Dormant state of quiescent neural stem cells links Shank3 mutation to autism development.

Autism spectrum disorders (ASDs) are common neurodevelopmental disorders characterized by deficits in social interactions and communication, restricted interests, and repetitive behaviors. Despite extensive study, the molecular targets that control ASD development remain largely unclear. Here, we report that the dormancy of quiescent neural stem cells (qNSCs) is a therapeutic target for controlling the development of ASD phenotypes driven by Shank3 deficiency. Using single-cell RNA sequencing (scRNA-seq) and transposase accessible chromatin profiling (ATAC-seq), we find that abnormal epigenetic features including H3K4me3 accumulation due to up-regulation of Kmt2a levels lead to increased dormancy of qNSCs in the absence of Shank3. This result in decreased active neurogenesis in the Shank3 deficient mouse brain. Remarkably, pharmacological and molecular inhibition of qNSC dormancy restored adult neurogenesis and ameliorated the social deficits observed in Shank3-deficient mice. Moreover, we confirmed restored human qNSC activity rescues abnormal neurogenesis and autism-like phenotypes in SHANK3-targeted human NSCs. Taken together, our results offer a novel strategy to control qNSC activity as a potential therapeutic target for the development of autism.

Bifidobacterium bifidum BGN4 and Bifidobacterium longum BORI promotes neuronal rejuvenation in aged mice.

An increasing number of studies have indicated that alterations in gut microbiota affect brain function, including cognition and memory ability, via the gut-brain axis. In this study, we aimed to determine the protective effect of Bifidobacterium bifidum BGN4 (B. bifidum BGN4) and Bifidobacterium longum BORI (B. longum BORI) on age-related brain damage in mice. We found that administration of B. bifidum BGN4 and B. longum BORI effectively elevates brain-derived neurotrophic factor expression which was mediated by increased histone 3 lysine 9 trimethylation. Furthermore, administration of probiotic supplementation reversed the DNA damage and apoptotic response in aged mice and also improved the age-related cognitive and memory deficits of these mice. Taken together, the present study highlights the anti-aging effects of B. bifidum BGN4 and B. longum BORI in the aged brain and their beneficial effects for age-related brain disorders.

Activation of melatonin receptor 1 by CRISPR-Cas9 activator ameliorates cognitive deficits in an Alzheimer's disease mouse model.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the presence of neurotoxic beta-amyloid (Aß) in the brain. Melatonin receptors have been reported to associate with aging and AD, and their expression decreased with the progression of AD. As an alternative to AD treatment, overexpression of melatonin receptors may lead to melatonin-like effects to treat alleviate the symptoms of AD. Here, we successfully activated the type 1 melatonin receptor (Mt1) in vivo brain using a Cas9 activator as a novel AD therapeutic strategy. The Cas9 activator efficiently activated the endogenous Mt1 gene in the brain. Activation of Mt1 via Cas9 activators modulated anti-amyloidogenic and anti-inflammatory roles in 5xFAD AD mice brain. Moreover, activation of Mt1 with the CRISPR/Cas9 activator improved cognitive deficits in an AD model. These results demonstrated the therapeutic potential of melatonin receptor activation via CRISPR/Cas9 activator for AD.

Neural induction of porcine-induced pluripotent stem cells and further differentiation using glioblastoma-cultured medium.

Prior to transplantation, preclinical study of safety and efficacy of neural progenitor cells (NPCs) is needed. Therefore, it is important to generate an efficient in vitro platform for neural cell differentiation in large animal models such as pigs. In this study, porcine-induced pluripotent stem cells (iPSCs) were seeded at high cell density to a neural induction medium containing the dual Sma- and Mad-related protein (SMAD) inhibitors, a TGF-ß inhibitor and BMP4 inhibitor. The dSMADi-derived NPCs showed NPC markers such as PLAG1, NESTIN and VIMENTIN and higher mRNA expression of Sox1 compared to the control. The mRNA expression of HOXB4 was found to significantly increase in the retinoic acid-treated group. NPCs propagated in vitro and generated neurospheres that are capable of further differentiation in neurons and glial cells. Gliobalstoma-cultured medium including injury-related cytokines treated porcine iPSC-NPCs survive well in vitro and showed more neuronal marker expression compared to standard control medium. Collectively, the present study developed an efficient method for production of neural commitment of porcine iPSCs into NPCs.

Nac1 facilitates pluripotency gene activation for establishing somatic cell reprogramming.

Transcription factors play a central role in pluripotency transcription circuitry for establishing pluripotent reprogramming. Master transcription factors Oct4, Nanog, and Sox2 are known to form the core of the pluripotency transcription network. Other transcription factors also play critical roles for further refining the core circuitry for pluripotency in induced pluripotent stem (iPS) cells. Here, we reported that Nac1 interacted with the master pluripotent factors Oct4 and Nanog co-occupies gene promoters bound by these transcriptional factors for establishing pluripotency. Moreover, this interaction coordinates gene expression with H3K4me3 in the somatic cell reprogramming. Knockdown of Nac1 suppressed somatic cell reprogramming, whereas overexpression of Nac1 resulted in enhanced efficiency of induced pluripotent cell generation. Altogether, these results reveal the genome wide role for Nac1 in the contribution to the pluripotency circuitry and the regulation of the establishing pluripotent state.

Tendon Subluxation After Surgical Release of the First Dorsal Compartment in De Quervain Disease.

We aimed to determine whether dorsoulnar incision elevating radial flap and immobilization for the treatment of de Quervain disease have an advantage over simple midline incision and early mobilization, respectively, in terms of tendon subluxation and clinical outcomes. Forty-six patients with de Quervain disease were randomly divided into 2 groups (midline incision vs dorsoulnar incision) and 2 subgroups (immobilization vs early mobilization). Subluxation of intracompartmental tendons was measured in dynamic wrist positions at 12 and 24 weeks using ultrasonography. The DASH (Disabilities of the Arm, Shoulder, and Hand) and visual analog scale scores and grip and pinch strengths were evaluated. At 24 weeks, the tendons were displaced voloradially in wrist volar flexion (1.25 mm in midline incision vs 0.36 mm in dorsoulnar incision, P = 0.001), whereas the tendons were displaced dorsoulnarly in wrist extension (0.95 mm in midline incision vs 1.78 mm in dorsoulnar incision, P = 0.041). There were no significant differences in tendon displacement between early mobilization and immobilization groups. Clinical outcome measures showed no variation between the groups, and no significant correlation occurred with tendon subluxation. Dorsoulnar incision and postoperative immobilization do not have advantage over midline incision and early mobilization, respectively. However, tendon subluxation after release of the first dorsal compartment for de Quervain disease does not affect clinical outcomes.

Inhibition of Drp1 Ameliorates Synaptic Depression, Aß Deposition, and Cognitive Impairment in an Alzheimer's Disease Model.

Excessive mitochondrial fission is a prominent early event and contributes to mitochondrial dysfunction, synaptic failure, and neuronal cell death in the progression of Alzheimer's disease (AD). However, it remains to be determined whether inhibition of excessive mitochondrial fission is beneficial in mammal models of AD. To determine whether dynamin-related protein 1 (Drp1), a key regulator of mitochondrial fragmentation, can be a disease-modifying therapeutic target for AD, we examined the effects of Drp1 inhibitor on mitochondrial and synaptic dysfunctions induced by oligomeric amyloid-ß (Aß) in neurons and neuropathology and cognitive functions in Aß precursor protein/presenilin 1 double-transgenic AD mice. Inhibition of Drp1 alleviates mitochondrial fragmentation, loss of mitochondrial membrane potential, reactive oxygen species production, ATP reduction, and synaptic depression in Aß-treated neurons. Furthermore, Drp1 inhibition significantly improves learning and memory and prevents mitochondrial fragmentation, lipid peroxidation, BACE1 expression, and Aß deposition in the brain in the AD model. These results provide evidence that Drp1 plays an important role in Aß-mediated and AD-related neuropathology and in cognitive decline in an AD animal model. Therefore, inhibiting excessive Drp1-mediated mitochondrial fission may be an efficient therapeutic avenue for AD.SIGNIFICANCE STATEMENT Mitochondrial fission relies on the evolutionary conserved dynamin-related protein 1 (Drp1). Drp1 activity and mitochondria fragmentation are significantly elevated in the brains of sporadic Alzheimer's disease (AD) cases. In the present study, we first demonstrated that the inhibition of Drp1 restored amyloid-ß (Aß)-mediated mitochondrial dysfunctions and synaptic depression in neurons and significantly reduced lipid peroxidation, BACE1 expression, and Aß deposition in the brain of AD mice. As a result, memory deficits in AD mice were rescued by Drp1 inhibition. These results suggest that neuropathology and combined cognitive decline can be attributed to hyperactivation of Drp1 in the pathogenesis of AD. Therefore, inhibitors of excessive mitochondrial fission, such as Drp1 inhibitors, may be a new strategy for AD.

Salusin-ß mediate neuroprotective effects for Parkinson's disease.

Neuropeptides, small peptides found in many mammalian brain, play key roles in communicating with each other to modulate neuronal activity. Here, we reported that endogenous neuropeptide salusin-ß has neuroprotective effects on the midbrain dopamine neurons and can be used as an effective therapeutic treatment for Parkinson's disease (PD). We found that the MrgprA1 receptor mediates the neuroprotective effects of salusin-ß on the midbrain dopamine neurons. Importantly, intranasal administration of salusin-ß in a PD mouse model show the neuroprotection of dopaminergic neurons and increased the survival of midbrain dopamine neurons. Furthermore, inhibition of the salusin-ß receptor, MrgprA1, abolished the neuroprotective effects induced by salusin-ß. Taken together, these results demonstrate the novel role of salusin-ß in the central nervous system and salusin-ß can be used as a novel therapeutic to effectively treat PD.

Modelling APOE ɛ3/4 allele-associated sporadic Alzheimer's disease in an induced neuron.

The recent generation of induced neurons by direct lineage conversion holds promise for in vitro modelling of sporadic Alzheimer's disease. Here, we report the generation of induced neuron-based model of sporadic Alzheimer's disease in mice and humans, and used this system to explore the pathogenic mechanisms resulting from the sporadic Alzheimer's disease risk factor apolipoprotein E (APOE) ɛ3/4 allele. We show that mouse and human induced neurons overexpressing mutant amyloid precursor protein in the background of APOE ɛ3/4 allele exhibit altered amyloid precursor protein (APP) processing, abnormally increased production of amyloid-ß42 and hyperphosphorylation of tau. Importantly, we demonstrate that APOE ɛ3/4 patient induced neuron culture models can faithfully recapitulate molecular signatures seen in APOE ɛ3/4-associated sporadic Alzheimer's disease patients. Moreover, analysis of the gene network derived from APOE ɛ3/4 patient induced neurons reveals a strong interaction between APOE ɛ3/4 and another Alzheimer's disease risk factor, desmoglein 2 (DSG2). Knockdown of DSG2 in APOE ɛ3/4 induced neurons effectively rescued defective APP processing, demonstrating the functional importance of this interaction. These data provide a direct connection between APOE ɛ3/4 and another Alzheimer's disease susceptibility gene and demonstrate in proof of principle the utility of induced neuron-based modelling of Alzheimer's disease for therapeutic discovery.

Editorial Commentary: The Practical Goal of Arthroscopic Osteosynthesis for the Treatment of Unstable Scaphoid Nonunion.

Arthroscopic reduction with osteosynthesis using bone grafting has become a successful alternative to open techniques for the treatment of chronically unstable scaphoid nonunions. Several studies have demonstrated that arthroscopic techniques are safe and reproducible in addition to causing less soft tissue damage and providing promising short- and mid-term results. However, these techniques have limitations in restoring normal carpal alignment, especially in patients with unstable scaphoid nonunion and carpal collapse deformities, although this does not affect the recovery of clinical function. Therefore, the practical goal of arthroscopic technique should be kept in mind when treating unstable scaphoid nonunions.

Does Bowstringing Affect Hand Function in Patients Treated With A1 Pulley Release for Trigger Fingers?: Comparison Between Percutaneous Versus Open Technique.

We aimed to inspect bowstringing after percutaneous and open release of the A1 pulley for trigger digits and its influence on hand function. Sixty-two patients with a resistant trigger digit were randomized to undergo either open release or percutaneous release of the A1 pulley. We quantified bowstringing of the digit using ultrasonography preoperatively and at 12 and 24 weeks after surgery. Pain on a visual analog scale; Disabilities of the Arm, Shoulder, and Hand questionnaire; pinch power; and grip strength were assessed. Bowstringing was significantly increased at 12 weeks after surgery in both groups, and the mean value of the open release group was significantly greater than that of the percutaneous group (2.30 ± 0.58 mm vs 1.46 ± 0.51 mm, respectively; P = 0.035). However, the bowstringing was decreased at 24 weeks without showing significant difference between the 2 groups. The clinical outcomes of each cohort improved significantly, with no difference between the groups at final follow-up. No association was found between bowstringing and any clinical outcome measure. Bowstringing occurred by A1 pulley release with either the percutaneous or open technique does not affect clinical hand function in patients with trigger fingers.

Prominent synovial plicae in radiocapitellar joints as a potential cause of lateral elbow pain: clinico-radiologic correlation.

BACKGROUND: Thickened synovial plicae in the radiocapitellar joint have been reported as a cause of lateral elbow pain. However, few reports regarding diagnosis based on detailed physical examination and magnetic resonance imaging (MRI) findings are available. The aims of this study were to characterize the clinical manifestations of this syndrome and to investigate the clinical outcomes of arthroscopic surgery. METHODS: We analyzed 20 patients who received a diagnosis of plica syndrome and underwent arthroscopic débridement between 2006 and 2011. The diagnosis was based on physical examination and MRI findings. Elbow symptoms were assessed using a visual analog scale for pain; the Mayo Elbow Performance Index; and the Disabilities of the Arm, Shoulder and Hand score at a minimum of 2 years after surgery. The thickness of plicae on MRI was compared with the normal data in the literature. RESULTS: Plicae were located on the anterior side in 1 patient, on the posterior side in 15, and on both sides in 4. Radiocapitellar joint tenderness and pain with terminal extension were observed in 65% of patients. MRI showed enlarged plicae consistent with intraoperative findings. The mean plica thickness on MRI was 3.7 ± 1.0 mm, which was significantly thicker than the normal value. The mean lengths (mediolateral length, 9.4 ± 1.6 mm; anteroposterior length, 8.2 ± 1.7 mm) were also greater than the normal values. The visual analog scale score for pain decreased from 6.3 to 1.0 after surgery. The Mayo Elbow Performance Index and Disabilities of the Arm, Shoulder and Hand scores improved from 66 to 89 and from 26 to 14, respectively. CONCLUSIONS: Specific findings of the physical examination and MRI provide clues for the diagnosis of plica syndrome. Painful symptoms were successfully relieved after arthroscopic débridement.

Generation of Integration-Free Induced Neurons Using Graphene Oxide-Polyethylenimine.

Direct conversion of somatic cells into induced neurons (iNs) without inducing pluripotency has great therapeutic potential for treating central nervous system diseases. Reprogramming of somatic cells to iNs requires the introduction of several factors that drive cell-fate conversion, and viruses are commonly used to deliver these factors into somatic cells. However, novel gene-delivery systems that do not integrate transgenes into the genome are required to generate iNs for safe human clinical applications. In this study, it is investigated whether graphene oxide-polyethylenimine (GO-PEI) complexes are an efficient and safe system for messenger RNA delivery for direct reprogramming of iNs. The GO-PEI complexes show low cytotoxicity, high delivery efficiency, and directly converted fibroblasts into iNs without integrating factors into the genome. Moreover, in vivo transduction of reprogramming factors into the brain with GO-PEI complexes facilitates the production of iNs that alleviated Parkinson's disease symptoms in a mouse model. Thus, the GO-PEI delivery system may be used to safely obtain iNs and could be used to develop direct cell reprogramming-based therapies for neurodegenerative diseases.

Effects of a combination treatment of KD5040 and L-dopa in a mouse model of Parkinson's disease.

BACKGROUND: Although the dopamine precursor L-3, 4-dihydroxyphenylalanine ( l -dopa) remains the gold standard pharmacological therapy for patients with Parkinson's disease (PD), long-term treatment with this drug has been known to result in several adverse effects, including l -dopa-induced dyskinesia (LID). Recently, our group reported that KD5040, a modified herbal remedy, had neuroprotective effects in both in vitro and in vivo models of PD. Thus, the present study investigated whether KD5040 would have synergistic effects with l -dopa and antidyskinetic effects caused by l -dopa as well. METHODS: The effects of KD5040 and l -dopa on motor function, expression levels of substance P (SP) and enkephalin (ENK) in the basal ganglia, and glutamate content in the motor cortex were assessed using behavioral assays, immunohistochemistry, Western blot analyses, and liquid chromatography tandem mass spectrometry in a mouse model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In addition, the antidyskinetic effects of KD5040 on pathological movements triggered by l -dopa were investigated by testing abnormal involuntary movements (AIMs) and measuring the activations of FosB, cAMP-dependent phosphor protein of 32 kDa (DARPP-32), extracellular signal-regulated kinases (ERK), and cAMP response element-binding (CREB) protein in the striatum. RESULTS: KD5040 synergistically improved the motor function when low-dose l -dopa (LL) was co-administered. In addition, it significantly reversed MPTP-induced lowering of SP, improved ENK levels in the basal ganglia, and ameliorated abnormal reduction in glutamate content in the motor cortex. Furthermore, KD5040 significantly lowered AIMs and controlled abnormal levels of striatal FosB, pDARPP-32, pERK, and pCREB induced by high-dose l -dopa. CONCLUSIONS: KD5040 lowered the effective dose of l -dopa and alleviated LID. These findings suggest that KD5040 may be used as an adjunct therapy to enhance the efficacy of l -dopa and alleviate its adverse effects in patients with PD.

Topographical Anatomy of the Distal Ulna Attachment of the Radioulnar Ligament.

PURPOSE: The deep component of the distal radioulnar ligament provides translational stability and rotational guidance to the forearm. However, controversy exists regarding the importance of this structure as well as the nature of its attachment to the distal ulna. We aimed to evaluate the topographic anatomy of the distal ulna attachment of both the superficial and the deep components of the radioulnar ligament and to assess the relationship between its internal and its external morphometry. METHODS: Thirteen human distal ulnae attached by ulnar part of the distal radioulnar ligament were scanned using micro-computed tomography and reconstructed in 3 dimensions. In addition, the distal radioulnar ligaments were examined under polarized light microscopy to determine the histological characteristics of collagen contained within the ligaments. RESULTS: The deep limbs have broad marginal insertions at the fovea, whereas the superficial limbs have a circular and condensed insertion to the ulnar styloid. The center of the deep limb was separated from the base of the ulnar styloid by a mean of 2.0 ± 0.76 mm, and this distance was positively correlated with the width of the ulnar styloid. The mean distance between the center of the ulnar head and the center of the fovea was 2.4 ± 0.58 mm. The proportion of collagen type I was lower in the deep limb than in the superficial limb. CONCLUSIONS: This new observation of the footprint of the radioulnar ligament in the distal ulna indicates that the deep limb may serve as an internal capsular ligament of the distal radioulnar joint, whereas the superficial limb as the external ligament. CLINICAL RELEVANCE: Knowledge of the topographic anatomy of the radioulnar ligament's attachment to the distal ulna may provide a better understanding of distal radioulnar ligament-related pathologies.

MPTP-induced vulnerability of dopamine neurons in A53T α-synuclein overexpressed mice with the potential involvement of DJ-1 downregulation.

Familial Parkinson's disease (PD) has been linked to point mutations and duplication of the α-synuclein (α-syn) gene. Mutant α-syn expression increases the vulnerability of neurons to exogenous insults. In this study, we developed a new PD model in the transgenic mice expressing mutant hemizygous (hemi) or homozygous (homo) A53T α-synuclein (α-syn Tg) and their wildtype (WT) littermates by treatment with sub-toxic (10 mg/kg, i.p., daily for 5 days) or toxic (30 mg/kg, i.p., daily for 5 days) dose of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Tyrosine hydroxylase and Bcl-2 levels were reduced in the α-syn Tg but not WT mice by sub-toxic MPTP injection. In the adhesive removal test, time to remove paper was significantly increased only in the homo α-syn Tg mice. In the challenging beam test, the hemi and homo α-syn Tg mice spent significantly longer time to traverse as compared to that of WT group. In order to find out responsible proteins related with vulnerability of mutant α-syn expressed neurons, DJ-1 and ubiquitin enzyme expressions were examined. In the SN, DJ-1 and ubiquitin conjugating enzyme, UBE2N, levels were significantly decreased in the α-syn Tg mice. Moreover, A53T α-syn overexpression decreased DJ-1 expression in SH-SY5Y cells. These findings suggest that the vulnerability to oxidative injury such as MPTP of A53T α-syn mice can be explained by downregulation of DJ-1.

The Outcomes of Arthroscopic Repair Versus Debridement for Chronic Unstable Triangular Fibrocartilage Complex Tears in Patients Undergoing Ulnar-Shortening Osteotomy.

PURPOSE: The aim of this study was to compare the results of arthroscopic peripheral repair (AR) and arthroscopic debridement (AD) for the treatment of chronic unstable triangular fibrocartilage complex (TFCC) tears in ulnar-positive patients undergoing ulnar-shortening osteotomy (USO). METHODS: A total of 31 patients who underwent arthroscopic treatments combined with USO for unstable TFCC tears and were followed-up at a minimum of 24 months were included in this retrospective cohort study. Fifteen patients were treated with AR, and 16 patients were treated with AD while at the same time undergoing a USO. Outcome measures included wrist range of motion, grip strength, Disabilities of the Arm, Shoulder, and Hand (DASH) and Patient-Rated Wrist Evaluation (PRWE) scores, and overall outcomes according to the modified Mayo wrist scoring system. In addition, a stress test to assess distal radioulnar joint (DRUJ) stability was performed before and after surgery to compare the 2 cohorts. RESULTS: Both respective cohorts showed significant improvements in grip strength and subjective scores at the final follow-up. Grip strength, DASH, and PRWE scores were better in the AR group than in the AD group. The recovery rate from DRUJ instability observed during the preoperative examination was superior in the AR group. CONCLUSIONS: Both AD and AR of the TFCC combined with USO are reliable procedures with satisfactory clinical outcomes for unstable TFCC tears in ulnar-positive patients. However, AR of the TFCC is suggested if DRUJ stability is concomitantly compromised. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

p53 signalling mediates acupuncture-induced neuroprotection in Parkinson's disease.

Parkinson's disease (PD) is a progressive neurodegenerative disorder associated with a selective loss of dopamine (DA) neurons in the substantia nigra of the midbrain. Recently, it has been demonstrated that acupuncture treatment has protective effects in PD. However, to date, the molecular mechanisms underlying acupuncture's effect on DA neuronal protection are largely unknown. In this study, we report that p53 signalling mediates the protective effects of acupuncture treatment in a mouse model of PD. We found that the acupuncture treatment in the mouse PD model results in significant recovery to the normal in the context of behaviour and molecular signatures. We found that the gene network associated with p53 signalling is closely involved in the protective effects of acupuncture treatment in PD. Consistent with this idea, we demonstrated that specific knockout of the p53 gene in the midbrain DA neurons abrogates the acupuncture induced protective effects in the mouse model of PD. Thus, these data suggest that p53 signalling mediates the protective effects of acupuncture treatment in PD.

Sonographic Quantification of Pronator Quadratus Activity During Gripping Effort.

OBJECTIVES: The aim of this study was to obtain quantitative data related to the activity of each head of the pronator quadratus based on dynamic sonographic parameters during gripping effort and to assess their relationships with grip and pronation strengths. METHODS: The forearms of 33 healthy volunteers were evaluated at 5 positions of axial rotation (full supination, 45° supination, neutral, 45° pronation, and full pronation). Echogenic intensity ratios and muscle thicknesses of each head of the pronator quadratus were measured from transverse cross-sectional sonograms obtained during maximal grip and release. Grip strengths and maximal isokinetic pronation torques at 90°/s and 360°/s were evaluated as strength parameters and correlated with sonographic measures. RESULTS: Echogenic intensity ratios of both heads significantly decreased during power grip (P ≤ .002). Changes in echogenic intensity ratios of the superficial head were greater when the forearm was pronated compared to supination (P < .001), whereas changes in echogenic intensity ratios of the deep head were constant at all forearm positions. Muscle thicknesses of the superficial head maximally increased at the neutral position during power grip (P < .001), whereas muscle thicknesses of the deep head did not change. There were significant negative correlations between grip strength and echogenic intensity ratios of both heads at all respective forearm positions (P ≤ .048). Pronation torque was significantly correlated with echogenic intensity ratios of the superficial head at all forearm positions and the deep head at 45° and full pronation positions (P ≤ .034). CONCLUSIONS: The data revealed that the superficial head of the pronator quadratus more actively contracts when the forearm is in pronation, whereas the deep head constantly contracts at all positions. This study suggests that both heads of the pronator quadratus also play a role in grip strength, but the superficial head contributes more to pronation strength.