Mouse transient receptor potential melastatin 2 (TRPM2) isoform 7 attenuates full-length mouse TRPM2 activity through reductions in its expression by targeting it to ER-associated degradation.

Transient receptor potential melastatin 2 (TRPM2) assembles into tetramers to function as an oxidative stress-sensitive Ca2+ channel at the surface membrane. Limited information is currently available on the 10 protein isoforms of mouse TRPM2 (mTRPM2) identified. This study investigated whether these isoforms function as Ca2+ channels and examined their effects on full-length mTRPM2 activity using the HEK 293 cell exogenous expression system. Only full-length mTRPM2, isoform 1 localized to the surface membrane and was activated by oxidative stress. Isoform 7 was clearly recognized by protein quality control systems and degraded by endoplasmic reticulum-associated degradation after transmembrane proteolysis. In the co-expression system, the activation and expression of full-length mTRPM2 were attenuated by its co-expression with isoform 7, but not with the other isoforms. This decrease in the expression of full-length mTRPM2 was recovered by the proteasomal inhibitor. The present results suggest that isoforms other than isoform 1 did not function as oxidative stress-sensitive channels and also that only isoform 7 attenuated the activation of full-length mTRPM2 by targeting it to endoplasmic reticulum-associated degradation. The present study will provide important information on the functional nature of mTRPM2 isoforms for the elucidation of their roles in physiological and patho-physiological responses in vivo using mouse models.

Inactivation Activities of Ozonated Water, Slightly Acidic Electrolyzed Water and Ethanol against SARS-CoV-2.

This study aimed to compare the SARS-CoV-2-inactivation activity and virucidal mechanisms of ozonated water (OW) with those of slightly acidic electrolyzed water (SAEW) and 70% ethanol (EtOH). SARS-CoV-2-inactivation activity was evaluated in a virus solution containing 1%, 20% or 40% fetal bovine serum (FBS) with OW, SAEW or EtOH at a virus-to-test solution ratio of 1:9, 1:19 or 1:99 for a reaction time of 20 s. EtOH showed the strongest virucidal activity, followed by SAEW and OW. Even though EtOH potently inactivated the virus despite the 40% FBS concentration, virus inactivation by OW and SAEW decreased in proportion to the increase in FBS concentration. Nevertheless, OW and SAEW showed potent virucidal activity with 40% FBS at a virus-to-test solution ratio of 1:99. Real-time PCR targeting the viral genome revealed that cycle threshold values in the OW and SAEW groups were significantly higher than those in the control group, suggesting that OW and SAEW disrupted the viral genome. Western blotting analysis targeting the recombinant viral spike protein S1 subunit showed a change in the specific band into a ladder upon treatment with OW and SAEW. OW and SAEW may cause conformational changes in the S1 subunit of the SARS-CoV-2 spike protein.

Antimicrobial susceptibility surveillance of bacterial isolates recovered in Japan from odontogenic infections in 2013.

We report on the findings of the first antimicrobial susceptibility surveillance study in Japan of isolates recovered from odontogenic infections. Of the 38 facilities where patients representing the 4 groups of odontogenic infections were seen, 102 samples were collected from cases of periodontitis (group 1), 6 samples from pericoronitis (group 2), 84 samples from jaw inflammation (group 3) and 54 samples from phlegmon of the jaw bone area (group 4) for a total of 246 samples. The positivity rates of bacterial growth on culture were 85.3%, 100%, 84% and 88.9%, respectively, for groups 1, 2, 3 and 4. Streptococcus spp. isolation rates according to odontogenic infection group were 22% (group 1), 17.7% (group 3) and 20.7% (group 4). Anaerobic isolation rates were 66.9% (group 1), 71.8% (group 3) and 68.2% (group 4). Drug susceptibility tests were performed on 726 strains excluding 121 strains that were undergrown. The breakdown of the strains subjected to testing was 186 Streptococcus spp., 179 anaerobic gram-positive cocci, 246 Prevotella spp., 27 Porphyromonas spp., and 88 Fusobacterium spp. The isolates were tested against 30 antimicrobial agents. Sensitivities to penicillins and cephems were good except for Prevotella spp. The low sensitivities of Prevotella spp is due to ß-lactamase production. Prevotella strains resistant to macrolides, quinolones, and clindamycin were found. No strains resistant to carbapenems or penems were found among all strains tested. No anaerobic bacterial strain was resistant to metronidazole. Antimicrobial susceptibility testing performed on the S. anginosus group and anaerobic bacteria, which are the major pathogens associated with odontogenic infections, showed low MIC90 values to the penicillins which are the first-line antimicrobial agents for odontogenic infections; however, for Prevotella spp., penicillins combined with ß-lactamase inhibitor showed low MIC90 values.

Optical vortex-induced forward mass transfer: manifestation of helical trajectory of optical vortex.

The orbital angular momentum of an optical vortex field is found to twist high viscosity donor material to form a micron-scale 'spin jet'. This unique phenomenon manifests the helical trajectory of the optical vortex. Going beyond both the conventional ink jet and laser induced forward mass transfer (LIFT) patterning technologies, it also offers the formation and ejection of a micron-scale 'spin jet' of the donor material even with an ultrahigh viscosity of 4 Pa·s. This optical vortex laser induced forward mass transfer (OV-LIFT) patterning technique will enable the development of next generation printed photonic/electric/spintronic circuits formed of ultrahigh viscosity donor dots containing functional nanoparticles, such as quantum dots, metallic particles and magnetic ferrite particles, with ultrahigh spatial resolution. It can also potentially explore a completely new needleless drug injection.

Gene expression analysis in the potent bactericidal activity of sitafloxacin against Streptococcus pneumoniae.

We investigated the degree of expression of Streptococcus pneumoniae genes associated with bacteriolysis and cell death in relation to the rapid bactericidal activity of sitafloxacin. S. pneumoniae ATCC 49619 was added to brain heart infusion containing sitafloxacin and garenoxacin concentrations equivalent to the Cmax achieved with the usual single dose and 4 h post-Cmax concentration. RNA was extracted and cDNA was prepared using reverse transcriptase. Following RNA extraction and cDNA synthesis, quantitative PCR was performed to determine the amount of gene expression for 13 genes associated with cell death. Of the 13 genes analyzed, S. pneumoniae exposed for 10 min to a sitafloxacin concentration of 4 h post-Cmax showed 3.9 times increased expression of lytA compared to the control strain. Furthermore, we observed a slightly increased expression for cibA encoding a competence induced bacteriocin. Our study suggests that the induction of a lytic enzyme and bacteriocin may reflect gene expression in response to sitafloxacin accounting for part of its rapid bactericidal activity against S. pneumoniae.

A Case of Early Pneumoparotid Presenting With Oral Noises.

A 53-year-old man presented with the chief complaint of oral noises. No lesion could be observed in the oral cavity. Ultrasound detected several high-echogenicity areas inside the bilateral parotid ducts, and the initial stage of pneumoparotid was diagnosed. It was considered that air had entered each duct in retrograde fashion through the parotid papilla because of repeated compression of the bilateral parotid glands by the patient who had the habit of compressing the buccal region. This case suggests that ultrasound is effective for diagnosing the initial stage of pneumoparotid.

Binding Properties of Split tRNA to the C-terminal Domain of Methionyl-tRNA Synthetase of Nanoarchaeum equitans.

The C-terminal domain of methionyl-tRNA synthetase (MetRS-C) from Nanoarchaeum equitans is homologous to a tRNA-binding protein consisting of 111 amino acids (Trbp111) from Aquifex aeolicus. The crystal structure of MetRS-C showed that it existed as a homodimer, and that each monomer possessed an oligonucleotide/oligosaccharide-binding fold (OB-fold). Analysis using a quartz crystal microbalance indicated that MetRS-C freshly isolated from N. equitans was bound to tRNA. However, binding of the split 3'-half tRNA species was stronger than that of the 5'-half species. The T-loop and the 3'-end regions of the split 3'-half tRNA were found to be responsible for the binding. The minimum structure for binding to MetRS-C might be a minihelix-like stem-loop with single-stranded 3'-terminus. After successive duplications of such a small hairpin structure with the assistance of a Trbp-like structure, the interaction of the T-loop region of the 3'-half with a Trbp-like structure could have been evolutionarily replaced by RNA-RNA interactions, along with many combinational tertiary interactions, to form the modern tRNA structure.

Evaluation of Early-phase Biodistribution in 123I-ioflupane SPECT.

It is reported that pharmacokinetics after intravenous injection of 123I-ioflupane may reflect cerebral blood flow. In this study, the early-phase pharmacokinetics of 123I-ioflupane in 10 healthy volunteers was analyzed over time using dynamic single-photon emission computed tomography (SPECT) immediately after intravenous injection. We also examined the correlation between the 123I-IMP imaging and the 123I-ioflupane early-phase image for 14 cases in which both dopamine transporter (DaT) imaging by 123I-ioflupane and cerebral blood flow imaging by 123I-IMP were performed on the same camera. The time-activity curve between cerebellum (CBL) area and each area of anterior cerebral artery (ACA), middle cerebral artery (MCA), posterior cerebral artery (PCA) showed distribution characteristics similar to 123I-IMP from immediately after intravenous injection until 20 minutes after administration, and there was no conspicuous washout. The regression line and the correlation coefficient of the Z-score of three-dimensional stereotactic surface projections (3DSSP) (decrease) of the early-phase imaging of 123I-ioflupane and the 123I-IMP imaging are y=0.7546x+0.3562, r=0.8169 (P<0.01) at 0-10 minutes of 123I-ioflupane, and y=0.7412x+0.3027, r=0.8280 (P<0.01) at 0-15 minutes of 123I-ioflupane, and y=0.7400x+0.2456, r=0.8449 (P<0.01) at 0-20 minutes of 123I-ioflupane, showing a strong correlation at all timings. Therefore, 123I-ioflupane early-phase pharmacokinetics after intravenous showed distribution characteristics similar to 123I-IMP, indicating the possibility that early images may be useful in a clinical practice.

Impact of Right Ventricular Geometry on Mitral Regurgitation After Transcatheter Closure of Atrial Septal Defect.

Worsening of mitral regurgitation (MR) is sometimes observed after closure of an atrial septal defect (ASD). However, since the mechanism of this deterioration remains unclear, the aim of our study was to investigate the effect of left (LV) and right ventricular (RV) geometry on MR after transcatheter closure of ASD.We studied 27 patients with ASD who underwent transcatheter closure. Echocardiography was performed before and 6 ± 2 months after the procedure. In addition to conventional echocardiographic parameters, full volume data of the whole LV and RV heart was obtained with 3-dimensional echocardiography. MR was quantified by measuring the width of the vena contracta, and was graded as mild (< 3.0 mm), moderate (3.0 to 6.9 mm), or severe (≥ 7.0 mm).Ten patients (37%) were classified as having worsening MR and the remaining 17 (63%) as not having worsening MR. The two groups showed similar baseline characteristics, except for patients with worsening MR being more likely to be older (P = 0.009) and having a larger left-to-right shunt of pulmonary and systemic blood flow ratio (P = 0.02). It is noteworthy that the horizontal-to-vertical ratio of basal-RV at end-systole for patients with worsening MR was significantly smaller than that for patients without worsening MR (1.0 ± 0.2 versus 1.4 ± 0.2, P < 0.0001). Furthermore, multivariate analysis showed that the horizontal-to-vertical ratio of basal-RV at end-systole was the independent predictor of worsening MR during follow-up (P < 0.001).RV geometry may affect MR after closure of ASD. The pre-operative horizontal-to-vertical ratio of basal-RV is considered useful for predicting worsening of MR after closure of ASD.

Severe retinopathy following radiation therapy with a moderate dose for orbital mucosa-associated lymphoid tissue lymphoma.

Mucosa-associated lymphoid tissue (MALT) lymphoma is a radiosensitive malignancy. We report on a case of severe retinopathy following radiation therapy with a moderate dose for orbital MALT lymphoma. A 69-year-old woman with orbital MALT lymphoma received definitive radiation therapy with a total dose of 36 Gy in 18 fractions. The patient showed complete response but had severe retinopathy along with marked deterioration in visual acuity at 2 years after irradiation. Although the patient underwent treatments for retinopathy, including laser photocoagulation and steroid injection, improvement of the visual acuity was modest. This case developed severe radiation-induced retinopathy after radiation therapy with the moderate dose of 36 Gy that is considered to be usually safe.

Left ventricular endocardial dysfunction in patients with preserved ejection fraction after receiving anthracycline.

BACKGROUND: Anthracycline chemotherapy generates progressive dose-dependent left ventricular (LV) dysfunction associated with a poor prognosis. Early detection of minor LV myocardial dysfunction caused by the cardiotoxicity of anthracycline is thus important for predicting global LV dysfunction. METHODS: Fifty patients with preserved ejection fraction (all ≥55%) after receiving anthracycline chemotherapy were recruited for this study. Two-dimensional speckle tracking was used to assess global radial and circumferential strains from mid-LV short-axis views and global longitudinal strain from the apical four- and two-chamber view as peak global strain curves. Three-dimensional (3D) radial, circumferential, and longitudinal myocardial function was quantified as a peak global strain curve using 3D speckle tracking from all 16 LV segments. 3D speckle tracking imaging was used to evaluate LV endocardial area change ratio (area strain) quantified as peak global area strain curve (3D-GAS) to determine LV endocardial function. Twenty age-, gender-, and EF-matched normal volunteers were studied for comparisons. RESULTS: Only 3D-GAS and peak 3D global circumferential strains of the anthracycline group were significantly worse than those of the control group (-43.3 ± 3.1 vs. -45.8 ± 4.3% and -31.6 ± 3.5% vs. -34.4 ± 4.2%, respectively; P = 0.008, P = 0.004) even though global LV systolic and diastolic functions were similar. 3D-GAS correlated significantly with the cumulative doxorubicin dose (r = 0.316, P = 0.026). It was noteworthy that multivariate analysis showed only 3D-GAS (ß = 0.323, P = 0.025) was independently associated with cumulative doxorubicin dose. CONCLUSIONS: Three-dimensional speckle tracking area strain was found useful for early detection of minor LV endocardial dysfunction associated with the use of anthracycline, and may thus prove to be clinically useful for predicting global LV dysfunction.

Combined baseline strain dyssynchrony index and its acute reduction predicts mid-term left ventricular reverse remodeling and long-term outcome after cardiac resynchronization therapy.

The objective of this study was to test the hypothesis that combining assessment of baseline radial strain dyssynchrony index (SDI), that expressed both left ventricular (LV) dyssynchrony and residual myocardial contractility, and of acute changes in this index can yield more accurate prediction of mid-term responders and long-term outcome after cardiac resynchronization therapy (CRT). Radial SDI for 75 CRT patients was calculated as the average difference between peak and end-systolic speckle tracking strain from 6 segments of the mid-LV short-axis view before and 8 ± 2 days after CRT. Mid-term responder was defined as ≥ 15% decrease in LV end-systolic volume 6 ± 2 months after CRT. Long-term outcome was tracked over 5 years. Baseline radial SDI ≥ 6.5% is considered predictive of responder and favorable outcome, as previously reported. Acute reduction in radial SDI ≥ 1.5% was found to be the best predictor of mid-term responders with CRT. Furthermore, patients with acute reductions in radial SDI ≥1.5% were associated with a significantly more favorable long-term outcome after CRT than those with radial SDI <1.5% (log rank P < 0.001). An important findings were that baseline radial SDI ≥6.5% and acute reductions in radial SDI ≥ 1.5% in 42 patients were associated with the highest event-free survival rate of 92%, whereas, 21 patients corresponding values of <6.5% and <1.5% were associated with low event-free survival rate of 46% (log rank P < 0.001). Combined assessment of baseline radial SDI and its acute reduction after CRT may have clinical implications for predicting responders and thus patients' care.

A manual of Eustachian tube function tests-illustration of representative test results obtained from healthy subjects and typical disorders with suggestion of the appropriate test method of choice.

In the 19th century, Politzer devised a method to measure passage of the Eustachian tube (ET) by pressurizing the nasopharyngeal cavity, which marked the beginning of the ET function test. Since then, various examination methods have been developed. While ET function testing is important, recent advancements in diagnostic imaging and treatments have renewed interest on its importance. In Japan, the main objective methods used for examining ET function include tubotympanoaero-dynamic graphy (TTAG), sonotubometry, and the inflation-deflation test. The Japan Otological Society (JOS) Eustachian Tube Committee has proposed a manual of ET function tests, which presents typical patterns of the normal ear and typical diseases and suggests the ET function test of choice for each disease. However, the diagnosis of each disease should be made based on a comprehensive history and various examination findings, with ET function tests playing a supplemental role in the diagnosis.

Stem cell self-renewal factors Bmi1 and HMGA2 in head and neck squamous cell carcinoma: clues for diagnosis.

Head and neck squamous cell carcinoma (HNSCC) includes both morphological and functional cellular heterogeneity, as would be expected if it arose from dysregulated stem or progenitor cells as opposed to the simple clonal expansion of a mutated cell; however, stemness molecule expression levels and distribution in HNSCC remain unclear. To clarify this, stemness molecule expressions were determined in HNSCC, as well as their properties and prognosis. Two proto-oncogenic chromatin regulators, Bmi-1 and high-mobility-group A2 (Hmga2), were identified in 12 pair cases of HNSCC tumor regions by comparison with their non-cancerous background tissues using cDNA microarray. Both Bmi-1 and Hmga2 are known to promote stem cell self-renewal by negatively regulating the expressions of Ink4a and Arf tumor suppressors. Despite similar targets, Bmi-1 protein was expressed in an early cancerous region and HMGA2 protein was expressed in a region showing more progression. Similarly, Bmi1 expression had no significance with regard to overall survival (P=0.67), whereas HMGA2 expression was associated with decreased overall survival (P=0.05). Quantitative real-time reverse transcription polymerase chain reaction analyses also correlated with protein levels. These findings suggest that Bmi-1 is an early detection marker to distinguish cancerous from non-cancerous regions, whereas HMGA2 is presumed to be a tumor prognosis marker. Among our HNSCC analyses, these stemness molecules expressed fewer primitive rare cells in the tumor than all other cells in the tumor. HNSCC cells with high expression of stemness molecules partly behave like stem cells.

Dynamic left ventricular dyssynchrony assessed on 3-dimensional speckle-tracking area strain during dobutamine stress has a negative impact on cardiovascular events in patients with idiopathic dilated cardiomyopathy.

BACKGROUND: Left ventricular (LV) dyssynchrony is not a stable phenomenon, but rather, changes dynamically. Given that the prognostic impact of dynamic dyssynchrony has not yet been elucidated, the objective was to investigate the clinical impact of dynamic dyssynchrony on patients with dilated cardiomyopathy (DCM). METHODS AND RESULTS: Seventy DCM patients with ejection fraction 32±9% were retrospectively recruited, and 3-dimensional speckle-tracking area strain was used to measure both contractile reserve and changes in dyssynchrony during dobutamine stress. The standard deviation of time-to-peak area strain was adopted as the systolic dyssynchrony index. Event-free survival was then tracked over a 13-month period. A ≥7.55% increase in systolic dyssynchrony index during dobutamine stress (Δsystolic dyssynchrony index) was the best predictor of cardiovascular events with 77% sensitivity and 88% specificity. Multivariate Cox analysis indicated that not only the absence of contractile reserve (Δglobal area strain ≤21.1%: hazard ratio [HR], 15.29; P=0.01), but the presence of dynamic dyssynchrony (ΔLV dyssynchrony ≥7.55%: HR: 7.591; P=0.003) was an independent predictor of cardiovascular events. Importantly, absence of dynamic dyssynchrony and presence of contractile reserve were associated with the most favorable outcome (98%), whereas the reverse condition was associated with the worst outcome (20%, P<0.001). CONCLUSIONS: Dynamic dyssynchrony is a potential predictor of cardiovascular events in patients with DCM, while assessment of dynamic dyssynchrony in combination with contractile reserve may further improve prognostic risk stratification.

[Bactericidal activity of sitafloxacin and other new quinolones against antimicrobial resistant Streptococcus pneumoniae].

We conducted a study assess the bactericidal activity of sitafloxacin (STFX) against Streptococcus pneumoniae isolates recovered from respiratory infections including penicillin-resistant (PRSP) isolates, macrolide resistant isolates possessing mefA and ermB resistance genes and quinolone resistance isolates with mutations in gyrA or gyrA and parC. Each isolate tested was grown in hemosupplemented Mueller-Hinton broth and adjusted to approximately 10(5) CFU/ mL. Isolates were than exposed to a Cmax antimicrobial blood level that would be attained with routine antimicrobial administration and an antimicrobial level that would be expected 4 hours post-Cmax (Cmax 4hr). Bactericidal activity was measured for up to 8 hours. Excluding a subset of S. pneumoniae isolates with mutations in the quinolone resistance determining region (QRDR), all quinolones showed bactericidal activity at Cmax and Cmax 4 hr antimicrobial concentrations for up to 8 hours. Against S. pneumoniae isolates with either gyrA or gyrA and parC mutations, bactericidal activity of STFX was shown for up to 4 to 8 hours following Cmax based on a limit of detection of < 1.3 log CFU/mL. Garenoxacin (GRNX) did not showed bactericidal activity below the limit of detection for up to 8 hours with exposure to Cmax and no bactericidal activity was seen with levofloxacin. When all quinolones tested where adjusted to concentrations corresponding to their MICs, STFX showed the most rapid bactericidal activity against PRSP. This rapid bactericidal activity in PRSP is a key to the effectiveness of STFX. Our findings show that beyond inhibition of bacterial replication by blocking their DNA replication pathway and synthesis of proteins, STFX demonstrated characteristics contributing to greater bactericidal activity compared to GRNX. In conclusion, of the newer quinolones, STFX showed the strongest bactericidal activity against S. pneumoniae isolates with mutations in the QRDR which indicates that it may show the most effective clinical utility among the quinolones in respiratory infections.

A Case of Phlebolith in the Tip of Tongue.

The differential diagnosis of a tongue mass containing calcified bodies includes a phlebolith associated with vascular lesions, such as hemangioma and vascular malformation, and diseases such as neoplasm, osseous choristoma and hypercalcemic states, including hyperparathyroidism. The appearance of the calcified bodies on plain radiographs may help to differentiate these entities. Computed tomography, magnetic resonance imaging, and ultrasonography are also useful for differentiating these soft tissue lesions. We report a 40-year-old man with a small mass containing a calcified body in the tip of tongue. The mass was surgically resected and histologically evaluated, confirming the diagnosis of phlebolith. Our case was a rare phlebolith that did not involve a vascular lesion.

Large Palatal Pleomorphic Adenoma Complicated by Dysphagia: A Case Report.

A 60-year-old Japanese woman presented with a palatal pleomorphic adenoma measuring 5 cm in size. In addition to impairments during the oral preparatory and oral transport phases, dysphagia with nasopharyngeal closure disorder was observed in the pharyngeal phase. After resection of the tumor, dysphagia resolved, and the patient was immediately able to eat a standard meal. A videofluoroscopic swallowing study confirmed improvement in the movement of the soft palate compared with the pre-operative condition.

Effect of left ventricular dyssynchrony on cardiac sympathetic activity in heart failure patients with wide QRS duration.

BACKGROUND: Dyssynchrony has various detrimental effects on cardiac function, but its effect on cardiac sympathetic activity is not fully understood. METHODS AND RESULTS: We studied 50 heart failure patients who underwent cardiac resynchronization therapy (CRT). Cardiac sympathetic activity was assessed by (123)I-metaiodobenzylguanidine ((123)I-MIBG) scintigraphy as the delayed heart-to-mediastinum ratio (H/M ratio). Echocardiography was performed before and 7 months after CRT, and response was defined as a ≥15% decrease in end-systolic volume. Dyssynchrony was determined by the time difference between the anteroseptal-to-posterior wall using speckle-tracking radial strain (≥130 ms predefined as significant). H/M ratio in patients with dyssynchrony was less than that in patients without dyssynchrony (1.62 ± 0.31 vs. 1.82 ± 0.36, P<0.05), even though ejection fraction was not significantly different (24 ± 6% vs. 25 ± 7%). Patients with dyssynchrony and H/M ratio ≥1.6 had a higher frequency of response to CRT (94%) and favorable long-term outcome over 3.0 years. In contrast, patients without dyssynchrony and H/M ratio <1.6 were more likely to show a lower frequency of response to CRT (0%) and unfavorable long-term outcome after CRT. CONCLUSIONS: Dyssynchrony is associated with cardiac sympathetic activity, and (123)I-MIBG scintigraphy may be valuable for predicting the response to CRT.

Impact of left ventricular afterload on longitudinal dyssynchrony in patients with severe aortic stenosis and preserved ejection fraction.

BACKGROUND: The purpose of this study was to investigate whether patients with severe aortic stenosis (AS) and preserved ejection fraction (EF) have dyssynchrony and whether it improves after aortic valve replacement (AVR). METHODS AND RESULTS: We studied 30 consecutive patients with severe AS and preserved EF undergoing AVR. For baseline comparison, we studied 17 EF-matched patients with mild-to-moderate AS, and 18 EF-matched normal volunteers. Longitudinal dyssynchrony was determined as the standard deviation for time-to-peak speckle-tracking strain in apical 4- and 2-chamber views at the basal- and mid-levels. Radial and circumferential dyssynchrony was determined as the difference for time-to-peak strain between the anteroseptum and posterior wall from the mid-left ventricular (LV) short-axis view. Each of the myocardial functions was also evaluated by averaging each peak systolic strain. Longitudinal dyssynchrony and function in patients with severe AS was significantly worse than in the patients with mild-to-moderate AS and the controls (94 ± 46 vs. 66 ± 18 ms* and 52 ± 17 ms*, and 12.5 ± 3.7% vs. 16 ± 3.5%* and 18.7 ± 3.7%*, respectively, *P<0.05, vs. severe AS). In contrast, radial and circumferential dyssynchrony were similar for the 3 groups. Importantly, the dyssynchrony of patients with severe AS significantly improved after AVR from 94 ± 46 ms to 68 ± 22 ms (P<0.005). CONCLUSIONS: Significant longitudinal dyssynchrony was present in patients with severe AS and preserved EF, and it improved after AVR.