Prognostic implication of early recurrence after cryoballoon ablation in patients with atrial fibrillation.

BACKGROUND: It remains uncertain whether the implication of early recurrence and blanking period can be applied to patients with atrial fibrillation (AF) treated with cryoballoon ablation (CBA). We aimed to explore the prognostic value of early recurrence in patients with AF treated with CBA. METHODS: We studied consecutive AF patients who were treated with CBA between April 2019 and September 2020 in two tertiary medical institutes and followed for up to 12 months. The endpoint was the late recurrence of atrial arrhythmia, including AF, atrial flutter, and atrial tachycardia, following a 90-day blanking period. Atrial arrhythmia during the blanking period was defined as early recurrence and was not considered as an endpoint. RESULTS: This study included 406 patients with AF who underwent CBA. During the follow-up, 147 (36.2%) cases of late recurrence were observed. Of the 104 patients with early recurrence, 85 experienced late recurrence during follow-up. Early recurrence was associated with an increased risk of late recurrence in the univariate and multivariate analyses (P < 0.001). When we classified the patients into paroxysmal AF and persistent AF groups, early recurrence was still significantly associated with a higher risk of late recurrence (P = 0.005 and P < 0.001, respectively). CONCLUSION: Early recurrence after CBA was an independent risk factor for late recurrence in all patients as well as in those with paroxysmal AF and persistent AF. Therefore, further prospective studies could be considered to verify the risks and benefits of early rhythm control in patients with early recurrence.

Feasibility of facial nerve monitoring using adhesive surface electrodes during parotidectomy: a comparative study with needle electrodes.

PURPOSE: Electrophysiological monitoring of the facial nerve during parotidectomy has been reported as an adjunctive method to prevent facial nerve injury. Classically, a needle electrode is used to obtain electromyographic (EMG) signals from facial muscles during facial nerve monitoring (FNM) of parotid surgery, likewise adhesive surface electrodes. This study aimed to investigate the feasibility of performing FNM with surface electrodes during parotid surgery and to compare EMG values with needle electrodes. METHODS: Thirty patients who underwent parotidectomy under FNM using adhesive surface and needle electrodes were included. Two pairs of adhesive surface electrodes and needle electrodes were used for FNM during parotid surgery. Mean amplitudes were collected after electrical facial nerve stimulation at 1 mA after specimen removal. RESULTS: The mean amplitude of the adhesive surface electrodes was 226.50 ± 118.44 µV (orbicularis oculi muscle) and 469.6 ± 306.06 µV (orbicularis oris muscle), respectively. The mean amplitude of the needle electrodes was 449.85 ± 248.10 µV (orbicularis oculi muscle) and 654.66 ± 395.71 µV (orbicularis oris muscle), respectively. The mean amplitude of the orbicularis oris muscle was significantly greater than that of the orbicularis oculi. The amplitude values measured in the orbicularis oculi muscle showed significant differences between the needle and skin electrodes. CONCLUSIONS: Facial nerve monitoring (FNM) using adhesive surface electrodes is feasible in parotid surgery. Although the mean amplitude value of the surface electrode was relatively lower than that of the needle electrode, the surface electrode is considered a feasible and safe EMG recording device for FNM in parotid surgery.

The Effects of Vasodilation Induced by Brachial Plexus Block on the Development of Postoperative Thrombosis of the Arteriovenous Access in Patients with End-Stage Renal Disease: A Retrospective Study.

Although brachial plexus block (BPB)-induced vasodilation reduces the incidence of arteriovenous access (AC) thrombosis, BPB cannot completely prevent its development. Therefore, we retrospectively investigated the factors affecting BPB-induced vasodilation and their effects on AC thrombosis development. Ninety-five patients undergoing AC surgery under BPB were analyzed. Vessel diameters were measured before and 20 min after BPB. The surgery abandoned before the BPB placement was performed when the BPB-induced increases in vessel diameters met its indications. Complete occlusive access thrombosis (COAT) was defined as loss of pulse, thrill, or bruit. Fourteen patients (14.7%) developed COAT. The outflow vein was more dilated by BPB than the inflow artery (0.6 versus 0.1 mm in median, p < 0.001). The original surgery plan was changed for seven patients (7.4%). Diabetes mellitus (DM) and ischemic heart disease (IHD) decreased the extent of increases in the inflow artery by -0.183 mm (95% confidence interval [CI] [-0.301, -0.065], p = 0.003) and outflow vein diameters by -0.402 mm (95% CI [-0.781, -0.024], p = 0.038), respectively. However, DM, IHD, and changes in the vessel diameters had insignificant effects on the development of COAT. In conclusion, although DM and IHD attenuate the vasodilating effects of BPB, they do not contribute to the development of COAT.

The Fabrication of Cesium Lead Bromide-Coated Cellulose Nanocomposites and Their Effect on the Detection of Nitrogen Gas.

In this work, we fabricate cesium lead bromide nanofibers (CsPbBr3 NFs) via the attachment of cesium lead bromide nanocrystals (CsPbBr3 NCs) on the surface of electrospun cellulose nanofibers (CNFs) and employ them in a sensor to effectively detect gaseous nitrogen. The CsPbBr3 NFs are produced initially by producing CsPbBr3 NCs through hot injection and dispersing on hexane, followed by dipping CNFs and ultrasonicate for 1 h. Morphological characterization through visual, SEM and TEM image, and crystalline structure analysis by XRD and FT-IR analysis of CsPbBr3 NFs and NCs show similar spectra except for PL due to unavoidable damage during the ultrasonication. Gaseous nitrogen is subsequently detected using the photoluminescence (PL) property of CsPbBr3 NFs, in which the PL intensity dramatically decreases under various flow rate. Therefore, we believe that the proposed CsPbBr3 NFs show significant promise for use in detection sensors in various industrial field and decrease the potential of fatal damage to workers due to suffocation.

Clinical features and prognosis of severe-to-profound sudden sensorineural hearing loss.

PURPOSE: Sudden sensorineural hearing loss (SSNHL) is an otologic emergency. Despite multiple efforts to clarify the factors affecting the prognosis of severe-to-profound SSNHL, various studies showed inconsistent results and lack of clinical significance. Therefore, we examined the clinical features and outcomes of severe-to-profound SSNHL. MATERIALS AND METHODS: We included patients who experienced SSNHL between 2018 and 2021 and were diagnosed according to the American Academy of Otolaryngology-Head and Neck Surgery criteria; hearing loss over 70 dB on initial pure tone audiometry (PTA) was used to define severe-to-profound SSNHL. We retrospectively examine the demographic, laboratory, radiologic, and audiometric data of SSNHL patients. We also evaluated the final hearing gain of these patients by assessing their PTA findings and word-recognition scores. RESULTS: Of the 178 patients, 94 (52.81%) and 84 (47.19%) showed profound (>90 dB) and severe (>70 to 90 dB) hearing loss, respectively. The presence of vertigo and hypertension differed significantly between the severe and profound groups (p < 0.001 and p = 0.012, respectively), as did the initial serum creatinine level (p = 0.043). Recovery in PTA showed a reliable correlation with the interval between onset and treatment in the severe group and periventricular white-matter findings in the profound group (p < 0.001 and p = 0.011, respectively). The presence of hypertension was related to recovery of low tone (p = 0.023 for 250 Hz; p = 0.034 for 500 Hz), while glycated hemoglobin level was related to recovery of high tone in the severe group (p = 0.049 for 4000 Hz; p = 0.047 for 8000 Hz). CONCLUSIONS: Severe-to-profound SSNHL showed poor prognosis for hearing gain. The interval from onset to treatment was a significant prognostic factor for severe SSNHL, while the presence of vertigo, estimated glomerular filtration rate, and periventricular white-matter findings were significant prognostic factors for profound SSNHL.

Medicarpin Increases Antioxidant Genes by Inducing NRF2 Transcriptional Level in HeLa Cells.

The nuclear factor erythroid-derived 2-related factor 2 (NRF2) plays a pivotal role in the regulation of genes involved in oxidative stress and drug detoxification. Therefore, it is important to find NRF2 inducers to protect cells from excessive oxidative damage. Here, we investigated the effect of medicarpin isolated from the root of Robinia pseudoacacia L. on the activity of NRF2 in HeLa cells. Medicarpin significantly induced the antioxidant response elements (ARE)-luciferase activity in a concentration-dependent manner. Furthermore, medicarpin not only induced HO-1, GCLC, and NQO1 mRNA by translocating NRF2 to the nucleus but also induced the mRNA level of NRF2. To verify the NRF2 induction mechanism by medicarpin, ~2 kb of NRF2 promoter-luciferase assay was executed. As a result, medicarpin significantly induced NRF2-luciferase activity. Moreover, medicarpin strongly inhibited the ubiquitin-dependent proteasomal degradation of NRF2. Thus, medicarpin might protect cells by promoting the NRF2 transcriptional activity.

4-Methoxycinnamic acid attenuates schizophrenia-like behaviors induced by MK-801 in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Scrophularia buergeriana has been used for traditional medicine as an agent for reducing heat in the blood and for nourishing kidney 'Yin'. Therefore, S. buergeriana might be a potential treatment for mental illness, especially schizophrenia, which may be attenuated by supplying kidney Yin and reducing blood heat. In a pilot study, we found that S. buergeriana alleviated sensorimotor gating dysfunction induced by MK-801. AIM OF THE STUDY: In the present study, we attempted to reveal the active component(s) of S. buergeriana as a candidate for treating sensorimotor gating dysfunction, and we identified 4-methoxycinnamic acid. We explored whether 4-methoxycinnamic acid could affect schizophrenia-like behaviors induced by hypofunction of the glutamatergic neurotransmitter system. MATERIALS AND METHODS: Mice were treated with 4-methoxycinnamic acid (3, 10, or 30 mg/kg, i.g.) under MK-801-induced schizophrenia-like conditions. The effect of 4-methoxycinnamic acid on schizophrenia-like behaviors were explored using several behavioral tasks. We also used Western blotting to investigate which signaling pathway(s) is involved in the pharmacological activities of 4-methoxycinnamic acid. RESULTS: 4-Methoxycinnamic acid ameliorated MK-801-induced prepulse inhibition deficits, social interaction disorders and cognitive impairment by regulating the phosphorylation levels of PI3K, Akt and GSK-3ß signaling in the prefrontal cortex. And there were no adverse effects in terms of catalepsy and motor coordination impairments. CONCLUSION: Collectively, 4-methoxycinnamic acid would be a potential candidate for treating schizophrenia with fewer adverse effects, especially the negative symptoms and cognitive dysfunctions.

The Association of Estrogen Receptor Activity, Interferon Signaling, and MHC Class I Expression in Breast Cancer.

PURPOSE: The expression of major histocompatibility complex class I (MHC I) has previously been reported to be negatively associated with estrogen receptor (ER) expression. Furthermore, MHC I expression, level of tumor-infiltrating lymphocytes (TILs), and expression of interferon (IFN) mediator MxA are positively associated with one another in human breast cancers. This study aimed to investigate the mechanisms of association of MHC I with ER and IFN signaling. MATERIALS AND METHODS: The human leukocyte antigen (HLA)-ABC protein expression was analyzed in breast cancer cell lines. The expressions of HLA-A and MxA mRNAs were analyzed in MCF-7 cells in Gene Expression Omnibus (GEO) data. ER and HLA-ABC expressions, Ki-67 labeling index and TIL levels in tumor tissue were also analyzed in ER+/ human epidermal growth factor receptor 2 (HER2)- breast cancer patients who randomly received either neoadjuvant chemotherapy or estrogen modulator treatment followed by resection. RESULTS: HLA-ABC protein expression was decreased after ß-estradiol treatment or hESR-GFP transfection and increased after fulvestrant or IFN-γ treatment in cell lines. In GEO data, HLA-A and MxA expression was increased after ESR1 shRNA transfection. In patients, ER Allred score was significantly lower and the HLA-ABC expression, TIL levels, and Ki-67 were significantly higher in the estrogen modulator treated group than the chemotherapy treated group. CONCLUSION: MHC I expression and TIL levels might be affected by ER pathway modulation and IFN treatment. Further studies elucidating the mechanism of MHC I regulation could suggest a way to boost TIL influx in cancer in a clinical setting.

Surgical hip dislocation and varus derotation osteotomy for extra-articular cause of femoroacetabular impingement: a single case report.

Femoral retroversion is an extra-articular cause of cam-type femoroacetabular impingement (FAI) via early engagement with anterior rim. Valgus hip also causes extra-articular FAI by decreasing the range of motion. We present a case of valgus hip accompanied by femoral retroversion, which was refractory to prior arthroscopic femoroplasty. As a reasonable strategy, we have performed extra-articular correction via femoral subtrochanteric varus derotation osteotomy as well as intra-articular decompression by surgical hip dislocation. Femoral varus derotation osteotomy with surgical hip dislocation is a rational and appropriate solution in patients with extra-articular FAI, which is refractory to arthroscopic FAI surgery. Extra-articular causes of FAI should be suspected in every refractory case.

Experiences of magnetic resonance imaging scanning in patients with pacemakers or implantable cardioverter-defibrillators.

BACKGROUND/AIMS: Despite the U.S. Food and Drug Adminstration approving a magnetic resonance imaging (MRI)-conditional pacemaker system in 2011, many physicians remain reluctant to perform MRI scanning in patients with cardiac implantable electronic devices. Herein, we aimed to evaluate the real-world safety of MRI in these patients. METHODS: This single-center retrospective study examined the interrogation data and outcomes of patients with pacemakers or implantable cardioverter defibrillators who underwent MRI. MRI interrogation data were collected pre- and post-MRI and after 1 month of follow-up; these included the lead impedance, measured P- and R-wave amplitudes, and capture threshold. We compared these results between the magnetic resonance (MR)-conditional and conventional groups. RESULTS: From September 2013 to December 2015, 35 patients with cardiac implantable electronic devices underwent 43 MRI scans, with a mean follow-up of 5 months. Among these 35 patients, 14 (40%) had MR-conditional devices and 21 (60%) had conventional devices. Seven patients had high voltage devices, which were all the conventional type. There were no adverse events associated with MRI during the follow-up period, and there were no significant differences in the interrogation data changes between the conventional and MR-conditional groups. CONCLUSION: This single-center retrospective study found that MRI can be performed safely in patients with pacemakers or implantable cardioverter defibrillators, regardless of the MRI support, as long as appropriate precautions are taken.

Lipidomic profiling reveals free fatty acid alterations in plasma from patients with atrial fibrillation.

Atrial fibrillation (AF) is the most common cardiac arrhythmia, and its incidence is increasing worldwide. One method used to restore sinus rhythm is direct current cardioversion (DCCV). Despite the high success rate of DCCV, AF typically recurs within the first 2 weeks. However, our understanding of the pathophysiology of AF recurrence, incidence, and progression are highly limited. Lipidomic profiling was applied to identify altered lipids in plasma from patients with AF using ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry coupled with multivariate statistical analysis. Partial least-squares discriminant analysis revealed a clear separation between AF patients and healthy controls. The levels of several lipid species, including fatty acids and phospholipids, were different between AF patients and healthy controls, indicating that oxidative stress and inflammation are associated with the pathogenesis of AF. Similar patterns were also detected between recurrent and non-recurrent AF patients. These results suggest that the elevated saturated fatty acid and reduced polyunsaturated fatty acid levels in AF patients may be associated with enhanced inflammation and that free fatty acid levels may play a crucial role in the development and progression of AF.

Angiotensin II affects inflammation mechanisms via AMPK-related signalling pathways in HL-1 atrial myocytes.

Inflammation is a common cause of cardiac arrhythmia. Angiotensin ІІ (Ang ІІ) is a major contributing factor in the pathogenesis of cardiac inflammation; however, its underlying molecular mechanism remains unclear. Here, we explored the effect of Ang ІІ on inflammatory mechanisms and oxidative stress using HL-1 atrial myocytes. We showed that Ang ІІ activated c-Jun N-terminal kinase (JNK) phosphorylation and other inflammatory markers, such as transforming growth factor-ß1 (TGF-ß1) and tumor necrosis factor-α (TNF-α). Ang ІІ decreased oxygen consumption rate, which resulted in reactive oxygen species (ROS) generation and inhibition of ROS blocked Ang II-mediated JNK phosphorylation and TGF-ß1 induction. Ang ІІ induced the expression of its specific receptor, AT1R. Ang II-induced intracellular calcium production associated with Ang ІІ-mediated signalling pathways. In addition, the generated ROS and calcium stimulated AMPK phosphorylation. Inhibiting AMPK blocked Ang II-mediated JNK and TGF-ß signalling pathways. Ang ІІ concentration, along with TGF-ß1 and tumor necrosis factor-α levels, was slightly increased in plasma of patients with atrial fibrillation. Taken together, these results suggest that Ang ІІ induces inflammation mechanisms through an AMPK-related signalling pathway. Our results provide new molecular targets for the development of therapeutics for inflammation-related conditions, such as atrial fibrillation.

Relation between secondhand smoke exposure and cardiovascular risk factors in never smokers.

OBJECTIVE: Secondhand smoke exposure (SHSE) in nonsmokers has been associated with premature cardiovascular mortality and ischemic heart disease. We conducted a cross-sectional, population-based study evaluating the relationship between SHSE, measured by subjective and objective methods, and conventional cardiovascular risks such as blood pressure, lipid profiles, and fasting glucose. METHODS: We extracted information on 7376 healthy adults who had never smoked, for whom there were available urine cotinine levels, from the Korea National Health and Nutrition Examination Survey 2008-2011. SHSE was defined using self-report questionnaires and urine cotinine levels. The main outcomes included SBP and DBP, serum lipid profiles, and fasting glucose. RESULTS: The mean age of the study population was 45.4 ±â€Š0.4 years and 75.2% were women. Self-reported SHSE had no significant association with study outcomes except for DBP, which had marginally positive relationships (P = 0.060). Unadjusted analysis showed higher cotinine levels were associated with lower SBP, total cholesterol, LDL cholesterol, and triglyceride. All associations lost statistical significance after multivariable adjustment. Fasting glucose had a positive relationship with urine cotinine in quartiles but not with logarithm-transformed cotinine. CONCLUSION: Although SHSE is associated with increased risk of cardiovascular mortality and morbidity, we did not find any consistent relationship among SHSE and blood pressure, lipid, or fasting glucose levels in this cross-sectional study. Using objective measurements of urine cotinine did not alter this relationship. Further long-term prospective studies are needed to evaluate the effect of SHSE as a cardiovascular risk factor.

Patient Characteristics and the Incidence of Radiation-induced Dermatitis Following Radiofrequency Catheter Ablation.

BACKGROUND AND OBJECTIVES: Radiofrequency catheter ablation (RFCA) exposes patients to fixed angle radiation for extended periods of time. We investigated the incidence and characteristics of radiation-induced dermatitis (RID) associated with RFCA. SUBJECTS AND METHODS: We screened 1347 consecutive patients from 2000 to 2011 who underwent RFCA for any indication and reviewed patients with dermatologic issues at the 1-month follow-up. Skin lesions were classified into three groups: most likely RID, probable RID, and possible RID. RESULTS: Of the 1347 enrolled patients, 12 (0.89%) experienced dermatologic issues within 1 month after RFCA, including six patients (0.45%) clinically classified as 'most likely RID' and four patients (0.30%) with 'probable RID'. Ten patients, including most likely RID or probable RID patients, developed skin lesions on the right back and upper arm. Skin lesions did not improve without meticulous treatment, and three cases required surgical intervention. We compared the RID group to the remaining 1335 patients (normal group). The mean body mass indices (BMIs) of the RID and normal groups were 29.3 and 23.9 kg/m2, respectively (p<0.001). Radiation exposure times were longer in the RID group (180±31.0 vs. 47±49.9 minutes, p<0.001). We further analyzed 44 patients (6 RID cases and 38 normal patients) that had BMIs >26 kg/m2 and exposure times >115 minutes based on receiver operator characteristic curve analyses. Among the 35 patients without RID, 29 patients (82.9%) did not use biplane fluoroscopy. CONCLUSIONS: Patients with high BMIs have a higher risk of developing severe RID with increasing fluoroscopy times using biplane fluoroscopy.

Effects of propolis and gamma-cyclodextrin on intestinal neoplasia in normal weight and obese mice.

Obesity is associated with colorectal cancer (CRC). This effect might be attributed to adipokine-supported signaling. We have established that propolis suppresses survival signaling in CRC cells in vitro; therefore, we ascertained the ability of a propolis supplement to modulate intestinal neoplastic development in C57BL/6J-ApcMin/+/J mice in the lean and obese state. To induce obesity, mice were fed with a Western diet containing 40% fat. Since the propolis supplement includes gamma-cyclodextrin, the interventions included diets supplemented with or without gamma-cyclodextrin. The animals were administered the following diets: (1) control diet, (2) control diet/gamma-cyclodextrin, (3) control diet/propolis, (4) Western diet, (5) Western diet/gamma-cyclodextrin, and (6) Western diet/propolis. Western diet, resulting in obesity, accelerated neoplastic progression, as evidenced by the larger size and higher grade dysplasia of the neoplasms. In the context of normal weight, gamma-cyclodextrin and propolis affected neoplastic progression, as determined by the size of the lesions and their grade of dysplasia. A statistically significant decrease in the number of adenomas was detected in mice fed a control diet with the propolis supplement (61.8 ± 10.6 vs. 35.3 ± 7.6, P = 0.008). Although there was no significant difference in the polyp numbers between the six groups, the mice with the lowest number and size of adenomas were those fed a Western diet with gamma-cyclodextrin. This unexpected outcome might be explained by the increased levels of apoptosis detected in the intestinal tissues of these obese mice. We posit that butyrate derived from the metabolism of gamma-cyclodextrin may contribute to the decreased neoplastic burden in the context of obesity; however, future studies are required to address this possibility.

Underweight is a risk factor for atrial fibrillation: A nationwide population-based study.

BACKGROUND: Obesity is a well-known risk factor for development of atrial fibrillation (AF). However, the impact of underweight on AF has not been previously recognized. We sought to determine the risk of AF in subjects with underweight in this study. METHODS: We analyzed clinical data from a total of 132,063 individuals with the age of 40years or older who received health care checkups arranged by the national insurance program between 2003 and 2004. Newly diagnosed nonvalvular AF was identified using claim data during a median follow-up duration of 9.0years. RESULTS: The mean body mass index (BMI) of patients was 23.9kg/m(2), and 3,323 individuals (2.5%) were classified as being underweight (BMI <18.5kg/m(2)). During the study period, 3,237 individuals (2.5%) developed AF. There was a U-shaped relationship between BMI and AF occurrence: Each 1.0kg/m(2) increase of BMI above 20kg/m(2) was associated with a 6% increased risk of AF (p<0.001), while each 1.0kg/m(2) lower BMI below 20kg/m(2) was associated with a 13% increased risk of AF (p<0.001) after multivariable adjustment. Underweight was significantly associated with 23% increased risk of AF, while obesity classes I and II were with 26% and 120% increased risk of AF, respectively. Excess risk of AF in the underweight was independent of thyroid disease, chronic lung disease, or history of malignancy, and was not attributable to cigarette smoking, low socioeconomic status, excessive physical activity, or heavy alcohol consumption. CONCLUSION: BMI has a U-shaped relationship with the risk of AF. Underweight was an independent risk factor for AF independent of confounding factors such as chronic lung disease and malignancy. These findings suggest that underweight is associated with biological effects that contribute to the development of AF.

Dclk1 Defines Quiescent Pancreatic Progenitors that Promote Injury-Induced Regeneration and Tumorigenesis.

The existence of adult pancreatic progenitor cells has been debated. While some favor the concept of facultative progenitors involved in homeostasis and repair, neither a location nor markers for such cells have been defined. Using genetic lineage tracing, we show that Doublecortin-like kinase-1 (Dclk1) labels a rare population of long-lived, quiescent pancreatic cells. In vitro, Dclk1+ cells proliferate readily and sustain pancreatic organoid growth. In vivo, Dclk1+ cells are necessary for pancreatic regeneration following injury and chronic inflammation. Accordingly, their loss has detrimental effects after cerulein-induced pancreatitis. Expression of mutant Kras in Dclk1+ cells does not affect their quiescence or longevity. However, experimental pancreatitis converts Kras mutant Dclk1+ cells into potent cancer-initiating cells. As a potential effector of Kras, Dclk1 contributes functionally to the pathogenesis of pancreatic cancer. Taken together, these observations indicate that Dclk1 marks quiescent pancreatic progenitors that are candidates for the origin of pancreatic cancer.

Female sex, central lymph node metastasis and dissection are causes of globus symptom after thyroidectomy.

Globus symptoms are not uncommon after an uncomplicated thyroidectomy. However, their associated factors and etiology have not been investigated. We investigated the etiology and factors related to globus symptoms after thyroidectomy. The medical records of 289 patients who underwent thyroidectomy and completed a voice analysis, psychiatric screening, and voice-related questionnaires before and 1 month after the surgery were reviewed. Patients were excluded if they had globus symptoms before surgery or scored high on the psychiatric questionnaire. The selected patients were divided into two groups according to development of globus symptoms after surgery. Clinicopathological parameters and results of the voice analysis and voice-related questionnaires were compared between the two groups. A total of 157 patients were enrolled, and more than half (80/155, 51 %) showed development of globus symptoms 1 month after thyroidectomy. Female patients [hazard ratio (HR), 2.605; P = 0.010], patients who had central lymph node metastasis (HR, 3.533; P = 0.001), and patients who underwent central neck dissection (HR, 3.652; P = 0.014) had a higher probability of developing globus symptoms. Patients who developed globus symptoms scored higher on the voice-related questionnaire, and had a greater decrease in speaking fundamental frequency (P < 0.001). Globus symptoms developed after 1 month in more than half of patients who underwent thyroidectomy. Female sex and central lymph node metastasis and dissection increased the possibility of developing the symptoms.

AFAP1 Is a Novel Downstream Mediator of TGF-ß1 for CCN2 Induction in Osteoblasts.

BACKGROUND: CCN2 acts as an anabolic growth factor to regulate osteoblast differentiation and function. CCN2 is induced by TGF-ß1 and acts as a mediator of TGF-ß1 induced matrix production in osteoblasts and Src is required for CCN2 induction by TGF-ß1; however, the molecular mechanisms that control CCN2 induction in osteoblasts are poorly understood. AFAP1 binds activated forms of Src and can direct the activation of Src in certain cell types, however a role for AFAP1 downstream of TGF-ß1 or in osteoblats is undefined. In this study, we investigated the role of AFAP1 for CCN2 induction by TGF-ß1 in primary osteoblasts. RESULTS: We demonstrated that AFAP1 expression in osteoblasts occurs in a biphasic pattern with maximal expression levels occurring during osteoblast proliferation (~day 3), reduced expression during matrix production/maturation (~day 14-21), an a further increase in expression during mineralization (~day 21). AFAP1 expression is induced by TGF-ß1 treatment in osteoblasts during days 7, 14 and 21. In osteoblasts, AFAP1 binds to Src and is required for Src activation by TGF-ß1 and CCN2 promoter activity and protein induction by TGF-ß1 treatment was impaired using AFAP1 siRNA, indicating the requirement of AFAP1 for CCN2 induction by TGF-ß1. We also demonstrated that TGF-ß1 induction of extracellular matrix protein collagen XIIa occurs in an AFAP1 dependent fashion. CONCLUSIONS: This study demonstrates that AFAP1 is an essential downstream signaling component of TGF-ß1 for Src activation, CCN2 induction and collagen XIIa in osteoblasts.

A 14-week randomized, placebo-controlled, double-blind clinical trial to evaluate the efficacy and safety of ginseng polysaccharide (Y-75).

BACKGROUND: The Y-75 (Ginsan) acidic polysaccharide from Korean Panax ginseng has been shown to function as an immunomodulatory molecule. However, the efficacy of Y-75 has not been evaluated in clinical trial. METHODS: We verified Y-75 (6 g/day) for safety and immune efficacy in 72 healthy volunteers aged 50-75 years using a randomized, placebo-controlled, parallel, double-blind study. The activities of natural killer (NK) cells and peripheral blood phagocytes, as well as serum levels of monocyte-derived mediators, were assessed before and after administration for 8 and 14 weeks. This trial is registered at ClinicalTrials.gov (NCT02161198). RESULTS: Y-75 significantly enhanced NK cell cytotoxic activity by 35.2% and 40.2% from baseline after administration for 8 and 14 weeks, respectively. The phagocytic activity of peripheral blood cells was also significantly increased by 25.2% and 39.4% and serum level of TNF-α by 38.2% and 44.5% after treatment for 8 and 14 weeks, respectively. Differences in the efficacy of variables compared to the placebo group were also significant. Administration of Y-75 was well tolerated without treatment-related adverse events or alteration of complete blood cell count or blood chemistry over the entire study period. CONCLUSION: Y-75 was shown to be a safe and potentially effective natural alternative for enhancing immune function.