Prediction of outliers in pain, analgesia requirement, and recovery of function after childbirth: a prospective observational cohort study.

BACKGROUND: Prediction models to identify parturients who experience protracted pain, prolonged opioid use, and delayed self-assessed functional recovery are currently inadequate. METHODS: For this study, 213 nulliparous women who planned vaginal delivery were enrolled and assessed daily until they completed three outcomes: (1) pain resolution; (2) opioid cessation; and (3) self-assessed functional recovery to predelivery level. The primary composite endpoint, 'pain and opioid-free functional recovery' was the time required to reach all three endpoints. The subjects were divided into two categories (the worst (longest time) 20% and remaining 80%) for reaching the primary composite endpoint, and each individual component. Prediction models for prolonged recovery were constructed using multivariate logistic regression with demographic, obstetric, psychological, and health-related quality of life characteristics as candidate predictors. RESULTS: Labour induction (vs spontaneous labour onset) predicted the worst 20% for the primary composite endpoint in the final multivariate model. Labour induction and higher postpartum day 1 numerical rating score for pain were predictors for being in the worst 20% for both functional recovery and pain burden. Labour type, delivery type, Patient-Reported Outcomes Measurement Information System (PROMIS) anxiety score, RAND 36 Item Health Survey 1.0 (SF-36) physical health composite score, and postpartum breastfeeding success were predictive of delayed opioid cessation. CONCLUSIONS: Labour induction and elevated numerical rating score for pain are predictive of poor recovery after childbirth. Further research is necessary to determine whether modification would benefit mothers at risk for poor recovery.

Steroid administration after anaesthetic induction with etomidate does not reduce in-hospital mortality or cardiovascular morbidity after non-cardiac surgery.

BACKGROUND: We tested the primary hypothesis that corticosteroid administration after etomidate exposure reduces a composite of in-hospital mortality and cardiovascular morbidity after non-cardiac surgery. METHODS: We evaluated ASA physical status III and IV patients who had non-cardiac surgery with general anaesthesia at the Cleveland Clinic. Amongst 4275 patients in whom anaesthesia was induced with etomidate, 804 were also given steroid intraoperatively, mostly dexamethasone at a median dose of 6 mg. We successfully matched 582 steroid patients with 1023 non-steroid patients. The matched groups were compared on composite of in-hospital mortality and cardiovascular morbidity using a generalized-estimating-equation model. Secondly, the matched groups were compared on length of hospital stay using a Cox proportional hazard model, and were descriptively compared on intraoperative blood pressures using a standardized difference. RESULTS: There was no significant association between intraoperative steroid administration after anaesthetic induction with etomidate and the composite of in-hospital mortality or cardiovascular morbidity; the estimated common odds ratio across the two components of the composite was 0.86 [95% confidence interval (CI): 0.64, 1.16] for steroid vs non-steroid, P=0.33. The duration of postoperative hospitalisation was significantly shorter amongst steroid patients [median (Q1, Q3): 6 (3, 10) days] than non-steroid patients [7 (4, 11) days], with an estimated hazard ratio of 0.89 (0.80, 0.98) for steroid vs non-steroid, P=0.01. Intraoperative blood pressures were similar in steroid and non-steroid patients. CONCLUSIONS: Steroid administration after induction of anaesthesia with etomidate did not reduce mortality or cardiovascular morbidity.

Dissecting the structural basis for the intracellular delivery of OSW-1 by fluorescent probes.

The structural basis for the intracellular delivery of OSW-1 is investigated using fluorescent derivatives of OSW-1 and its closely related congeners. Despite the large differences in activity, all the fluorescent probes are found to translocate across the plasma membrane to the ER and Golgi apparatus. This observation suggests that the glycosylated cholestane moiety plays an important role in the cell internalization and intracellular localization property of OSW-1.

A comparison of the Airway Scope and McCoy laryngoscope in patients with simulated restricted neck mobility.

We compared the efficacy of the Airway Scope and McCoy laryngoscope as intubation tools with the neck stabilised by a rigid cervical collar. After induction of anaesthesia and neck stabilisation, 100 patients were randomly assigned to tracheal intubation with an Airway Scope or McCoy laryngoscope. Overall intubation success rate, time required for intubation, number of intubation attempts required for successful intubation, and airway complications related to intubation were recorded. Overall intubation success rates were 100% with both devices and a similar number of intubation attempts were required. However, the mean (SD) time required for successful intubation was shorter with the Airway Scope (30 (7) s) than with the McCoy laryngoscope (40 (14) s; p < 0.0001). The incidences of intubation complications were similar, but oesophageal intubation (in six cases) occurred only with McCoy laryngoscope.

Effect of nasal cannula oxygen administration on oxygen concentration at facial and adjacent landmarks.

An oxygen-enriched atmosphere enhances the potential for operating-room fires. We thus determined oxygen concentrations at various facial landmarks during oxygen administration via nasal cannulae. Thirteen supine volunteers were draped similarly to patients undergoing a cervical-node biopsy. Oxygen was delivered in random order through nasal cannulae at rates of 2, 4, and 6 l x min(-1). Oxygen concentration was measured at pre-determined facial landmarks and also distal to the drape at non-facial sites. At a flow of 2 l x min(-1), oxygen concentrations exceeded 23% only within a few centimetres of the nasal cannula. Concentration increased as a function of flow, but rarely exceeded 26%. At all flow rates, concentrations distal to the drape were < 24%. To reduce combustion risk, ignition sources should be kept at least 10 cm from the oxygen outlet when using nasal cannula at a flow rate > or = 4 l x min(-1).

Deciphering the influence of paraimmunobiotic bifidobacteria on the innate antiviral immune response of bovine intestinal epitheliocytes by transcriptomic analysis.

Previously, we reported that the non-viable immunomodulatory Bifidobacterium infantis MCC12 and Bifidobacterium breve MCC1274 strains (paraimmunobiotic bifidobacteria) were able to increase the protection against rotavirus infection in bovine intestinal epithelial (BIE) cells. In order to gain insight into the influence of paraimmunobiotic bifidobacteria on the innate antiviral immune response of BIE cells, their effect on the transcriptomic response triggered by Toll-like receptor 3 (TLR3) activation was investigated. By using microarray technology and qPCR analysis, we obtained a global overview of the immune genes involved in the innate antiviral immune response in BIE cells. Activation of TLR3 by poly(I:C) in BIE cells significantly increased the expression of interferon (IFN)-α and IFN-ß, several interferon-stimulated genes, cytokines, and chemokines. It was also observed that both paraimmunobiotic bifidobacteria differently modulated immune genes expression in poly(I:C)-challenged BIE cells. Most notable changes were found in genes involved in antiviral defence (IFN-ß, MX1, OAS1X, MDA5, TLR3, STAT2, STAT3), cytokines (interleukin (IL)-6), and chemokines (CCL2, CXCL2, CXCL6) that were significantly increased in bifidobacteria-treated BIE cells. B. infantis MCC12 and B. breve MCC1274 showed quantitative and qualitative differences in their capacities to modulate the innate antiviral immune response in BIE cells. B. breve MCC1274 was more efficient than the MCC12 strain to improve the production of type I IFNs and antiviral factors, an effect that could be related to its higher ability to protect against rotavirus replication in BIE cells. Interestingly, B. infantis MCC12 showed a remarkable anti-inflammatory effect. The MCC12 strain was more efficient to reduce the expression of inflammatory cytokines and chemokines (IL-16, IL-20, CX3CL1) when compared with B. breve MCC1274. These results provided valuable information for the deeper understanding of the antiviral immune response of intestinal epithelial cells as well as the host-paraimmunobiotic interaction in the bovine host.

Estimating the number of HIV infections averted: an approach and its issues.

OBJECTIVE: To propose a methodology to estimate the number of new HIV infections averted. Knowledge of HIV infection has increased tremendously and modelling tools to project current epidemics into the future have greatly improved. Different types of models can be used to estimate HIV infections averted, although the number of new HIV infections averted cannot be measured directly. METHOD: Using cohort-component population projections, a disease modelling-based approach was used to compare the observed epidemiology of a disease after programme initiation with an expected epidemiology from past trends before programme initiation. The concept of modelling infections averted in a disease modelling-based approach involves a comparison between an "expected" or baseline epidemic with an "estimated" one. A hypothetical example was featured in order to demonstrate the proposed methodology. Using both the Estimation and Projection Package (EPP) and the Spectrum demographic modelling program, the underlying annual incidence levels implied by both the baseline and estimated epidemics were examined. RESULTS: The difference between baseline and estimated incidence levels is interpreted as "infections averted". Strengths and limitations of the approach are discussed. CONCLUSIONS: In this study an expected epidemiological approach was compared to one based on observation. Once sufficient data become available, the validation of various country data including HIV prevalence, mortality, and behaviour must be done. Additional information related to behaviour change may be critical to further support arguments for a change in disease trend. It is therefore important to use all available data, consequently strengthening findings from a disease modelling-based approach on HIV infections averted.

Airway scope and gum elastic bougie with Macintosh laryngoscope for tracheal intubation in patients with simulated restricted neck mobility.

BACKGROUND: /st> Airway Scope is a new videolaryngoscope which requires less cervical movement during intubation than direct laryngoscopy. Thus, in patients wearing a rigid cervical collar, we compared the efficacy of the Airway Scope and the gum elastic bougie with Macintosh laryngoscope during tracheal intubation. METHODS: /st> Anaesthesia was induced with propofol, fentanyl, and rocuronium. A rigid cervical collar was applied, and patients were randomly assigned to tracheal intubation with an Airway Scope (n=48) or multiple-use gum elastic bougie with Macintosh laryngoscope (n=48). Measurements included intubation time, gum elastic bougie insertion time, intubation success rate, and insertion and intubation attempts. Airway complications were also recorded. RESULTS: /st> The time required for successful intubation was significantly shorter with the Airway Scope compared with the gum elastic bougie with Macintosh laryngoscope [mean (sd) 34 (13) vs 49 (27) s, P=0.001], although the overall success rate of the Airway Scope (100%) compared with the gum elastic bougie with Macintosh laryngoscope (90%) did not reach the statistical significance (P=0.056). Oesophageal intubation (n=8) occurred only with the gum elastic bougie with Macintosh laryngoscope. Incidence of mucosal trauma and lip injury was similar with each device. No dental injury or hypoxia occurred with either device. CONCLUSIONS: /st> The Airway Scope shortens intubation time, is less likely to result in oesophageal intubation, and may offer a marginally higher intubation success rate in patients with simulated restricted neck mobility.

Lactobacillus fermentum UCO-979C beneficially modulates the innate immune response triggered by Helicobacter pylori infection in vitro.

Helicobacter pylori infection is associated with important gastric pathologies. An aggressive proinflammatory immune response is generated in the gastric tissue infected with H. pylori, resulting in gastritis and a series of morphological changes that increase the susceptibility to cancer development. Probiotics could present an alternative solution to prevent or decrease H. pylori infection. Among them, the use of immunomodulatory lactic acid bacteria represents a promising option to reduce the severity of chronic inflammatory-mediated tissue damage and to improve protective immunity against H. pylori. We previously isolated Lactobacillus fermentum UCO-979C from human gastric tissue and demonstrated its capacity to reduce adhesion of H. pylori to human gastric epithelial cells (AGS cells). In this work, the ability of L. fermentum UCO-979C to modulate immune response in AGS cells and PMA phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 (human monocytic leukaemia) macrophages in response to H. pylori infection was evaluated. We demonstrated that the UCO-979C strain is able to differentially modulate the cytokine response of gastric epithelial cells and macrophages after H. pylori infection. Of note, L. fermentum UCO-979C was able to significantly reduce the production of inflammatory cytokines and chemokines in AGS and THP-1 cells as well as increase the levels of immunoregulatory cytokines, indicating a remarkable anti-inflammatory effect. These findings strongly support the probiotic potential of L. fermentum UCO-979C and provide evidence of its beneficial effects against the inflammatory damage induced by H. pylori infection. Although our findings should be proven in appropriate experiments in vivo, in both H. pylori infection animal models and human trials, the results of the present work provide a scientific rationale for the use of L. fermentum UCO-979C to prevent or reduce H. pylori-induced gastric inflammation in humans.

Remifentanil for general anaesthesia: a systematic review.

We performed a quantitative systematic review of randomised, controlled trials that compared remifentanil to short-acting opioids (fentanyl, alfentanil, or sufentanil) for general anaesthesia. Eighty-five trials were identified and these included a total of 13 057 patients. Intra-operatively, remifentanil was associated with clinical signs of deeper analgesia and anaesthesia, such as fewer responses to noxious stimuli (relative risk 0.65, 95% CI 0.48-0.87), more frequent episodes of bradycardia (1.46, 1.04-2.05), more hypotension (1.68, 1.36-2.07) and less hypertension (0.60, 0.46-0.78). Postoperatively, remifentanil was associated with faster recovery (difference in extubation time of -2.03, 9.5% CI, -2.92 to -1.14 min), more frequent postoperative analgesic requirements (1.36, 1.21-1.53) and fewer respiratory events requiring naloxone (0.25, 0.14-0.47). Remifentanil had no overall impact on postoperative nausea (1.03, 0.97-1.09) or vomiting (1.06, 0.96-1.17), but was associated with twice as much shivering (2.15, 1.73-2.69). Remifentanil does not seem to offer any advantage for lengthy, major interventions, but may be useful for selected patients, e.g. when postoperative respiratory depression is a concern.

Synthesis of a fluorescent photoaffinity probe of OSW-1 by site-selective acylation of an inactive congener and biological evaluation.

A novel fluorescent photoaffinity probe of OSW-1 was prepared in two steps from a naturally occurring inactive congener by a sequential site-selective acylation strategy using Me2SnCl2. It displayed highly potent anticancer activity and a similar intracellular localization property to that of a fluorescently-tagged OSW-1, thereby demonstrating its potential utility in live cell studies.

Correction: Synthesis of a fluorescent photoaffinity probe of OSW-1 by site-selective acylation of an inactive congener and biological evaluation.

Correction for 'Synthesis of a fluorescent photoaffinity probe of OSW-1 by site-selective acylation of an inactive congener and biological evaluation' by K. Sakurai et al., Chem. Commun., 2017, DOI: .

Lysosomal accumulation of oxidized phosphatidylcholine-apolipoprotein B complex in macrophages: intracellular fate of oxidized low density lipoprotein.

Oxidized phosphatidylcholine (OxPC) formed in oxidized low density lipoprotein (OxLDL) is thought to be involved in the development of atherosclerosis. OxPC has been found in foam cells in atherosclerotic lesions and suggested to be the epitope for OxLDL recognition by macrophages. OxPC is present as a complex with apolipoprotein B (apoB) in OxLDL, since some OxPC can bind with proteins. In the current study, the intracellular fate of OxPC-apoB complexes after internalization of OxLDL by macrophages was investigated. Murine macrophage cell line J774.1 was incubated with either OxLDL or acetylated LDL for 24 h, then the cells were further incubated for up to 24 h in new medium without lipoprotein. Modified apoB in the cells was quantitated by sandwich ELISA using monoclonal antibodies against OxPC and apoB. Intracellular OxLDL decreased rapidly for the first 4 h to approx. 20% of that before medium change, with the apparent metabolism of OxPC-apoB complex ceasing. OxPC-apoB complexes that remained in the cells after 24 h chasing increased as the period of OxLDL loading in macrophages prolongs. Acetylated LDL in the cells decreased quickly and disappeared after 4 h of chasing. Subcellular fractionation using sucrose density gradient ultracentrifugation of macrophages, which had already accumulated OxPC-apoB complexes by 24 h of incubation with OxLDL and further 24 h chasing, showed that the complex was co-localized with endosomal and lysosomal markers. Immunohistochemical double staining studies demonstrated that OxPC and apoB co-localize in foam cells in early atherosclerotic lesions obtained from human coronary artery. These results suggest that OxPC-apoB complexes originating from OxLDL accumulate in foam cells in human atherosclerotic lesions as well as in macrophages in vitro.

Elevated levels of oxidized low density lipoprotein show a positive relationship with the severity of acute coronary syndromes.

BACKGROUND: There is accumulating data that acute coronary syndromes relate to recent onset activation of inflammation affecting atherosclerotic plaques. Increased blood levels of oxidized low density lipoprotein (ox-LDL) could play a role in these circumstances. METHODS AND RESULTS: Ox-LDL levels were measured in 135 patients with acute myocardial infarction (AMI; n=45), unstable angina pectoris (UAP; n=45), and stable angina pectoris (SAP; n=45) and in 46 control subjects using a sandwich ELISA method. In addition, 33 atherectomy specimens obtained from a different cohort of patients with SAP (n=10) and UAP (n=23) were studied immunohistochemically for ox-LDL. In AMI patients, ox-LDL levels were significantly higher than in patients with UAP (P<0.0005) or SAP (P<0.0001) or in controls (P<0.0001) (AMI, 1.95+/-1.42 ng/5 microgram LDL protein; UAP, 1.19+/-0.74 ng/5 microgram LDL protein; SAP, 0.89+/-0.48 ng/5 microgram LDL protein; control, 0.58+/-0.23 ng/5 microgram LDL protein). Serum levels of total, HDL, and LDL cholesterol did not differ among these patient groups. In the atherectomy specimens, the surface area containing ox-LDL-positive macrophages was significantly higher in patients with UAP than in those with SAP (P<0.0001). CONCLUSIONS: This study demonstrates that ox-LDL levels show a significant positive correlation with the severity of acute coronary syndromes and that the more severe lesions also contain a significantly higher percentage of ox-LDL-positive macrophages. These observations suggest that increased levels of ox-LDL relate to plaque instability in human coronary atherosclerotic lesions.

Glucagonostatic and insulinotropic action of glucagonlike peptide I-(7-36)-amide.

We examined the effect of glucagonlike peptides (GLPs), which are cleaved from preproglucagon in the enteroglucagon cells, on rat endocrine pancreas with the isolated perfused system. GLP-I-(7-36)-amide, a truncated form of full-sequence GLP-I-(1-37), showed a potent inhibitory effect on glucagon secretion. This inhibitory effect of GLP-I-(7-36)-amide was demonstrated at concentrations of 0.25, 2.5, and 25 nM in 11.2 and 2.8 mM glucose. In contrast, insulin release was significantly stimulated by GLP-I-(7-36)-amide at its concentration from 0.025 to 25 nM in a high glucose concentration, whereas in a low glucose concentration, the stimulation was seen only at the highest concentration (25 nM). Neither GLP-I-(1-37) nor GLP-II showed any effect on glucagon and insulin release. Although several gastrointestinal hormones have been nominated as incretins, none of them may suppress the glucagon secretion. A truncated form of GLP-I, GLP-I-(7-36)-amide thus seems to be a unique incretin that exerts glucagonostatic action.

Short-term effect of buformin, a biguanide, on insulin sensitivity, soluble fraction of tumor necrosis factor receptor and serum lipids in overweight patients with type 2 diabetes mellitus.

AIMS/HYPOTHESIS: The UK Prospective Diabetes Study (UKPDS) showed that biguanide therapy in overweight patients reduced the risk for any diabetes-related endpoint and all-cause mortality. Biguanides lower the blood glucose values without stimulation of insulin release. We have investigated the short-term effect of buformin on insulin sensitivity, solved tumor necrosis factor receptors (sTNFRs), and serum lipids in overweight subjects with type 2 diabetes mellitus (DM). METHOD: Thirteen overweight subjects with type 2 DM were examined. The subjects who were fed 20 kcal/kg body weight were divided into two subgroups according to whether they were treated by buformin (Buformin group), or dietary therapy alone (Diet group). Six patients were in Buformin group and seven patients were in Diet group. We calculated insulin-mediated glucose uptake by the liver and peripheral tissues using euglycemic hyperinsulinemic clamp combined with an oral glucose load before and after buformin treatment or diet therapy for 2 weeks. RESULTS: Fasting plasma glucose, total cholesterol (T-chol), LDL-cholesterol (LDL-chol), and sTNFR2 were significantly decreased, and hepatic glucose uptake significantly increased from 32 +/- 7 to 42 +/- 7% (P < 0.05) in Buformin group but did not changed significantly in Diet group. However, the glucose infusion rate thought to express insulin sensitivity in peripheral tissue, TNF-alpha, sTNFR1, fasting plasma insulin, C-peptide, and NEFA levels did not change significantly in both the groups after treatment. CONCLUSION/INTERPRETATION: Buformin improved insulin sensitivity in the liver and decreased T-chol, LDL-chol, and sTNFR2. The mechanism of action for buformin likely involves inhibition of TNF-alpha. Buformin lowers insulin resistance and risk factors for cardiovascular disease including serum lipid and will therefore, be useful in management of overweight type 2 DM patients.

Glucagon-like peptide-1 (7-36 amide): a potent glucagonostatic and insulinotropic hormone.

Glucagon-like peptide-1 (GLP-1) (1-37) and the fraction derived from it, GLP-1 (7-36 amide), are peptides encoded by the preproglucagon gene and possibly co-secreted with enteroglucagon. When added at a 25-nM concentration, GLP-1 (7-36 amide) decreased the release of glucagon from the perfused rat pancreas from 68.5 +/- 9.0 pg/ml to 41.5 +/- 11.5 pg/ml at 2 min in the presence of 11.2 mM glucose (P less than 0.01), and from 196.0 +/- 32.5 pg/ml to 87.0 +/- 23.5 pg/ml at 5 min in the presence of 2.8 mM glucose (P less than 0.05). Insulin levels increased from 12.6 +/- 3.0 microU/ml to 48.9 +/- 14.0 microU/ml at 10 min in the presence of 11.2 mM glucose (P less than 0.05) and from 2.0 +/- 0.4 microU/ml to 8.2 +/- 2.3 microU/ml at 2 min in the presence of 2.8 mM glucose (P less than 0.05). Glucagon and insulin release were not affected significantly by GLP-1 (1-37), irrespective of glucose concentration. We suggest that GLP-1 (7-36 amide) rather than enteroglucagon may be the true physiologic gut hormone and that it may act as 'incretin' in the enteroinsular axis. We suggest further that the glucagonostatic and insulinotropic activities of this peptide are unique and might be important in islet-cell function.

Glucagon-glucose (GG) test for the estimation of the insulin reserve in diabetes.

The residual B-cell function was examined by means of the plasma C-peptide response 6 min after a combined injection of glucagon and glucose (GG test) or conventional glucagon test (G test) in four insulin-dependent diabetic patients (IDDM group), in 18 diabetic patients treated with insulin (Insulin group), 31 treated with oral hypoglycemic agents (SU group) and 27 treated with diet only (Diet group) and in 22 borderline cases. By GG test, 6-min C-peptide values of the IDDM group were 0.27 +/- 0.05 nM (n = 4) and were significantly lower than those of the Insulin group (0.89 +/- 0.09 nM, n = 12), the SU group (1.42 +/- 0.10 nM, n = 13), the Diet group (2.47 +/- 0.22 nM, n = 11) and the borderline cases (3.38 +/- 0.22 nM, n = 11). Patients with a 6-min C-peptide concentration below 0.75 nM by GG test appeared to be insulin-requiring patients. In the G test, plasma C-peptide concentrations at 6 min were 0.35 +/- 0.08 nM in the IDDM group (n = 2), 0.72 +/- 0.20 nM in the Insulin group (n = 7), 1.08 +/- 0.09 nM in the SU group (n = 20), 1.40 +/- 0.19 nM in the Diet group (n = 17) and 2.05 +/- 0.21 nM in the borderline cases (n = 12). Some of the Diet group patients showed extremely low C-peptide responses. When comparing the GG test and G test in individual cases, a greater C-peptide response was seen with the GG test in all cases except for IDDM patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of glucagon-(1-21)-peptide on secretin-stimulated pancreatic exocrine secretion in anesthetized dogs.

The effects of glucagon-(1-21)-peptide on pancreatic exocrine secretion and plasma glucose levels were studied and compared with those of native glucagon in anesthetized dogs. Intravenous bolus administration of 1 nmol or 10 nmol/kg of glucagon-(1-21)-peptide evoked a significant inhibition of secretin-stimulated pancreatic juice secretion and protein output in a dose-dependent manner, as equimolar doses of glucagon did. Native glucagon induced an immediate and transient increase in pancreatic juice volume, which was followed by a significant inhibition. However, glucagon-(1-21)-peptide showed only the inhibitory action. Glucagon-(1-21)-peptide had no effect on plasma glucose levels even when a dose of 10 nmol/kg was given. The results suggest that the N-terminal amino-acid residues of glucagon play an important role in the inhibition of pancreatic exocrine secretion.