogenesis, restraining osteoprogenitor proliferation, promoting osteoblast differentiation, coordinating organized collagen matrix deposition, and maintaining osteocyte survival. Emerging data shows that connexin43 regulates both the exchange of small molecules among osteoblast lineage cells and the docking of signaling proteins to the gap junction, affecting the efficiency of signal transduction.

Defective signaling, osteoblastogenesis and bone remodeling in a mouse model of connexin 43 C-terminal truncation.

In skeletal tissue, loss or mutation of the gap junction protein connexin 43 (Cx43, also known as GJA1) in cells of the osteoblast lineage leads to a profound cortical bone phenotype and defective tissue remodeling. There is mounting evidence in bone cells that the C-terminus (CT) of Cx43 is a docking platform for signaling effectors and is required for efficient downstream signaling. Here, we examined this function, using a mouse model of Cx43 CT-truncation (Gja1 K258Stop).

Deficiency of the intermediate filament synemin reduces bone mass in vivo.

While the type IV intermediate filament protein, synemin, has been shown to play a role in striated muscle and neuronal tissue, its presence and function have not been described in skeletal tissue. Here, we report that genetic ablation of synemin in 14-wk-old male mice results in osteopenia that includes a more than 2-fold reduction in the trabecular bone fraction in the distal femur and a reduction in the cross-sectional area at the femoral middiaphysis due to an attendant reduction in both the periosteal and endosteal perimeter. Analysis of serum markers of bone formation and static histomorphometry revealed a statistically significant defect in osteoblast activity and osteoblast number in vivo.

Thyroglossal Duct Carcinoma in a Cat.

A 14 yr old castrated domestic shorthair cat presented for a fluid-filled structure in the ventral cervical region that had been present for 1 yr and had not resolved after repeated aspiration and drainage. Cervical computed tomography showed an approximately 10 cm, fluid-filled, multilobulated mass located on the ventrolateral right side of the cervical region extending into the thoracic inlet. Cytologic examination of the fluid revealed cystic fluid with evidence of chronic hemorrhage.

Communication of cAMP by connexin43 gap junctions regulates osteoblast signaling and gene expression.

Connexin43 (Cx43) containing gap junctions play an important role in bone homeostasis, yet little is known about the second messengers communicated by Cx43 among bone cells. Here, we used MC3T3-E1 pre-osteoblasts and UMR106 rat osteosarcoma cells to test the hypothesis that cAMP is a second messenger communicated by bone cells through Cx43 containing gap junctions in a manner that is sufficient to impact osteoblast function. Overexpression of Cx43 markedly enhanced the activity of a cAMP-response element driven transcriptional luciferase reporter (CRE-luc) and increased phospho-CREB and phospho-ERK1/2 levels following expression of a constitutively active Gsα or by treatment with prostaglandin E2 (PGE2), 3-Isobutyl-1-methyl xanthine (IBMX) or forskolin.

Drinking Motives and Alcohol Use Behaviors among African American College Students: The Mediating Role of Protective Behavioral Strategies.

Drinking motives are robust predictors of alcohol use behaviors among college students. However, less is known about the link between drinking motives and alcohol use behaviors among African American college students. This study explored the associations between drinking motives and alcohol use behaviors in a sample of 215 African American college students.