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Background The use of assays detecting cytomegalovirus (CMV)–specific T cell–mediated immunity may individualize the duration of antiviral prophylaxis after transplantation. Methods In this randomized trial, kidney and liver transplant recipients from 6 centers in Switzerland were enrolled if they were CMV-seronegative with seropositive donors or CMV-seropositive receiving antithymocyte globulins. Patients were randomized to a duration of antiviral prophylaxis based on immune monitoring (intervention) or a fixed duration (control). Patients in the control group were planned to receive 180 days (CMV-seronegative) or 90 days (CMV-seropositive) of valganciclovir. Patients were assessed monthly with a CMV ELISpot assay (T-Track CMV); prophylaxis in the intervention group was stopped if the assay was positive. The co-primary outcomes were the proportion of patients with clinically significant CMV infection and reduction in days of prophylaxis. Between-group differences were adjusted for CMV serostatus. Results Overall, 193 patients were randomized (92 in the immune-monitoring group and 101 in the control group), of whom 185 had evaluation of the primary outcome (87 and 98 patients). CMV infection occurred in 26 of 87 (adjusted percentage, 30.9%) in the immune-monitoring group and in 32 of 98 (adjusted percentage, 31.1%) in the control group (adjusted risk difference, −0.1; 95% confidence interval [CI], −13.0% to 12.7%; P =.064). The duration of prophylaxis was shorter in the immune-monitoring group (adjusted difference, −26.0 days; 95%, CI, −41.1 to −10.8 days; P <.001). Conclusions Immune monitoring resulted in a significant reduction of antiviral prophylaxis, but we were unable to establish noninferiority of this approach on the co-primary outcome of CMV infection. Clinical Trials Registration NCT02538172. [ABSTRACT FROM AUTHOR]

Simple Summary: Although shear-wave elastography has been utilized in diagnosing a malignant breast lesion and axillary lymph node metastasis, its potential role in predicting treatment response to neoadjuvant chemotherapy has not been thoroughly explored. In this study, we aimed to assess the possibility of elasticity values measured using SWE as a predictive marker for neoadjuvant chemotherapy in breast cancer. Our findings indicate that low tumor stiffness, as measured using SWE, was significantly associated with an excellent treatment response following neoadjuvant chemotherapy. This relationship was particularly evident in hormone-receptor-positive, HER2-negative breast cancer, and triple-negative breast cancer. Furthermore, we identified an inverse correlation between tumor stiffness and the tumor-infiltrating lymphocyte level, suggesting that tumors with high TIL levels tend to exhibit lower stiffness. Our findings suggest that SWE could be a useful tool in predicting treatment response and guiding treatment decisions in neoadjuvant chemotherapy for patients with breast cancer. Shear-wave elastography (SWE) is an effective tool in discriminating malignant lesions of breast and axillary lymph node metastasis in patients with breast cancer. However, the association between the baseline elasticity value of breast cancer and the treatment response of neoadjuvant chemotherapy is yet to be elucidated. Baseline SWE measured mean stiffness (E-mean) and maximum stiffness (E-max) in 830 patients who underwent neoadjuvant chemotherapy and surgery from January 2012 to December 2022. Association of elasticity values with breast pCR (defined as ypTis/T0), pCR (defined as ypTis/T0, N0), and tumor-infiltrating lymphocytes (TILs) was analyzed. Of 830 patients, 356 (42.9%) achieved breast pCR, and 324 (39.0%) achieved pCR. The patients with low elasticity values had higher breast pCR and pCR rates than those with high elasticity values. A low E-mean (adjusted odds ratio (OR): 0.620; 95% confidence interval (CI): 0.437 to 0.878; p = 0.007) and low E-max (adjusted OR: 0.701; 95% CI: 0.494 to 0.996; p = 0.047) were independent predictive factors for breast pCR. Low elasticity values were significantly correlated with high TILs. Pretreatment elasticity values measured using SWE were significantly associated with treatment response and inversely correlated with TILs, particularly in HR+HER2- breast cancer and TNBC. [ABSTRACT FROM AUTHOR]

Introduction: The role of inflammation in the pathophysiology of polycythemia vera (PV) is important. The presence of JAK2 mutations is important in the diagnosis of PV, and serum levels of erythropoietin (EPO) also play a supporting role. However, serum EPO levels show some limitations. The neutrophil‐to‐lymphocyte ratio (NLR) and platelet‐to‐lymphocyte ratio (PLR) are a readily available marker of inflammation. Thus, we examined whether NLR & PLR might diagnose PV in erythrocytosis patients. We compared NLR & PLR and EPO diagnostic values. Methods: We retrospectively reviewed clinical and laboratory data from two referral hospitals. Two hundred and eighty‐five patients with erythrocytosis who underwent a test for the JAK2 mutation were included. It wac classified as the PV group and the secondary polycythemia (SP) group. Results: The median NLR & PLR in the PV group (n = 70) was significantly higher than that in the SP group (n = 170) (NLR: 6.04 vs. 1.77, PLR: 283.18 vs. 101.56, respectively, p < 0.001). In the receiver operating characteristic analysis, the area under the curve of NLR & PLR was significantly higher than that of serum EPO (NLR vs EPO: 0.921 vs. 0.827, p = 0.003; PLR vs EPO: 0.917 vs 0.827, p = 0.003). Conclusion: In conclusion, NLR & PLR were higher in PV than in SP and showed better diagnostic value than serum EPO level, highlighting their potential as minor diagnostic criteria in patients with PV. [ABSTRACT FROM AUTHOR]

Tissue-specific gene expression generates fundamental differences in the function of each tissue and affects the characteristics of the tumors that are created as a result. However, it is unclear how much the tissue specificity is conserved during grafting of the primary tumor into an immune-compromised mouse model. Here, we performed a comparative RNA-seq analysis of four different primary-patient derived xenograft (PDX) tumors. The analysis revealed a conserved RNA biotype distribution of primary−PDX pairs, as revealed by previous works. Interestingly, we detected significant changes in the splicing pattern of PDX, which was mainly comprised of skipped exons. This was confirmed by splicing variant-specific RT-PCR analysis. On the other hand, the correlation analysis for the tissue-specific genes indicated overall strong positive correlations between the primary and PDX tumor pairs, with the exception of gastric cancer cases, which showed an inverse correlation. These data propose a tissue-specific change in splicing events during PDX formation as a variable factor that affects primary−PDX integrity. [ABSTRACT FROM AUTHOR]

Simple Summary: This research investigates the potential link between gum disease and stomach cancer in the Korean population. In this study, we analyzed data from over 10,000 people with gastric cancer and 40,000 healthy individuals. The results indicate that individuals who had gum disease in the past one to two years were more likely to develop stomach cancer. This association was consistently observed in different groups, such as men under 65 years old. The study emphasizes the importance of regular screening for stomach cancer, particularly for those at high risk, such as individuals with a history of gum disease. These findings contribute to our understanding of the connection between oral health and stomach cancer and may guide future preventive measures. There is limited information regarding the potential association between chronic periodontitis (CP) and gastric cancer, especially in the Korean population. This study aimed to explore this relationship. This nested case–control study analyzed data from 10,174 patients with gastric cancer and 40,696 controls from the Korean National Health Insurance Service–National Sample Cohort using propensity score matching. Standardized differences were used to compare baseline characteristics between study groups. Logistic regression analyses adjusted for confounders were conducted to assess the association between history of CP and gastric cancer occurrence. CP histories and comprehensive subgroup analyses in the 1- and 2-year periods preceding the index date were evaluated. Individuals with a history of CP within the 1-year and 2-year periods showed an increased likelihood of developing gastric cancer. Subgroup analyses consistently supported these findings in male participants aged <65 years and individuals with various income levels or living in residential areas. However, no significant associations were observed among participants aged ≥65 years. In conclusion, CP may be a potential risk factor for gastric cancer development in the Korean population. Regular screening for gastric cancer may be necessary for high-risk individuals, specifically men aged <65 years with a history of CP. [ABSTRACT FROM AUTHOR]

Background: High-flow nasal oxygenation and the oxygen reserve index (ORI), which is a non-invasive and innovative modality that reflects the arterial oxygen content, are used in general anaesthesia. This study compares the preoxygenation efficiency (measured by the ORI) of high-flow nasal oxygenation and facemask ventilation during the induction process. Methods: This single-centre, two-group, randomised controlled trial included 197 patients aged ≥ 20 years who underwent orotracheal intubation for general anaesthesia for elective surgery. The patients were randomly allocated to receive preoxygenation via facemask ventilation or high-flow nasal oxygenation. The ORI was measured and compared between both groups. Results: The ORI increased during preoxygenation in all patients. At 1 min of preoxygenation, the ORI was significantly higher in the high-flow nasal oxygenation group (0.34 ± 0.33) than in the facemask ventilation group (0.21 ± 0.28; P = 0.003). The highest ORI was not significantly different between the two groups (0.68 ± 0.25 in the high-flow nasal oxygenation group vs. 0.70 ± 0.28 in the facemask ventilation group; P = 0.505). Conclusions: High-flow nasal oxygenation results in an oxygenation status similar to that provided by facemask ventilation during the induction process of general anaesthesia; therefore, high-flow nasal oxygenation is a feasible preoxygenation method. Trial Registration: Clinicaltrials.gov (NCT04291339). [ABSTRACT FROM AUTHOR]

Patients with cartilage invasion in hypopharyngeal squamous cell carcinoma (HPSCC) would benefit from partial laryngopharyngectomy (PLP). The purpose of this study was to examine the treatment outcomes of PLP for HPSCC with cartilage invasion, with a focus on the oncological safety and the function preservation. We performed a retrospective review of 28 patients with HPSCC with thyroid or cricoid cartilage invasion who had undergone upfront surgery and were followed for more than one year between 1993 and 2019. Twelve patients treated with PLP (42.9%) and 16 patients treated with total laryngopharyngectomy (TLP) for cartilage invasion in HPSCC were identified. There was no significant difference in recurrence between the PLP group (7/12, 58.3%) and the TLP group (8/16, 50.0%) (p =.718). PLP was not associated with decreased five-year disease free survival (p =.662) or disease specific survival (p =.883) rates compared to TLP. Nine patients receiving PLP could be decannulated and retained intelligible speech (9/12, 75%). Gastrostomy tubes were placed in the PLP group (5/12, 42.9%) and TLP group (1/16, 6.2%) (p =.057). PLP appears to be a feasible option for the treatment of thyroid or cricoid cartilage invasion in HPSCC. [ABSTRACT FROM AUTHOR]

Objective: This clinical trial was conducted to investigate whether discontinuing methotrexate (MTX) for 1 week after seasonal influenza vaccination is noninferior to discontinuing for 2 weeks after vaccination in patients with rheumatoid arthritis (RA). Methods: In this multicenter, prospective, randomized, parallel‐group noninferiority trial, RA patients receiving a stable dose of MTX were randomly assigned at a ratio of 1:1 to discontinue MTX for 1 week or for 2 weeks after they received the quadrivalent 2021–2022 seasonal influenza vaccine containing H1N1, H3N2, B/Yamagata, and B/Victoria strains. The primary outcome measure was the proportion of patients with a satisfactory vaccine response, which was defined as ≥4‐fold increase in antibody titers, as determined with the hemagglutination inhibition assay, against ≥2 of the 4 vaccine strains at 4 weeks after vaccination. Results: The modified intent‐to‐treat population included 90 patients in the 1‐week MTX hold group and 88 patients in the 2‐week MTX hold group. The mean ± SD MTX doses were 12.6 ± 3.4 mg/week in the 1‐week MTX hold group and 12.9 ± 3.3 mg/week in the 2‐week MTX hold group. The proportion of satisfactory vaccine responses did not differ between the groups (68.9% versus 75.0%; P = 0.364). The rate of seroprotection and the fold increase in antibody titers for each of the 4 influenza antigens were similar between the groups. Conclusion: A temporary discontinuation of MTX for 1 week after vaccination was noninferior to a discontinuation of MTX for 2 weeks after vaccination, regarding induction of a satisfactory vaccine response to a seasonal influenza vaccine in patients with RA receiving a stable dose of MTX. [ABSTRACT FROM AUTHOR]

Simple Summary: Though women account for approximately 30% of newly diagnosed head and neck cancer, women have comprised only 17% of the study population in landmark clinical trials so far. Caution is therefore required when applying research outcomes directly to women in actual clinical practice. We hypothesized that there is no difference in treatment strategies and their effect on survival in treating locally advanced head and neck squamous cell carcinoma (LA-HNSCC) in the real world. We aimed to compare multidisciplinary treatment modalities and their outcomes by sex in 445 patients with stage III to IVB LA-HNSCC. In our overall and propensity-matched cohorts, there were no significant differences in the treatment strategy or OS by gender. In the present era, in which a multidisciplinary approach is emphasized, we conclude that there is no apparent sex-based disparity in the treatment modalities and outcomes in treating LA-HNSCC. We aimed to compare treatment modalities and outcomes by gender in patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC). We characterized the sex-specific differences and compared the overall survival (OS) between male and female patients in a multicenter cohort of LA-HNSCC. To minimize the observed confounding, propensity score matching was utilized. The study included 445 patients; 385 (86.5%) were men and 60 (13.5%) were women. In terms of age, smoking habits, drinking habits, and primary tumor locations, there was a significant imbalance in sex before the matching. Propensity score matching yielded 60 patient pairs, with no statistical difference between the sexes in terms of their characteristics. As for the treatment strategies, there were no significant differences between the sexes before (p = 0.260) and after (p = 0.585) the propensity score matching. When comparing the survival probabilities between the sexes, OS was not significantly different in the overall (HR 1.02; 95% CI 0.59–1.76; p = 0.938) and propensity-score-matched population (HR 1.46; 95% CI 0.68–3.17; p = 0.331). These results suggest that there was no difference in prognosis by gender in the treatment modalities and outcomes of LA-HNSCC in real-world practice. [ABSTRACT FROM AUTHOR]

Summary: TBS algorithm has been updated to account for regional soft tissue noise. In postmenopausal women with osteoporosis, denosumab improved tissue thickness–adjusted TBS vs placebo independently of bone mineral density over 3 years, with the magnitude of changes from baseline or placebo numerically greater than body mass index–adjusted TBS. Introduction: To evaluate the effect of denosumab on bone microarchitecture assessed by trabecular bone score (TBS) in the FREEDOM study using the updated algorithm that accounts for regional soft tissue thickness (TBSTT) in dual-energy X-ray absorptiometry (DXA) images and to compare percent changes from baseline and placebo with classical body mass index (BMI)–adjusted TBS (TBSBMI). Methods: Postmenopausal women with lumbar spine or total hip bone mineral density (BMD) T score < − 2.5 and ≥ − 4.0 received placebo or denosumab 60 mg subcutaneously every 6 months. TBSBMI and TBSTT were assessed on lumbar spine DXA scans at baseline and months 1, 12, 24, and 36 in a subset of 279 women (129 placebo, 150 denosumab) who completed the 3-year FREEDOM DXA substudy and rolled over to open-label extension study. Results: Baseline characteristics were similar between groups. TBSTT in the denosumab group showed numerically greater changes from both baseline and placebo than TBSBMI at months 12, 24, and 36. Denosumab led to progressive increases in BMD (1.2, 5.6, 8.1, and 10.5%) and TBSTT (0.4, 2.3, 2.6, and 3.3%) from baseline to months 1, 12, 24, and 36, respectively. Both TBS changes were significant vs baseline and placebo from months 12 to 36 (p < 0.0001). As expected, BMD and TBSTT were poorly correlated both at baseline and for changes during treatment. Conclusion: In postmenopausal women with osteoporosis, denosumab significantly improved bone microstructure assessed by TBSTT over 3 years. TBSTT seemed more responsive to denosumab treatment than TBSBMI and was independent of BMD. [ABSTRACT FROM AUTHOR]

Introduction: We evaluated the radiologic and clinical outcomes of a lateral incision single plate with and a single-incision double plating in elderly patients with osteoporotic distal femoral fractures. Materials and methods: We performed a retrospective study of 82 cases of distal femoral fractures from May 2004 to June 2018. Group A consisted of 42 patients who underwent single-plate fixation. Group B consisted of 40 patients who underwent double-plate fixation. The mean patient age was 77 years (67–87 years) and 76 years (64–86 years) in groups A and B, respectively. All patients were evaluated for procedure duration, time to union, range of knee motion, Lysholm knee score, and presence of complications. Results: The average procedure time was 81 min (66–92 min) and 110 min (95–120 min) in groups A and B, respectively (p = 0.33). One case in group B required bone grafting after 5 months. The average time to union was 14 weeks (9–19 weeks) and 12.2 weeks (8–19 weeks) (p = 0.63), and the mean range of knee motion was 105° (90–125°) and 110.7° (90°–130°) (p = 0.37) in groups A and B, respectively. There was no significant statistical difference between the two groups in the Lysholm knee score (p = 0.44) and knee society score (p = 0.53). Conclusion: The clinical and radiological outcomes were similar in the 2 groups. In elderly patients, double plate fixation for distal femoral fractures is an useful method for several advantages such as adequate exposure, easy manipulation, anatomical reduction and stable fixation. [ABSTRACT FROM AUTHOR]

Background Data on the clinical and virological characteristics of the Delta variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are limited. This prospective cohort study compared the characteristics of the Delta variant to other variants. Methods Adult patients with mild coronavirus disease 2019 (COVID-19) who agreed to daily saliva sampling at a community isolation facility in South Korea between July and August 2021 were enrolled. Scores of 28 COVID-19-related symptoms were recorded daily. The genomic RNA and subgenomic RNA from saliva samples were measured by real-time reverse-transcription polymerase chain reaction (PCR). Cell cultures were performed on saliva samples with positive genomic RNA results. Results A total of 141 patients (Delta group, n = 108 [77%]; non-Delta group, n = 33 [23%]) were enrolled. Myalgia was more common in the Delta group than in the non-Delta group (52% vs 27%, P  = .03). Total symptom scores were significantly higher in the Delta group between days 3 and 10 after symptom onset. Initial genomic RNA titers were similar between the 2 groups; however, during the late course of disease, genomic RNA titers were higher in the Delta group. Negative conversion of subgenomic RNA was slower in the Delta group (median 9 vs 5 days; P  < .001). The duration of viral shedding in terms of positive viral culture was also longer in the Delta group (median 5 vs 3 days; P  = .002). Conclusions COVID-19 patients infected with the Delta variant exhibited prolonged viable viral shedding with more severe symptoms than those infected with non-Delta variants. [ABSTRACT FROM AUTHOR]

There is growing interest in conservative treatment of Achilles tendon rupture. However, the majority of experimental studies of Achilles tendon have been performed by open tenotomy. More appropriate model of conservative treatment of Achilles tendon rupture is required. We performed an experimental study to evaluate whether outcomes differ between open tenotomy and percutaneous tenotomy of the Achilles tendon in rats. The Achilles tendons of 48 rats were transected. The animals were divided into two groups according to surgical technique: open tenotomy or microscopy‐assisted percutaneous tenotomy. After 1, 2, and 4 weeks, functional, biomechanical, and histological analyses were performed. Western blot was performed for quantitative molecular analysis at 1 week. The Achilles functional index was superior in the percutaneous tenotomy group, compared with the open tenotomy group, at 1 week. The cross‐sectional area was significantly larger in the percutaneous tenotomy group than in the open tenotomy group at 4 weeks. Relative to the native tendons, load to failure and stiffness yielded comparable results at 2 weeks in the percutaneous tenotomy group and at 4 weeks in the open tenotomy group. The histological score was significantly better in the percutaneous tenotomy group than in the open tenotomy group at 1 week. At 1 week, interleukin‐1β expression in the open tenotomy group was higher than in the percutaneous tenotomy group. In summary, Achilles tendon healing was substantially affected by the tenotomy method. We presume that our percutaneous tenotomy method might constitute a useful experimental animal model for conservative treatment of Achilles tendon rupture. [ABSTRACT FROM AUTHOR]

This study focused on the nonlinear rheological characterization of three types of cellulose nanofibril (CNF) suspensions under large amplitude oscillatory shear (LAOS) flow. Three different CNFs were produced, two by mechanical fibrillation alone under different conditions [here named microfibrillated cellulose (MFC) and U-CNF] and the other by mechanical fibrillation after carboxymethylation (CM-CNF). MFC and U-CNF had broad width distributions, whereas CM-CNF had narrower fibril width and width distribution due to the presence of charged carboxymethyl groups. Nonlinear stress responses of the prepared suspensions were analyzed using the sequence of physical processes method. All CNF suspensions exhibited intracycle rheological transitions composed of three physical processes: (1) structure recovery, (2) elastic deformation to early stage yielding, and (3) late-stage yielding. MFC and U-CNF suspensions exhibited similar rheological transitions overall. However, CM-CNF suspension had a higher network recovery rate within a shorter time and showed an additional yielding step due to the complex interplay between recovery and yielding dynamics. This result originated from complete nanofibrillation and charged functional groups on fibril surfaces. Rapid reformation of effective fibril–fibril contacts in CM-CNF suspension was attributed to electrostatic repulsions and complete nanosized lateral dimensions. In addition, excitation frequency was found to influence intracycle rheological transitions. A range of intracycle rheological transitions became narrower on increasing frequency because the time period for each transition was not enough under faster flow conditions. In particular, the characteristic yielding step of CM-CNF suspension disappeared on increasing frequency, which suggested that high-frequency excitation might be unfavorable for the nonlinear viscoelastic characterization of soft materials under LAOS flow. [ABSTRACT FROM AUTHOR]

Objectives: The food delivery market is growing rapidly. As most delivery riders use motorcycles, motorcycle crashes will increase along with the growing delivery market size. This study aimed at examining the proportions of motorcycle crashes and characteristics of injuries incurred while using motorcycles for occupational purposes.Methods: This retrospective analysis included motorcycle crash patients aged 16 years or older, who were treated in 23 emergency rooms in Korea, between 2014 and 2018. Patients were divided into two groups: delivery riders (delivery group) and others (nondelivery group). Crash and injury characteristics were compared between the two groups. In addition, trends of patients in the delivery group were compared from 2014 to 2018.Results: This study examined 26,982 motorcycle crash patients, including 3894 (14.43%) patients in the delivery group and 23,088 (85.57%) in the nondelivery group. The number of patients in the delivery group increased drastically from 583 in 2014 to 1029 in 2018, whereas the number of patients in the nondelivery group did not considerably increase (4411 in 2014 and 4462 in 2018). The delivery group had a higher proportion of crashes caused by collisions with cars or other motorcycles (p < 0.001); however, injury severity was lower. The delivery group had a lower proportion of head and face injuries but a higher proportion of extremity injuries. Furthermore, 39.9% of all crashes in this group occurred between 17:00 and 21:00. Over time, there were neither any changes in the injury severities, nor any changes in the characteristics of the delivery group, with the exception of increases in both the proportion of motorist insurance and the proportion of wearing a helmet.Conclusions: The results indicated differences in characteristics between delivery motorcycle crashes and other motorcycle crashes. Although delivery motorcycle crash severity was low compared to other motorcycle crashes, the number of patients increased significantly. Therefore, to prevent crashes, it is necessary to improve the working environment. In addition, to prevent the extremity injuries of delivery riders, the policy of wearing extremity protective gears should be considered. [ABSTRACT FROM AUTHOR]

Introduction: Exposure to suicidal death may cause trauma and change the bereaved family/friends' attitudes towards suicide and increase their suicide-related behavior. We aimed to examine the life-time prevalence of loss experience among the general population of South Korea, the relationship between attitudes towards suicide and suicidal intensity, and the moderation effect of interest in news media.Methods: After analyzing 2973 structured interviews, we hypothesized structural equation model and conducted a moderation analysis.Results: A total of 10.1% (n = 301) respondents had experienced the suicide of acquaintances. Acceptive attitudes such as "suicide as right" and "suicide as normal-common" were higher in the "experienced" group. All fit indices of the hypothesized model were satisfied, and experience of suicidal loss was positively associated with both acceptive attitudes and suicidal intensity. "Suicide as normal-common" positively affected suicidal intensity, but "suicide as right" was not significant. "Interest in news media" significantly moderated the relationship between loss experience and suicidal intensity.Limitations: Since our study was cross-sectional design, further longitudinal studies are needed to draw casual inferences between factors. We used the at home interview method, which might have resulted underestimated experience of suicidal loss.Conclusion: Our findings showed that experiencing suicide death of any acquaintances could increase individual's acceptance of suicide and also increase the risk of suicide. Frequent exposure to suicide-related news amplified their risk of suicide. To reduce the suicide risk behavior, targeted intervention with those bereaved by suicide and restriction of media reports on suicide news will be needed as prevention strategies. [ABSTRACT FROM AUTHOR]

Hypertension is a leading risk factor for cardiovascular events and death. Despite differences in clinical implications of hypertension between men and women, guidelines establishing optimal blood pressure (BP) targets are still debated. The aim of this study was to investigate sex differences in the BP level associated with increased risks of major adverse cardiac and cerebral events (MACCEs) among antihypertensive-treated patients. Using data from the Korean National Health Insurance Service-National Sample Cohort, we enrolled antihypertensive-treated patients and divided them into four categories: Group 1: SBP < 120 and DBP < 80 mm Hg; Group 2: 120 ≤ SBP < 130 and DBP < 80 mm Hg; Group 3: 130 ≤ SBP < 140 or 80 ≤ DBP < 90 mm Hg; and Group 4: SBP ≥ 140 or DBP ≥ 90 mm Hg. We performed time-dependent cox regression analysis to investigate sex differences in the BP levels that increased the risk of MACCEs. Most of the 98 267 patients fell into Group 3 (53.2% men and 52.8% women) and Group 4 (30.5% men and 28.1% women). During 8.34 ± 2.07 years, there were 8,813 MACCEs and 791 deaths. The incidences of MACCEs and death tended to increase as the BP increased in both sexes. Compared to Group 1, the risk of MACCEs significantly increased only in Group 4 for men, while it significantly increased in Groups 3 and 4 for women. This study shows that there are sex differences in the BP level at which the risk of MACCEs increases. Our finding suggests that sex should be significantly considered when determining the optimal BP target in patients undergoing hypertension treatment. [ABSTRACT FROM AUTHOR]

Background: Metabolism including anabolism and catabolism is a prerequisite phenomenon for all living organisms. Anabolism refers to the synthesis of the entire compound needed by a species. Catabolism refers to the breakdown of molecules to obtain energy. Many metabolic pathways are undisclosed and many organism-specific enzymes involved in metabolism are misplaced. When predicting a specific metabolic pathway of a microorganism, the first and foremost steps is to explore available online databases. Among many online databases, KEGG and MetaCyc pathway databases were used to deduce trehalose metabolic network for bacteria Variovorax sp. PAMC28711. Trehalose, a disaccharide, is used by the microorganism as an alternative carbon source. Results: While using KEGG and MetaCyc databases, we found that the KEGG pathway database had one missing enzyme (maltooligosyl-trehalose synthase, EC 5.4.99.15). The MetaCyc pathway database also had some enzymes. However, when we used RAST to annotate the entire genome of Variovorax sp. PAMC28711, we found that all enzymes that were missing in KEGG and MetaCyc databases were involved in the trehalose metabolic pathway. Conclusions: Findings of this study shed light on bioinformatics tools and raise awareness among researchers about the importance of conducting detailed investigation before proceeding with any further work. While such comparison for databases such as KEGG and MetaCyc has been done before, it has never been done with a specific microbial pathway. Such studies are useful for future improvement of bioinformatics tools to reduce limitations. [ABSTRACT FROM AUTHOR]

Background: Trifolium pratense (red clover) ethanolic extract (TPEE) has been used as a popular over-the-counter remedy for the management of menopausal symptoms. Prolonged consumption of herbal extract has been shown to regulate the composition of gut microbiota. This study was designed to elucidate the influence of TPEE on the gut microbiota composition in the ovariectomized (OVX) rats. Methods: OVX rats were treated with TPEE at 125, 250, 500 mg/kg/day, or controls (pomegranate extract, 500 mg/kg/day; estradiol, 25 μg/kg/day) for 12 weeks. Gut microbiota analysis was conducted by extracting the microbial DNA from fecal samples and microbiome taxonomic profiling was carried out by using next-generation sequencing. The levels of serum biomarkers were analyzed using enzyme-linked immunosorbent assay (ELISA) kit. The prediction of functional biomarker of microbiota was performed using PICRUSt to investigate the potential pathways associated with gut health and serum lipid profile regulation. To study the correlation between gut microbiota composition and serum lipid levels, Spearman's correlation coefficients were defined and analyzed. Additionally, gas chromatography–mass spectrometry analysis was conducted to uncover additional physiologically active ingredients. Results: TPEE-treated OVX rats showed significant reduction in serum triglycerides (TG), total cholesterols (TCHOL), and LDL/VLDL levels but increase in HDL level. The alteration in the pathways involve in metabolism was the most common among the other KEGG categories. Particularly, TPEE also significantly reduced the relative abundance of sequences read associated with inflammatory bowel disease (IBD) and the peroxisome proliferator-activated receptor (PPAR) signalling pathway. TPEE intervention was seen to reduce the Firmicutes to Bacteroidetes (F/B) ratio in the OVX rats, denoting a reduction in microbial dysbiosis in the OVX rats. Correlation analysis at the phylum level revealed that Bacteriodetes and Proteobacteria were strongly correlated with serum TG, TCHOL and HDL levels. At the species level, Bifidobacterium pseudolongum group was seen to positively correlate with serum HDL level and negatively correlated with serum AST, ALT, LDL/VLDL, TCHOL, and TG levels. Conclusions: TPEE treatment showed therapeutic benefits by improving the intestinal microbiota composition which strongly correlated with the serum lipid and cholesterol levels in the OVX rats. [ABSTRACT FROM AUTHOR]

Background: Short stature is the most consistent characteristic feature of Turner syndrome (TS). To improve final heights of children with TS effectively, it is important to provide them with early and appropriate treatment using growth hormone (GH). The objective of this study was to assess the efficacy and safety of a new recombinant human GH, Growtropin®-II (DA-3002, Dong-A ST Co., Ltd) versus a comparator (Genotropin®, Pfizer Inc.) for Korean children with TS. Methods: This open-label, active-controlled, parallel-group, randomized controlled phase III trial was conducted at 11 hospitals in Korea. Eligible patients (n = 58) were randomized to two groups: 1) DA-3002 group (administrated with DA-3002 at 0.14 IU [0.0450–0.050 mg] /kg/day); and 2) comparator group (administrated with the comparator at 0.14 IU [0.0450–0.050 mg] /kg/day). Results: The change from baseline in annualized height velocity (HV) after a 52-week treatment period was 4.15 ± 0.30 cm/year in the DA-3002 group and 4.34 ± 0.29 cm/year in the comparator group. The lower bound of 95% two-sided confidence interval for group difference in the change of annualized HV (− 1.02) satisfied the non-inferiority margin (− 1.5). The change in height standard deviation score (HtSDS) at 52-week was 0.70 ± 0.23 for the DA-3002 group and 0.66 ± 0.39 for the comparator group, showing no significant (p = 0.685) difference between the two groups. The change of skeletal maturity defined as change in bone age/change in chronological age between the two groups was not significantly different (1.25 ± 0.58 for the DA-3002 group and 1.47 ± 0.45 for the comparator group, p = 0.134). Changes from baseline in serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) after 52 weeks of treatment did not differ significantly between the two groups (p = 0.565 and p = 0.388, respectively) either. The occurrence of adverse events was not statistically different between groups. Conclusions: This study demonstrates that the efficacy and safety of GH treatment with DA-3002 in children with TS are comparable with those of the comparator. It is expected to analysis the long-term effect of DA-3002 on the increase of final adult height in children with TS and possible late-onset complications in the future. Trial registration: The study was registered at ClinicalTrials.gov. ClinicalTrials.gov identifier: NCT01813630 (19/03/2013). [ABSTRACT FROM AUTHOR]

Objective: The risk of procedure-related complications and rhythm outcomes differ between men and women after atrial fibrillation catheter ablation (AFCA). We evaluated whether consistent sex differences existed in mapping and rhythm outcomes in repeat ablation procedures.Methods: Among 3282 patients in the registry, we analysed 443 consecutive patients (24.6% female, 58.5±10.3 years old, 61.5% with paroxysmal atrial fibrillation) who underwent a second AFCA. We compared the clinical factors, mapping, left atrial (LA) pressure, complications and long-term clinical recurrences after propensity score matching.Results: LA volume index (43.1±18.6 vs 35.8±11.6 mL/m2, p<0.001) was higher, but LA dimension (40.0±6.8 vs 41.6±6.3 mm, p=0.018), LA voltage (0.94±0.55 vs 1.20±0.68 mV, p=0.002) and pericardial fat volume (89.5±43.1 vs 122.1±53.9 cm3, p<0.001) were lower in women with repeat ablation than in their male counterparts. Pulmonary vein (PV) reconnections were lower (58.7% vs 74.9%, p=0.001), but the proportion of extra-PV triggers (27.5% vs 17.0%, p=0.026) and elevated LA pulse pressures (79.7% vs 63.7%, p=0.019) was significantly higher in women than in men. There was no significant sex difference in the rate of procedure-related complications (4.6% vs 4.2%, p=0.791). During a 31-month (8-60) median follow-up, clinical recurrences were significantly higher in women after both the de novo procedure (log-rank p=0.039, antiarrhythmic drug (AAD)-free log-rank p<0.001) and the second procedure (log-rank p=0.006, AAD-free log-rank p=0.093). Female sex (HR 1.51, 95% CI 1.06 to 2.15, p=0.023), non-paroxysmal atrial fibrillation (HR 1.78, 95% CI 1.30 to 2.34, p<0.010) and extra-PV triggers (HR 1.88, 95% CI 1.28 to 2.75, p=0.001) were independently associated with clinical recurrences after repeat procedures.Conclusions: During repeat AFCA procedures, PV reconnections were lower in women than in men, and the existence of extra-PV triggers and an LA pressure elevation were more significant, which resulted in poor rhythm outcomes.Trial Registration Number: NCT02138695. [ABSTRACT FROM AUTHOR]

Background: We assessed the prognostic accuracy of the standardized electroencephalography (EEG) patterns ("highly malignant," "malignant," and "benign") according to the EEG timing (early vs. late) and investigated the EEG features to enhance the predictive power for poor neurologic outcome at 1 month after cardiac arrest.Methods: This prospective, multicenter, observational, cohort study using data from Korean Hypothermia Network prospective registry included adult patients with out-of-hospital cardiac arrest (OHCA) treated with targeted temperature management (TTM) and underwent standard EEG within 7 days after cardiac arrest from 14 university-affiliated teaching hospitals in South Korea between October 2015 and December 2018. Early EEG was defined as EEG performed within 72 h after cardiac arrest. The primary outcome was poor neurological outcome (Cerebral Performance Category score 3-5) at 1 month.Results: Among 489 comatose OHCA survivors with a median EEG time of 46.6 h, the "highly malignant" pattern (40.7%) was most prevalent, followed by the "benign" (33.9%) and "malignant" (25.4%) patterns. All patients with the highly malignant EEG pattern had poor neurologic outcomes, with 100% specificity in both groups but 59.3% and 56.1% sensitivity in the early and late EEG groups, respectively. However, for patients with "malignant" patterns, 84.8% sensitivity, 77.0% specificity, and 89.5% positive predictive value for poor neurologic outcome were observed. Only 3.5% (9/256) of patients with background EEG frequency of predominant delta waves or undetermined had good neurologic survival. The combination of "highly malignant" or "malignant" EEG pattern with background frequency of delta waves or undetermined increased specificity and positive predictive value, respectively, to up to 98.0% and 98.7%.Conclusions: The "highly malignant" patterns predicted poor neurologic outcome with a high specificity regardless of EEG measurement time. The assessment of predominant background frequency in addition to EEG patterns can increase the prognostic value of OHCA survivors. Trial registration KORHN-PRO, NCT02827422 . Registered 11 September 2016-Retrospectively registered. [ABSTRACT FROM AUTHOR]

Objective: To identify patterns of physical activity (PA) participation, exercise preference, and barriers of stage 2–3 prostate cancer survivors across cancer trajectories based on selected demographic and medical variables. Design: The current study is a descriptive cross-sectional study which included data from a total of 111 prostate cancer survivors, at Shinchon Severance Hospital, Seoul, Korea. The survey includes PA levels before and after prostate cancer diagnosis, exercise barriers, and preferences. Results: Moderate- to vigorous-intensity PA levels were significantly lower after cancer diagnosis (vigorous PA:41.9 ± 123.1 min/week vs. 4.6 ± 29.8 min/week, p < 0.001; moderate PA: 159.9 ± 240.0 min/week vs. 56.8 ± 129.7 min/week, p <.001) compared to their PA level before cancer diagnosis. Perceived exercise barriers were distinctly different according to participants' age and time since surgery. The two most prevalent exercise barriers among prostate cancer survivors <65 years were lack of time (28.6%) and poor health (26.5%), whereas the exercise barriers for prostate cancer survivors aged ≥65 years were lack of exercise facilities (21.4%) and lack of exercise information (17.9%). Furthermore, within 6 months after surgery, prostate cancer survivors perceived poor health (29.5%) and pain at the surgery site (29.5%) to be the two most prevalent exercise barriers. 6 months after surgery, prostate cancer survivors perceived lack of time (21.3%) and poor health (14.8%) to be the two most prevalent exercise barriers. Walking, pelvic floor and Kegel exercises were three most preferred exercises among prostate cancer survivors in our study, which uniquely differ according to time since surgery. Conclusion: This study showed significant reduction in PA levels among prostate cancer survivors and their perceived exercise barriers were distinct according to their age and time since surgery. Therefore, PA and exercise recommendation should be specific to their personal characteristics such as age and time since surgery. [ABSTRACT FROM AUTHOR]

Type 2 diabetes is a multifactorial disease with multiple underlying aetiologies. To address this heterogeneity, investigators of a previous study clustered people with diabetes according to five diabetes subtypes. The aim of the current study is to investigate the etiology of these clusters by comparing their molecular signatures. In three independent cohorts, in total 15,940 individuals were clustered based on five clinical characteristics. In a subset, genetic (N = 12,828), metabolomic (N = 2,945), lipidomic (N = 2,593), and proteomic (N = 1,170) data were obtained in plasma. For each data type, each cluster was compared with the other four clusters as the reference. The insulin-resistant cluster showed the most distinct molecular signature, with higher branched-chain amino acid, diacylglycerol, and triacylglycerol levels and aberrant protein levels in plasma were enriched for proteins in the intracellular PI3K/Akt pathway. The obese cluster showed higher levels of cytokines. The mild diabetes cluster with high HDL showed the most beneficial molecular profile with effects opposite of those seen in the insulin-resistant cluster. This study shows that clustering people with type 2 diabetes can identify underlying molecular mechanisms related to pancreatic islets, liver, and adipose tissue metabolism. This provides novel biological insights into the diverse aetiological processes that would not be evident when type 2 diabetes is viewed as a homogeneous disease. [ABSTRACT FROM AUTHOR]

Stereo photogrammetry is a fundamental technique for 3D measurements in different applications. As passive stereo methods struggle in texture-less regions, different light-coded patterns are projected to solve the correspondence problem. When the reconstruction method requires a series of sequentially coded light patterns, the system is prone to movement-related errors. A single pattern is utilized where the potential subjects are dynamic or change the position rapidly. A random speckle pattern is a good candidate for such systems. Primarily, there are two approaches to generate the speckle pattern in stereoscopic systems. The speckles can be generated by the coherent illumination of a laser diode, and the laser speckle-like pattern can also be simulated and projected by a professional projector. The purpose of both is to solve the stereo correspondence problem; however, the performance of both can differ, subjective to employed 3D sensing algorithm. In this Letter, we compare the performance of both for single-shot 3D reconstruction. We have discussed the pros and cons of both methods and analyze their ability to resolve long range 3D reconstruction. [ABSTRACT FROM AUTHOR]

Cerebrovascular lesions are widely prevalent in patients with Alzheimer's disease (AD), but their relationship to the pathophysiology of AD remains poorly understood. An improved understanding of the interaction of cerebrovascular damage with AD is crucial for the development of therapeutic approaches. Herein, we investigated the effects of chronic cerebral hypoperfusion (CCH) in a 5XFAD transgenic (Tg) mouse model of AD. We established CCH conditions in both Tg and non-Tg mice by inducing unilateral common carotid artery occlusion (UCCAO). Cognitive performance in mice was evaluated, and their brain tissue was examined for amyloid-beta (Aβ) pathology to elucidate possible mechanisms. We found that UCCAO-operated Tg mice showed impaired cognitive flexibility in the reversal phase of the hidden-platform water maze task compared to sham-operated Tg mice. Interestingly, UCCAO-operated Tg mice used fewer spatial cognitive strategies than sham-operated Tg mice during reversal learning. These cognitive deficits were accompanied by increased Aβ plaque burden and Aβ42 levels in the hippocampus and prefrontal cortex, 2 regions that play essential roles in the regulation of cognitive flexibility. Furthermore, changes in cognitive flexibility are strongly correlated with the expression levels of enzymes related to Aβ clearance, such as neprilysin and insulin-degrading enzymes. These findings suggest that, in 5XFAD mice, impaired cognitive flexibility is related to CCH, and that Aβ clearance might be involved in this process. [ABSTRACT FROM AUTHOR]

Background: Continuous glucose monitoring (CGM)-derived metrics, including time in range (TIR), are attracting attention as new indicators, beyond hemoglobin A1c, of glycemic control and diabetes complications. This study investigated the associations between CGM-derived TIR, hyperglycemia, and hypoglycemia metrics and cardiovascular autonomic neuropathy (CAN) in patients with type 2 diabetes. Methods: A total of 284 patients with type 2 diabetes who underwent CGM using GOLD™ (Medtronic MiniMed) for 3 days or iPro™2 (Medtronic MiniMed) for 6 days and autonomic function tests within 3 months based on outpatient data were recruited. The definition of CGM-derived metrics was subject to the most recent international consensus. CAN was defined as an abnormal result in two or more parasympathetic test, and the severity of CAN was estimated as the sum of the scores of the five cardiovascular autonomic function tests. Results: A total of 84 patients (29.6%) were diagnosed with CAN, and the mean TIR was 57.0% ± 7.0%. A multiple logistic regression analysis revealed that the odds ratio (OR) of presence of CAN was 0.876 [95% confidence interval (CI): 0.79-0.98] per 10% increase in the TIR 70-180 mg/dL, after adjusting for age, sex, diabetes duration, any medications, and glycemic variability. A 10% increase in the TIR was significantly inversely associated with the severity of CAN (OR: 0.89, 95% CI: 0.81-0.98). Among the metrics of hyperglycemia, each 10% increase in a time above range (TAR) >180 mg/dL was also independently correlated with the presence of CAN (OR: 1.141, 97.5% CI: 1.01-1.29) and the severity of CAN (OR: 1.13, 97.5% CI: 1.01-1.26). Conclusion: A TIR 70-180 mg/dL and a TAR >180 mg/dL were significantly associated with CAN in outpatients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background: To investigate the impacts of depression screening, diagnosis and treatment on major adverse cardiac events (MACEs) in acute coronary syndrome (ACS). Methods: Prospective cohort study including a nested 24-week randomised clinical trial for treating depression was performed with 5–12 years after the index ACS. A total of 1152 patients recently hospitalised with ACS were recruited from 2006 to 2012, and were divided by depression screening and diagnosis at baseline and 24-week treatment allocation into five groups: 651 screening negative (N), 55 screening positive but no depressive disorder (S), 149 depressive disorder randomised to escitalopram (E), 151 depressive disorder randomised to placebo (P) and 146 depressive disorder receiving medical treatment only (M). Results: Cumulative MACE incidences over a median 8.4-year follow-up period were 29.6% in N, 43.6% in S, 40.9% in E, 53.6% in P and 59.6% in M. Compared to N, screening positive was associated with higher incidence of MACE [adjusted hazards ratio 2.15 (95% confidence interval 1.63–2.83)]. No differences were found between screening positive with and without a formal depressive disorder diagnosis. Of those screening positive, E was associated with a lower incidence of MACE than P and M. M had the worst outcomes even compared to P, despite significantly milder depressive symptoms at baseline. Conclusions: Routine depression screening in patients with recent ACS and subsequent appropriate treatment of depression could improve long-term cardiac outcomes. [ABSTRACT FROM AUTHOR]

We investigated the therapeutic effect of a postoperative hospital-based systemic rehabilitation protocol on ankle function in chronic ankle instability (CAI) patients. Thirty-five patients who underwent a modified Broström procedure for CAI were recruited in this prospective randomized controlled trial. Fifty-minute sessions of hospital-based rehabilitation were performed three times weekly for 12 weeks in the intervention group. Education-based rehabilitation was conducted at home in the control group. The outcomes were evaluated at baseline (T0), 12 weeks (T1), and 16 weeks (T2). The primary outcome was the foot and ankle outcome score (FAOS). Ankle motor strength and spatiotemporal gait metrics were assessed as secondary outcomes. There were significant time and group interaction effects on the pain, symptoms, activities of daily living, sports activities, and quality of life (QOL) domains of the FAOS (P < 0.05 , all). The patients in the intervention group showed larger improvements in all domains of the FAOS than did the control group at both T1 and T2 (P < 0.05 , all). The time and group interaction effects on invertor and evertor strength were also significant (P = 0.047 and P = 0.044). Invertor and evertor strength improved significantly more in the intervention group than in the control group at T1 and T2 (P < 0.05 , all). The preferred walking velocity, cadence, step length on the affected side, and double stance phase duration tended to improve over time. Postoperative hospital-based rehabilitation helped improve CAI pain, symptoms, independence in activities of daily living, sports activity levels, and QOL more effectively than did conventional rehabilitation at home. [ABSTRACT FROM AUTHOR]

Background: Some sea anemone toxins cause renal injuries resembling hemolytic uremic syndrome (HUS). To date, only a few cases of HUS caused by sea anemone stings have been reported. In this case report, we have described an HUS case caused by a sea anemone sting.Case Presentation: In November 2019, a 37-year-old man with no underlying disease was admitted to our hospital. He presented with intense pain, a rash on, and swelling in his right thigh. Two days prior, he had been stung by a sea anemone while scuba diving in Cebu, Philippines. His blood tests revealed renal dysfunction, and his platelet count was normal. However, on day three, the platelet count decreased rapidly. His blood haptoglobin level decreased, and schistocytes were identified on the peripheral blood smear. We suspected thrombotic microangiopathy and started the conventional treatment, comprising hemodialysis, blood transfusion, and antibiotic administration. ADAMTS-13 and genetic test results associated with atypical HUS were normal. Therefore, the patient was diagnosed with HUS caused by a sea anemone toxin.Conclusions: HUS caused by a sea anemone toxin is rare, but it is a serious medical disease. Clinicians should consider HUS in patients with such clinical presentations, and they should make prompt treatment-related decisions. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate the effect of androgen suppression therapy (AST), comprising a 5-α reductase inhibitor (5-ARi) and androgen deprivation therapy (ADT), on the risk of bladder cancer incidence, recurrence, and mortality.Materials and Methods: We used the PRISMA statement to report the methods and results of this meta-analysis. Bladder cancer incidence, recurrence, and mortality after 5-ARi treatment and ADT were assessed using risk ratios (RRs) and hazard ratios (HRs) with 95% confidence intervals (CIs). The protocol of this study is registered in the PROSPERO database (No. CRD42018118627).Results: We analyzed nine studies (n = 377,427) assessing the secondary effect of AST, with a mean follow-up period of 6 years (range, 2-13 years). Our result showed that the incidence of bladder cancer was significantly reduced when 5-ARi treatment (RR, 0.69; 95% CI, 0.58-0.81; I2 =0%) and ADT (HR, 0.81; 95% CI, 0.70-0.94; I2 =33%) were initiated before diagnosing bladder cancer. When treatment was initiated after diagnosing bladder cancer, 5-ARi treatment reduced cancer-specific mortality (RR, 0.29; 95% CI, 0.20-0.42; I2 =4.1%), whereas ADT reduced bladder cancer recurrence (HR, 0.30; 95% CI, 0.19-0.49; I2 =0%).Conclusions: This study corroborates that the use of 5-ARi and ADT could be helpful in managing bladder cancer and should not be limited to prostatic abnormalities. [ABSTRACT FROM AUTHOR]

Background and Purpose: Charcot-Marie-Tooth (CMT) disease is the most common hereditary peripheral neuropathy. CMT type 1A (CMT1A) accounts for approximately 50% of CMT patients and is linked to PMP22 gene duplication. Histone deacetylase-6 (HDAC6) has pleiotropic effects, such as regulating lipid homeostasis and cellular stress. Although HDAC6 has been regarded as a promising drug target for neurodegenerative diseases, its inhibition has not yet been tested in CMT1A. Here we have tested the therapeutic potential of CKD-504, a clinical stage HDAC6 inhibitor, in a mouse model of CMT1A EXPERIMENTAL APPROACH: The potency and selectivity of CKD-504 was evaluated, using a HDAC enzyme panel assay and western blots. The therapeutic potential of CKD-504 was evaluated using behavioural testing and electrophysiological assessments in the C22 mouse model of CMT1A. PMP22 protein expression and aggregation were analysed in mesenchymal stem cell-derived Schwann cells from CMT1A patients and sciatic nerves from C22 mice.Key Results: The HDAC6 inhibitor, CKD-504, modulated molecular chaperon proteins such as HSP90 and HSP70, which are involved in the folding/refolding of proteins such as PMP22. CKD-504 treatment restored myelination in both mesenchymal stem cell-derived Schwann cells from CMT1A patients and sciatic nerves of C22 mice and improved the axonal integrity of the sciatic nerve, leading to behavioural, electrophysiological, and histological improvements in C22 mice.Conclusion and Implications: A novel HDAC6 inhibitor, CKD-504, has potent therapeutic efficacy for CMT1A. [ABSTRACT FROM AUTHOR]

Functional analyses of genes are crucial for unveiling biological responses, genetic engineering, and developing new medicines. However, functional analyses have largely been restricted to model organisms, representing a major hurdle for functional studies and industrial applications. To resolve this, comparative genome analyses can be used to provide clues to gene functions as well as their evolutionary history. To this end, we present Prometheus, a web-based omics portal that contains more than 17,215 sequences from prokaryotic and eukaryotic genomes. This portal supports interkingdom comparative analyses via a domain architecture-based gene identification system and Gene Search, and users can easily and rapidly identify single or entire gene sets in specific pathways. Bioinformatics tools for further analyses are provided in Prometheus or through Bio-Express, a cloud-based bioinformatics analysis platform. Prometheus is a new paradigm for comparative analyses of large amounts of genomic information. [ABSTRACT FROM AUTHOR]

Background: The number of technology-dependent children (TDC) is increasing in South Korea, but available healthcare services after their discharge are poor. This study aimed to examine how TDC and caregivers live at home and identify their difficulties and needs regarding home care with few services to support them.Methods: This cross-sectional study was conducted in a tertiary hospital for children in South Korea. A self-reported questionnaire was completed by primary caregivers of TDC who were younger than 19 years and had been dependent on medical devices for more than 3 months. Technologies included home mechanical ventilation, oxygen supplementation, suction equipment, enteral feeding tube, and home total parenteral nutrition. Patterns of healthcare use and home care of TDC and caregivers' perception toward child were assessed.Results: A total of 74 primary caregivers of TDC completed a self-reported questionnaire. About 60% children were aged under 5 years. There were 31.1% children who required both respiratory and nutritional support. On average, caregivers took care of a child for 14.4 (±6.1) hours, slept for 5.6 (±1.6) hours, and spent 2.4 h per day on personal activities. Children used hospital services for 41.3 (±45.6) days in 6 months, and most (78.1%) were transported through private car/ambulance. Participants (75.6%) reported taking more than an hour to get to the hospital. More than 80% of caregivers responded that child care is physically very burdensome. The only statistically significant relationships was between economic status and financial burden (p = 0.026).Conclusions: Caregivers of TDC reported having significant time pressure regarding childcare-related tasks, insufficient time for personal activities, and inefficient hospital use because of inadequate medical services to support them in South Korea. Thus, it is necessary to support caregivers and develop a home care model based on current medical environment. [ABSTRACT FROM AUTHOR]

Background: Suicide is a major cause of death in many countries, and previous suicidal attempt is known to be the predictor of future suicide. Korea is considered one of the countries with the highest suicide rate among the Organisation for Economic Co-operation and Development (OECD) members for over a decade. We aimed to investigate the epidemiologic characteristics of hospitalised patients after suicidal acts in Korea.Methods: Data from the Korean National Hospital Discharge In-depth Injury Survey were analysed, and patients older than 9 years admitted to nationwide hospitals after suicidal acts from 2005 to 2016 were included. Their epidemiologic characteristics were explored, and we divided them into groups according to suicidal means (injury vs. poisoning) and treatment outcome (good vs. poor). The association of each characteristic with injury as suicidal means and with poor treatment outcome were explored.Results: The sample included 7609 patients (corresponding to 227,571 in national population). More patients were female than male, and most were in their 40s in both sexes. Hospitalisation rate peaked in patients older than 80 years for both sexes. Male and young patients aged 10-19 years and capital residents showed relatively higher odds of choosing injury as suicidal means. Males and patients aged 40-64 and ≥65 years showed relatively higher odds of poor treatment outcome.Limitations: Some suicide attempters were excluded from the survey such as those who did not visit a hospital after the suicide attempt.Conclusions: This epidemiologic feature of suicide attempters might serve as baseline data for preventive policies regarding suicide. [ABSTRACT FROM AUTHOR]

Objective: There are few studies on cerebral palsy (CP) in African children and our study aimed to describe the aetiology, characteristics and severity of CP in children from Nigeria.Design: A population-based study using key informant methodology (KIM) was conducted as part of a clinical research trial. Children aged 4-15 years were clinically assessed for CP.Results: The estimated prevalence of CP using KIM was 2.3/1000 children (95% CI 2.0 to 2.5/1000). 388 children were diagnosed with CP, with Gross Motor Function Classification System level 1 in 70 (18.1%), II in 156 (40.2%), III in 54 (13.9%), IV in 54 (13.9%), V in 54 (13.9%). 300/388 (77.3%) had Manual Ability Classification Scale of level 1-3 and 88 (22.7%) of level 4-5. CP types were spastic in 271 (70%), with 60% of these bilateral and 40% unilateral, ataxic 38 (9.8%), dystonic 18 (4.6%), choreoathetoid 29 (7.5%) and unclassifiable 32 (8.3%). Postneonatal risk factors for CP were seen in 140 (36.1%) children including malaria with seizures 101/140 (72.1%), malaria with coma 21/140 (15.0%), meningitis 12/140 (8.6%), tuberculosis 2/140 (1.4%), sickle cell disease 3/140 (2.2%), HIV 1/221 (0.7%). Prenatal/perinatal risk factors were seen in 248 (63.9%%), birth asphyxia 118 (47.6%) and clinical congenital rubella syndrome 8 (3.3%) and hyperbilirubinaemia 59 (23.8%) were identified as preventable risk factors for CP.Conclusion: The profile of CP in this population is similar to that found in other low-income and middle-income countries (LMIC). Some risk factors identified were preventable. Prevention and management strategies for CP designed for LMIC are needed. [ABSTRACT FROM AUTHOR]

Background: We postulated that the use of robotics may improve outcomes in hiatal hernia repair.Methods: We performed a retrospective analysis of a prospectively collected Society of Thoracic Surgery database at a single institution of patients who underwent elective hiatal hernia repair from 2012 to 2017 using either laparoscopy or the da Vinci Xi robot. We compared patient characteristics and outcomes and then performed univariate and multivariate logistic regression modeling to determine the factors associated with postoperative morbidity.Results: There were 293 consecutive patients who underwent elective hiatal hernia repair using either a laparoscopic (n = 151) or a robotic (n = 142) technique. There were no significant differences in age, gender, BMI, smoking history, presence of comorbidity, or hiatal hernia type. Seventy percent of the cases were a repair of either type III or type IV hiatal hernia. There were significantly higher ASA III and IV (7.9% vs. 4.2%, P = 0.03), higher Toupet fundoplication (83.4% vs. 44.4%, P < 0.001), and lower redo-repair (7.3% vs. 20.4%, P = 0.001) in the laparoscopic group compared to the robotic group. The hospital length of stay was significantly shorter (1.3 ± 1.8 vs. 1.8 ± 1.5 days, P = 0.003) and there were significantly lower rates of complications (6.3 vs. 19.2%, P = 0.001) after robotic compared to laparoscopic hiatal hernia repair. There was no difference in readmission rate and mortality. Multiple logistic regression analysis showed that older age and laparoscopic technique were associated with higher complications after surgery.Conclusion: The use of the Da Vinci Xi robot in our institution was associated with improved outcomes compared to laparoscopic hiatal hernia repair despite a higher incidence of re-operative cases in the robotic group. Thus, short-term outcomes of Da Vinci Xi robot-assisted hiatal hernia repair are not inferior to laparoscopic hiatal hernia repair. Further studies are needed to determine if Da Vinci Xi robot provides superior short-term and long-term outcome in treatment of symptomatic hiatal hernia. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) is a lethal and highly vascular type of brain tumor. We previously reported that isolinderalactone enhances GBM apoptosis in vitro and in vivo, but its role in tumor angiogenesis is unknown. Here, we investigated the anti-angiogenic activity of isolinderalactone and its mechanisms. In a human GBM xenograft mouse model, isolinderalactone significantly reduced tumor growth and vessels. Isolinderalactone decreased the expression of vascular endothelial growth factor (VEGF) mRNA, protein, and VEGF secretion in hypoxic U-87 GBM cells and also in xenograft GMB tissue. In addition, we demonstrated that isolinderalactone significantly inhibited the proliferation, migration, and capillary-like tube formation of human brain microvascular endothelial cells (HBMECs) in the presence of VEGF. We also found that isolinderalactone decreased sprout diameter and length in a 3D microfluidic chip, and strongly reduced VEGF-triggered angiogenesis in vivo Matrigel plug assay. Isolinderalactone downregulated hypoxia-inducible factor-1α (HIF-1α) and HIF-2α proteins, decreased luciferase activity driven by the VEGF promoter in U-87 cells under hypoxic conditions, and suppressed VEGF-driven phosphorylation of VEGFR2 in HBMECs. Taken together, our results suggest that isolinderalactone is a promising candidate for GBM treatment through tumor angiogenesis inhibition. [ABSTRACT FROM AUTHOR]

Background: Intratympanic gentamicin injection (ITG) is a well-accepted means to treat intractable Meniere's disease (MD). Aims/Objectives: To investigate change of vestibule-ocular reflex (VOR) gain and pure-tone threshold after low-dose ITG for MD. Methods: Sixteen patients with definite MD who were treated by low-dose ITG were retrospectively reviewed. We defined VOR gain difference as an amount of decreased gain in video head impulse test one month after ITG. Patients were classified into two groups: single injection vs. multiple injections. Multiple injections group was composed of patients with poor vertigo control after initial ITG who required second or third ITG later in follow up period. Results: VOR gain differences of both horizontal and posterior canal plane were higher than those of anterior canal plane. Between two groups, mean VOR gain difference of horizontal canal plane in multiple injections group was lower than that in single injection group. Only two patients showed increased pure-tone threshold more than 10 dB. Conclusion and significance: Our results suggest that ITG appears to cause a differential loss of function across three semicircular canals. Furthermore, if VOR gain difference of horizontal canal is relatively low after initial ITG, patient might have poor vertigo control and be required another ITG. [ABSTRACT FROM AUTHOR]

Background: Despite advances in medical technology, resources for pediatric palliative care (PPC) for children with serious illnesses are limited in South Korea. Physicians' awareness of and willingness to provide general palliative care and refer to specialized palliative care are key elements for providing PPC. Objective: The aim of this study was to explore physicians' perceptions of PPC and the differences therein between nononcologists and oncologists. Design: A nationwide survey was conducted among physicians caring for children in 45 tertiary hospitals in South Korea. Measurements: A questionnaire was developed to identify the confidence in and need for PPC, appropriate timing for PPC referrals, and perceived barriers to PPC. Results: Overall, 141 physicians responded (response rate: 10.4%). Physicians' confidence in PPC was low, although most reported a high need for PPC. Lack of workforce and facilities specialized in PPC (60.2%) and patients' or caregivers' negative recognition (55.9%) were reported as the main barriers to PPC implementation. Specialized PPC services in children's hospitals were preferred as the model of care (84.2%). Compared with nononcologists, oncologists showed higher confidence levels in decision making and communication with patients and families with poor prognosis (p = 0.041) and education and providing end-of-life care (p < 0.001). Furthermore, oncologists preferred earlier referrals than did nononcologists. Conclusions: To promote PPC provision and improve the quality of life of pediatric patients and their families, it is important to introduce PPC early into disease-modifying treatment at any level of health care. Developing education and training curricula regarding PPC for health care providers caring for children with severe illnesses is crucial. [ABSTRACT FROM AUTHOR]

Although lenalidomide plus dexamethasone (RD) is a therapeutic option for relapsed/refractory multiple myeloma (RRMM), limited real-world clinical data exist. The purpose of this study was to estimate efficacy and safety of RD in RRMM patients of the clinical practice. Data from patients at 25 university hospitals in South Korea between October 2009 and December 2016 were collected retrospectively. We report the effectiveness and safety of RD in 546 RRMM patients in routine clinical practice in South Korea. Patients (median age, 65 years) typically received median 7 cycles of RD, and 184 (33.7%) patients were treated with 10 or more cycles of RD. Patients with renal impairment (CLCr < 40 mL/min; 10.4%), comorbid conditions (≥ 2; 12.0%), and poor performance status (≥ 2; 25.1%) were included. The overall response rate was 64.2%: complete response (13.1%), very good partial response (VGPR 19.9%). With median follow-up duration of 18.6 months, median PFS and OS were 11.2 months and 25.2 months, respectively. In multivariate analysis, less than 2 comorbid conditions, normal LDH, failed one chemotherapy prior to RD, and ≥ 10 cycles of RD therapy had significantly prolonged PFS (P = 0.007, P = 0.011, P = 0.007, and P < 0.001, respectively). Adverse events were acceptable. RD is effective and safe in real-life clinical practice, including patients with comorbidities. RD is an effective and safe treatment in a real clinical setting which includes patients with comorbidities. Early and continual use of RD treatment may improve RRMM survival outcomes. [ABSTRACT FROM AUTHOR]

Background: Panic disorder (PD) is a prevalent and highly disabling mental condition. However, less is known about relationships between biomarkers that may together predict a better response to pharmacological treatment. The objective of the present study was to compare the brain white matter (WM) connectivity between treatment-responsive patients with panic disorder (RPD) and non-responsive patients with panic disorder (NRPD) after 12 weeks of pharmacotherapy.Methods: Sixty-four patients with PD were enrolled in this study (RPD, n = 37; NRPD, n = 27). All patients were examined by using magnetic resonance imaging at 3 Tesla. The Panic Disorder Severity Scale (PDSS), Albany Panic and Phobia Questionnaire (APPQ), Anxiety Sensitivity Inventory-Revised (ASI-R), Beck Anxiety Inventory (BAI), and Beck Depression Inventory (BDI) were administered at baseline of the study. Fractional anisotropy (FA) data were compared using tract-based spatial statistics (TBSS).Results: TBSS results showed that the FA values of the patients with NRPD were significantly higher than of those with RPD in the WM regions such as the precentral gyrus, parahippocampal gyrus, posterior corona radiata, posterior thalamic radiation, posterior parts of the corpus callosum, and precuneus. Symptom severity scales, such as ASI-R scores, showed significant positive correlations of the FA values with the fronto-temporal WM regions in NRPD.Conclusions: These results suggest that structural changes to areas such as the fronto-limbic regions and the posterior part of default mode network, could influence medication response in PD. Further studies with a larger number of patients should be performed to confirm our findings. [ABSTRACT FROM AUTHOR]

Background: Rectal preservation against medical advice after neoadjuvant chemoradiotherapy for rectal cancer may increase oncologic uncertainty. This study aimed to compare the oncologic outcomes of patients undergoing rectal preservation as intended by the surgeon, and the outcomes of patients refusing rectal resection against medical advice. Methods: The study population consisted of patients in whom the rectum was preserved after neoadjuvant chemoradiotherapy for clinical stage I–III mid or low rectal cancer between May 2003 and August 2017 (n = 2883); these patients were divided into those in whom rectal preservation was intended by their surgeon (intended rectal preservation, group A, n = 41) and those in whom the rectum was not resected against medical advice (unintended rectal preservation, group B, n = 101), defined as non-operative management or local excision. Results: The tumor distance, age, and performance status of patients were not significantly different between the groups, while the clinical T stage before chemoradiotherapy was lower in group A than in group B (P < 0.001). During the median follow-up period of 34 months (interquartile range 18.0–72.0 months), the 3-year overall survival in group B (59.7%) was worse than that in group A (90.1%; P < 0.001), and 80.2% of group B patients had residual or unknown disease status. Conclusions: This study showed that unintended rectal preservation increases oncologic risk after neoadjuvant chemoradiotherapy for rectal cancer regardless of short-term follow-up. Therefore, these findings could be shared with rectal cancer patients who choose to ignore medical advice after chemoradiotherapy to preserve their rectum. [ABSTRACT FROM AUTHOR]

Background: The association between diabetes mellitus (DM) and bone diseases is acknowledged. However, the mechanistic pathways leading to the alveolar bone (AB) destruction remain unclear. This study aims to elucidate the mechanical forces (MF)-induced AB destruction in DM and its underlying mechanism.Methods: In vivo periodontal tissue responses to MF were evaluated in rats with diabetes. In vitro human periodontal ligament (PDL) cells were either treated with advanced glycation end products (AGEs) alone or with AGEs and MF.Results: In vivo, the transcription of VEGF-A, colony stimulating factor-1 (CSF-1), and Ager was upregulated in diabetes, whereas changes in DDOST and Glo1 mRNAs were negligible. DM induced VEGF-A protein in the vascular cells of the PDL and subsequent angiogenesis, but DM itself did not induce osteoclastogenesis. MF-induced AB resorption was augmented in DM, and such augmentation was morphologically substantiated by the occasional undermining resorption as well as the frontal resorption of the AB by osteoclasts. The mRNA levels of CSF-1 and vascular endothelial growth factor (VEGF) during MF application were highly elevated in diabetes, compared with those of the normal counterparts. In vitro, AGEs treatment elevated Glut-1 and CSF-1 mRNA levels via the p38 and JNK pathways, whereas OGT and VEGF levels remained unchanged. Compressive MF especially caused upregulation of VEGF, CSF-1, and Glut-1 levels, and such upregulation was further enhanced by AGEs treatment.Conclusions: Overloaded MF and AGEs metabolites may synergistically aggravate AB destruction by upregulating CSF-1 and VEGF. Therefore, regulating the compressive overloading of teeth, as well as the levels of diabetic AGEs, may prove to be an effective therapeutic modality for managing DM-induced AB destruction. [ABSTRACT FROM AUTHOR]

Background and aims: Subcutaneous fat mass is negatively correlated with atherogenic risk factors, but its putative benefits remain controversial. We hypothesized that genetic variants that influence subcutaneous fat mass would modulate lipid and glucose metabolism and have interactions with lifestyles in Korean middle-aged adults with high visceral fat. Materials and methods: Subcutaneous fat mass was categorized by dividing the average of subscapular skin-fold thickness by BMI and its cutoff point was 1.2. Waist circumferences were used for representing visceral fat mass with Asian cutoff points. GWAS of subjects aged 40–65 years with high visceral fat (n = 3303) were conducted and the best gene-gene interactions from the genetic variants related to subcutaneous fat were selected and explored using the generalized multifactor dimensionality reduction. Genetic risk scores (GRS) were calculated by weighted GRS that was divided into low, medium and high groups. Results: Subjects with high subcutaneous fat did not have dyslipidemia compared with those with low subcutaneous fat, although both subject groups had similar amounts of total fat. The best model to influence subcutaneous fat included IL17A_rs4711998, ADCY2_rs326149, ESRRG_rs4846514, CYFIP2_rs733730, TCF7L2_rs7917983, ZNF766_rs41497444 and TGFBR3_rs7526590. The odds ratio (OR) for increasing subcutaneous fat was higher by 2.232 folds in the high-GRS group, after adjusting for covariates. However, total and LDL cholesterol, triglyceride and C-reactive protein concentrations in the circulation were not associated with GRS. Subjects with high-GRS had higher serum HDL cholesterol levels than those with low-GRS. Physical activity and GRS had an interaction with subcutaneous fat. In subjects with low physical activity, the odds ratio for high subcutaneous fat increased by 2.232, but subcutaneous fat deposition was not affected in the high-GRS group with high physical activity. Conclusion: Obese adults with high-GRS had more subcutaneous fat, but they did not show more dyslipidemia and inflammation compared to low-GRS. High physical activity prevented subcutaneous fat deposition in subjects with high GRS for subcutaneous fat. [ABSTRACT FROM AUTHOR]

Background: Post-laparoscopic shoulder pain (PLSP) frequently follows a laparoscopic cholecystectomy. A proposed mechanism for PLSP is the irritation or injury of the phrenic nerve by the CO2 pneumoperitoneum during laparoscopic surgery. Here, we investigated whether a phrenic nerve block (PNB), performed under ultrasound guidance, could reduce the incidence and severity of PLSP after laparoscopic cholecystectomy.Method: Sixty patients were randomized into two groups, with one group receiving PNB with 4 ml (30 mg) of 0.75% ropivacaine (group P, n = 28) and a control group (group C, n = 32). The existence and severity of PLSP were assessed for 2 days postoperatively. A pulmonary function test (PFT) and diaphragmatic excursion test were performed pre- and postoperatively.Results: With ultrasound guidance, all PNBs were performed successfully in group P. In group P, the overall incidence and severity of PLSP decreased significantly. There were no significant differences in incisional pain, visceral pain, and analgesic requirements between the groups. Right-side diaphragmatic excursion decreased significantly in group P at 1 h postoperatively. The PFT results and respiratory discomfort assessed by a modified Borg's scale were not different significantly between the groups.Conclusion: Based on these findings, ultrasound-guided PNB can prevent or reduce the PLSP without clinically significant respiratory discomfort. [ABSTRACT FROM AUTHOR]

Background: Robotic modified radical neck dissection (MRND) using a gasless transaxillary approach has been reported to be a safe and meticulous technique in patients with papillary thyroid carcinoma (PTC) and lateral neck node metastasis (N1b). Few studies, however, have attempted to assess the long-term oncologic outcomes of robotic MRND in these patients. This study aimed to compare perioperative and 5-year oncologic outcomes of robotic MRND with conventional open procedures in patients with N1b PTC.Methods: Between September 2007 and February 2010, 193 patients with N1b PTC underwent total thyroidectomy and MRND by a single surgeon. Of these, 42 (21.8 %) underwent robotic procedures and 151 (78.2 %) underwent conventional open procedures. All patients received 3.7- to 5.5-GBq radioactive iodine (RAI) ablation, post-therapy whole-body scans (TxWBSs), and diagnostic WBS (DxWBSs) during follow-up. An exact 1:3 matching for age and stage was performed to minimize selection bias, and perioperative and 5-year oncologic outcomes were compared in the matched groups.Results: The mean follow-up period was 66.0 months (range 60-90 months). Number of retrieved cervical lymph nodes (LNs) (p = .102) and postoperative ablation success rates (p = .864) were similar between the two groups. TSH-suppressed serum Tg concentrations after 5 years (0.7 ± 1.5 vs. 2.4 ± 14.1 ng/ml; p = .471) and recurrence rates in the robotic and open groups (1/41 [2.4 %] vs. 3/102 [2.9 %]; p = .864) were similar for the 5-year follow-up period. Four patients experienced recurrence: Three exhibited regional lymph node metastasis, and one showed bilateral lung metastases.Conclusion: The perioperative and 5-year oncologic outcomes were similar after robotic and conventional open MRND. Large, prospective randomized controlled trials with long-term follow-up data are needed to validate these results. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the diagnostic performance of breast magnetic resonance imaging (MRI) in preoperative evaluation of axillary lymph node metastasis (ALNM) in breast cancer patients and to assess whether breast MRI can be used to exclude advanced nodal disease.Methods: A total of 425 patients were included in this study and breast MRI findings were retrospectively reviewed. The diagnostic performance of breast MRI for diagnosis of ALNM was evaluated in all patients, patients with neoadjuvant chemotherapy (NAC), and those without NAC (no-NAC). We evaluated whether negative MRI findings (cN0) can exclude advanced nodal disease (pN2-pN3) using the negative predictive value (NPV) in each group.Results: The sensitivity and NPV of breast MRI in evaluation of ALNM was 51.3 % (60/117) and 83.3 % (284/341), respectively. For cN0 cases on MRI, pN2-pN3 manifested in 1.8 % (6/341) of the overall patients, 0.4 % (1/257) of the no-NAC group, and 6 % (5/84) of the NAC group. The NPV of negative MRI findings for exclusion of pN2-pN3 was higher for the no-NAC group than for the NAC group (99.6 % vs. 94.0 %, p = 0.039).Conclusions: Negative MRI findings (cN0) can exclude the presence of advanced nodal disease with an NPV of 99.6 % in the no-NAC group.Key Points: • Breast MRI can be used to exclude advanced nodal disease (pN2-3). • Negative MRI allows breast cancer patients to avoid unnecessary axillary surgery (98.2 %). • Negative MRI findings exclude 99.6 % of pN2-pN3 in the no-NAC group. • Negative MRI findings exclude 96.0 % of pN2-pN3 in the NAC group. [ABSTRACT FROM AUTHOR]

Background: Acute unilateral vestibulopathy (AUV) is common but, the course of disease recovery is variable. Moreover, the final recovery status might vary between subjects. The remaining symptoms of these patients indicate the poor recovery of static imbalance, which could limit social activities and decrease their quality of life. Objective: To determine the possible predictive parameters of prolonged static imbalance (PSI) among acute AUV, we compared several vestibular function test (VFT) results between control vestibulopathy (CV) and PSI patients. Materials and methods: Subjects were divided into two groups: PSI and CV. PSI was determined by the observation of spontaneous nystagmus at 1 month after discharge from the hospital. VFT results taken during the initial symptoms were compared. Results: Increased phase lead was observed in low-frequency stimulations (p <.05), while the other test results failed to reveal a significant difference. These results indicate that a larger phase lead, which is related to a decrease in the time constant, could be responsible for the delayed recovery of static imbalance. Conclusion and significance: The phase lead was higher in the PSI group compared to the CV group, suggesting the possible role of phase as a parameter to predict the delayed compensation of static imbalance. [ABSTRACT FROM AUTHOR]

Diet-induced weight loss and regain leads to physiological and metabolic changes, some of which are potentially harmful. However, the specific metabolic processes and dysfunctions associated with weight regain, and how they differ from initial weight gain, remain unclear. Thus, we examined the metabolic profiles of mice following weight regain compared to initial weight gain. Mice were fed a normal diet or a high-fat diet or were cycled between the two diets to alternate between obese and lean states. Liver samples were collected and hepatic metabolites were profiled using nuclear magnetic resonance (NMR). The identified metabolites associated with weight regain were quantified using gas chromatography/mass spectrometry (GC/MS) and lipid profiles were assessed using ultra-high-performance liquid chromatography-quadrupole time-of-flight MS (UPLC-QTOF-MS). In addition, changes in expression of pro-inflammatory cytokines and gluconeogenic enzymes were investigated using polymerase chain reaction (PCR) and western blotting, respectively. Hepatic levels of several amino acids were reduced in mice during weight regain compared with initial weight gain. In addition, gluconeogenic enzyme levels were increased following weight regain, indicating an up-regulation of gluconeogenesis. Lipidomic profiling revealed that levels of ceramide and sphingomyelin, which are related to obesity-induced inflammation, were significantly increased during weight regain compared to initial weight gain. Moreover, tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1) levels were significantly up-regulated during weight regain. In this study, weight regains lead to an up-regulation of gluconeogenesis and aggravated inflammation. Additionally, weight regain can worsen the metabolic dysfunction associated with obesity. [ABSTRACT FROM AUTHOR]