Electrogenic transport and K(+) ion channel expression by the human endolymphatic sac epithelium.

The endolymphatic sac (ES) is a cystic organ that is a part of the inner ear and is connected to the cochlea and vestibule. The ES is thought to be involved in inner ear ion homeostasis and fluid volume regulation for the maintenance of hearing and balance function. Many ion channels, transporters, and exchangers have been identified in the ES luminal epithelium, mainly in animal studies, but there has been no functional study investigating ion transport using human ES tissue. We designed the first functional experiments on electrogenic transport in human ES and investigated the contribution of K(+) channels in the electrogenic transport, which has been rarely identified, even in animal studies, using electrophysiological/pharmacological and molecular biological methods. As a result, we identified functional and molecular evidence for the essential participation of K(+) channels in the electrogenic transport of human ES epithelium. The identified K(+) channels involved in the electrogenic transport were KCNN2, KCNJ14, KCNK2, and KCNK6, and the K(+) transports via those channels are thought to play an important role in the maintenance of the unique ionic milieu of the inner ear fluid

Peripheral arterial endothelial dysfunction predicts future cardiovascular events in diabetic patients with albuminuria: a prospective cohort study

Background Reactive hyperemia-peripheral arterial tonometry (RH-PAT) is a noninvasive and simple test for evaluating the endothelial function. There has been sparse evidence on the usefulness of the RH-PAT index (RHI) in predicting future cardiovascular diseases among diabetic patients. Methods Asymptomatic diabetic patients with albuminuria were selected; their medical history and laboratory findings were evaluated every 3 to 4 months, respectively. The primary outcome was a composite of three-point major adverse cardiovascular events (3-point MACE): death from cardiovascular causes, acute coronary events, or nonfatal stroke. On the contrary, secondary outcomes included a composite of 3-point MACE, hospitalization for heart failure, or chronic kidney disease (CKD) progression. RHI was measured using the Endo-PAT2000 at the baseline. RHI < 1.67 was considered to indicate peripheral endothelial dysfunction (PED). Results In total, 149 subjects were included (mean age, 61.8 ± 9.2 years; duration of diabetes was 12 years). During the follow-up period (median, 49.7 months), of the 149 subjects, primary outcomes were detected in 12 (1 [2.3%] and 11 [10.5%] of those without and with PED, respectively). The presence of PED in baseline measurements significantly increased both primary and secondary outcomes, following adjustment for age, sex, hypertension, glycated hemoglobin, low-density lipoprotein cholesterol, triglyceride, systolic blood pressure, baseline estimated glomerular filtration rate, overt proteinuria, duration of diabetes, premedical history of ischemic events, anti-platelet agents, and smoking history (hazard ratio [HR]: 10.95; 95% confidence interval CI 1.00–119.91 for the primary outcome; HR, 4.12; 95% CI 1.37–12.41 for secondary outcome). In addition, PED could predict secondary outcomes independent of the risk score according to the American College of Cardiology/American Heart Association (HR: 3.24; 95% CI 1.14–9.17). Conclusions PED can independently predict future cardiovascular events among diabetic patients with albuminuria.This study was supported by Health Connect Research Fund (No. 16-2013-87)

Delayed surgical intervention in central cord syndrome with cervical stenosis

Study Design Review of the literature. Objective It is generally accepted that surgical treatment is necessary for central cord syndrome (CCS) with an underlying cervical stenosis. However, the surgical timing for decompression is controversial in spondylotic cervical CCS. The purpose of this study is to review the results of early and delayed surgery in patients with spondylotic cervical CCS. Methods MEDLINE was searched for English-language articles on CCS. There were 1,653 articles from 1940 to 2012 regarding CCS, 5 of which dealt with the timing of surgery for spondylotic cervical CCS. Results All five reports regarding the surgical timing of spondylotic cervical CCS were retrospective. Motor improvement, functional independence measures, and walking ability showed similar improvement in early and late surgery groups in the studies with follow-up longer than 1 year. However, greater improvement was seen in the early surgery group in the studies with follow-up shorter than 1 year. The complication rates did not show a difference between the early and late surgery groups. However, there are controversies regarding the length of intensive care unit stay or hospital stay for the two groups. Conclusions There was no difference in motor improvement, functional independence, walking ability, and complication rates between early and late surgery for spondylotic cervical CCS

Asymptomatic subjects with diabetes have a comparable risk of coronary artery disease to Non-diabetic subjects presenting chest pain: a 4-year community-based prospective study

This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background Although diabetes mellitus is an important risk factor of coronary artery disease (CAD), routine screening for CAD is not recommended for asymptomatic diabetic patients. We assessed the impact of chest pain on CAD risk according to the presence or absence of diabetes mellitus. Methods We investigated the future CAD event rate in subjects with and without chest pain according to the presence or absence of diabetes in a prospective large-scale community-based study in Korea. Results Among 8,574 subjects (4,032 men and 4,542 women) without a history of CAD, 0.8% and 2.2% of non-diabetic and diabetic subjects, respectively, reported newly developed CAD events during 4 years of follow-up. Although the presence of chest pain at baseline was also significantly associated with an increased risk of CAD of more than 2-fold in both non-diabetic and diabetic subjects (P < 0.01), the risk of future CVD event in asymptomatic diabetic patients was not significantly different from that in non-diabetic subjects with chest pain (hazard ratio, 0.907; 95% confidence interval, 0.412 – 1.998). Conclusions The CAD event rate of asymptomatic subjects with diabetes was comparable to that of non-diabetic subjects reporting chest pain. Considering the high risk of CAD in asymptomatic diabetic patients, more clinical trials aimed at formulating strategies to screen asymptomatic diabetic subjects should be carried out

Dynamic changing smoking habits and cardiovascular events in patients newly diagnosed with hypertension, diabetes, or dyslipidemia: a national cohort study

Background and aimsThis study aimed to examine the association between dynamic smoking habit change and cardiovascular risk in a population newly diagnosed with hypertension, diabetes, and dyslipidemia.MethodsThis study included 49,320 individuals who had received health examinations provided by the Korea National Health Insurance Service. To determine the hazard ratios (HRs) and 95% confidence intervals (CIs) for incident major adverse cardiac events (MACE) and all-cause mortality based on dynamic smoking habit changes for 2 years, multivariable Cox proportional hazard models were utilized.ResultsDuring the follow-up, there were 1,004 (2.2%), 3,483 (7.6%), and 334 (0.7%) cases of myocardial infarction, stroke events, and cardiovascular death, respectively. The group with worsening smoking habits had an increased risk of cardiovascular events and death (HR: 1.33, 95% CI: 1.26–1.40) compared to improved smoking habits. The robustness of the results determined by a series of sensitivity analyses further strengthened the main findings.ConclusionsOur findings suggest that worsening of smoking habits, even for a short period of time, may increase the risk of myocardial infarction, stroke, and cardiovascular death in patients diagnosed with hypertension, diabetes, and dyslipidemia. For the primary prevention of cardiovascular events in patients with underlying diseases, dynamic modification of smoking habits should be actively considered

Efficacy of Antibiotics Sprayed into Surgical Site for Prevention of the Contamination in the Spinal Surgery

Study DesignRetrospective study.PurposeTo evaluate the effect of intraoperative wound application of vancomycin on preventing surgical wound contamination during instrumented lumbar spinal surgery.Overview of LiteraturePostoperative infection is the one of the most devastating complications of lumbar surgery. There are a few reports showing the benefits of intraoperative wound application of vancomycin during spinal surgery. However, there is no report about the effectiveness of local vancomycin instillation in prevention of surgical wound contamination.MethodsEighty-six patients underwent instrumented lumbar spinal surgery. Mean patient age was 65.19 years (range, 23-83 years). There were 67 females and 19 males. During surgery, vancomycin powder was applied into the surgical site before closure in 43 patients (antibiotic group) and vancomycin powder was not applied into the surgical site before closure in 43 patients (control group). The tip of the surgical drain was cultured to evaluate surgical wound contamination. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were measured on the first, third, seventh, and fourteenth day after the operation.ResultsWe found two patients with a positive culture from the tip of surgical drains in the antibiotic group, and one patient with a positive culture from the tip of the surgical drain in the control group. Postoperative ESR and CRP levels did not show significant differences between the two groups. On the third postoperative day, ESR in patients of the antibiotic group was more significantly decreased than that in patients of the control group, while CRP level did not show a significant difference between the two groups.ConclusionsThere was no evidence to suggest that intraoperative vancomycin application is effective in decreasing the risk of postoperative wound infection after instrumented posterior lumbar fusion surgery

Vitamin D deficiency is associated with disease activity in patients with Crohn’s disease

Background/Aims Previous data suggest that vitamin D has a significant role in inflammatory bowel disease (IBD). We investigated the incidence of vitamin D deficiency in Korean patients with IBD and the correlation between serum vitamin D level and disease activity. Methods We retrospectively analyzed the medical records of patients with IBD whose serum vitamin D levels were checked. Deficiency of 25-hydroxyvitamin D was defined as <20 ng/mL. Disease activity was evaluated using the partial Mayo score for ulcerative colitis (≥2 defined as active disease) and Harvey-Bradshaw index for Crohn’s disease (≥4 defined as active disease). Results We enrolled 87 patients with IBD (ulcerative colitis [UC], 45; Crohn’s disease [CD], 42). Among them, 65.5% (57/87) were men, with a mean age of 44.9±15.1 years (range, 18–75 years). The mean duration of disease was 4.7±4.8 years (range, 0.1–17.1 years). Vitamin D deficiency was found in 73.6% (64/87) of patients with IBD. Patients with IBD (mean vitamin D level, 16.3±9.0 ng/mL) showed lower vitamin D level than the healthy control group (mean vitamin D level, 20.4±7.0 ng/mL), with no statistically significant difference (P=0.136). Disease activity was inversely correlated with vitamin D deficiency in patients with CD (P=0.007). However, no correlation was observed in patients with UC (P=0.134). Conclusions Approximately 75% of Korean patients with IBD showed vitamin D deficiency state. Vitamin D deficiency is associated with disease activity, particularly in patients with CD

β-Lapachone Significantly Increases the Effect of Ionizing Radiation to Cause Mitochondrial Apoptosis via JNK Activation in Cancer Cells

β-lapachone (β-lap), has been known to cause NQO1-dependnet death in cancer cells and sensitize cancer cells to ionizing radiation (IR). We investigated the mechanisms underlying the radiosensitization caused by β-lap. cells induced ROS generation, triggered ER stress and stimulated activation of ERK and JNK. Inhibition of ROS generation by NAC effectively attenuated the activation of ERK and JNK, induction of ER stress, and subsequent apoptosis. Importantly, inhibition of ERK abolished ROS generation and ER stress, whereas inhibition of JNK did not, indicating that positive feedback regulation between ERK activation and ROS generation triggers ER stress in response to combined treatment. Furthermore, prevention of ER stress completely blocked combination treatment-induced JNK activation and subsequent apoptotic cell death. In addition, combined treatment efficiently induced the mitochondrial translocation of cleaved Bax, disrupted mitochondrial membrane potential, and the nuclear translocation of AIF, all of which were efficiently blocked by a JNK inhibitor. Caspases 3, 8 and 9 were activated by combined treatment but inhibition of these caspases did not abolish apoptosis indicating caspase activation played a minor role in the induction of apoptosis. cells are treated with combination of IR and β-lap, positive feedback regulation between ERK and ROS leads to ER stress causing JNK activation and mitochondrial translocation of cleaved Bax. The resultant decrease in mitochondrial membrane leads to translocation of AIF and apoptosis

전립선 선암종에서 Methylenetetrahydrofolate Reductase 유전자형에 따른 CpG 섬 좌, LINE-1 및 Alu의 메틸화 양상 분석

Background : Genetic polymorphism of methylenetetrahydrofolate reductase (MTHFR), in association with the influence of MTHFR upon DNA methylation, may cause differences of the methylation profile of cancer. Thus, we investigated the relationship between the methylation status of prostate adenocarcinoma and the genetic polymorphism of MTHFR. Methods : We examined 179 cases of prostate adenocarcinoma for determining the genotypes of MTHFR 677 and 1298, the methylation status of 16 CpG island loci and the methylation levels of the LINE-1 and Alu repeats with using polymerase chain reaction/restriction fragment length polymorphism, methylation-specific polymerase chain reaction and combined bisulphite restriction analysis, respectively. Results : There was a higher proportion of the CT genotype of MTHFR 677 in the prostate adenocarcinoma than that in the normal control. The TT genotype of MTHFR 677 showed the highest frequency of methylation in six out of nine major CpG island loci, and these were which were frequently hypermethylated in prostate adenocarcinoma. The CT type showed the lowest methylation levels of LINE-1 and Alu among the MTHFR 677 genotypes. Interestingly, the CC type of MTHFR 1298 demonstrated favorable prognostic factors. Conclusions : Our study is the first to examine the methylation profile of prostate adenocarcinoma according to the MTHFR genotypes. The differences of the cancer risk, the genomic hypomethylation and the prognosis between the MTHFR genotypes in prostate adenocarcinoma should be further explored.Johansson M, 2007, CANCER CAUSE CONTROL, V18, P1169, DOI 10.1007/s10552-007-9055-zHubner RA, 2007, INT J CANCER, V120, P1027, DOI 10.1002/ijc.22440Cho NY, 2007, J PATHOL, V211, P269, DOI 10.1002/path.2106Pereira TV, 2006, CANCER EPIDEM BIOMAR, V15, P1956, DOI 10.1158/1055-9965.EPI-06-0334Larsson SC, 2006, GASTROENTEROLOGY, V131, P1271, DOI 10.1053/j.gastro.2006.08.010Cadieux B, 2006, CANCER RES, V66, P8469, DOI 10.1158/0008-5472.CAN-06-1547Graziano F, 2006, INT J CANCER, V118, P628, DOI 10.1002/ijc.21397Karpf AR, 2005, CANCER RES, V65, P8635, DOI 10.1158/0008-5472Kono S, 2005, CANCER SCI, V96, P535, DOI 10.1111/j.1349-7006.2005.00090.xLe Marchand L, 2005, CANCER EPIDEM BIOMAR, V14, P1198Friso S, 2005, CURR DRUG METAB, V6, P37Weisenberger DJ, 2005, NUCLEIC ACIDS RES, V33, P6823, DOI 10.1093/nar/gki987Chalitchagorn K, 2004, ONCOGENE, V23, P8841, DOI 10.1038/sj.onc.1208137Cicek MS, 2004, CANCER EPIDEM BIOMAR, V13, P1331Castro R, 2004, J MED GENET, V41, P454, DOI 10.1136/jmg.2003.017244Kim YI, 2004, CANCER EPIDEM BIOMAR, V13, P511Yang AS, 2004, NUCLEIC ACIDS RES, V32, DOI 10.1093/nar/gnh032Nelson WG, 2003, NEW ENGL J MED, V349, P366Gaudet F, 2003, SCIENCE, V300, P489Bariol C, 2003, AM J PATHOL, V162, P1361Shen HB, 2001, INT J CANCER, V95, P332, DOI 10.1002/1097-0215(20010920)95:53.0.CO2-9Kimura F, 2000, PROSTATE, V45, P225Weisberg I, 1998, MOL GENET METAB, V64, P169Esteller M, 1997, CARCINOGENESIS, V18, P2307Blount BC, 1997, P NATL ACAD SCI USA, V94, P3290Ma J, 1997, CANCER RES, V57, P1098Chen J, 1996, CANCER RES, V56, P4862FROSST P, 1995, NAT GENET, V10, P111

The effects of music therapy on labor pain, childbirth experience, and self-esteem during epidural labor analgesia in primiparas: a non-randomized experimental study

Purpose This non-randomized study was performed to evaluate the effects of music therapy on labor pain, the childbirth experience, and self-esteem in women during vaginal delivery. Methods In total, 136 primiparous women over 37 weeks of gestation receiving epidural analgesia during vaginal delivery were recruited via convenience sampling. To minimize diffusion effects, data from the control group (n=71) were collected first (April 2020 to March 2021), followed by data from the music group (n=65; April 2021 to May 2022). Participants in the music group listened to classical music during labor, while the control group was offered usual care (no music). Labor pain was measured using a numeric rating scale (NRS), and self-esteem and childbirth experience were collected using self-report questionnaires. Data were analyzed using the independent t-test, chi-square test and Cronbach’s α coefficients. Results The overall pain level (NRS) at baseline was 0 in both groups. Mothers in the music therapy group had lower levels of latent pain (t=1.95, p=.005), active pain (t=3.69, p<.001) and transition-phase pain (t=7.07, p<.001) than the control group. A significant difference was observed between the two groups, and the music therapy group expressed more positive perceptions of the childbirth experience (t=-1.36, p=.018). For self-esteem, the experimental group’s score was slightly higher, but without a statistically significant difference from the control group. Conclusion Using music therapy during labor decreased labor pain and improved the childbirth experience. Music therapy can be clinically recommended as a non-pharmacological, safe, and easy method for nursing care in labor. Clinical trail number: KCT00856