A randomised controlled trial of the analgesia nociception index for intra-operative remifentanil dose and pain after gynaecological laparotomy.

We aimed to investigate the effect of the analgesia nociception index on postoperative pain. We randomly allocated 170 women scheduled for gynaecological laparotomy and analysed results from 159: in 80 women, remifentanil was infused to maintain analgesia nociception indices 50-70; and in 79 women, remifentanil was infused to maintain systolic blood pressure < 120% of baseline values. The primary outcome was the proportion of women with pain scores ≥ 5 (scale 0-10) within 40 min of admission to recovery. The proportion of women with pain scores ≥ 5 was 62/80 (78%) vs. 64/79 (81%), p = 0.73. Mean (SD) doses of fentanyl in recovery were 53.6 (26.9) µg vs. 54.8 (20.8) µg, p = 0.74. Intra-operative remifentanil doses were 0.124 (0.050) µg.kg-1 .min-1 vs. 0.129 (0.044) µg.kg-1 .min-1 , p = 0.55.

Regional and annual patterns in respiratory virus co-infection etiologies and antibiotic prescriptions for pediatric mycoplasma pneumoniae pneumonia.

OBJECTIVE: Mycoplasma pneumoniae (M. pneumoniae) pneumonia is the second-most common cause of community-acquired pneumonia (CAP). This study aimed at investigating into the prevalence of macrolide-resistant M. pneumoniae (MRMP) with respiratory virus co-infection and the antibiotic prescriptions in children with CAP in four provinces in Korea, and to assess the variations in the findings across regions and throughout the year. PATIENTS AND METHODS: This prospective study was conducted in 29 hospitals in Korea between July 2018 and June 2020. Among the enrolled 1,063 children with CAP, all 451 patients with M. pneumoniae underwent PCR assays of M. pneumoniae and respiratory viruses, and the presence of point mutations of residues 2063 and 2064 was evaluated. RESULTS: Gwangju-Honam (88.6%) showed the highest prevalence of MRMP pneumonia, while Daejeon-Chungcheong (71.3%) showed the lowest, although the differences in prevalence were not significant (p=0.074). Co-infection of M. pneumoniae pneumonia and respiratory virus was observed in 206 patients (45.4%), and rhinovirus co-infection (101 children; 22.2%) was the most frequent. The prevalence of MRMP pneumonia with respiratory virus co-infection and the antibiotic prescriptions differed significantly among the four provinces (p < 0.05). The monthly rate of MRMP pneumonia cases among all cases of M. pneumoniae pneumonia and tetracycline or quinolone prescriptions did not differ significantly among the four regions (trend p > 0.05) during the study period. CONCLUSIONS: The prevalence of M. pneumoniae pneumonia with virus co-infection and antibiotic prescriptions could differ according to region, although the MRMP pneumonia rate showed no difference within Korea.

Computational modeling of drug dissolution in the human stomach: Effects of posture and gastroparesis on drug bioavailability.

The oral route is the most common choice for drug administration because of several advantages, such as convenience, low cost, and high patient compliance, and the demand and investment in research and development for oral drugs continue to grow. The rate of dissolution and gastric emptying of the dissolved active pharmaceutical ingredient (API) into the duodenum is modulated by gastric motility, physical properties of the pill, and the contents of the stomach, but current in vitro procedures for assessing dissolution of oral drugs are limited in their ability to recapitulate this process. This is particularly relevant for disease conditions, such as gastroparesis, that alter the anatomy and/or physiology of the stomach. In silico models of gastric biomechanics offer the potential for overcoming these limitations of existing methods. In the current study, we employ a biomimetic in silico simulator based on the realistic anatomy and morphology of the stomach (referred to as "StomachSim") to investigate and quantify the effect of body posture and stomach motility on drug bioavailability. The simulations show that changes in posture can potentially have a significant (up to 83%) effect on the emptying rate of the API into the duodenum. Similarly, a reduction in antral contractility associated with gastroparesis can also be found to significantly reduce the dissolution of the pill as well as emptying of the API into the duodenum. The simulations show that for an equivalent motility index, the reduction in gastric emptying due to neuropathic gastroparesis is larger by a factor of about five compared to myopathic gastroparesis.

Dynamic interactions of lactic acid bacteria in Korean sourdough during back-slopping process.

AIMS: This study aimed to clarify the cause of quality reduction in Korean sourdough after successive back-slopping. METHODS AND RESULTS: We investigated the dynamic changes in lactic acid bacteria during the back-slopping process using genetic fingerprinting techniques. During the initial propagation phases, the dominant lactic acid bacteria were Fructilactobacillus sanfranciscensis (<5 log CFU per g sourdough), Latilactobacillus curvatus (9·5 log CFU per g sourdough) and Levilactobacillus brevis (6·5 log CFU per g sourdough). However, after the 11th propagation, F. sanfranciscensis became more prominent (>9·0 log CFU per g sourdough), whereas L. curvatus and L. brevis rapidly decreased. Monitoring these bacteria in the co-culture system revealed that acid-tolerant F. sanfranciscensis rapidly utilized maltose (1·65 g l-1  h-1 ) and produced large amounts of lactic acid, whereas L. brevis and L. curvatus consumed maltose slowly and L. curvatus was poorly tolerant to lactic acid. CONCLUSION: The results indicate that competition exists between the lactic acid bacteria in sourdough during the back-slopping process, and microbial succession by acid-tolerant species results in quality reduction of sourdough. SIGNIFICANCE AND IMPACT OF THE STUDY: This study uncovered the cause of microbial changes during the propagation of Korean sourdough and proposed a strategy to develop starters to produce high-quality bakery products.

Clinical usefulness of two-phase 18F-sodium-fluoride (18F-NaF) bone PET/CT for evaluating treatment response of bone metastases from breast cancer: Case report. / Utilidad clínica de la PET/TC ósea doble fase con 18F-fluoruro de sodio (18F-NaF) para valorar la respuesta terapéutica de las metástasis óseas del cáncer de mama: informe de un caso.

We report the case of a breast cancer patient in whom a two-phase 18F-sodium-fluoride (18F-NaF) bone PET/CT was useful for detecting hidden bone metastases and assessing treatment response. The patient underwent a two-phase bone PET/CT to evaluate a newly developed lesion found on bone scintigraphy following surgery. In the perfusion and bone phase PET/CT images, focally increased perfusion and bony uptake were found in the sacrum and L5 vertebra, suggesting bone metastases of breast cancer. Therefore, the patient subsequently underwent palliative treatment. In another twoPET/CT studies (each including two-phase bone images) performed after 3and 6months of follow-up, the perfusion phase images showed an improvement of the lesion uptake more clearly than in the bone phase images in the visual and semi-quantitative analyses, and thus the perfusion phase images were more useful for clarifying the treatment response earlier than the bone phase images. This is the first case showing the clinical usefulness of 18F-NaF bone PET/CT with the perfusion imaging technique for evaluating bone metastases and the therapeutic response of metastatic bone lesions.

Extracellular production of functional single-chain variable fragment against aflatoxin B1 using Escherichia coli.

scFv-BM3 is a single-chain variable fragment (scFv) against aflatoxin B1 (AFB1 ) engineered by affinity maturation and site-directed mutagenesis, and thus has a 31-fold higher affinity than its wild-type. To apply scFv-BM3 to immunological detection of AFB1 , periplasmic expression in Escherichia coli was attempted to produce a functional form of scFv-BM3. scFv-BM3 accumulated as inactive aggregates in the cells. However, it was found that scFv-BM3 secreted into the culture medium had binding activity to AFB1 . Expression conditions for scFv-BM3 were further manipulated to enhance secretion into the culture medium. This extracellular secretion of functional scFv-BM3 was significantly improved by supplementation with Triton X-100 and optimization of expression conditions. The scFv-BM3 purified from the culture medium exhibited a typical antiparallel ß-sheet structure and adopted a proper conformation to bind AFB1 with high affinity and specificity in various biophysical and biochemical analyses. SIGNIFICANCE AND IMPACT OF THE STUDY: Single-chain variable fragments (scFvs) are recombinant antibodies that are difficult to produce as a functional form in Escherichia coli. This study demonstrates the production of functional scFvs against aflatoxin B1 (AFB1 ) (scFv-BM3) using Escherichia coli by extracellular secretion. While periplasmic expression of scFv-BM3 resulted in formation of inactive aggregates in E. coli, the scFv-BM3 secreted into the culture medium adopted a properly folded structure for specific binding to AFB1 . This study promotes the application of functional scFv-BM3 to the immunological detection of AFB1 in biotechnology fields.

Randomised trial comparing forced-air warming to the upper or lower body to prevent hypothermia during thoracoscopic surgery in the lateral decubitus position.

BACKGROUND: In the supine position, forced-air warming is more effective on the lower body than on the upper body to prevent intraoperative hypothermia. However, it is unknown in the lateral decubitus position. We thus compared forced-air warming on the upper and lower bodies in the lateral position. METHODS: Patients (n=123) were randomised to receive forced-air warming on the upper body or lower body during thoracoscopic surgery in the lateral position. We measured the nasopharyngeal temperature at 0, 30, 60, 90, and 120 min after lateral positioning during surgery and the infrared tympanic membrane temperature at 0, 30, 60, 90, and 120 min after surgery. Patients received both upper and lower body warming at a temperature of <35.5°C. The primary outcome was the incidence of intraoperative hypothermia with a temperature of <36.0°C. RESULTS: Intraoperative hypothermia was less frequent with the upper body warming than with the lower body warming {21/62 vs 35/61, risk ratio [95% confidence interval (CI)] 0.6 (0.4-0.9), P=0.011}. The intraoperative temperature was higher with the upper body warming than with the lower body warming at 30 (P=0.002), 60 (P<0.001), and 90 (P<0.001) min after lateral positioning, and the postoperative temperature was higher at 0 (P<0.001) and 30 (P=0.001) min after surgery. Fewer patients received both upper and lower body warming in the upper body warming group than in the lower body warming group during surgery (1 vs 7, P=0.032). CONCLUSIONS: Forced-air warming was more effective on the upper body than on the lower body to prevent hypothermia during thoracoscopic surgery in the lateral decubitus position. CLINICAL TRIAL REGISTRATION: NCT02993666.

Strongly Coupled Magnetic and Electronic Transitions in Multivalent Strontium Cobaltites.

The topotactic phase transition in SrCoO x (x = 2.5-3.0) makes it possible to reversibly transit between the two distinct phases, i.e. the brownmillerite SrCoO2.5 that is a room-temperature antiferromagnetic insulator (AFM-I) and the perovskite SrCoO3 that is a ferromagnetic metal (FM-M), owing to their multiple valence states. For the intermediate x values, the two distinct phases are expected to strongly compete with each other. With oxidation of SrCoO2.5, however, it has been conjectured that the magnetic transition is decoupled to the electronic phase transition, i.e., the AFM-to-FM transition occurs before the insulator-to-metal transition (IMT), which is still controversial. Here, we bridge the gap between the two-phase transitions by density-functional theory calculations combined with optical spectroscopy. We confirm that the IMT actually occurs concomitantly with the FM transition near the oxygen content x = 2.75. Strong charge-spin coupling drives the concurrent IMT and AFM-to-FM transition, which fosters the near room-T magnetic transition characteristic. Ultimately, our study demonstrates that SrCoO x is an intriguingly rare candidate for inducing coupled magnetic and electronic transition via fast and reversible redox reactions.

Intraoperative naloxone reduces remifentanil-induced postoperative hyperalgesia but not pain: a randomized controlled trial.

Background: Intraoperative use of a high-dose remifentanil may induce postoperative hyperalgesia. Low-dose naloxone can selectively reverse some adverse effects of opioids without compromising analgesia. We thus hypothesized that the intraoperative use of a high-dose remifentanil combined with a low-dose naloxone infusion reduces postoperative hyperalgesia compared with the use of remifentanil alone. Methods: Patients undergoing elective thyroid surgery were randomly assigned into one of three groups, depending on the intraoperative effect-site concentration of remifentanil, with or without a continuous infusion of naloxone: 4 ng ml-1 remifentanil with 0.05 µg kg-1 h-1 naloxone in the high-remifentanil with naloxone group, and 4 or 1 ng ml-1 remifentanil with a placebo in the high- or low-remifentanil groups, respectively. We measured the pain thresholds (primary outcome) to mechanical stimuli using von Frey filaments and incidence of hyperalgesia on the peri-incisional area 24 h after surgery. We also measured pain intensity, analgesic consumptions and adverse events up to 48 h after surgery. Results: The pain threshold presented as von Frey numbers [median (interquartile range)] was significantly lower in the high-remifentanil group (n=31) than in the high-remifentanil with naloxone (n=30) and the low-remifentanil (n=30) groups [3.63 (3.22-3.84) vs 3.84 (3.76-4.00) vs 3.80 (3.69-4.08), P=0.011]. The incidence of hyperalgesia was also higher in the high-remifentanil group than in the other groups [21/31 vs 10/30 vs 9/30, P=0.005]. Postoperative pain intensity, analgesic consumptions and adverse events were similar between groups. Conclusions: The intraoperative use of low-dose naloxone combined with high-dose remifentanil reduced postoperative hyperalgesia but not pain. Clinical trial registration: NCT02856087.

Infrared probe of pseudogap in electron-doped Sr2IrO4.

We report on infrared spectroscopy experiments on the electronic response in (Sr1-x La x )2IrO4 (x = 0, 0.021, and 0.067). Our data show that electron doping induced by La substitution leads to an insulator-to-metal transition. The evolution of the electronic structure across the transition reveals the robustness of the strong electronic correlations against the electron doping. The conductivity data of the metallic compound show the signature of the pseudogap that bears close similarity to the analogous studies of the pseudogap in the underdoped cuprates. While the low energy conductivity of the metallic compound is barely frequency dependent, the formation of the pseudogap is revealed by the gradual suppression of the featureless conductivity below a threshold frequency of about 17 meV. The threshold structure develops below about 100 K which is in the vicinity of the onset of the short-range antiferromagnetic order. Our results demonstrate that the electronic correlations play a crucial role in the anomalous charge dynamics in the (Sr1-x La x )2IrO4 system.

Use of supplemental anti-HBc testing of donors showing non-discriminating reactive results in multiplex nucleic acid testing.

BACKGROUND AND OBJECTIVES: The Korean Red Cross began nucleic acid amplification testing (NAT) for HIV and HCV in February 2005, and added HBV NAT beginning in June 2012. The current NAT system utilizes a multiplex assay for simultaneous detection of HBV DNA, HCV RNA and HIV-1 RNA. For samples that are reactive in the multiplex assay, we do specific tests for each virus. However, there have been cases of non-discriminated reactive (NDR) results which appear to be the result of non-specific reactions or cross-contamination, although some cases are considered to arise from the presence of low levels of HBV DNA due to occult hepatitis B infection. MATERIALS AND METHODS: We examined the incidence of NDR results in previous donations of some NAT-reactive donors. Additionally, for those donors with NDR results, we performed an HBV core antibody (anti-HBc) assay. RESULTS: From November 2015 to March 2016, there were 408 NAT-reactive donors. Of these, nineteen HBV NAT-reactive donors showed a history of NDR results in the past donations. Seven donors showed NDR results more than once. Of 771 NDR donors, 362 (47·0%) were anti-HBc reactive. CONCLUSION: The NDR donors had a substantially higher rate of anti-HBc reactivity than other blood donors indicating that some with anti-HBc reactivity represent donors with occult HBV. Therefore, the incorporation of an anti-HBc testing for NDR donors could improve blood safety testing for the Korean Red Cross.

Calling the patient's own name facilitates recovery from general anaesthesia: a randomised double-blind trial.

People can hear and pay attention to familiar terms such as their own name better than general terms, referred to as the cocktail party effect. We performed a prospective, randomised, double-blind trial to investigate whether calling the patient's name compared with a general term facilitated a patient's response and recovery from general anaesthesia. We enrolled women having breast cancer surgery with general anaesthesia using propofol and remifentanil. Patients were randomly allocated into two groups depending on whether the patient's name or a general term was called, followed by the verbal command - 'open your eyes!' - during emergence from anaesthesia; this pre-recorded sentence was played to the patient using headphones. Fifty patients were allocated to the name group and 51 to the control group. Our primary outcome was the time from discontinuation of anaesthesia until eye opening. The mean (SD) time was 337 (154) s in the name group and 404 (170) s in the control group (p = 0.041). The time to i-gel® removal was 385 (152) vs. 454 (173) s (p = 0.036), the time until achieving a bispectral index of 60 was 174 (133) vs. 205 (160) s (p = 0.3), and the length of stay in the postanaesthesia care unit was 43.8 (3.4) vs. 47.3 (7.1) min (p = 0.005), respectively. In conclusion, using the patient's name may be an easy and effective method to facilitate recovery from general anaesthesia.

Atopic dermatitis phenotype with early onset and high serum IL-13 is linked to the new development of bronchial hyperresponsiveness in school children.

BACKGROUND: Atopic dermatitis (AD) is characterized by a heterogeneous clinical spectrum, and some forms of AD are associated with the initial steps of allergic march. The aims of this study were to determine AD phenotypes in school-age children and investigate their associations with the allergic march in each cluster. METHODS: We included 242 children (6-8 years) with current AD from the Children's HEalth and Environmental Research study, a 4-year prospective follow-up study with 2-year survey intervals. Latent class analysis was used. Serum IL-13 and thymic stromal lymphopoietin (TSLP) levels at the time of enrollment were measured using ELISA. RESULTS: We identified four current AD phenotypes in children, characterized as 'early onset with low atopy' (26.4% of the sample; group 1), 'early onset with high atopy and high eosinophil percentages' (48.3%; group 2), 'late onset with low atopy' (9.9%; group 3), and 'late onset with high atopy and normal eosinophils' (15.3%; group 4). Although groups 2 and 4 demonstrated high atopic burden, children in group 2 showed the persistence of AD and eosinophilia associated with a high prevalence of new cases of bronchial hyper-responsiveness and asthma symptoms during follow-up. The serum IL-13 level was significantly increased in the early-onset AD groups, but there was no significant difference in the serum TSLP levels across all four groups. CONCLUSION: An allergic march-associated AD phenotype exists that is characterized by early onset of AD with its persistence, increased serum IL-13 levels, high atopy, and a persistently increased blood eosinophil percentage.