Cryo-EM structure of the inhibited (10S) form of myosin II.

Myosin II is the motor protein that enables muscle cells to contract and nonmuscle cells to move and change shape1. The molecule has two identical heads attached to an elongated tail, and can exist in two conformations: 10S and 6S, named for their sedimentation coefficients2,3. The 6S conformation has an extended tail and assembles into polymeric filaments, which pull on actin filaments to generate force and motion. In 10S myosin, the tail is folded into three segments and the heads bend back and interact with each other and the tail3-7, creating a compact conformation in which ATPase activity, actin activation and filament assembly are all highly inhibited7,8. This switched-off structure appears to function as a key energy-conserving storage molecule in muscle and nonmuscle cells9-12, which can be activated to form functional filaments as needed13-but the mechanism of its inhibition is not understood. Here we have solved the structure of smooth muscle 10S myosin by cryo-electron microscopy with sufficient resolution to enable improved understanding of the function of the head and tail regions of the molecule and of the key intramolecular contacts that cause inhibition. Our results suggest an atomic model for the off state of myosin II, for its activation and unfolding by phosphorylation, and for understanding the clustering of disease-causing mutations near sites of intramolecular interaction.

Fast skeletal myosin-binding protein-C regulates fast skeletal muscle contraction.

Fast skeletal myosin-binding protein-C (fMyBP-C) is one of three MyBP-C paralogs and is predominantly expressed in fast skeletal muscle. Mutations in the gene that encodes fMyBP-C, MYBPC2, are associated with distal arthrogryposis, while loss of fMyBP-C protein is associated with diseased muscle. However, the functional and structural roles of fMyBP-C in skeletal muscle remain unclear. To address this gap, we generated a homozygous fMyBP-C knockout mouse (C2-/-) and characterized it both in vivo and in vitro compared to wild-type mice. Ablation of fMyBP-C was benign in terms of muscle weight, fiber type, cross-sectional area, and sarcomere ultrastructure. However, grip strength and plantar flexor muscle strength were significantly decreased in C2-/- mice. Peak isometric tetanic force and isotonic speed of contraction were significantly reduced in isolated extensor digitorum longus (EDL) from C2-/- mice. Small-angle X-ray diffraction of C2-/- EDL muscle showed significantly increased equatorial intensity ratio during contraction, indicating a greater shift of myosin heads toward actin, while MLL4 layer line intensity was decreased at rest, indicating less ordered myosin heads. Interfilament lattice spacing increased significantly in C2-/- EDL muscle. Consistent with these findings, we observed a significant reduction of steady-state isometric force during Ca2+-activation, decreased myofilament calcium sensitivity, and sinusoidal stiffness in skinned EDL muscle fibers from C2-/- mice. Finally, C2-/- muscles displayed disruption of inflammatory and regenerative pathways, along with increased muscle damage upon mechanical overload. Together, our data suggest that fMyBP-C is essential for maximal speed and force of contraction, sarcomere integrity, and calcium sensitivity in fast-twitch muscle.

The myosin interacting-heads motif present in live tarantula muscle explains tetanic and posttetanic phosphorylation mechanisms.

Striated muscle contraction involves sliding of actin thin filaments along myosin thick filaments, controlled by calcium through thin filament activation. In relaxed muscle, the two heads of myosin interact with each other on the filament surface to form the interacting-heads motif (IHM). A key question is how both heads are released from the surface to approach actin and produce force. We used time-resolved synchrotron X-ray diffraction to study tarantula muscle before and after tetani. The patterns showed that the IHM is present in live relaxed muscle. Tetanic contraction produced only a very small backbone elongation, implying that mechanosensing-proposed in vertebrate muscle-is not of primary importance in tarantula. Rather, thick filament activation results from increases in myosin phosphorylation that release a fraction of heads to produce force, with the remainder staying in the ordered IHM configuration. After the tetanus, the released heads slowly recover toward the resting, helically ordered state. During this time the released heads remain close to actin and can quickly rebind, enhancing the force produced by posttetanic twitches, structurally explaining posttetanic potentiation. Taken together, these results suggest that, in addition to stretch activation in insects, two other mechanisms for thick filament activation have evolved to disrupt the interactions that establish the relaxed helices of IHMs: one in invertebrates, by either regulatory light-chain phosphorylation (as in arthropods) or Ca2+-binding (in mollusks, lacking phosphorylation), and another in vertebrates, by mechanosensing.

Myofibril orientation as a metric for characterizing heart disease.

Myocyte disarray is a hallmark of many cardiac disorders. However, the relationship between alterations in the orientation of individual myofibrils and myofilaments to disease progression has been largely underexplored. This oversight has predominantly been because of a paucity of methods for objective and quantitative analysis. Here, we introduce a novel, less-biased approach to quantify myofibrillar and myofilament orientation in cardiac muscle under near-physiological conditions and demonstrate its superiority as compared with conventional histological assessments. Using small-angle x-ray diffraction, we first investigated changes in myofibrillar orientation at increasing sarcomere lengths in permeabilized, relaxed, wild-type mouse myocardium from the left ventricle by assessing the angular spread of the 1,0 equatorial reflection (angle σ). At a sarcomere length of 1.9 µm, the angle σ was 0.23 ± 0.01 rad, decreased to 0.19 ± 0.01 rad at a sarcomere length of 2.1 µm, and further decreased to 0.15 ± 0.01 rad at a sarcomere length of 2.3 µm (p < 0.0001). Angle σ was significantly larger in R403Q, a MYH7 hypertrophic cardiomyopathy model, porcine myocardium (0.24 ± 0.01 rad) compared with wild-type myocardium (0.14 ± 0.005 rad; p < 0.0001), as well as in human heart failure tissue (0.19 ± 0.006 rad) when compared with nonfailing samples (0.17 ± 0.007 rad; p = 0.01). These data indicate that diseased myocardium suffers from greater myofibrillar disorientation compared with healthy controls. Finally, we showed that conventional, histology-based analysis of disarray can be subject to user bias and/or sampling error and lead to false positives. Our method for directly assessing myofibrillar orientation avoids the artifacts introduced by conventional histological approaches that assess myocyte orientation and only indirectly evaluate myofibrillar orientation, and provides a precise and objective metric for phenotypically characterizing myocardium. The ability to obtain excellent x-ray diffraction patterns from frozen human myocardium provides a new tool for investigating structural anomalies associated with cardiac diseases.

Amino terminus of cardiac myosin binding protein-C regulates cardiac contractility.

Phosphorylation of cardiac myosin binding protein-C (cMyBP-C) regulates cardiac contraction through modulation of actomyosin interactions mediated by the protein's amino terminal (N')-region (C0-C2 domains, 358 amino acids). On the other hand, dephosphorylation of cMyBP-C during myocardial injury results in cleavage of the 271 amino acid C0-C1f region and subsequent contractile dysfunction. Yet, our current understanding of amino terminus region of cMyBP-C in the context of regulating thin and thick filament interactions is limited. A novel cardiac-specific transgenic mouse model expressing cMyBP-C, but lacking its C0-C1f region (cMyBP-C∆C0-C1f), displayed dilated cardiomyopathy, underscoring the importance of the N'-region in cMyBP-C. Further exploring the molecular basis for this cardiomyopathy, in vitro studies revealed increased interfilament lattice spacing and rate of tension redevelopment, as well as faster actin-filament sliding velocity within the C-zone of the transgenic sarcomere. Moreover, phosphorylation of the unablated phosphoregulatory sites was increased, likely contributing to normal sarcomere morphology and myoarchitecture. These results led us to hypothesize that restoration of the N'-region of cMyBP-C would return actomyosin interaction to its steady state. Accordingly, we administered recombinant C0-C2 (rC0-C2) to permeabilized cardiomyocytes from transgenic, cMyBP-C null, and human heart failure biopsies, and we found that normal regulation of actomyosin interaction and contractility was restored. Overall, these data provide a unique picture of selective perturbations of the cardiac sarcomere that either lead to injury or adaptation to injury in the myocardium.

Interacting-heads motif has been conserved as a mechanism of myosin II inhibition since before the origin of animals.

Electron microscope studies have shown that the switched-off state of myosin II in muscle involves intramolecular interaction between the two heads of myosin and between one head and the tail. The interaction, seen in both myosin filaments and isolated molecules, inhibits activity by blocking actin-binding and ATPase sites on myosin. This interacting-heads motif is highly conserved, occurring in invertebrates and vertebrates, in striated, smooth, and nonmuscle myosin IIs, and in myosins regulated by both Ca2+ binding and regulatory light-chain phosphorylation. Our goal was to determine how early this motif arose by studying the structure of inhibited myosin II molecules from primitive animals and from earlier, unicellular species that predate animals. Myosin II from Cnidaria (sea anemones, jellyfish), the most primitive animals with muscles, and Porifera (sponges), the most primitive of all animals (lacking muscle tissue) showed the same interacting-heads structure as myosins from higher animals, confirming the early origin of the motif. The social amoeba Dictyostelium discoideum showed a similar, but modified, version of the motif, while the amoeba Acanthamoeba castellanii and fission yeast (Schizosaccharomyces pombe) showed no head-head interaction, consistent with the different sequences and regulatory mechanisms of these myosins compared with animal myosin IIs. Our results suggest that head-head/head-tail interactions have been conserved, with slight modifications, as a mechanism for regulating myosin II activity from the emergence of the first animals and before. The early origins of these interactions highlight their importance in generating the inhibited (relaxed) state of myosin in muscle and nonmuscle cells.

Is Thumb Proprioception Decreased in Patients With Trapeziometacarpal Joint Osteoarthritis?

Proprioception is thought to be essential for normal joint homeostasis, and its decreased function has been associated with an increased risk of joint diseases. However, only a few studies have been performed on the association between proprioceptive function in the trapeziometacarpal joint (TMCJ) and osteoarthritis. The purpose of this study was to compare TMCJ proprioceptive function in elderly women with radiographic TMCJ osteoarthritis relative to age-matched control women without osteoarthritis. We enrolled 19 women (mean age, 66 years) with symptomatic, radiographic Eaton and Littler grade 2, 3, and 4 TMCJ osteoarthritis and 19 age-matched control women without osteoarthritis. We evaluated thumb proprioception by using a joint-position reproduction test and compared the reposition error (RE) between the groups. We carried out a multivariate analysis for factors potentially associated with increased RE, such as age, body mass index, hand dominance, the presence of diabetes, pain level, and the presence of osteoarthritis. Also, a logistic regression analysis was performed for factors associated with the occurrence of TMCJ osteoarthritis. Patients with TMCJ osteoarthritis had greater RE than did the control patients in the joint-position reproduction test at 20°, 30°, and 40° of thumb palmar abduction. The multivariate analysis indicated that increased RE was associated with the presence of osteoarthritis, but not with the other factors assessed. The occurrence of TMCJ osteoarthritis was associated with increased RE at 20°, 30°, and 40° of thumb palmar abduction. This study showed that decreased proprioceptive function was associated with the presence of osteoarthritis in the TMCJ, although the causality remains unknown. Further studies on the role of proprioception in the pathogenesis of TMCJ osteoarthritis and the potential role of its training for disease prevention or treatment are required.

Postoperative Intravenous Iron Supplementation Does Not Improve Hemoglobin Level and Transfusion Rate Following Staged Bilateral Total Knee Arthroplasty.

BACKGROUND: We determined whether postoperative intravenous (IV) iron supplementation could reduce transfusion rate in patients undergoing staged bilateral total knee arthroplasty (TKA). Furthermore, we examined whether hemoglobin (Hb) levels and iron profile differed between patients with and without postoperative IV iron supplementation. METHODS: This retrospective, comparative cohort study included 126 patients who underwent primary staged bilateral TKA during a single hospitalization. The second TKA was performed at a week's interval. Group iron (n = 65) received IV iron immediately after each surgery, while patients in group no-iron (n = 61) received no iron after surgery. Transfusion rate, change in Hb levels, and iron profile including serum iron, ferritin, total iron binding capacity, and transferrin saturation were evaluated preoperatively; on postoperative days 1, 2, and 4 after the first TKA; and postoperative days 1, 2, 4, and 7, 6 weeks, and 3 months after the second TKA. RESULTS: There were no significant differences in Hb levels and transfusion rate following staged bilateral TKA between patients with and without postoperative IV iron supplementation although serum iron profiles were improved in patients with IV iron supplementation. CONCLUSION: Postoperative IV iron supplementation immediately after acute blood loss caused by TKA was not effective in improving the transfusion rate. Therefore, surgeons should use protocols other than postoperative IV iron supplementation for reducing the transfusion rate in patients undergoing staged bilateral TKA in a single hospitalization. LEVEL OF EVIDENCE: III.

Sleep and cognitive decline: A prospective nondemented elderly cohort study.

OBJECTIVE: To investigate sleep disturbances that induce cognitive changes over 4 years in nondemented elderlies. METHODS: Data were acquired from a nationwide, population-based, prospective cohort of Korean elderlies (2,238 normal cognition [NC] and 655 mild cognitive impairment [MCI]). At baseline and 4-year follow-up assessments, sleep-related parameters (midsleep time, sleep duration, sleep latency, subjective sleep quality, sleep efficiency, and daytime dysfunction) and cognitive status were measured using the Pittsburgh Sleep Quality Index and Consortium to Establish a Registry for Alzheimer's Disease Assessment, respectively. We used logistic regression models adjusted for covariates including age, sex, education, apolipoprotein E genotype, Geriatric Depression Scale, Cumulative Illness Rating Scale, and physical activity. RESULTS: In participants with NC, long sleep latency (>30 minutes), long sleep duration (≥7.95 hours), and late midsleep time (after 3:00 am) at baseline were related to the risk of cognitive decline at 4-year follow-up assessment; odds ratio (OR) was 1.40 for long sleep latency, 1.67 for long sleep duration, and 0.61 for late midsleep time. These relationships remained significant when these variables maintained their status throughout the follow-up period. Newly developed long sleep latency also doubled the risk of cognitive decline. In those with MCI, however, only long sleep latency reduced the chance of reversion to NC (OR = 0.69). INTERPRETATION: As early markers of cognitive decline, long sleep latency can be used for elderlies with NC or MCI, whereas long sleep duration and relatively early sleep time might be used for cognitively normal elderlies only. Ann Neurol 2018;83:472-482.

Gait Variability Can Predict the Risk of Cognitive Decline in Cognitively Normal Older People.

BACKGROUND: The aim of this study was to investigate the association of gait speed and gait variability, an index of how much gait parameters, such as step time, fluctuate step-to-step, with risk of cognitive decline in cognitively normal elderly individuals. While high gait variability is emerging as an early indicator of dementing illnesses, there is little research on whether high gait variability predicts cognitive decline in cognitively normal elderly who have no evidence of cognitive impairment. METHODS: In this 4-year prospective cohort study on 91 community-dwelling cognitively normal elderly individuals without cerebral ischemic burden or Parkinsonism, we evaluated gait speed and step time variability using a tri-axial accelerometer placed on the center of body mass, and diagnosed mild cognitive impairment (MCI) according to the International Working Group on MCI. We performed Kaplan-Meier analysis with consecutive log-rank testing for MCI-free survival by cohort-specific tertiles of gait speed; hazard ratios (HR) of incident MCI were estimated using Cox proportional hazards regression analysis adjusted for age, sex, education level, Cumulative Illness Rating Scale score, GDS score, and presence of the apolipoprotein E ε4 allele. RESULTS: Out of the 91 participants in the baseline assessment, 87 completed one or more 2-year follow-up assessments, and the median duration of follow-up was 47.1 months. Kaplan-Meier curves of incident MCI show evident differences in risk by gait variability group (χ2 = 9.64, p = 0.002, log-rank test). Mean MCI-free survival in the high variability group was 12% shorter than in the mid-to-low tertile group (47.4 ± 1.74 [SD] vs. 54.04 ± 0.52 months), while it was comparable between gait speed groups (51.59 ± 0.70 vs. 50.64 ± 1.77 months; χ2 = 1.16, p = 0.281). In multivariate analysis, subjects with high gait variability showed about 12-fold higher risk of MCI (HR = 11.97, 95% CI = 1.29-111.37) than those with mid-to-low variability. However, those with slow gait speed showed comparable MCI risk to those with mid-to-high speed (HR = 5.04, 95% CI = 0.53-48.18). CONCLUSIONS: Gait variability may be a better predictor of cognitive decline than gait speed in cognitively normal elderly individuals without cerebral ischemic burden or Parkinsonism.

N-glycan maturation is crucial for cytokinin-mediated development and cellulose synthesis in Oryza sativa.

To explore the physiological significance of N-glycan maturation in the plant Golgi apparatus, gnt1, a mutant with loss of N-acetylglucosaminyltransferase I (GnTI) function, was isolated in Oryza sativa. gnt1 exhibited complete inhibition of N-glycan maturation and accumulated high-mannose N-glycans. Phenotypic analyses revealed that gnt1 shows defective post-seedling development and incomplete cell wall biosynthesis, leading to symptoms such as failure in tiller formation, brittle leaves, reduced cell wall thickness, and decreased cellulose content. The developmental defects of gnt1 ultimately resulted in early lethality without transition to the reproductive stage. However, callus induced from gnt1 seeds could be maintained for periods, although it exhibited a low proliferation rate, small size, and hypersensitivity to salt stress. Shoot regeneration and dark-induced leaf senescence assays indicated that the loss of GnTI function results in reduced sensitivity to cytokinin in rice. Reduced expression of A-type O. sativa response regulators that are rapidly induced by cytokinins in gnt1 confirmed that cytokinin signaling is impaired in the mutant. These results strongly support the proposed involvement of N-glycan maturation in transport as well as in the function of membrane proteins that are synthesized via the endomembrane system.

Structure, sarcomeric organization, and thin filament binding of cardiac myosin-binding protein-C.

Myosin-binding protein-C (MyBP-C) is an accessory protein of the myosin filaments of vertebrate striated muscle. In the heart, it plays a key role in modulating contractility in response to ß-adrenergic stimulation. Mutations in the cardiac isoform (cMyBP-C) are a leading cause of inherited hypertrophic cardiomyopathy. Understanding cMyBP-C function and its role in disease requires knowledge of the structure of the molecule, its organization in the sarcomere, and its interactions with other sarcomeric proteins. Here we review the main structural features of this modular, elongated molecule and the properties of some of its key domains. We describe observations suggesting that the bulk of the molecule extends perpendicular to the thick filament, enabling it to reach neighboring thin filaments in the sarcomere. We review structural and functional evidence for interaction of its N-terminal domains with actin and how this may modulate thin filament activation. We also discuss the effects that phosphorylation of cMyBP-C has on some of these structural features and how this might relate to cMyBP-C function in the beating heart.

Functional characterization of ObgC in ribosome biogenesis during chloroplast development.

The Spo0B-associated GTP-binding protein (Obg) GTPase, essential for bacterial viability, is also conserved in eukaryotes, but its primary role in eukaryotes remains unknown. Here, our functional characterization of Arabidopsis and rice obgc mutants strongly underlines the evolutionarily conserved role of eukaryotic Obgs in organellar ribosome biogenesis. The mutants exhibited a chlorotic phenotype, caused by retarded chloroplast development. A plastid DNA macroarray revealed a plastid-encoded RNA polymerase (PEP) deficiency in an obgc mutant, caused by incompleteness of the PEP complex, as its western blot exhibited reduced levels of RpoA protein, a component of PEP. Plastid rRNA profiling indicated that plastid rRNA processing is defective in obgc mutants, probably resulting in impaired ribosome biogenesis and, in turn, in reduced levels of RpoA protein. RNA co-immunoprecipitation revealed that ObgC specifically co-precipitates with 23S rRNA in vivo. These findings indicate that ObgC functions primarily in plastid ribosome biogenesis during chloroplast development. Furthermore, complementation analysis can provide new insights into the functional modes of three ObgC domains, including the Obg fold, G domain and OCT.

Ultrafast direct imaging using a single high harmonic burst.

We have demonstrated ultrafast direct soft x-ray microscopy imaging. Microscopy images were acquired using an objective zone plate and a single strong high harmonic burst generated from He in a two-color laser field. This zone-plate-based microscopy system delivered real-space images directly without any data processing. The spatial resolution of the microscope was estimated to be about 140 nm from the image of nanoscale grating patterns.

Dispersion and reaggregation of nanoparticles in the polypropylene copolymer foamed by supercritical carbon dioxide.

For the preparation of nanocomposites, we conducted environmentally benign foaming processing on polypropylene (PP) copolymer/clay nanocomposites via a batch process in an autoclave. We investigated the dispersion and the exfoliation of the nanoclay particles. Full exfoliation was achieved by the foamability of the matrix PP copolymer using supercritical carbon dioxide (sc CO2) and subcritical carbon dioxide (sub CO2). More and smaller cells were observed when the clay was blended as heterogeneous nuclei and sc CO2 was used. Small angle X-ray scattering showed that highly dispersed states (exfoliation) of the clay particles were obtained by the foaming process. Since the clay particles provided more nucleating sites for the foaming of the polymer, a well dispersed (or fully exfoliated) nanocomposite exhibited a higher cell density and a smaller cell size at the same clay particle concentration. Expansion of the adsorbed CO2 facilitated the exfoliation of the clay platelets; thus, sc CO2 at lower temperature was more efficient for uniform foaming-cell production. Fully dispersed clay platelets were, however, re-aggregated when subjected to a further melting processing. The reprocessed nanocomposites still had some exfoliated platelets as well as some aggregated intercalates. The dual role of the nanoclay particles as foaming nucleus and a crystallization nucleus was confirmed by cell growth observation and nonisothermal crystallization kinetics analysis. A low foaming temperature and a high saturation pressure were more favorable for obtaining a uniform foam. The PP copolymer was found to be foamed more easily than polypropylene. A small amount of other olefin moieties in the backbone of the polymer facilitated better foamability than the neat polypropylene.

The structural and functional integrities of porcine myocardium are mostly preserved by cryopreservation.

Structural and functional studies of heart muscle are important to gain insights into the physiological bases of cardiac muscle contraction and the pathological bases of heart disease. While fresh muscle tissue works best for these kinds of studies, this is not always practical to obtain, especially for heart tissue from large animal models and humans. Conversely, tissue banks of frozen human hearts are available and could be a tremendous resource for translational research. It is not well understood, however, how liquid nitrogen freezing and cryostorage may impact the structural integrity of myocardium from large mammals. In this study, we directly compared the structural and functional integrity of never-frozen to previously frozen porcine myocardium to investigate the consequences of freezing and cryostorage. X-ray diffraction measurements from hydrated tissue under near-physiological conditions and electron microscope images from chemically fixed porcine myocardium showed that prior freezing has only minor effects on structural integrity of the muscle. Furthermore, mechanical studies similarly showed no significant differences in contractile capabilities of porcine myocardium with and without freezing and cryostorage. These results demonstrate that liquid nitrogen preservation is a practical approach for structural and functional studies of myocardium.

Open Foveal Repair of the Triangular Fibrocartilage Complex Tears Associated with Symptomatic Ulnar Styloid Non-union.

Background: Symptomatic ulnar styloid non-union can be treated by excision of the ulnar styloid fragment. For combined triangular fibrocartilage complex (TFCC) tears, several repair techniques such as arthroscopic repair, open repair to the fracture site or reconstruction using a tendon graft have been introduced. This study reports the technique and outcomes of open foveal repair of the TFCC with excision of the ulnar styloid fragment in patients with symptomatic ulnar styloid non-union and distal radioulnar joint (DRUJ) instability. Methods: Consecutive patients with symptomatic ulnar styloid non-union with TFCC tears and DRUJ instability who underwent excision of the ulnar styloid fragment and open foveal repair of the TFCC were retrospectively reviewed. After excising the ulnar styloid fragment, a capsular window was created between the triquetrum and TFCC, followed by attaching the TFCC to the fovea using three sutures through a bone tunnel from the ulnar cortex to the fovea. Additional ulnar shortening osteotomies were performed in patients with positive ulnar variance and ulnar impaction test. The outcomes were evaluated in terms of DRUJ stability and the Quick Disabilities of the Arm, Shoulder and Hand (DASH) scores. Results: In total, 21 patients with a mean age of 40 were enrolled in the study. All patients demonstrated DRUJ stability at a mean follow-up duration of 14 months. The mean Quick DASH score significantly improved from 18.9 ± 11.7 to 2.5 ± 4.1 (p < 0.05). Eleven patients underwent combined ulnar shortening osteotomies, and no difference in the Quick DASH score was found between patients who underwent ulnar shortening osteotomy and those who did not. Conclusions: This study demonstrates that open foveal repair of the TFCC with ulnar styloid fragment excision is an effective strategy to surgically treat patients with symptomatic ulnar styloid non-union with TFCC tear and DRUJ instability. Level of Evidence: Level III (Therapeutic).

Radiocapitellar incongruity of the radial head in magnetic resonance imaging correlates with pathologic changes of the lateral elbow stabilizers in lateral epicondylitis.

OBJECTIVE: Post-traumatic posterolateral rotatory instability (PLRI) can be shown as radiocapitellar incongruity or posterior translation (PT) of the radial head in magnetic resonance imaging (MRI). We aimed to evaluate whether PT correlated with pathologic changes of lateral elbow stabilizers in patients with lateral epicondylitis. MATERIALS AND METHODS: In MRIs of 160 patients with lateral epicondylitis, we measured PT of the radial head in the sagittal images. We qualitatively graded five lesions of the lateral elbow structures that included common extensor tendon (CET) lesion (grade 1-3), lateral collateral ligament complex (LCLC) insufficiency (grade 0-2), and absence or presence of bone marrow signal change, osteochondral lesion, and calcification. We analyzed whether the PT correlated with pathologic changes of the lateral elbow stabilizers and evaluated the diagnostic value of the PT for severe lesions. RESULTS: The average PT was 1.9 mm. The PT correlated with both the CET lesion (p < 0.001) and LCLC insufficiency (p < 0.001). The optimal cutoff values of the PT for grade 3 CET lesion and grade 2 LCLC lesion were 2.6 and 2.8 mm, respectively. When potential PLRI was defined as the PT of > 3.4mm as suggested for post-traumatic PLRI, 21 patients had potential PLRI. The positive predictive values of the PT > 3.4mm were 76% for grade 3 CET lesions and 67% for grade 2 LCLC insufficiency. CONCLUSION: This study demonstrates that PT of the radial head correlates with pathological changes of the lateral elbow stabilizers. As radiocapitellar incongruity is easy to measure quantitatively, it can be used for screening potential PLRI in patients with lateral epicondylitis.

Screening major depressive disorder using vocal acoustic features in the elderly by sex.

BACKGROUND: Vocal acoustic features are potential biomarkers of elderly depression. Previous automated diagnostic tests for depression have employed unstandardized speech samples, and few studies have considered differences in voice reactivity. We aimed to develop a voice-based screening test for depression measuring vocal acoustic features of elderly Koreans while they read a series of mood-inducing sentences (MIS). METHODS: In this case-control study, we recruited 61 individuals with major depressive disorder and 143 healthy controls (mean age [SD]: 72 [6]; female, 70%) from the community-dwelling elderly population. Participants were asked to read MIS and their variation pattern of acoustic features represented by the correlation distance between two MIS were analyzed as input features using the univariate feature selection technique and subsequently classified by AdaBoost. RESULTS: Acoustic features showing significant discriminatory performances were spectral and energy-related features for males (sensitivity 0.95, specificity 0.88, and accuracy 0.86) and prosody-related features for females (sensitivity 0.73, specificity 0.86, and accuracy 0.77). The correlation distance between negative and positive MIS was significantly shorter in the depressed group than in the healthy control (F = 18.574, P < 0.001). LIMITATIONS: Small sample size and relatively homogenous clinical profile of depression could limit the generalizability. CONCLUSIONS: While reading MIS, spectral and energy-related acoustic features for males and prosody-related features for females are good discriminators for major depressive disorder. These features may be used as biomarkers of depression in the elderly.

Different Strategies in Making Transseptal Portal for the Different Purposes.

The purpose of this study was to find the most suitable and safe position of the transseptal portal in anatomic anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) reconstructions. The hypothesis of this study was that area and position of the transseptal portal are different between ACL and PCL reconstructions for the observation of native footprint. A matched-pair comparison study was conducted on the arthroscopic images of 100 consecutive patients who underwent ACL reconstruction and 50 consecutive patients who underwent PCL reconstruction. The transseptum was divided into six compartments. The opened compartments for each surgery were then evaluated to find which anatomical structures are well seen. The anterior middle and upper parts were necessary for the ACL reconstruction, whereas middle and lower portions of the anterior and posterior compartments were necessary for the PCL reconstruction. A larger opening was necessary for PCL reconstruction than that for ACL reconstruction. The ACL posterior one-third, ACL femoral attachment, and apex of the deep cartilage margin (DCM) were viewed in 100% of the patients during ACL reconstruction. The PCL posterior one-third, PCL tibial attachment, PCL fovea margin, and medial meniscus around posterior margin were always viewed during PCL reconstruction. The anterior part of the septum, from the middle to the upper portions of the transseptum, was necessary to be opened for visualization of the femoral footprint and DCM of the lateral femoral condyle during ACL reconstruction. The anterior and posterior parts of the septum, from the middle to the lower portions of the transseptum, were necessary for excellent visualization of the PCL tibial footprint during PCL reconstruction. These paths of the transseptal portal for each surgery will help surgeons obtain both anatomic footprint restoration and maximal remnant preservation through the most suitable and safe means. This is a case-control study; level of evidence is 3.