Extracellular C1qbp inhibits myogenesis by suppressing NFATc1.

Aging and lack of exercise are the most important etiological factors for muscle loss. We hypothesized that new factors that contribute to muscle loss could be identified from ones commonly altered in expression in aged and exercise-limited skeletal muscles. Mouse gastrocnemius muscles were subjected to mass spectrometry-based proteomic analysis. The muscle proteomes of hindlimb-unloaded and aged mice were compared to those of exercised and young mice, respectively. C1qbp expression was significantly upregulated in the muscles of both hindlimb-unloaded and aged mice. In vitro myogenic differentiation was not affected by altering intracellular C1qbp expression but was significantly suppressed upon recombinant C1qbp treatment. Additionally, recombinant C1qbp repressed the protein level but not the mRNA level of NFATc1. NFATc1 recruited the transcriptional coactivator p300, leading to the upregulation of acetylated histone H3 levels. Furthermore, NFATc1 silencing inhibited p300 recruitment, downregulated acetylated histone H3 levels, and consequently suppressed myogenic differentiation. The expression of C1qbp was inversely correlated with that of NFATc1 in the gastrocnemius muscles of exercised or hindlimb-unloaded, and young or aged mice. These findings demonstrate a novel role of extracellular C1qbp in suppressing myogenesis by inhibiting the NFATc1/p300 complex. Thus, C1qbp can serve as a novel therapeutic target for muscle loss.

Systemic antibiotics cause deterioration of emphysema associated with exaggerated inflammation and autophagy.

The interaction between the microbial environment and the host is important for immune homeostasis. Recent research suggests that microbiota dysbiosis can be involved in respiratory diseases. Emphysema is a chronic inflammatory disease, but it is unclear whether dysbiosis caused by antibiotics can affect disease progression. Here, we tried to elucidate the effect of systemic antibiotics on smoking-exposed emphysema models. In this study, the antibiotic mixture caused more alveolar destruction and airspace expansion in the smoking group than in the smoking only or control groups. This emphysema aggravation as a result of antibiotic exposure was associated with increased levels of inflammatory cells, IL-6, IFNγ and protein concentrations in bronchoalveolar lavage fluid. Proteomics analysis indicated that autophagy could be involved in antibiotic-associated emphysema aggravation, and increased protein levels of LC3B, atg3, and atg7 were identified by Western blotting. In microbiome and metabolome analyses, the composition of the gut microbiota was different with smoking and antibiotic exposure, and the levels of short-chain fatty acids (SCFAs), including acetate and propionate, were reduced by antibiotic exposure. SCFA administration restored emphysema development with reduced inflammatory cells, IL-6, and IFNγ and decreased LC3B, atg3, and atg7 levels. In conclusion, antibiotics can aggravate emphysema, and inflammation and autophagy may be associated with this aggravation. This study provides important insight into the systemic impact of microbial dysbiosis and the therapeutic potential of utilizing the gut microbiota in emphysema.

Autophagy Suppresses Toll-Like Receptor 3-Mediated Inflammatory Reaction in Human Epidermal Keratinocytes.

Autophagy, one mechanism of programmed cell death, is fundamental to cellular homeostasis. Previous studies have identified autophagy as a novel mechanism by which cytokines control the immune response. However, its precise role in immune-related inflammatory skin diseases such as psoriasis remains unclear. Thus, this study explored the functional role of autophagy in psoriatic inflammation of epidermal keratinocytes. Strong light chain 3 immunoreactivity was observed in epidermal keratinocytes of both human psoriatic lesions and imiquimod-induced mice psoriatic model, and it was readily induced by polycytidylic acid (poly (I:C)), which stimulates Toll-like receptor 3 (TLR3), in human epidermal keratinocytes in vitro. Rapamycin-induced activation of autophagy significantly reduced poly (I:C)-induced inflammatory reaction, whereas, inhibition of autophagy by 3-methyladeine increased that. Our results indicate that the induction of autophagy may attenuate TLR3-mediated immune responses in human epidermal keratinocytes, thus providing novel insights into the mechanisms underlying the development of inflammatory skin diseases including psoriasis.

Interactive tissue reactions of 1064-nm focused picosecond-domain laser and dermal cohesive polydensified matrix hyaluronic acid treatment in in vivo rat skin.

BACKGROUND: Picosecond-domain laser treatment using a microlens array (MLA) or a diffractive optical element (DOE) generates micro-injury zones in the epidermis and upper dermis. OBJECTIVE: To investigate interactive tissue reactions between MLA-type picosecond laser pulses and cohesive polydensified matrix hyaluronic acid (CPMHA) filler in the dermis. METHODS: In vivo rats with or without CPMHA pretreatment were treated with a 1064-nm picosecond-domain neodymium:yttrium-aluminum-garnet (Nd:YAG) laser using an MLA or DOE. Skin samples were obtained at post-treatment days 1, 10, and 21 and histologically and immunohistochemically analyzed. RESULTS: Picosecond-domain Nd:YAG laser treatment with an MLA-type or a DOE-type handpiece generated fractionated zones of pseudo-cystic cavitation along the lower epidermis and/or upper papillary dermis at Day 1. At Day 21, epidermal thickness, dermal fibroblasts, and collagen fibers had increased. Compared to CPMHA-untreated rats, rats pretreated with CPMHA showed marked increases in fibroblasts and collagen fibers in the papillary dermis. Immunohistochemical staining for the hyaluronic acid receptor CD44 revealed that MLA-type picosecond laser treatment upregulated CD44 expression in the basilar epidermis and dermal fibroblasts. CONCLUSIONS: We suggest that the hyaluronic acid-rich environment associated with CPMHA treatment may enhance MLA-type picosecond-domain laser-induced tissue reactions in the epidermis and upper dermis.

Effects of argon and nitrogen plasma pulses on the skin and skin appendages in an in vivo animal model.

BACKGROUND: For medical purposes, plasma can be generated from inert gaseous sources in a device by ultra-high-frequency generators and emitted to target tissue at a pulse duration in the milliseconds. OBJECTIVE: To evaluate argon and nitrogen plasma pulse-induced tissue reactions in the skin and skin appendages of an in vivo animal model. METHODS: Argon and nitrogen plasma pulses were non-invasively delivered to in vivo rat skin at various experimental settings. Specimens were histologically evaluated following hematoxylin and eosin and Masson's trichrome staining. RESULTS: At low-energy settings of 1.0, 1.5, and 2.0 J, nitrogen plasma treatments generated noticeable tissue coagulation at the depths of 31.5 ± 8.3, 94.9 ± 16.9, and 171.6 ± 19.7 µm, respectively, at Day 0. At high-energy settings of 2.5 and 3.0 J, nitrogen plasma treatments generated marked tissue coagulation at the depths of 381.7 ± 33.6 µm and 456.3 ± 75.7 µm, respectively, at Day 0. CONCLUSIONS: Treatment with argon plasma induces microscopic changes in the epidermis, dermis, and sebaceous glands without generating excessive thermal injury, whereas that with nitrogen plasma elicits energy-dependent thermal coagulation in the epidermis and dermis with remarkable neocollagenesis.

Systematic review and meta-analysis: Effect of Helicobacter pylori eradication on chronic spontaneous urticaria.

BACKGROUND: Helicobacter pylori (HP) infection is considered to play a role in the pathogenesis of chronic spontaneous urticaria (CSU). However, the efficacy of HP eradication therapy on CSU symptom improvement has not been well established. This meta-analysis was conducted to estimate the association between HP infection and CSU and to evaluate whether HP eradication therapy benefits patients with CSU. MATERIAL AND METHODS: In October 2018, we searched databases for studies investigating the efficacy of HP eradication therapy for patients with CSU. Risk ratios (RRs) and 95% confidence intervals (CIs) were pooled using random effects models. RESULTS: The meta-analysis included 22 studies with a total of 1385 patients with CSU. When comparing the spontaneous remission of urticarial symptom in patients with HP-positive to HP-negative patients, HP-negative patients showed significantly higher spontaneous remission of urticarial symptoms. (risk ratio 0.39; 95% confidence interval: 0.19-0.81). Among HP-positive CSU patients, remission of CSU was more likely shown in HP eradication therapy group compared to untreated group, aside from achieving HP elimination (risk ratio 2.10; 95% confidence interval: 1.20-3.68). However, there was no significant difference in the remission of CSU whether antibiotic therapy was successful in eradication of HP or not (risk ratio 1.00; 95% confidence interval: 0.65-1.54). CONCLUSIONS: The results of this meta-analysis show that HP might be associated with the occurrence and persistence of CSU. The effectiveness of HP eradication therapy in suppressing CSU symptoms was significant. Interestingly, we found that resolution of CSU was not associated with successful eradication of HP infection. CSU Patients who were undergone antibiotic therapy for HP eradication showed significant higher CSU remission with or without HP eradication. Further studies are recommended to evaluate the mechanisms associated with relation of HP with CSU.

Effective dose of dobutamine in augmenting free flap blood flow during reconstructive surgery of the lower extremity.

Success of surgical free flap transfer depends on achieving and maintaining adequate perfusion across the microvascular anastomosis. The purpose of this prospective study was to determine the optimal infusion rate of dobutamine to augment duplex ultrasound measured blood flow to the tissue flap during surgery.Twenty-one patients undergoing general anesthesia for lower limb reconstructive surgery were recruited. The optimal dobutamine dose was evaluated using the modified Dixon's up-and-down method, starting at 6 µg·kg·min, and then titrated in increments of 1 µg·kg·min.The optimal dose of dobutamine for improving blood flow to the tissue flap was 3.50 ±â€Š0.57 µg·kg·min in 50% of patients. The 95% effective dose of dobutamine calculated by probit analysis was 4.46 µg·kg·min (95% confidence interval: 3.99-7.00 µg·kg·min).The results of our study suggest that a dobutamine infusion rate less than 5 µg·kg·minprovides significant improvement of blood flow to the tissue flap, while minimizing cardiovascular side effects.

Effect of heated humidified ventilation on bronchial mucus transport velocity in general anaesthesia: a randomized trial.

OBJECTIVE: To evaluate the effects of heated humidified ventilation on mucociliary function during general anaesthesia. METHODS: Male patients (ASA physical status 1 or 2), scheduled for elective radical retropubic prostatectomy, were allocated to receive sevoflurane general anaesthesia with conventional or heated humidified ventilation. Bronchial mucus transport velocity was assessed via fibreoptic bronchoscope and methylene blue dye at 3h after induction of anaesthesia. RESULTS: Median (SE) bronchial mucus transport velocity was significantly higher in the heated humidified group (n = 26) than the conventional ventilation group (n = 24) (1.7 [0.3] mm/min vs 0.9 [0.1] mm/min). CONCLUSION: Heated humidified ventilation effectively maintains mucociliary clearance of patients during sevoflurane general anaesthesia.

Palonosetron has superior prophylactic antiemetic efficacy compared with ondansetron or ramosetron in high-risk patients undergoing laparoscopic surgery: a prospective, randomized, double-blinded study.

BACKGROUND: Postoperative nausea and vomiting (PONV) continues to be a major problem, because PONV is associated with delayed recovery and prolonged hospital stay. Although the PONV guidelines recommended the use of 5-hydroxy-tryptamine (5-HT3) receptor antagonists as the first-line prophylactic agents in patients categorized as high-risk, there are few studies comparing the efficacies of ondansetron, ramosetron, and palonosetron. The aim of present study was to compare the prophylactic antiemetic efficacies of three 5HT3 receptor antagonists in high-risk patients after laparoscopic surgery. METHODS: In this prospective, randomized, double-blinded trial, 109 female nonsmokers scheduled for elective laparoscopic surgery were randomized to receive intravenous 4 mg ondansetron (n = 35), 0.3 mg ramosetron (n = 38), or 75 µg palonosetron (n = 36) before anesthesia. Fentanyl-based intravenous patient-controlled analgesia was administered for 48 h after surgery. Primary antiemetic efficacy variables were the incidence and severity of nausea, the frequency of emetic episodes during the first 48 h after surgery, and the need to use a rescue antiemetic medication. RESULTS: The overall incidence of nausea/retching/vomiting was lower in the palonosetron (22.2%/11.1%/5.6%) than in the ondansetron (77.1%/48.6%/28.6%) and ramosetron (60.5%/28.9%/18.4%) groups. The rescue antiemetic therapy was required less frequently in the palonosetron group than the other groups (P < 0.001). Kaplan-Meier analysis showed that the order of prophylactic efficacy in delaying the interval to use of a rescue emetic was palonosetron, ramosetron, and ondansetron. CONCLUSIONS: Single-dose palonosetron is the prophylactic antiemetics of choice in high-risk patients undergoing laparoscopic surgery.

Intraoperative infusion of 0.6-0.9 µg·kg(-1)·min(-1) remifentanil induces acute tolerance in young children after laparoscopic ureteroneocystostomy.

BACKGROUND: Intraoperative infusion of opioids has been associated with increased postoperative pain and analgesic requirements, but the development of tolerance in young children is less clear. This prospective, randomized, double-blinded study was designed to test the hypothesis that the intraoperative administration of remifentanil results in postoperative opioid tolerance in a dose-related manner in young children. METHODS: We enrolled 60 children (aged 1-5 yr) who were undergoing elective laparoscopic ureteroneocystostomy. Patients were randomized and received an intraoperative infusion of 0, 0.3, 0.6, or 0.9 µg·kg·min remifentanil. Postoperative pain was managed by a parent/nurse-controlled analgesia pump using fentanyl. The primary outcome included the total fentanyl consumptions at 24 and 48 h postsurgery. Secondary outcomes were the postoperative pain scores and adverse effects. RESULTS: The children who received 0.6 and 0.9 µg·kg·min remifentanil required more postoperative fentanyl than the children who received saline or 0.3 µg·kg·min remifentanil (all P < 0.001) for 24 h after surgery. The children who received 0.3-0.9 µg·kg·min intraoperative remifentanil reported higher pain scores at 1 h after surgery than the children who received saline (P = 0.002, P = 0.023, and P = 0.006, respectively). No significant intergroup differences in recovery variables were observed, but vomiting was more frequent in the 0.9 µg·kg·min remifentanil group than in the other groups (P = 0.027). CONCLUSIONS: The intraoperative use of 0.3 µg·kg·min remifentanil for approximately 3 h (range: 140-265 min) did not induce acute tolerance, but the administration of 0.6 and 0.9 µg·kg·min remifentanil to young children resulted in acute tolerance for 24 h after surgery in an apparently dose-related manner.

Psychological and behavioral effects of chloral hydrate in day-case pediatric surgery: a randomized, observer-blinded study.

BACKGROUND/PURPOSE: This prospective, randomized, and observer-blinded study was performed to evaluate the effects of oral chloral hydrate on perioperative psychological and behavioral phenomena in children. METHODS: In total, 100 boys (age, 1-5 years) scheduled for day-case unilateral orchiopexy were randomly allocated into 2 groups and orally administered either 40 mg/kg of chloral hydrate (CH group) or placebo (control group) 30 minutes before surgery, followed by assessment of anxiety, induction compliance, emergence delirium, postoperative pain, and maladaptive behavioral changes. RESULTS: Anxiety scores were significantly lower in the CH group compared with the control group (45.7 vs 28.8). The induction compliance of the CH group was better than that of the control group (3.2 vs 4.8). Postoperative sedation was more frequent (62.7% vs 20.4%); however, the incidence of vomiting was lower (2.0% vs 14.3%) in the CH group than in the control group. Postoperative emergence delirium and maladaptive behavior changes were similar between the 2 groups. CONCLUSION: Decreasing preoperative anxiety with oral chloral hydrate improves induction compliance and reduces postoperative pain intensity without delaying recovery in young boys. However, chloral hydrate had little impact on emergence delirium and postoperative maladaptive behavior.

Effect of anesthetic methods on cerebral oxygen saturation in elderly surgical patients: prospective, randomized, observational study.

BACKGROUND: Intraoperative cerebral oxygen desaturation was reported to be associated with postoperative cognitive dysfunction in elderly patients. The effect of the anesthesia method on regional cerebral oxygen saturation (rSO(2)) is still a question under debate. The purpose of this study was to compare the effects of three common anesthesia methods on intraoperative rSO(2) changes in elderly patients. METHODS: In this prospective randomized clinical trial, 87 patients scheduled for elective transurethral prostatectomy were allocated to receive general inhalational anesthesia (GA group, n = 30), spinal anesthesia (SA group, n = 28), or spinal anesthesia plus sedation with midazolam (SA+S group, n = 29). RESULTS: The numbers of patients showing a decrease in rSO(2) below the baseline value were higher in the SA (92.9 %) and SA+S (100 %) groups than in the GA group (33.3 %). The number of patients with a ≥ 50 % decrease in rSO(2) below baseline was greater in the SA+S (31.0 %) group than in the GA (0 %) or SA (3.6 %) group. During surgery, patients subjected to general anesthesia had higher rSO(2) than those with spinal anesthesia. Blood pressures and heart rates were similar in three groups except 5 and 10 min after anesthesia. Intraoperative SpO(2) was higher in the GA group than in the two spinal anesthesia groups. CONCLUSIONS: Spinal anesthesia is associated with more frequent cerebral desaturation than general anesthesia; and it was aggravated when combined with midazolam sedation. The cerebral effects of anesthesia should be considered when managing high-risk elderly patients.

Preoperative comorbidities and relationship of comorbidities with postoperative complications in patients undergoing transurethral prostate resection.

PURPOSE: We retrospectively identified preoperative comorbidities and analyzed the relationship of the comorbidities to postoperative complications in patients treated with transurethral prostate resection. MATERIALS AND METHODS: We reviewed the surgical and clinical records of 1,878 patients who underwent transurethral prostate resection at a single university hospital between January 2006 and December 2009. Variables included preoperative comorbidities, intraoperative data and postoperative complications, including mortality. RESULTS: Only 32.6% of the patients had no observed preoperative comorbidity and the other 67.4% had at least 1. The incidence of comorbidities increased with age (p <0.001). The overall postoperative complication rate was 5.8%. There were 3 deaths for an overall 0.16% 30-day mortality rate. The postoperative complication rate was significantly higher in patients who had a comorbidity preoperatively and were 50 to 59 (p = 0.043), 60 to 69 (p = 0.028) and 70 to 79 years old (p = 0.017). The Charlson comorbidity index was significantly associated with postoperative complications (r(2) = 0.221, p = 0.012). CONCLUSIONS: Almost two-thirds of the patients who underwent transurethral prostate resection had various preoperative comorbidities. The fact that the preoperative comorbidity was significantly related to postoperative complications after transurethral prostate resection should be considered in perioperative management in this population.

Changes of dorsalis pedis artery flow pattern after caudal block in children: observational study using a duplex sonography.

OBJECTIVE: To evaluate the changes of the flow velocity, the volume flow, and the diameter of dorsalis pedis artery using a duplex ultrasonography after caudal block with sevoflurane anesthesia in children. AIM: To know the acute change in peripheral arterial flow patterns of sympathetically blocked lower limbs in anesthetized children. BACKGROUND: Caudal analgesia in combination with general anesthesia may affect the circulatory hemodynamics due to sympatholytic vasodilating effects. METHODS: After approval by the Ethics Committee, we evaluated the changes of peripheral hemodynamics using a duplex ultrasonography before and after a caudal block in sevoflurane-anesthetized children. RESULTS: A caudal block using 0.15% ropivacaine 1.5 ml·kg(-1) significantly altered the arterial flow patterns; increased peak velocity (24%) and volume flow (76%), and the diameter of the dorsalis pedis artery (20%) in children. However, blood pressures and heart rates were not affected significantly by caudal block. CONCLUSIONS: Duplex sonographic measurements indicate that a caudal block changes the flow patterns of the dorsalis pedis artery significantly in the anesthetized children.

Fentanyl-sparing effect of acetaminophen as a mixture of fentanyl in intravenous parent-/nurse-controlled analgesia after pediatric ureteroneocystostomy.

BACKGROUND: Although acetaminophen has been used widely and is well tolerated in children, its efficacy and safety have not been clarified when combined with an opioid in intravenous parent-/nurse-controlled postoperative analgesia. METHODS: Sixty-three children (aged 6-24 months) who had undergone elective ureteroneocystostomies were enrolled in this prospective, randomized, double-blinded study. After the surgery, an analgesic pump was programmed to deliver fentanyl at a basal infusion rate of 0.25 microg.kg(-1).h(-1) and 0.25 microg/kg bolus after a loading dose of 0.5 microg/kg(-1). In the fentanyl-acetaminophen group, acetaminophen was coadministered as a solution mixture at a basal infusion rate of 1.5 mg.kg(-1).h(-1) and 1.5 mg/kg bolus after a loading dose of 15 mg/kg, whereas saline was administered to the fentanyl group. RESULTS: Postoperative pain scores were similar between the two groups. The total dose (micrograms per kilogram per day, mean+/-SD) of fentanyl at postoperative days 1 (8.3+/-3.7 vs. 18.1+/-4.6, P=0.021) and 2 (7.0+/-2.4 vs. 16.6, P=0.042) was significantly less in the fentanyl-acetaminophen group compared with that in the fentanyl group. The incidences of vomiting (16.1 vs. 56.3%, P=0.011) and sedation (9.7 vs. 46.9%, P=0.019) were significantly lower in the fentanyl-acetaminophen group than those in the fentanyl group. CONCLUSIONS: Acetaminophen has significant fentanyl-sparing effects and reduces side effects when combined with fentanyl in intravenous parent-/nurse-controlled analgesia for postoperative pediatric pain management.

Pulmonary edema after da Vinci-assisted laparoscopic radical prostatectomy: a case report.

A 63 year-old man developed sudden pulmonary edema after uneventful robot-assisted laparoscopic radical prostatectomy (RALP) for prostate cancer despite normal preoperative laboratory findings and appropriate anesthetic management. The pulmonary edema was attributed to prolonged (4 hrs) pneumoperitoneum with concomitant high intraabdominal pressure (15-20 mmHg).

Effect of head rotation on overlap and relative position of internal jugular vein to carotid artery in infants and children: a study of the anatomy using ultrasonography.

PURPOSE: The aim of this study was to evaluate the influence of head rotation on the relative anatomy of internal jugular vein (IJV) and carotid artery (CA) in infants and children. MATERIALS AND METHODS: Two hundred pediatric patients (26.5 +/- 23.3 months old) who were undergoing elective surgery were eligible for this consecutive and prospective study. Using 2-dimensional ultrasound, the amount of overlap and the relative position of the 2 vessels were compared between heads in the neutral position and in 90 degrees of rotation. RESULTS: The mean percentage overlap of CA by IJV in the neutral position increased significantly as the head was rotated to the right (23.3% vs 39.2%) and left (35.3% vs 52.8%). The incidence of lateral positioning of IJV to CA decreased significantly when the head was rotated (40% vs 21% in right, 26.5% vs 10.5% in left). The right IJV is associated with less overlap of the CA than the left, regardless of head position. CONCLUSIONS: The head should be kept in as near a neutral position as possible because the overlap increased by head rotation in both sides. In addition, the right IJV should be preferred because of less CA overlap and more lateral positioning than the left.