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Hallux valgus is a progressive angular deformity of the big toe, the degree of which is aggravated in weightbearing stance. Hallux valgus and intermetatarsal angles on postoperative weightbearing images are usually larger than those of intraoperative fluoroscopic and immediate postoperative non-weightbearing images. Here, we hypothesized that various angular parameters of hallux valgus would increase postoperatively with weightbearing. A total of 66 feet (58 patients) of moderate to severe hallux valgus were reviewed on consecutive plain foot anteroposterior radiographs. The changes of hallux valgus, intermetatarsal, hallux valgus interphalangeal, and distal metatarsal articular angles were compared. Hallux valgus and intermetatarsal angles were significantly increased with weightbearing postoperatively (p.001). Hallux valgus interphalangeal and distal metatarsal articular angles did not show significant changes with weightbearing (p.5). Hallux valgus and intermetatarsal angles were increased with weightbearing after hallux valgus surgery. Mean angular changes were 5.3 and 2.7 degrees, respectively. These values should be considered in the preoperative planning and intraoperative correction processes.

Background: The goal of this article was to investigate the feasibility of 64Cu labeling in prostate-specific membrane antigen imaging and therapy (PSMA I&T) for PSMA positron emission tomography (...

Moyamoya syndrome (MMS) associated with hyperthyroidism, such as Graves’ disease, is a rare condition that causes ischemic stroke with thyrotoxicity. A 43-year-old woman with symptoms of right hemiparesis was admitted. Brain magnetic resonance imaging revealed a small cerebral infarction in the left frontal lobe. Cerebral angiography revealed multi-vessel intracranial occlusive disease. Several days later, neurologic deterioration and aggravation of cerebral infarction developed due to a thyroid storm. A thyroid function test revealed the following: thyroid-stimulating hormone (TSH) ＜0.01 μunits/mL (reference range, 0.55–4.78 μunits/mL); triiodo-thyronine ＞8.0 ng/mL (reference range, 0.77–1.81 ng/mL); free thyroxine (T4) of 9.47 pmol/L (reference range, 11.4–22.6 pmol/L); and TSH receptor antibody of 37.10 U/L (reference range, 0–10 U/L). For thyroid storm management, we initiated treatment with methimazole, Gemstein’s solution, and hydrocortisone. Finally, the thyroid disease was controlled, and neurologic deficits improved. We describe a case of acute cerebral infarction combined with a thyroid storm in a patient with Moyamoya syndrome and Graves’ disease. Hyperthyroidism such as Graves’ disease should be considered in the differential diagnosis for patho-etiologic mechanisms associated with MMS. A cerebrovascular disease with a thyroid storm can lead to severe mortality and morbidity. Prompt diagnosis and strict treatment are important.

The incidence of Achilles tendon rupture is increasing. Postoperative rehabilitation after repairing acute Achilles tendon rupture is very important because the choice of treatment during the rehabilitation period can influence the results. Moreover, the method of functional rehabilitation varies and is developing steadily. Recent studies recommend a functional rehabilitation protocol, and this approach is accepted widely. This study aimed to introduce our most accelerated functional rehabilitation protocol following surgery for acute Achilles tendon rupture and to review the results retrospectively. From July 2014 to July 2016, 67 patients underwent surgery for acute Achilles tendon rupture by one surgeon. Age, sex, body mass index, injury mechanism, rehabilitation method and progress, time to return to previous physical activity, and complications were evaluated. The mean time to be able to squat fully was 10 ± 4.7 (4-20) weeks. Full squatting was possible in 92.8% (52 patients). The mean time to perform a single-limb heel rise and repetitive single-limb heel rise was 12.6 ± 3.9 (6-24) and 23.3 ± 7.7 (8-40) weeks, respectively. The mean time to return to sports was 20.6 ± 5.2 (12-32) weeks. The major complication rate was 3.5% (one re-rupture and one tendon elongation). The mean pre- and postoperative Achilles Tendon Total Rupture Score was 29.5 ± 3.7 (20-38) and 79.3 ± 18.5 (20-98) points, respectively. The increase was significant (p < .01). In conclusion, immediate full weightbearing and ankle motion exercise after repair of acute Achilles tendon rupture can provide a good rehabilitation option with a low re-rupture rate and satisfactory functional results.

Despite previous neuroimaging studies demonstrating morphological abnormalities of the thalamus and other subcortical structures in patients with schizophrenia, the potential role of the thalamus and its subdivisions in the pathophysiology of this illness remains elusive. It is also unclear whether similar changes of these structures occur in individuals at high risk for psychosis. In this study, magnetic resonance imaging was employed with the Multiple Automatically Generated Templates (MAGeT) brain segmentation algorithm to determine volumes of the thalamic subdivisions, the striatum (caudate, putamen, and nucleus accumbens), and the globus pallidus in 62 patients with schizophrenia, 38 individuals with an at-risk mental state (ARMS) [4 of whom (10.5%) subsequently developed schizophrenia], and 61 healthy subjects. Cognitive function of the patients was assessed by using the Brief Assessment of Cognition in Schizophrenia (BACS) and the Schizophrenia Cognition Rating Scale (SCoRS). Thalamic volume (particularly the medial dorsal and ventral lateral nuclei) was smaller in the schizophrenia group than the ARMS and control groups, while there were no differences for the striatum and globus pallidus. In the schizophrenia group, the reduction of thalamic ventral lateral nucleus volume was significantly associated with lower BACS score. The pallidal volume was positively correlated with the dose of antipsychotic treatment in the schizophrenia group. These results suggest that patients with schizophrenia, but not those with ARMS, exhibit volume reduction in specific thalamic subdivisions, which may underlie core clinical features of this illness.

Purpose: The patient perception of study medication (PPSM) questionnaire consists of 12 questions designed to quantify patient satisfaction with the efficacy of study treatment by focusing on specific changes that patients experience during the study period. This study aimed to develop a Korean version of the PPSM questionnaire.Methods: The linguistic validation process consisted of obtaining permission for translation, forward translation, reconciliation, backward translation, cognitive debriefing, and proofreading. Two independent bilingual translators translated the original version of the questionnaire, and a panel discussed and combined the 2 versions. Another independent translator performed backward translation of the reconciled version, after which 15 patients underwent the cognitive debriefing.Results: The 12 questions and 4 response scales of the PPSM questionnaire were forward translated into 2 Korean versions. The terms were adjusted to conceptually equivalent expressions in Korean. After backward translation, the panel made minor changes to the forward translations for brevity and better readability. No difficulties were experienced during cognitive debriefing by 15 patients, and all items were reported to be generally easy to understand.Conclusions: The Korean version of the PPSM questionnaire has been successfully translated and validated. The questionnaire is appropriate for assessing symptom satisfaction in patients that undergo benign prostatic hyperplasia pharmacotherapy.

Supplemental material, sj-docx-1-wso-10.1177_17474930231168742 for Dual antiplatelet Use for extended period taRgeted to AcuTe ischemic stroke with presumed atherosclerotic OrigiN (DURATION) trial: Rationale and design by Joon-Tae Kim, Jihoon Kang, Beom Joon Kim, Jun Yup Kim, Moon-Ku Han, Ki-Hyun Cho, Man-Seok Park, Kang-Ho Choi, Jong-Moo Park, Kyusik Kang, Yong Soo Kim, Soo Joo Lee, Jae Guk Kim, Jae-Kwan Cha, Dae-Hyun Kim, Tai Hwan Park, Sang-Soon Park, Jin Kyo Choi, Kyungbok Lee, Kwang-Yeol Park, Hae-Bong Jeong, Jun Lee, Doo Hyuk Kwon, Yong-Jin Cho, Keun-Sik Hong, Hong-Kyun Park, Byung-Chul Lee, Kyung-Ho Yu, Mi Sun Oh, Minwoo Lee, Dong-Eog Kim, Dong-Seok Gwak, Jay Chol Choi, Joong-Goo Kim, Chul-Hoo Kang, Jee-Hyun Kwon, Wook-Joo Kim, Dong-Ick Shin, Kyu Sun Yum, Sung Il Sohn, Jeong-Ho Hong, Hyungjong Park, Chulho Kim, Sang-Hwa Lee, Juneyoung Lee, Philip B Gorelick, Bo Norrving and Hee-Joon Bae in International Journal of Stroke

Background The clinical features of pediatric rhabdomyolysis differ from those of the adults with rhabdomyolysis; however, multicenter studies are lacking. This study aimed to investigate the characteristics of pediatric rhabdomyolysis and reveal the risk factors for acute kidney injury (AKI) in such cases. Methods This retrospective study analyzed the medical records of children and adolescents diagnosed with rhabdomyolysis at 23 hospitals in South Korea between January 2007 and December 2016. Results Among 880 patients, those aged 3 to 5 years old composed the largest subgroup (19.4%), and all age subgroups were predominantly male. The incidence of AKI was 11.3%. Neurological disorders (53.6%) and infection (39.0%) were the most common underlying disorder and cause of rhabdomyolysis, respectively. The median age at diagnosis in the AKI subgroup was older than that in the non-AKI subgroup (12.2 years vs. 8.0 years). There were no significant differences in body mass index, myalgia, dark-colored urine, or the number of causal factors between the two AKI-status subgroups. The multivariate logistic regression model indicated that the following factors were independently associated with AKI: multiorgan failure, presence of an underlying disorder, strong positive urine occult blood, increased aspartate aminotransferase and uric acid levels, and reduced calcium levels. Conclusions Our study revealed characteristic clinical and laboratory features of rhabdomyolysis in a Korean pediatric population and highlighted the risk factors for AKI in these cases. Our findings will contribute to a greater understanding of pediatric rhabdomyolysis and may enable early intervention against rhabdomyolysis-induced AKI.

Background Patient discomfort is often inevitable during transrectal ultrasonography (TRUS), a widely used modality for evaluating benign prostate hyperplasia/lower urinary tract symptoms. Music has been suggested as a method of pain relief during urologic procedures. In this study, we investigated the effect of music on pain relief during TRUS. Methods In a pilot study conducted from March to June 2019, pain scores of 316 patients who underwent TRUS with or without music were quantified using the visual analog scale (VAS). One-to-one propensity score matching was performed by matching the subjects between the groups. Patients with hemorrhoids of grade ≥ III were excluded (n = 4). Results Among the 312 patients included in the study (VAS score = 3.3 ± 2.4), 177 listened to music during the procedure. There were significant differences in age, prostate-specific antigen, prostate volume, International Prostate Symptom Score symptom/life score, and VAS score between the music (+) and music (−) groups. After adjusting for relevant variables, VAS scores were significantly lower in male patients aged ≥65.0 years who underwent music intervention than in those who did not (1.5 ± 1.4 vs. 3.0 ± 1.4, p = 0.002). Conclusion Age was negatively associated with pain during TRUS, and music had a relieving effect on pain in patients aged ≥65.0 years. Our findings may help improve the quality of examinations in urologic outpatient offices.

Prostate cancer is the second most common malignancy in men worldwide. Systematic transrectal prostate biopsy is commonly used to obtain tissue to establish the diagnosis. In recent years, however,...

We developed a novel therapeutic radioligand, [177Lu]1h, with an albumin binding motif and evaluated it in a prostate-specific membrane antigen (PSMA)-expressing tumor xenograft mouse model. Fourteen PSMA target candidates were synthesized, and binding affinity was evaluated with an in vitro competitive binding assay. First, four compound candidates were selected depending on binding affinity results. Next, we selected four compounds ([68Ga]1e, [68Ga]1g, [68Ga]1h, and [68Ga]1k) were screened for tumor targeting efficiency by micro–positron emission tomography/computed tomography (micro-PET/CT) imaging. Finally, [177Lu]1h compound was evaluated the tumor targeting efficiency and therapeutic efficiency by micro–single-photon emission computed tomography/computed tomography (micro-SPECT/CT), biodistribution, and radiotherapy studies. Estimated human effective dose was calculated by biodistribution data. Compound 1h showed a high binding affinity (Ki value = 4.08 ± 0.08 nmol/L), and [177Lu]1h showed extended blood circulation (1 hour = 10.32 ± 0.31, 6 hours = 2.68 ± 1.07%ID/g) compared to [177Lu]PSMA-617 (1 h = 0.17 ± 0.10%ID/g). [177Lu]1h was excreted via the renal pathway and showed high tumor uptake (24.43 ± 3.36%ID/g) after 1 hour, which increased over 72 hours (72 hours = 51.39 ± 9.26%ID/g). Mice treated with 4 and 6 MBq of [177Lu]1h showed a median survival rate of >61 days. In particular, all mice treated with 6 MBq of [177Lu]1h survived for the entire monitoring period. The estimated human effective dose of [177Lu]1h was 0.07 ± 0.01 and 0.03 ± 0.00 mSv/MBq in total body and kidney, respectively. The current study indicates that [177Lu]1h has the potential for further investigation of metastatic castration-resistant prostate cancer (mCRPC) therapy in clinical trials.

This study aimed to validate and evaluate deep learning (DL) models for screening of high myopia using spectral-domain optical coherence tomography (OCT). This retrospective cross-sectional study included 690 eyes in 492 patients with OCT images and axial length measurement. Eyes were divided into three groups based on axial length: a “normal group,” a “high myopia group,” and an “other retinal disease” group. The researchers trained and validated three DL models to classify the three groups based on horizontal and vertical OCT images of the 600 eyes. For evaluation, OCT images of 90 eyes were used. Diagnostic agreements of human doctors and DL models were analyzed. The area under the receiver operating characteristic curve of the three DL models was evaluated. Absolute agreement of retina specialists was 99.11% (range: 97.78–100%). Absolute agreement of the DL models with multiple-column model was 100.0% (ResNet 50), 90.0% (Inception V3), and 72.22% (VGG 16). Areas under the receiver operating characteristic curves of the DL models with multiple-column model were 0.99 (ResNet 50), 0.97 (Inception V3), and 0.86 (VGG 16). The DL model based on ResNet 50 showed comparable diagnostic performance with retinal specialists. The DL model using OCT images demonstrated reliable diagnostic performance to identify high myopia.

Background Reduced gray matter volumes in the superior temporal gyrus and its subregions, such as Heschl's gyrus (HG) and the planum temporale (PT), have been reported in schizophrenia (Sz). However, it remains unclear whether patients exhibit an altered sulcogyral pattern on the superior temporal plane. Methods This magnetic resonance imaging study examined the distribution of HG duplication patterns [i.e., single HG, common stem duplication (CSD), or complete posterior duplication (CPD)] and their relationships with clinical variables and gray matter volumes in the HG and PT of 64 first-episode (FE) patients with Sz and 64 healthy controls. Results The prevalence of duplicated HG patterns was significantly higher and gray matter volumes in the HG and PT of both hemispheres were smaller in FESz patients than in healthy controls. The right CPD pattern in the FESz group was associated with less severe positive symptoms. In the FESz and control groups, CSD and CPD patterns correlated with larger volumes in the HG and PT, respectively. Conclusion The present results revealed an altered HG duplication pattern at the earliest phase of Sz, which may reflect early neurodevelopmental anomalies. However, reduced HG and PT volumes in the FESz were not explained by this sulcogyral pattern only, supporting the complex superior temporal pathology of Sz.

Objectives: Soy and hop extracts have been investigated as alternatives for hormone replacement therapy. However, their combined efficacy is not known. We investigated the efficacy and safety of a ...

Although arginase primarily participates in the last reaction of the urea cycle, we have previously demonstrated that arginase II is an important cytosolic calcium regulator through spermine production in a p32-dependent manner. Here, we demonstrated that rhaponticin (RPT) is a novel medicinal-plant arginase inhibitor and investigated its mechanism of action on Ca2+-dependent endothelial nitric oxide synthase (eNOS) activation. RPT was uncompetitively inhibited for both arginases I and II prepared from mouse liver and kidney. It also inhibited arginase activity in both aorta and human umbilical vein endothelial cells (HUVECs). Using both microscope and FACS analyses, RPT treatments induced increases in cytosolic Ca2+ levels using Fluo-4 AM as a calcium indicator. Increased cytosolic Ca2+ elicited the phosphorylations of both CaMKII and eNOS Ser1177 in a time-dependent manner. RPT incubations also increased intracellular L-arginine (L-Arg) levels and activated the CaMKII/AMPK/Akt/eNOS signaling cascade in HUVECs. Treatment of L-Arg and ABH, arginase inhibitor, increased intracellular Ca2+ concentrations and activated CaMKII-dependent eNOS activation in ECs of WT mice, but, the effects were not observed in ECs of inositol triphosphate receptor type 1 knockout (IP3R1-/-) mice. In the aortic endothelium of WT mice, RPT also augmented nitric oxide (NO) production and attenuated reactive oxygen species (ROS) generation. In a vascular tension assay using RPT-treated aortic tissue, cumulative vasorelaxant responses to acetylcholine (Ach) were enhanced, and phenylephrine (PE)-dependent vasoconstrictive responses were retarded, although sodium nitroprusside and KCl responses were not different. In this study, we present a novel mechanism for RPT, as an arginase inhibitor, to increase cytosolic Ca2+ concentration in a L-Arg-dependent manner and enhance endothelial function through eNOS activation. [BMB Reports 2021; 54(10): 516-521].

Objectives: This study demonstrated the positive effect of herbal medication on a suspected idiopathic thrombocytopenic purpura (ITP) patient-a 57-year-old male with suspected ITP and a decreased platelet count.Methods: The patient was treated with an herbal medicine named Nokyongdaebo-tang, and its effect was measured with periodic platelet blood tests.Results: Before taking the herbal medicine, the patient’s blood platelet count was 98 K/μl, but following treatment, the blood platelet count increased to 201 K/μl and maintained a continuously elevated level.Conclusion: The results indicated that herbal medication may improve the blood platelet count of suspected ITP patients.

Capsaicin is a specific agonist of transient receptor potential vanilloid 1 (TRPV1), which is enriched in nociceptors. Capsaicin not only produces acute pain but also leads to long-lasting analgesia in patients with chronic pain. Although capsaicin-induced TRPV1 and Ca 2+ /calpain-dependent ablation of axonal terminals is necessary for long-lasting analgesia, the mechanisms underlying capsaicin-induced ablation of axonal terminals and its association with analgesia are not fully understood. Microtubules are composed of tubulin polymers and serve as a main axonal cytoskeleton maintaining axonal integrity. In this study, we hypothesized that capsaicin would increase the depolymerization of microtubules and lead to axonal ablation and analgesia for trigeminal neuropathic pain. Paclitaxel, a microtubule stabilizer, decreased capsaicin-induced ablation of axonal terminals in time-lapsed imaging in vitro. Capsaicin increases free tubulin in dissociated sensory neurons, which was inhibited by paclitaxel. Consistently, subcutaneous injection of paclitaxel prevented capsaicin-induced axonal ablation in the hind paw skin. Capsaicin administration to the facial skin produced analgesia for mechanical hyperalgesia in mice with chronic constriction injury of the infraorbital nerve, which was prevented by the coadministration of paclitaxel and capsaicin. Whole-mount staining of facial skin showed that paclitaxel reduced capsaicin-induced ablation of peptidergic afferent terminals. Despite the suggested involvement of TRPV1 Ser801 phosphorylation on microtubule integrity, capsaicin-induced analgesia was not affected in TRPV1 S801A knock-in mice. In conclusion, capsaicin-induced depolymerization of axonal microtubules determined capsaicin-induced ablation of nociceptive terminals and the extent of analgesia. Further understanding of TRPV1/Ca 2+ -dependent mechanisms of capsaicin-induced ablation and analgesia may help to improve the management of chronic pain.

Magnetic resonance imaging (MRI)-based texture analysis (MRTA) is a novel image analysis tool that offers objective information about the spatial arrangement of MRI signal intensity. We aimed to investigate the value of MRTA in predicting the postoperative clinical outcome of patients with uterine cervical cancer. This retrospective study included 115 patients with surgically proven cervical cancer who underwent preoperative pelvic 3T-MRI, and MRTA was performed on T2-weighted images (T2), apparent diffusion coefficient (ADC) maps, and contrast-enhanced T1-weighted images (CE-T1). Filtration histogram-based texture analysis was used to generate six first-order statistical parameters [mean intensity, standard deviation (SD), mean of positive pixels (MPP), entropy, skewness, and kurtosis] at five spatial scaling factors (SSFs, 2–6 mm) as well as from unfiltered images. Cox proportional hazard models and time-dependent receiver operating characteristic analyses were used to evaluate the associations between parameters and recurrence-free survival (RFS). During a median follow-up of 36 months, tumor recurrence was found in 26 patients (22.6%). Multivariate analysis demonstrated that CE-T1 MPP and T2 kurtosis at SSF3–5, CE-T1 MPP at SSF6, and CE-T1 SD at unfiltered images were independent predictors of RFS (p optimal cutoff values demonstrated significantly worse survival than those with ≤ optimal cutoff values (p

Health literacy (HL) promotes healthy lifestyle behaviors among older adults, and its relationship with frailty remains unclear. This study examined whether HL is a predictor of frailty progression among community-dwelling older adults. Data from two surveys conducted in 2012 and 2016 involving older residents (mean age, 71.6 ± 4.6 years) of Kashiwa City, Chiba Prefecture, Japan were used. Only healthy individuals without frailty and cognitive impairments participated in the 2012 assessment, where the Kihon Checklist (KCL), HL, and other variables were assessed. Logistic and multiple logistic analyses were used to assess the effects of HL and other factors on frailty between the ‘high HL’ vs. ‘low HL’ groups in 2012 and between the ‘robust’ vs. ‘frailty-progressing’ groups in 2016. Of the 621 robust participants, 154 (25.4%) had progression of frailty in 2016, which was significantly associated with advanced age, higher KCL score, lower HL, poor mental health, and lack of social support. Furthermore, low HL was a predictor of frailty progression. Low HL may be associated with frailty progression. The obtained results suggest that increased health literacy should be effective in preventing frailty for community-dwelling older residents.

Purpose: This study aimed to determine the urodynamic characteristics of refractory enuresis and explored whether those characteristics can be managed through differential endoscopic injections with botulinum toxin.Methods: In total, 27 patients with nonmonosymptomatic enuresis who showed no response after conservative treatment for more than 12 months were included. The patients then underwent a videourodynamic study and received a differential endoscopic injection of botulinum toxin on the same day. Reduced capacity, detrusor overactivity, and bladder neck widening were the 3 major abnormal findings assessed during the filling phase, while sphincter hyperactivity was the only abnormality assessed during the emptying phase. An intravesical or intrasphincteric injection of botulinum toxin was attempted according to the videourodynamic study findings. Follow-up was conducted at 1, 3, 6, and 12 months after treatment.Results: The median age was 10 years (range, 7–31 years). Although 19 and 8 patients had a preoperative diagnosis of overactive bladder or dysfunctional voiding, respectively, the urodynamic diagnosis was different in more than half of the patients. Those showing detrusor overactivity benefited from intravesical botulinum toxin injection, whereas those with only sphincter hyperactivity benefited from both intravesical and intrasphincteric injections. Treatment resistance to botulinum toxin seemed to be attributable to bladder neck widening. Time had no apparent effect on efficacy, which persisted 6 months after the injection. More than 80% of the patients maintained the benefits of the injection after 1 year.Conclusions: Videourodynamic studies were useful for identifying the reasons underlying refractory nonmonosymptomatic enuresis and helpful for determining the appropriate site of botulinum toxin injection.

Ovarian clear cell carcinoma (OCCC) and ovarian endometrioid carcinoma (OEC) are both associated with endometriosis but differ in histologic phenotype, biomarker profile, and survival. Our objectives were to refine immunohistochemical (IHC) panels that help distinguish the histotypes and reassess the prevalence of mismatch repair deficiency (MMRd) in immunohistochemically confirmed OCCC. We selected 8 candidate IHC markers to develop first-line and second-line panels in a training set of 344 OCCC/OEC cases. Interobserver reproducibility of histotype diagnosis was assessed in an independent testing cohort of 100 OCC/OEC initially without and subsequently with IHC. The prevalence of MMRd was evaluated using the testing cohort and an expansion set of 844 ovarian carcinomas. The 2 prototypical combinations (OCCC: Napsin A+/HNF1B diffusely+/PR-; OEC: Napsin A-/HNF1B nondiffuse/PR+) occurred in 75% of cases and were 100% specific. A second-line panel (ELAPOR1, AMACR, CDX2) predicted the remaining cases with 83% accuracy. Integration of IHC improved interobserver reproducibility (κ=0.778 vs. 0.882, P

The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents a public health crisis, and the vaccines that can induce highly potent neutralizing antibodies are essential for ending the pandemic. The spike (S) protein on the viral envelope mediates human angiotensin-converting enzyme 2 (ACE2) binding and thus is the target of a variety of neutralizing antibodies. In this work, we built various S trimer-antibody complex structures on the basis of the fully glycosylated S protein models described in our previous work, and performed all-atom molecular dynamics simulations to get insight into the structural dynamics and interactions between S protein and antibodies. Investigation of the residues critical for S-antibody binding allows us to predict the potential influence of mutations in SARS-CoV-2 variants. Comparison of the glycan conformations between S-only and S-antibody systems reveals the roles of glycans in S-antibody binding. In addition, we explored the antibody binding modes, and the influences of antibody on the motion of S protein receptor binding domains. Overall, our analyses provide a better understanding of S-antibody interactions, and the simulation-based S-antibody interaction maps could be used to predict the influences of S mutation on S-antibody interactions, which will be useful for the development of vaccine and antibody-based therapy.

Aim The aim of this study was to evaluate the general characteristics, menstruation status, and fertility outcomes of patients with hypogonadotropic hypogonadism (HH). Methods We evaluated 16 patients with HH who visited our institution between April 2012 and March 2016 with a complaint of amenorrhea. Results Four (25%) patients had primary amenorrhea and the remaining 12 (75%) cases had secondary amenorrhea. Among the patients with primary amenorrhea, weight loss was considered to be the underlying cause in one (25%) patient, whereas the remaining three (75%) cases were idiopathic HH. Among HH cases with secondary amenorrhea, six (50%) developed amenorrhea following weight loss, whereas the remaining six cases were of unknown etiology. Among the 16 patients with HH, we observed the sporadic restart of the menstrual cycle in four (25%) women during follow-up. Infertility treatment was administered to nine patients with HH who wished to become pregnant. Clomiphene citrate was effective in four patients with secondary amenorrhea and induced follicular development. Seven of nine patients with HH (77.8%) became pregnant following infertility treatment. In some cases of HH, the serum levels of gonadotropin increased sporadically during follow-up, regardless of the recovery of menstruation. We followed one patient with HH for more than 20 years. Although her gonadotropin levels were generally low and sometimes fluctuated without spontaneous menstruation, they increased dramatically to menopausal levels at 50 years of age. However, they again decreased to hypogonadotropic levels. Conclusion As the pathophysiology varied widely among patients, the etiologic factors underlying HH might also vary.

Previous studies have largely failed to clarify the relationship between p16INK4A status and cervical adenocarcinoma prognosis. The current study aimed to examine the clinical and pathological significance of p16INK4A expression in several cervical adenocarcinoma subtypes. Eighty-two samples collected from patients with cervical adenocarcinoma were formalin fixed and paraffin embedded. Next, p16INK4A levels were analyzed with immunohistochemistry. Additionally, the relationship between p16INK4A expression and clinicopathological factors as well as prognosis was evaluated. The expression of p16INK4A was mostly detected in all usual cervical adenocarcinoma subtypes. In the gastric type, only a few cases were positive for p16INK4A expression. Results of the Kaplan–Meier analysis indicated that the positive p16INK4A expression in tumor cells was significantly associated with favorable progression-free survival and overall survival in patients with cervical adenocarcinoma (p = 0.018 and p = 0.047, respectively, log-rank test). Our findings suggest that the status of p16INK4A expression may influence prognosis. Thus, p16INK4A expression could be used as a biomarker for improving the prognosis of patients with cervical adenocarcinoma.

Background We identified pain variation according to prostate biopsy sites and compared differences in pain relief according to the site of periprostatic nerve block (PNB). Methods This retrospective study collected data from 312 patients who underwent transrectal prostate biopsies between January 2019 and August 2020. Patients were stratified into two groups according to the site of local anesthesia (base vs. base and apex PNB), with each block achieved with 2.5 cm3 of 2% lidocaine. Pain scores were assessed using the visual analog scale at the following time points: probe insertion, PNB at base, PNB at apex, each of the 12 core biopsy sites, and 15 min after biopsy. The results were analyzed using a linear mixed model. Results The average pain scores were significantly higher in the base-only PNB group than were those in the base and apex PNB group (3.88 vs 2.82, p p p Conclusions The pain scores varied at each site during the prostate biopsy. The provision of a base and apex PNB provided greater pain relief than does base-only PNB during prostate biopsy.

PURPOSE: The aim was to investigate the effect of dietary nitrate supplementation (in the form of beetroot juice, BRJ) for 20 days on salivary nitrite (a potential precursor of bioactive nitric oxide), exercise performance and high altitude (HA) acclimatisation in field conditions (hypobaric hypoxia). METHODS: This was a single-blinded randomised control study of 22 healthy adult participants (12 men, 10 women, mean age 28 ± 12 years) across a HA military expedition. Participants were randomised pre-ascent to receive two 70 ml dose per day of either BRJ (~12.5 mmol nitrate per day; n = 11) or non-nitrate calorie matched control (n = 11). Participants ingested supplement doses daily, beginning 3 days prior to departure and continued until the highest sleeping altitude (4800 m) reached on day 17 of the expedition. Data were collected at baseline (44 m altitude), at 2350 m (day 9), 3400 m (day 12) and 4800 m (day 17). RESULTS: BRJ enhanced the salivary levels of nitrite (p = 0.007). There was a significant decrease in peripheral oxygen saturation and there were increases in heart rate, diastolic blood pressure, and rating of perceived exertion with increasing altitude (p=

Purpose: To identify the indication for recommending prebiopsy magnetic resonance imaging (MRI) to prevent prostate cancer missed diagnoses in cases without prebiopsy MRI.Materials and Methods: Between January 2017 and September 2020, 585 patients suspected with prostate cancer underwent prostate biopsy after MRI. For patients with visible lesions, MRI-targeted biopsy using an image-based fusion program was performed in addition to the 12- core systematic biopsy. Patients for whom MRI was performed in other institutions (n=4) and patients who underwent target biopsy alone (n=7) were excluded.Results: Of 574 patients (median prostate-specific antigen [PSA] level, 6.88 ng/mL; mean age, 68.2 years), 342 (59.6%) were diagnosed with prostate cancer (visible lesions=312/449 [69.5%]; nonvisible lesions=30/123 [24.0%]). The detection rates of visible lesions stratified using the Prostate Imaging Reporting and Data System score (3 vs. 4 vs. 5) were 30.9% (54 of 175), 61.2% (150 of 245), and 90.1% (127 of 141), respectively. Multivariate analysis showed that PSA density was a significant factor for presence of visible lesions, prostate cancer, and significant prostate cancer diagnosis. Among patients with positive lesions, 27 (8.2%) were diagnosed with prostate cancer concomitant with negative systematic biopsy results. A PSA density of 0.15 ng/mL/cm3 was identified as the significant cutoff value for predicting positive target biopsy in groups with negative systematic biopsy. Sixty of the negative target lesions (26.1%) were diagnosed using systematic biopsy.Conclusions: To maximize cancer detection rates, both targeted and systematic biopsies should be implemented. PSA density was identified as a useful factor for recommending prebiopsy MRI to patients suspected with prostate cancer.

Osteopetrosis refers to a group of genetic skeletal disorders characterized by osteosclerosis and fragile bones. Osteopetrosis can be classified into autosomal dominant, autosomal recessive, or X-linked forms, which might differ in clinical characteristics and disease severity. Autosomal recessive osteopetrosis, also known as malignant osteopetrosis, has an earlier onset, more serious clinical symptoms, and is usually fatal. We encountered a 1-day-old girl who was born full-term via vaginal delivery, which was complicated by meconium-stained amniotic fluid, cephalo-pelvic disproportion, and nuchal cord. Routine neonatal care was provided, in addition to blood tests and chest radiography to screen for sepsis, as well as skull radiography to rule out head injuries. Initial blood tests revealed hypocalcemia, which persisted on follow-up tests the next day. Radiographic examinations revealed diffusely increased bone density and a "space alien" appearance of the skull. Based on radiographic and laboratory findings, the infantile form of osteopetrosis was suspected and genetic testing for identification of the responsible gene. Eventually, a heterozygous mutation of the T cell immune regulator 1, ATPase H+ transporting V0 subunit a3 (TCIRG1) gene (c.292C>T) was identified, making this the first reported case of neonatal-onset malignant osteopetrosis with TCIRG1 mutation in South Korea. Early-onset hypocalcemia is common and usually results from prematurity, fetal growth restriction, maternal diabetes, perinatal asphyxia, and physiologic hypoparathyroidism. However, if hypocalcemia persists, we recommend considering 'infantile of osteopetrosis' as a rare cause of neonatal hypocalcemia and performing radiographic examinations to establish the diagnosis.

Rationale Very early stage blood pressure (BP) levels may affect outcome in stroke patients who have successfully undergone recanalization following intra-arterial treatment, but the optimal target of BP management remains uncertain. Aim We hypothesized that the clinical outcome after intensive BP-lowering is superior to conventional BP control after successful recanalization by intra-arterial treatment. Sample-size estimates We aim to randomize 668 patients (334 per arm), 1:1. Methods and design We initiated a multicenter, prospective, randomized, open-label trial with a blinded end-point assessment (PROBE) design. After successful recanalization (thrombolysis in cerebral infarction score ≥ 2 b), patients with elevated systolic BP level, defined as the mean of two readings ≥ 140 mmHg, will be randomly assigned to the intensive BP-lowering (systolic BP Study outcomes The primary efficacy outcomes are from dichotomized analysis of modified Rankin Scale (mRS) scores at three months (mRS scores: 0–2 vs. 3–6). The primary safety outcomes are symptomatic intracerebral hemorrhage and death within three months. Discussion The OPTIMAL-BP trial will provide evidence for the effectiveness of active BP control to achieve systolic BP Clinical trial registration ClinicalTrials.gov Identifier: NCT04205305.

Objective We aimed to investigate the annual incidence and direct medical cost of adjustment disorder in general population using the National Health Insurance Service Database (NHID) in Korea.Methods To examine the incidence, we selected patients who had at least one medical claim for adjustment disorder and had not been diagnosed in the previous 365 days, from 2010 to 2017.Results The number of newly diagnosed cases of adjustment disorder from 2011 to 2017 were total 101,922. Annual incidence of adjustment disorder was ranged from 22.0 to 36.8 per 100,000 persons. The incidence of adjustment disorder was found more in female and highest among 70–79 years of age group and medical aid beneficiaries group. Annual prevalence of adjustment disorder was in the range from 95.4 to 116.4 per 100,000 persons. Estimated annual medical cost per person of adjustment disorder was ranged from 162 to 231.4 US dollars.Conclusion From 2011 to 2017, the annual incidence and direct medical cost of adjustment disorder in Korea were increased. Proper information on adjustment disorder will not only allows us to accumulate more knowledge but also lead to more appropriate therapeutic interventions.

Background and aim We aimed to develop a convolutional neural network (CNN)-based object detection model for the discrimination of gastric subepithelial tumors (SETs), such as gastrointestinal stromal tumors (GISTs) and leiomyomas, in endoscopic ultrasound (EUS) images. Methods We used 376 images from 114 patients with histologically confirmed gastric GIST or leiomyoma to train the EUS-CNN. We constructed the EUS-CNN using an EfficientNet CNN model for feature extraction and a weighted bi-directional feature pyramid network for object detection. We assessed the performance of our EUS-CNN by calculating its accuracy, sensitivity, specificity, and area under receiver operating characteristic curve (AUC) using a validation set of 170 images from 54 patients. Four EUS experts and 15 EUS trainees were asked to judge the same validation dataset, and the diagnostic yields were compared between the EUS-CNN and human assessments. Results In the per-image analysis, the sensitivity, specificity, accuracy, and AUC of our EUS-CNN were 95.6%, 82.1%, 91.2%, and 0.9234, respectively. In the per-patient analysis, the sensitivity, specificity, accuracy, and AUC for our object detection model were 100.0%, 85.7%, 96.3%, and 0.9929, respectively. The EUS-CNN outperformed human assessment in terms of accuracy, sensitivity, and negative predictive value. Conclusions We developed the EUS-CNN system, which demonstrated high diagnostic ability for gastric GIST prediction. This EUS-CNN system can be helpful not only for less-experienced endoscopists but also for experienced ones. Additional EUS image accumulation and prospective studies are required alongside validation in a large multicenter trial.

Rhinitis is among the most common respiratory diseases in children. Nonallergic rhinitis, which involves nasal symptoms without evidence of systemic allergic inflammation or infection, is a heterogeneous entity with diverse manifestations and intensities. Nonallergic rhinitis accounts for 16%–89% of the chronic rhinitis cases, affecting 1%–50% (median 10%) of the total pediatric population. The clinical course of nonallergic rhinitis is generally rather mild and less likely to be associated with allergic comorbidities than allergic rhinitis. Here, we aimed to estimate the rate of coexisting comorbidities of nonallergic rhinitis. Nonallergic rhinitis is more prevalent during the first 2 years of life; however, its underestimation for children with atopic tendencies is likely due to low positive rates of specific allergic tests during early childhood. Local allergic rhinitis is a recently noted phenotype with rates similar to those in adults (median, 44%; range, 4%–67%), among patients previously diagnosed with nonallergic rhinitis. Idiopathic rhinitis, a subtype of nonallergic rhinitis, has been poorly studied in children, and its rates are known to be lower than those in adults. The prevalence of nonallergic rhinitis with eosinophilia syndrome is even lower. A correlation between nonallergic rhinitis and pollution has been suggested owing to the recent increase in nonallergic rhinitis rates in highly developing regions such as some Asian countries, but many aspects remain unknown. Conventional treatments include antihistamines, intranasal corticosteroids, and recent treatments include combination of intranasal corticosteroids with azelastin or decongestants. Here we review the prevalence, diagnosis, comorbidities, and treatment recommendations for nonallergic rhinitis versus allergic rhinitis in children.

Background: Diabetic foot is one of the complications of diabetes mellitus, accompanied by infection, ulcer, deformity, and neuropathic arthropathy. The prevalence of diabetic foot is approximately 10% to 20% in adult diabetic patients over 30 years. Patients with diabetic foot show decreased life quality due to long-term treatment and hospital admission for various complications. Therefore, it is important to understand the etiology of diabetic foot and to prevent the accompanying complications.Current Concepts: Multiple complications of diabetic foot such as ulcers, infections, and deformities are derived from neuropathy (sensory, motor, and autonomic nerves) and angiopathy. Careful physical and radiologic examinations and laboratory evaluations are necessary to diagnose diabetic foot. Dressings, surgical decompressions, antibiotics, and vascular interventions are helpful for the treatment of ulcers in diabetic foot. Maintaining proper blood glucose levels and medication help control the neuropathies. Furthermore, patients should be educated on careful foot care to prevent complications.Discussion and Conclusion: Diabetic foot and its accompanying complications are difficult to treat and decrease patients’ quality of life. To prevent complications of diabetic foot, management of blood glucose, patient education on self-foot care, screening of high-risk factors, and cooperation of various medical specialists are needed.

Osteoporosis, one of the most serious public health concerns caused by an imbalance between bone resorption and bone formation, has a major impact on the population. Therefore, finding the effective osteogenic compounds for the treatment of osteoporosis is a promising research approach. In our study, tamarind (Tamarindus indica L.) seed polysaccharide (TSP) extracted from tamarind seed was subjected to synthesize its sulfate derivatives. The 1H NMR, FT-IR, SEM, monosaccharide compositions and elemental analysis data revealed that tamarind seed polysaccharide sulfate (TSPS) was successfully prepared. As the result, TSPS showed potent effects on inducing osteoblast differentiation via increasing alkaline phosphatase (ALP) activity up to 20% after 10 days and bone mineralization approximately 58% after four weeks at concentration of 20 μg/mL, whereas no statistically increase for both ALP activity and bone mineralization was observed in TSP treatment. Furthermore, TSPS enhanced expression of several marker genes in bone formation. Overall, the obtained data provided novelty on osteogenic compounds originated from TSP of T. indica, as well as scientific fundamentals on drug development and bone tissue engineering for the treatment of osteoporosis and other bone-related diseases.

Background This case report presents a case of Vulvar Crohn’s disease (VCD) in an adolescent, that is an uncommon manifestation of Crohn’s disease (CD) without gastrointestinal symptoms. Before treating CD itself with proper medication, vulvar abscess continued to recur without improvement. Case presentation We report the case of an 18-year-old woman with VCD. After treatment with azathioprine 50 mg daily and mesalazine 1 g three times daily, vulvar lesions resolved after 6 weeks. We collected electronic medical data on patient characteristics, and evaluated findings of physical examinations, pelvic MRI, and biopsy specimen obtained from gastroduodenoscopy/colonoscopy. Conclusions VCD is a rare manifestation of CD that may be misdiagnosed in the absence of gastrointestinal symptoms leading to delayed treatment. If a patient has an unexplained vulvar inflammatory lesion and with repeated failed surgical treatment, gynecologists should consider the possibility of a VCD.

In vertebrate embryogenesis, elongation of the posterior body is driven by de novo production of the axial and paraxial mesoderm as well as the neural tube at the posterior end. This process is presumed to depend on the stem cell-like population in the tail bud region, but the details of the gene regulatory network involved are unknown. Previous studies suggested the involvement of pou5f3, an Oct4-type POU gene in zebrafish, in axial elongation. In the present study, we first found that pou5f3 is expressed mainly in the dorsal region of the tail bud immediately after gastrulation, and that this expression is restricted to the posterior-most region of the elongating neural tube during somitogenesis. This pou5f3 expression was complementary to the broad expression of sox3 in the neural tube, and formed a sharp boundary with specific expression of tbxta (orthologue of mammalian T/Brachyury) in the tail bud, implicating pou5f3 in the specification of tail bud-derived cells toward neural differentiation in the spinal cord. When pou5f3 was functionally impaired after gastrulation by induction of a dominant-interfering pou5f3 mutant gene (en-pou5f3), trunk and tail elongation were markedly disturbed at distinct positions along the axis depending on the stage. This finding showed involvement of pou5f3 in de novo generation of the body from the tail bud. Conditional functional abrogation also showed that pou5f3 downregulates mesoderm-forming genes but promotes neural development by activating neurogenesis genes around the tail bud. These results suggest that pou5f3 is involved in formation of the posterior spinal cord.

BACKGROUND A decline in serum carbohydrate antigen 19-9 (CA19-9) levels during systemic chemotherapy is considered as a prognostic marker for patients with advanced pancreatic cancer. Neutrophil-to-lymphocyte ratio (NLR) has been extensively studied as a simple and useful indicator of prognosis in various cancers including pancreatic cancer. AIM To assess the prognostic significance of NLR and CA19-9 in patients with advanced pancreatic adenocarcinoma received first-line chemotherapy according to CA19-9 positivity. METHODS We retrospectively analyzed patients diagnosed with advanced pancreatic cancer who received first-line chemotherapy between January 2010 and July 2017 at the Catholic University of Seoul St. Mary’s Hospital. Patients were divided according to CA19-9 positivity (CA19-9-positive vs -negative groups) and pre-and post-treatment NLR levels. To determine cut-off value of NLR and CA19-9 reduction, time-dependent receiver operating characteristic curve was applied. We evaluated overall survival (OS) and progression-free survival (PFS) for each group using Kaplan-Meier method, and we performed multivariate analyses on the entire cohort. RESULTS We included 271 patients in this study. Cut-off value of NLR and CA19-9 reduction was determined as 2.62 and 18%. Multivariate analysis showed that post-treatment NLR < 2.62 and reduction of ≥ 18% of baseline CA19-9 were significantly associated with OS and PFS. Post-treatment NLR ≥ 2.62 showed hazard ratio (HR) of 2.47 [95% confidence interval (CI): 1.84-3.32, P < 0.001] and CA19-9 decline (≥ 18%) showed HR of 0.51 (95%CI: 0.39-0.67, P < 0.001) for OS. When CA19-9-positive patients were divided into groups according to CA19-9 response (responder vs non-responder) and post-treatment NLR (< 2.62 vs ≥ 2.62), CA19-9 responder and post-treatment NLR < 2.62 group showed better survival than CA19-9 non-responder and post-treatment NLR ≥ 2.62 group (OS 11.0 mo vs 3.9 mo, P < 0.001; PFS 6.3 mo vs 2.0 mo, P < 0.001). The combination of CA19-9 decline and post-treatment NLR showed a significant correlation with clinical response in CA 19-9 positive group. Within the CA19-9-negative group, the post-treatment NLR < 2.62 group showed better survival than the post-treatment NLR ≥ 2.62 group (OS 12.7 mo vs 7.7 mo, P < 0.001; PFS 6.7 mo vs 2.1 mo, P < 0.001), and post-treatment NLR showed correlation with clinical response. CONCLUSION In advanced pancreatic cancer patients positive for CA19-9 and treated with systemic chemotherapy, the combination of post-treatment NLR < 2.62 and 18% decline of CA19-9 at the first response evaluation is a good prognostic marker. Post-treatment NLR < 2.62 alone could be used as a prognostic marker and an adjunctive tool for response evaluation in CA19-9-negative patients.

Objective Symptoms of male overactive bladder (OAB) may be caused by several systemic pathophysiological factors rather than a single-source etiology. We investigated the clinical factors associated with the severity of OAB symptoms in treatment-naive men with coexisting benign prostatic hyperplasia. Methods We obtained records from a health promotion center database of male patients who visited between March 2019 and February 2020. Men without a history of treatment for lower urinary tract symptoms were evaluated using the International Prostate Symptom Score (IPSS), Overactive Bladder Symptom Score, transrectal ultrasonography, medical history, and carotid duplex ultrasound for the evaluation of atherosclerosis. Benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS) was defined as an IPSS of eight points or higher. Patients with comorbidities that may affect their voiding function were excluded. Results A total of 764 patients were divided into two groups based on their diagnosis: an OAB group and a non-OAB group. The non-OAB group consisted of 627 patients (82.1%) and the OAB group consisted of 137 patients (17.9%). Using multivariable analysis BPH/LUTS was identified as an independent risk factor for OAB. In the OAB group without BPH/LUTS, carotid atherosclerosis was significantly associated with the severity of OAB symptoms. A history of diabetes mellitus was the only variable that was associated with the severity of urinary urgency. Systolic blood pressure was associated with severity of urinary urgency in the OAB group with BPH/LUTS. Conclusions Factors associated with male OAB exhibit different pathophysiology in the severity of symptoms depending on the presence of BPH/LUTS. Treatment for atherosclerosis and associated systemic pathophysiological factors could lower OAB symptom severity in male patients without BPH/LUTS.

Kisspeptin and gonadotropin-releasing hormone (GnRH) are central regulators of the hypothalamic-pituitary-gonadal axis and control female reproductive functions. Recently established mHypoA-50 and mHypoA-55 cells are immortalized hypothalamic neuronal cell models that originated from the anteroventral periventricular nucleus (AVPV) and arcuate nucleus (ARC) regions of the mouse hypothalamus, respectively. mHypoA-50 or mHypoA-55 cells were stimulated with kisspeptin-10 (KP10) and GnRH, after which the expression of kisspeptin and GnRH was determined. Primary cultures of fetal rat brain cells were also examined. mHypoA-50 and mHypoA-55 cells expressed mRNA for Kiss-1 (which encodes kisspeptin) and GnRH as well as receptors for kisspeptin and GnRH. We found that Kiss-1 mRNA expression was significantly increased in mHypoA-50 AVPV cells by KP10 and GnRH stimulation. Kisspeptin protein expression was also increased by KP10 and GnRH stimulation in these cells. In contrast, GnRH expression was unchanged in mHypoA-50 AVPV cells by KP10 and GnRH stimulation. In mHypoA-55 ARC cells, kisspeptin expression was also significantly increased at the mRNA and protein levels by KP10 and GnRH stimulation; however, GnRH expression was also upregulated by KP10 and GnRH stimulation in these cells. KP10 and estradiol (E2) both increased Kiss-1 gene expression in mHypoA-50 AVPV cells, but combined stimulation with KP10 and E2 did not potentiate their individual effects on Kiss-1 gene expression. On the other hand, E2 did not increase Kiss-1 gene expression in mHypoA-55 ARC cells, and the KP10-induced increase of Kiss-1 gene expression was inhibited in the presence of E2 in these cells. KP10 and GnRH significantly increased c-Fos protein expression in the mHypoA-50 AVPV and mHypoA-55 ARC cell lines. In primary cultures of fetal rat neuronal cells, KP10 significantly increased Kiss-1 gene expression, whereas GnRH significantly increased GnRH gene expression. We found that kisspeptin and GnRH affected Kiss-1- and GnRH-expressing hypothalamic cells and modulated Kiss-1 and/or GnRH gene expression with a concomitant increase in c-Fos protein expression. A mutual- or self-regulatory system might be present in Kiss-1 and/or GnRH neurons in the hypothalamus.

This paper proposes a six-step operation strategy for direct self-control (DSC) method of interior permanent magnet synchronous motor (IPMSM) based on the torque angle. Conventional DSC methods for induction motors (IMs) have been studied for railway applications since these methods are suitable for controlling high-power traction drives and for extending voltage utilization through a six-step inverter operation. However, IPMSMs controlled via conventional DSC methods for IMs cannot be properly controlled through a six-step operation since the torque angle is not considered. In addition, synchronous frame rotation causes a phase error at high speeds owing to the time delay of digital controllers. This paper presents a torque angle compensation that improves the dynamic performance. The effectiveness of the proposed DSC method was verified through experimental results.

The glenohumeral internal rotation deficit (GIRD), primarily caused by the tightness of the posterior capsule, is a major risk factor for shoulder injuries in overhead throwing athletes. Quantitative evaluation of posterior capsular thickness and tightness can help determine the relationship between the posterior inferior capsule and GIRD. One previous study has assessed posterior capsule tightness using shear wave elastography (SWE), in college baseball players; however, it did not address the cutoff value of capsular elasticity that could be considered as abnormal capsular tightness. We aimed to re-evaluate effectiveness of SWE in quantifying posterior shoulder capsule tightness in college baseball players and determine the cutoff value of abnormal capsular elasticity that can predict impending throwing-related shoulder injuries associated with GIRD.Twenty-four college baseball players were enrolled in this study. External and internal rotation of the shoulder joint was assessed. The participants were classified into the GIRD group if their throwing shoulder showed20° of internal rotation loss compared with their nonthrowing shoulder. In a longitudinal ultrasonographic scan of the posterior inferior capsule, shear wave (SW) velocity and thickness were measured at the point nearest to the labrum on both shoulders.Of the 24 subjects, 6 had a GIRD. The mean value of the SW velocity in the throwing shoulder was greater in the GIRD group than in the non-GIRD group (P = .006). The SW velocity difference between the throwing and nonthrowing shoulder was also greater in the GIRD group than in the non-GIRD group (P.001). There was no significant difference in the thickness of the posterior inferior capsule between both groups. In correlation analysis, the difference in the SW velocity was more strongly correlated with the GIRD than with the SW velocity in the throwing shoulder. When we assume that a 20° GIRD is indicative of a shoulder at risk, the cutoff SW velocity in the throwing shoulder is 4.81 m/s and the SW velocity difference is 0.77 m/s.The SW velocity is closely associated with posterior shoulder capsular tightness and may be of quantitative value in baseball players.

Purpose: Adjuvant chemotherapy (AC) improves survival outcomes in patients with advanced gastric cancer (GC) after curative surgery; however, some patients do not receive or complete chemotherapy. This study aimed to identify factors related to patient compliance with chemotherapy after curative surgery for advanced GC.Methods: The data of patients who underwent curative gastrectomy for pathologic stage II–III GC between 2012 and 2016 were reviewed. Patients were divided into an AC completion group (group C), AC incompletion group (group I), and surgery-only group (group S). The AC regimen was either tegafur/gimeracil/oteracil (S-1) or capecitabine plus oxaliplatin (XELOX).Results: The study enrolled 417 patients; group C had 222 patients, group I had 110, and group S had 85. The most common reason for not initiating AC was poor general condition (36.5%), while chemotherapy-related complications was the common reason for AC incompletion (43.6%). In multivariate analysis, age over 65 years, Eastern Cooperative Oncology Group performance status ≥1, Charlson comorbidity index ≥1, and the presence of postoperative complications were independent risk factors for not initiating AC (odds ratio: 4.32, 2.62, 1.84, and 2.17, respectively). Age over 65 years, longer postoperative stay, and XELOX regimen were significant risk factors for incompletion of AC (odds ratio: 2.68, 1.72, and 2.23, respectively).Conclusion: Old age, poor performance status, comorbidities, and postoperative complications, longer postoperative hospital stay, and XELOX regimen were associated with poor compliance with AC in GC patients. Clinicians can improve compliance with AC by managing postoperative complications and selecting the most appropriate treatment regimen.

The purpose of this study was to evaluate the radiographic and clinical outcomes of patients with hallux valgus (HV) with concomitant metatarsus adductus (MA) treated with distal chevron metatarsal osteotomy (DCMO), without any procedure for the second or third metatarsal.A multicentre retrospective study involving four hospitals was conducted. A total of 45 feet from 38 patients who had received DCMO for HV with MA with at least one year post-operative follow-up were analysed. HV angle (HVâ), inter-metatarsal angle (IMâ), MA angle (MAâ), and the lateral sesamoid grade were measured. Foot function index (FFI) and visual analogue scale (VAS) were recorded. Patients were divided into mild (18° ≤ MAâ 20°) and moderate (20° ≤ MAâ) MA groups, and results were compared.The mean HVâ and IMâ improved significantly from 35.1° and 14.4° pre-operatively to 10.6° and 7.1° one year post-operatively (p 0.001). There were no differences in pre-operative HVâ, IMâ, or the sesamoid grade, and also no difference in post-operative HVâ or the sesamoid grade between mild and moderate MA groups. Only the mean post-operative IMâ showed a difference between the two groups (8.3° vs. 6.3°; p = 0.019). All clauses of FFI and VAS improved significantly (p 0.001). When the extent of improvement was compared between the two groups, there were no significant differences in any category (p 0.05). The total rate of recurrence (HVâ ≥ 20°) was 11.1% (5/45), and although the moderate group (4/29, 13.8%) had a higher proportion than the mild group (1/16, 6.3%), this was not statistically significant (p = 0.641).DCMO for patients with HV with MA had satisfactory radiographic and clinical outcomes with minimal recurrence. Except in cases of severe combined deformity, we recommend performing DCMO alone without any additional procedure or manipulation of the other metatarsals as a viable treatment option.

Background Peak oxygen uptake (peak VO2) is known not only as an index of aerobic fitness but also one of an index of life expectancy. Frailty, sarcopenia, and cachexia are associated with a poor prognosis and high mortality. The purpose of this study was to determine the relationships of peak VO2 with the features of sarcopenia, frailty, and cachexia, to provide insight into which might mediate the poor prognosis. Methods The first group of participants was 175 community‐dwelling older Japanese outpatients (58 men and 117 women; mean age 77.6 ± 6.4 years), in whom we assessed the features of sarcopenia, frailty, and cachexia, and measured peak VO2 during cardiopulmonary exercise. To confirm the relationships, we analysed another group of 162 participants (77.3 ± 5.5 years). Results There were significant correlations between peak VO2 and the features of sarcopenia, frailty, and cachexia, with the exception of high sensitivity C‐reactive protein. Multiple linear regression analysis for the prediction of peak VO2 (mL/min) identified following formula: predicted peak VO2 = −11.6 × age (years) + 25.5 × haemoglobin concentration (g/dL) + 114.2 × skeletal muscle mass index (kg/m2) + 8.9 × hand grip strength (kg) + 226.4 × usual walking speed (m/s) − 65.8 × fatiguability (absence 0, presence 1) − 177.4 × chronic heart failure (absence 0, presence 1) + 437.1 (R2 = 0.627, P

Polygonatum humile Fisch is commonly called Sookjuk in Korea. The roots of P. humile are typically used in traditional medicine as an anti-rheumatic, demulcent, and sedative agent. The aim of this study was to evaluate the potential of the P. humile extracts to treat depression. Mice were administered P. humile water extract (PH) and were subjected to the forced swim test (FST), tail suspension test (TST), and open-field test (OFT). The levels of brain monoamines including serotonin (5-HT), norepinephrine, and dopamine were evaluated. In addition, the PH antidepressant-like effects were studied based on the regulation of 5-HT-mediated Ca2+ and extracellular signal-regulated kinase 1/2 (ERK1/2) in human 1321N1 cells stably expressing the 5-HT subunit 6 receptor (5-HT6). In FST and TST, PH (300 mg/kg) significantly reduced the immobility time without changing the locomotor activity in mice. In addition, PH enhanced the level of 5-HT in the mice brain. The results further indicated an inhibitory activity of PH on both the 5-HT6 receptor expression level and the 5-HT6 receptor dependent downstream signal pathway ERK1/2.These findings indicated antidepressant-like effects of PH as evidenced by decreased immobility time in mice through a 5-HT6 receptor antagonistic mechanism.

Background Olanzapine, an FDA-approved atypical antipsychotic, is widely used to treat schizophrenia and bipolar disorder. In this study, the inhibitory effect of olanzapine on voltage-dependent K+ (Kv) channels in rabbit coronary arterial smooth muscle cells was investigated. Methods Electrophysiological recordings were performed in freshly isolated coronary arterial smooth muscle cells. Results Olanzapine inhibited the Kv channels in a concentration-dependent manner with an IC50 value of 7.76 ± 1.80 µM and a Hill coefficient of 0.82 ± 0.09. Although olanzapine did not change the steady-state activation curve, it shifted the inactivation curve to a more negative potential, suggesting that it inhibited Kv currents by affecting the voltage sensor of the Kv channel. Application of 1 or 2 Hz train pulses did not affect the olanzapine-induced inhibition of Kv channels, suggesting that its effect on Kv channels occurs in a use (state)-independent manner. Pretreatment with DPO-1 (Kv1.5 subtype inhibitor) reduced the olanzapine-induced inhibition of Kv currents. In addition, pretreatment with guangxitoxin (Kv2.1 subtype inhibitor) and linopirdine (Kv7 subtype inhibitor) partially decreased the degree of Kv current inhibition. Olanzapine induced membrane depolarization. Conclusion From these results, we suggest that olanzapine inhibits the Kv channels in a concentration-dependent, but state-independent, manner by affecting the gating properties of Kv channels. The primary Kv channel target of olanzapine is the Kv1.5 subtype.

Background and Purpose: Patients with acute stroke are often accompanied by comorbidities, such as active cancer. However, adequate treatment guidelines are not available for these patients. The purpose of this study was to evaluate the association between cancer and the outcomes of reperfusion therapy in patients with stroke. Methods: We compared treatment outcomes in patients who underwent reperfusion therapy, using a nationwide reperfusion therapy registry. We divided the patients into 3 groups according to cancer activity: active cancer, nonactive cancer, and without a history of cancer. We investigated reperfusion processes, 24-hour neurological improvement, adverse events, 3-month functional outcome, and 6-month survival and related factors after reperfusion therapy. Results: Among 1338 patients who underwent reperfusion therapy, 62 patients (4.6%) had active cancer, 78 patients (5.8%) had nonactive cancer, and 1198 patients (89.5%) had no history of cancer. Of the enrolled patients, 969 patients received intravenous thrombolysis and 685 patients underwent endovascular treatment (316 patients received combined therapy). Patients with active cancer had more comorbidities and experienced more severe strokes; however, they showed similar 24-hour neurological improvement and adverse events, including cerebral hemorrhage, compared with the other groups. Although the functional outcome at 3 months was poorer than the other groups, 36.4% of patients with active cancer showed functional independence. Additionally, 52.9% of the patients with determined stroke etiology showed functional independence despite active cancer. During the 6-month follow-up, 46.6% of patients with active cancer died, and active cancer was independently associated with poor survival (hazard ratio, 3.973 [95% CI, 2.528–6.245]). Conclusions: In patients with active cancer, reperfusion therapy showed similar adverse events and short-term outcomes to that of other groups. While long-term prognosis was worse in the active cancer group than the nonactive cancer groups, not negligible number of patients had good functional outcomes, especially those with determined stroke mechanisms.

Biallelic mutations in the dysferlin gene cause limb-girdle muscular dystrophy 2B or Miyoshi distal myopathy. We found that nonsense mutations are the most common mutation type among Korean patients with dysferlinopathy; more than half of the patients have at least one nonsense allele, which may be amenable to readthrough therapy. We generated a knockin mouse, dqx, harboring DYSF p.Q832∗ mutation. Homozygous dqx mice lacked dysferlin in skeletal muscle, while 2 weeks of oral ataluren restored dysferlin expression and ameliorated skeletal muscle pathology. Their physical performance improved, and protection against eccentric contractions was noted. The improvement was most evident in mice treated with oral ataluren of 0.9 mg/mL. These improvements were sustained for 8 weeks in ataluren-treated dqx mice, while the parameters of A/J mice treated with ataluren over the same period did not improve. These results support that readthrough therapy by oral ataluren may also be applicable to dysferlinopathy patients with nonsense mutation., Graphical abstract, Biallelic mutations in the dysferlin gene cause progressive muscle diseases. Many of the patients harbor nonsense mutation, which may be mitigated by readthrough therapy by ataluren. The authors report the first evidence of physical functional recovery by facilitation of nonsense readthrough in a dysferlin-deficient mouse model.