FoxO1 is a critical regulator of M2-like macrophage activation in allergic asthma.

BACKGROUND: The pathogenesis of asthma and airway obstruction is the result of an abnormal response to different environmental exposures. The scientific premise of our study was based on the finding that FoxO1 expression is increased in lung macrophages of mice after allergen exposure and human asthmatic patients. Macrophages are capable of switching from one functional phenotype to another, and it is important to understand the mechanisms involved in the transformation of macrophages and how their cellular function affects the peribronchial stromal microenvironment. METHODS: We employed a murine asthma model, in which mice were treated by intranasal insufflation with allergens for 2-8 weeks. We used both a pharmacologic approach using a highly specific FoxO1 inhibitor and genetic approaches using FoxO1 knockout mice (FoxO1fl/fl LysMcre). Cytokine level in biological fluids was measured by ELISA and the expression of encoding molecules by NanoString assay and qRT-PCR. RESULTS: We show that the levels of FoxO1 gene are significantly elevated in the airway macrophages of patients with mild asthma in response to subsegmental bronchial allergen challenge. Transcription factor FoxO1 regulates a pro-asthmatic phenotype of lung macrophages that is involved in the development and progression of chronic allergic airway disease. We have shown that inhibition of FoxO1 induced phenotypic conversion of lung macrophages and downregulates pro-asthmatic and pro-fibrotic gene expression by macrophages, which contribute to airway inflammation and airway remodeling in allergic asthma. CONCLUSION: Targeting FoxO1 with its downstream regulator IRF4 is a novel therapeutic target for controlling allergic inflammation and potentially reversing fibrotic airway remodeling.

Do psychosocial variables mediate the relationship between menopause symptoms and sexual function in middle-aged perimenopausal women?

AIM: To test a hypothetical path model evaluating the influence of menopause symptoms on sexual function among middle-aged perimenopausal women, as well as identify the mediating roles of body image, depression and sexual communication in this relationship. METHODS: We used a cross-sectional, correlational design. We included one exogenous variable (menopause symptoms) and four endogenous variables (body image, depression, sexual communication and sexual function) in the proposed model. All data were collected between January 19 and March 11, 2016, and analyzed using spss statistics 25.0 and AMOS 23.0. RESULTS: Eight of the nine hypothesized paths in the model were significant. Specifically, menopause symptoms were significantly associated with sexual function via the effects of body image, depression and sexual communication. CONCLUSION: This study may provide basic data for counseling and nursing programs to help improve sexual function in middle-aged perimenopausal women. Particularly, these programs should focus on the indirect paths via body image, depression and sexual communication, such as by improving body image and sexual communication and reducing depression.

Prospective study of bidet toilet use: Association of abnormal vaginal colonization and preterm birth in high-risk pregnant women.

AIM: This study aimed to evaluate the association of bidet toilet use with abnormal vaginal microbial colonization and preterm birth (PTB) in high-risk pregnancies. METHODS: This is a prospective cohort study of 208 women, who were admitted to a high-risk pregnancy unit, due to preterm labor, preterm premature rupture of the membrane, or short cervical length, in two tertiary hospitals from April 2015 to July 2017. Responses to a questionnaire about using bidet toilet and vaginal culture were obtained upon admission. Maternal baseline characteristics, vaginal culture results, and pregnancy and neonatal outcomes were compared between bidet toilet users and nonusers. RESULTS: Among the 204 subjects, 67 (32.8%) women were identified as bidet toilet users. Overall, bidet toilet use was associated with a higher rate of abnormal vaginal microbial colonization, compared to the nonusers (60.7% vs 44.2%, P = 0.036). Notably, Escherichia coli colonization rate was significantly higher in bidet toilet users than nonusers (13.1% vs 3.3%, P = 0.023). Bidet toilet users had a significantly higher rate of PTB before 37 weeks of gestation, compared to the nonusers (87.3% vs 73.0%, P = 0.040). CONCLUSION: Our study suggests that chronic use of a bidet toilet is associated with a higher rate of abnormal vaginal colonization by Gram-negative bacteria and PTB in high-risk pregnancies.

siRNA-mediated knock-down of COX-2 in melanocytes suppresses melanogenesis.

Cyclooxygenase-2 (COX-2) is an enzyme induced in response to multiple mitogenic and inflammatory stimuli, including UV light. UV-induced COX-2 expression induces production of prostaglandin E2 (PGE2) in keratinocytes, which mediates inflammation and cell proliferation. Until recently, studies regarding COX-2 and PGE2 in the skin have focused on keratinocytes and skin cancer and the effect of PGs produced by keratinocytes on melanocytes. However, the effects of COX-2 itself or COX-2 inhibitors on melanogenesis are not well known. Therefore, to establish the role of COX-2 in melanogenesis, we investigated the effects of knock-down of COX-2 in melanocytes on melanin production and the expression of melanogenic molecules through silencing of COX-2 expression with COX-2 short interfering RNA (siRNA). COX-2 knock-down in melanocytes decreased the expressions of tyrosinase, TRP-1, TRP-2, gp100 and MITF and also reduced tyrosinase enzyme activity. Furthermore, COX-2 siRNA-transfected melanocytes showed markedly reduced alpha-melanocyte stimulating hormone (α-MSH)-induced melanin production. In addition, α-MSH-induced COX-2 expression in both scrambled siRNA-transfected and COX-2 siRNA-transfected melanocytes was greater than α-MSH-untreated cells. Our results suggest that COX-2 might be a candidate target for the development of anti-melanogenic agents and α-MSH-induced pigmentation could be closely associated with COX-2 expression. COX-2 inhibitors might therefore be of particular use in whitening cosmetics for hyperpigmentation disorders such as melasma, postinflammatory hyperpigmentation and solar lentigo.

Can misoprostol reduce blood loss in laparoscopy-assisted vaginal hysterectomy?

BACKGROUND: Intraoperative blood loss is a concern in the surgical treatment of myomatous uteri. Misoprostol causes the myometrium and isolated uterine arteries to contract and has blood-saving effects in myomectomy. AIM: To assess the efficacy of rectal misoprostol in reducing haemorrhage during laparoscopy-assisted vaginal hysterectomy (LAVH). METHODS: Retrospective case-control study. Women who had undergone LAVH for leiomyoma were enrolled (n=117). Forty-nine women who used 400 µg of misoprostol rectally 1 h before LAVH were compared with 68 women who did not. The surgical outcomes were compared statistically with Mann-Whitney rank sum test, χ(2) test, or Fisher's exact test. RESULTS: The demographic variables were similarly distributed in both groups. There were no significant differences in the estimated blood loss, reduction in haemoglobin, operation time, or uterine weight between the two groups (P>0.05). The rates of operative complications (4.1 vs 10.3% for the misoprostol and control groups, respectively, P=0.21) were not different. There was no febrile morbidity (>38°C) within 24 h of the misoprostol insertion. CONCLUSION: These data do not support the use of rectal misoprostol to reduce blood loss during LAVH. The pharmacoclinical effects of misoprostol in the uterus should be clarified.

The effect of a sequential compression device on hemodynamics in arthroscopic shoulder surgery using beach-chair position.

PURPOSE: This study investigated the effect of intermittent compression by a sequential compression device (SCD) on the incidence of hypotension and other hemodynamic variables in the beach-chair position. METHODS: Fifty healthy patients undergoing elective shoulder arthroscopy under general anesthesia were randomly assigned to either the control group (n = 25) or SCD group (n = 25). A standardized protocol for pre-hydration and anesthetic technique was followed. Hemodynamic variables were measured before (pre-induction values) and 5 minutes after the induction of anesthesia in the supine position (baseline values) and 1, 3, and 5 minutes after the patient was raised to a 70 degrees sitting position. The incidence of hypotension was recorded and treated with ephedrine. RESULTS: The incidence of hypotension was significantly higher in the control group (16 of 25) than that in the SCD group (7 of 25) (P = .022; odds ratio, 0.219; 95% confidence interval, 0.066 to 0.723). Between the groups, mean arterial pressure, cardiac index, and stroke volume index were significantly higher in the SCD group compared with values in the control group at 1 minute after patients were raised to a 70 degrees sitting position (P = .035, P = .046, and P = .011, respectively). CONCLUSIONS: This study showed that the use of an SCD could reduce the incidence of hypotension from 64% to 28% and supports hemodynamic variables such as mean arterial pressure and stroke volume index when patients were changed from the supine to the beach-chair position in those undergoing shoulder arthroscopy. LEVEL OF EVIDENCE: Level I, therapeutic randomized controlled trial.

Clinical role of 18F-FDG PET-CT in suspected and potentially operable cholangiocarcinoma: a prospective study compared with conventional imaging.

OBJECTIVES: This study was conducted to evaluate the clinical role of integrated positron emission and computed tomography (PET-CT) in patients with suspected and potentially operable cholangiocarcinoma. METHODS: Between October 2005 and May 2007, 123 patients with suspected cholangiocarcinoma were enrolled in this study after diagnostic workup, including biliary dynamic computed tomography (CT) and magnetic resonance imaging/magnetic resonance cholangiopancreatography (MRI/MRCP) with magnetic resonance (MR) angiography. Patients with overt unresectable cholangiocarcinoma or gallbladder cancer diagnosed via conventional imaging were excluded. Consecutively, each enrolled patient underwent PET-CT. Data were prospectively collected and analyzed in comparison with CT and MRI/MRCP. RESULTS: The overall values for sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of PET-CT in primary tumor detection were 84.0%, 79.3%, 92.9%, 60.5%, and 82.9%, respectively. PET-CT demonstrated no statistically significant advantage over CT and MRI/MRCP in the diagnosis of primary tumor. According to different morphologic characteristics of cholangiocarcinoma, PET-CT showed no significant difference in detecting those of mass-forming, periductal-infiltrating, and intraductal-growing types. PET-CT revealed significantly higher accuracy over CT in the diagnosis of regional lymph nodes metastases (75.9%vs 60.9%, P= 0.004) and distant metastases (88.3%vs 78.7%, P= 0.004). Additional use of PET-CT for assessing resectability correctly showed different results from those determined by conventional imaging in 15 (15.9%) of 94 patients with cholangiocarcinoma. CONCLUSIONS: PET-CT improved the accuracy of preoperative staging in patients with cholangiocarcinoma planning to undergo curative resection. Thus, PET-CT had an important clinical impact on the selection of proper treatment.

A highly stretchable and conductive 3D porous graphene metal nanocomposite based electrochemical-physiological hybrid biosensor.

Recently, highly stretchable and flexible electrodes essential for wearable electronic devices has been reported. However, their electrical resistances are high, the fabrication processes are complicated and involve a high cost, and deformations such as stretching can lead to the degradation on electrical performance. To address these issues, a novel fabrication process (both inexpensive and simple) for the highly stretchable and conductive electrodes using well patterned 3D porous laser-induced graphene silver nanocomposite was developed. The fabricated electrode exhibited a high, uniform electrical conductivity even under mechanical deformations. Addition of platinum and gold nanoparticles (PtAuNP) on the 3D porous LIG greatly improved the electrochemical performance for wearable glucose sensor applications. The fabricated glucose sensor exhibited low detection limit (5 µM), and acceptable detection range from 0 to 1.1 mM (covers the glucose range in sweat), and high linearity (0.99). In addition, the fabricated pH sensor also exhibited a linear response (66 mV/pH) at the range from 4 to 7. This work successfully demonstrates the potential of this novel fabrication technique and stretchable LIG metal nanocomposite for wearable electrochemical-physiological hybrid biosensors.

Upregulation of endothelial adhesion molecules by lysophosphatidylcholine. Involvement of G protein-coupled receptor GPR4.

Lysophosphatidylcholine induces expression of adhesion molecules; however, the underlying molecular mechanisms of this are not well elucidated. In this study, the intracellular signaling by which lysophosphatidylcholine upregulates vascular cell adhesion molecule-1 and P-selectin was delineated using YPEN-1 and HEK293T cells. The results showed that lysophosphatidylcholine dose-dependently induced expression of vascular cell adhesion molecule-1 and P-selectin, accompanied by the activation of transcription factor nuclear factor kappaB. However, the nuclear factor kappaB inhibitor caffeic acid phenethyl ester (CAPE) and the antioxidant N-acetylcysteine only partially blocked lysophosphatidylcholine-induced adhesion molecules. Subsequently, we found that the lysophosphatidylcholine receptor G protein-coupled receptor 4 (GPK4) was expressed in YPEN-1 cells and triggered the cAMP/protein kinase A/cAMP response element-binding protein pathway, resulting in upregulation of adhesion molecules. Further evidence showed that overexpression of human GPK4 enhanced lysophosphatidylcholine-induced expression of adhesion molecules in YPEN-1 cells, and enabled HEK293T cells to express adhesion molecules in response to lysophosphatidylcholine. In conclusion, the current study suggested two pathways by which lysophosphatidylcholine regulates the expression of adhesion molecules, the lysophosphatidylcholine/nuclear factor-kappaB/adhesion molecule and lysophosphatidylcholine/GPK4/cAMP/protein kinase A/cAMP response element-binding protein/adhesion molecule pathways, emphasizing the importance of the lysophosphatidylcholine receptor in regulating endothelial cell function.

Prepuncture ultrasound-measured distance: an accurate reflection of epidural depth in infants and small children.

BACKGROUND AND OBJECTIVES: Epidural cannulation is technically difficult in children who have small anatomic structures. Ultrasound information regarding the distance of skin-to-ligament flavum may be useful, leading to an increase in success rate without dural puncture. This study was performed to assess whether ultrasound-measured, skin-to-ligament flavum distance would reflect the needle depth during epidural puncture in infants and children. METHODS: The study compromised 180 children, aged 2 to 84 months, undergoing urologic surgery. After induction of anesthesia, ultrasound images of the longitudinal median and transverse views were acquired from L4-L5 in lateral decubitus position. Measured distance of skin-to-ligament flavum in each view was compared with the perpendicular skin-to-epidural depth, which was obtained from needle depth and angle by use of a trigonometric ratio equation. Additionally, we evaluated the ultrasound visibility of the ligament flavum and dura mater, number of puncture attempts, and complications. RESULTS: The correlation coefficient between measured distance and perpendicular epidural depth was slightly higher in longitudinal median view (R2 = 0.848) than in transverse view (R2 = 0.788). The visibility of ligament flavum and dura mater was "good" in 91 and 170 of 180 patients, respectively, and "sufficient" in the remaining subjects. The epidural space was located on first puncture attempt in 179 of 180 cases (99.4%). No incidents of dural puncture or bloody tap occurred. CONCLUSIONS: Ultrasound, particularly in the longitudinal median view, provides accurate information on the distance of skin-to-ligament flavum in infants and children. With reference to the measured distance, epidural puncture can be performed with minimal risk of dural puncture (upper limit of 95% CI = 1.67%).

Abnormal vaginal colonization by gram-negative bacteria is significantly higher in pregnancy conceived through infertility treatment compared to natural pregnancy.

OBJECTIVE: To compare abnormal vaginal colonization between natural pregnancy and pregnancy by infertility treatment in high-risk parturient women and to examine the association between abnormal vaginal colonization and early-onset neonatal sepsis (EONS). METHODS: The clinical characteristics, vaginal culture result, and delivery outcome of patients who admitted to our high-risk unit between 2005 and 2014 were retrospectively reviewed and compared. We investigated the prevalence of EONS according to maternal vaginal colonization and examined the concordance between maternal vaginal bacteria and etiologic microorganism causing EONS. RESULTS: Among 1096 pregnancies, the rate of vaginal colonization by gram-negative bacteria, especially Escherichia coli was significantly higher in pregnancies by infertility treatment after adjustment of confounding variables (E. coli, OR [95% CI]: 2.47 [1.33-4.57], p = 0.004). The rate of EONS was significantly higher in neonates with maternal abnormal vaginal bacteria colonization (OR [95% CI]: 3.38 [1.44-7.93], p = 0.005) after adjusting for confounding variables. Notably, among microorganisms isolated from maternal vagina, E. coli and Staphylococcus aureus were consistent with the results from neonatal blood culture in EONS. CONCLUSIONS: Our data implicate a possible association between gram-negative bacteria colonization and infertility treatment and suggest that maternal vaginal colonization may be associated with EONS of neonates in high-risk pregnancy.

Comparison of surgical completeness between robotic total thyroidectomy versus open thyroidectomy.

OBJECTIVES/HYPOTHESIS: The aim of this study was to investigate the surgical completeness of robotic total thyroidectomy compared with conventional open thyroidectomy. STUDY DESIGN: Retrospective, case-control study. METHODS: We studied 245 patients with papillary thyroid carcinoma who underwent total thyroidectomy and postoperative radioactive iodine (RAI) ablation. Of these, 62 patients underwent robotic thyroidectomy by a gasless unilateral axillo-breast (GUAB) or axillary (GUA) approach, and 183 underwent conventional open thyroidectomy. We analyzed serum TSH-stimulated thyroglobulin (Tg) and RAI uptake at the time of RAI remnant ablation to compare surgical completeness in the two groups. RESULTS: Tumor characteristics and complications did not differ between the two groups except TNM stage. The mean TSH-stimulated Tg at the first RAI ablation was significantly higher in the robotic group (10.20 ± 9.98 ng/ml) than in the open group (3.85 ± 6.79 ng/ml) (P <0.001). In subgroup analysis of the robotic group by the period in which operations took place, TSH-stimulated Tg was significantly higher than in the open group in the first (13.28 ± 11.91 ng/ml) and second (10.45 ± 9.30 ng/ml) periods, but there was no significant difference in the third period (6.00 ± 6.26 ng/ml, P = 0.141). The RAI uptake rate at the first RAI ablation did not differ between the two groups, and TSH-stimulated Tg after RAI ablation was similar. CONCLUSION: The surgical completeness of robotic total thyroidectomy by a GUAB/GUB approach is comparable to that of open thyroidectomy, if performed by experienced robotic thyroid surgeons in properly selected patients. LEVEL OF EVIDENCE: 3b. Laryngoscope, 124:1042-1047, 2014.

Comparison of a bolus of fentanyl with an infusion of alfentanil during target-controlled propofol infusion in third molar extraction under conscious sedation.

PURPOSE: This study was designed to compare hemodynamic changes, respiratory depression, and patient satisfaction between a bolus of fentanyl and an infusion of alfentanil during target-controlled propofol infusion in third molar extraction under conscious sedation. PATIENTS AND METHODS: Forty patients were randomly assigned to receive either a bolus of fentanyl (n = 24) or an infusion of alfentanil (n = 16) in combination with target-controlled propofol infusion. Hemodynamic changes, respiratory depression, sedation, and cooperation scores were recorded during surgery and patient satisfaction scores were assessed after surgery. RESULTS: Changes in mean blood pressure, heart rate, or oxygen saturation within and between the groups were not significant throughout the procedure. There were no significant differences in sedation, cooperation, and patient satisfaction scores between the 2 groups. CONCLUSION: Because there was no difference in hemodynamic variables and patient satisfaction scores between a bolus of fentanyl and an infusion of alfentanil during target-controlled propofol infusion, both combinations are suitable for conscious sedation in third molar extraction.

Hepatic resection by the Cavitron Ultrasonic Surgical Aspirator increases the incidence and severity of venous air embolism.

UNLABELLED: The Cavitron Ultrasonic Surgical Aspirator (CUSA) is an innovative tool for resecting hepatic parenchyma, which reduces intraoperative blood loss and perioperative morbidity. We designed this study to compare the incidence and severity of venous air embolism (VAE) detected via transesophageal echocardiography (TEE) during hepatic resection by using either the clamp-crushing method or the CUSA method. Fifty patients scheduled for hepatic resection were randomly assigned to receive hepatic resection by the clamp-crushing method (CC group) or by CUSA (CUSA group). After the induction of anesthesia, the TEE probe was inserted into the patient's esophagus. An independent anesthesiologist graded VAE shown in the 4-chamber view of TEE. All patients in the CUSA group showed VAE during hepatic resection and 44% of the patients had air embolism filling more than half the right heart diameter. In CC group, 68% of the patients showed VAE, which filled less than half the right heart diameter. There were no significant differences in hemodynamics and end-tidal CO2 partial pressure between the two groups. In conclusion, hepatic resection by CUSA increases the incidence and severity of VAE. IMPLICATIONS: This study demonstrated that venous air embolism during hepatic resection was more frequent and severe when using the Cavitron Ultrasonic Surgical Aspirator. Although we found no evidence of hemodynamic compromise, increased venous air embolism may increase the risk of paradoxical embolism in patients with liver cirrhosis.

Dose-independent pharmacokinetics of torasemide after intravenous and oral administration to rats.

After intravenous (at doses of 1, 2, 5, and 10 mg/kg) and oral (at doses of 1, 5, and 10 mg/kg) administration of torasemide, the pharmacokinetic parameters were dose-independent. Hence, the extent of absolute oral bioavailability (F) was also independent of oral doses; the values were 95.6, 98.8, and 97.3% for oral doses of 1, 5, and 10 mg/kg, respectively. The high F values indicated that the first-pass (gastric, intestinal, and hepatic) effects of torasemide in rats could be almost negligible. After intravenous administration, the total body clearances of torasemide were extensively slower than the reported cardiac output in rats and hepatic extraction ratio was only 3-4% suggesting almost negligible first-pass effects of torasemide in the heart, lung, and liver in rats. Based on in vitro rat tissue homogenate studies, the tissues studied also showed negligible metabolic activities for torasemide. Equilibrium of torasemide between plasma and blood cells of rat blood reached fast and plasma-to-blood cells concentration ratio was independent of initial blood concentrations of torasemide, 1, 5, and 10 microg/ml; the mean value was 0.279. Protein binding of torasemide to fresh rat plasma was 93.9 +/- 1.53% using an equilibrium dialysis technique.