CYP8B1 downregulation mediates the metabolic effects of vertical sleeve gastrectomy in mice.

BACKGROUND AND AIMS: Although the benefits of vertical sleeve gastrectomy (VSG) surgery are well known, the molecular mechanisms by which VSG alleviates obesity and its complications remain unclear. We aim to determine the role of CYP8B1 (cytochrome P450, family 8, subfamily B, polypeptide 1) in mediating the metabolic benefits of VSG. APPROACH AND RESULTS: We found that expression of CYP8B1, a key enzyme in controlling the 12α-hydroxylated (12α-OH) bile acid (BA) to non-12α-OH BA ratio, was strongly downregulated after VSG. Using genetic mouse models of CYP8B1 overexpression, knockdown, and knockout, we demonstrated that overexpression of CYP8B1 dampened the metabolic improvements associated with VSG. In contrast, short hairpin RNA-mediated CYP8B1 knockdown improved metabolism similar to those observed after VSG. Cyp8b1 deficiency diminished the metabolic effects of VSG. Further, VSG-induced alterations to the 12α-OH/non-12α-OH BA ratio in the BA pool depended on CYP8B1 expression level. Consequently, intestinal lipid absorption was restricted, and the gut microbiota (GM) profile was altered. Fecal microbiota transplantation from wild type-VSG mice (vs. fecal microbiota transplantation from wild-type-sham mice) improved metabolism in recipient mice, while there were no differences between mice that received fecal microbiota transplantation from knockout-sham and knockout-VSG mice. CONCLUSIONS: CYP8B1 is a critical downstream target of VSG. Modulation of BA composition and gut microbiota profile by targeting CYP8B1 may provide novel insight into the development of therapies that noninvasively mimic bariatric surgery to treat obesity and its complications.

Carbon Source in Tertiary Denitrification Regulates Dissolved Organic Nitrogen in Wastewater Effluent.

With global eutrophication and increasingly stringent nitrogen discharge restrictions, dissolved organic nitrogen (DON) holds considerable potential to upgrade advanced wastewater denitrification because of its large contribution to low-nitrogen effluents and stronger stimulation effect for algae. Here, we show that DON from the postdenitrification systems dominates effluent eutrophication potential under different carbon sources. Methanol resulted in significantly lower DON concentrations (0.84 ± 0.03 mg/L) compared with the total nitrogen removal-preferred acetate (1.11 ± 0.02 mg/L) (p < 0.05, ANOVA). With our well-developed mathematical model (R2 = 0.867-0.958), produced DON instead of shared (persist in both influent and effluent) and/or removed DON was identified as the key component for effluent DON variation (Pearson r = 0.992, p < 0.01). The partial least-squares path modeling analysis showed that it is the microbial community (r = 0.947, p < 0.01) rather than the predicted metabolic functions (r = 0.040, p > 0.1) that affected produced DON. Carbon sources rebuild the microorganism-DON interaction by affecting the structure of microbial communities with different abilities to generate and recapture produced DON to finally regulate effluent DON. This study revalues the importance of carbon source selection and overturns the current rationality of pursuing only the total nitrogen removal efficiency by emphasizing DON.

Functional metabolomics characterizes the contribution of farnesoid X receptor in pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome.

Consumption of herbal products containing pyrrolizidine alkaloids (PAs) is one of the major causes for hepatic sinusoidal obstruction syndrome (HSOS), a deadly liver disease. However, the crucial metabolic variation and biomarkers which can reflect these changes remain amphibious and thus to result in a lack of effective prevention, diagnosis and treatments against this disease. The aim of the study was to determine the impact of HSOS caused by PA exposure, and to translate metabolomics-derived biomarkers to the mechanism. In present study, cholic acid species (namely, cholic acid, taurine conjugated-cholic acid, and glycine conjugated-cholic acid) were identified as the candidate biomarkers (area under the ROC curve 0.968 [95% CI 0.908-0.994], sensitivity 83.87%, specificity 96.55%) for PA-HSOS using two independent cohorts of patients with PA-HSOS. The increased primary bile acid biosynthesis and decreased liver expression of farnesoid X receptor (FXR, which is known to inhibit bile acid biosynthesis in hepatocytes) were highlighted in PA-HSOS patients. Furtherly, a murine PA-HSOS model induced by senecionine (50 mg/kg, p.o.), a hepatotoxic PA, showed increased biosynthesis of cholic acid species via inhibition of hepatic FXR-SHP singling and treatment with the FXR agonist obeticholic acid restored the cholic acid species to the normal levels and protected mice from senecionine-induced HSOS. This work elucidates that increased levels of cholic acid species can serve as diagnostic biomarkers in PA-HSOS and targeting FXR may represent a therapeutic strategy for treating PA-HSOS in clinics.

Vertical sleeve gastrectomy confers metabolic improvements by reducing intestinal bile acids and lipid absorption in mice.

Vertical sleeve gastrectomy (VSG) is one of the most effective and durable therapies for morbid obesity and its related complications. Although bile acids (BAs) have been implicated as downstream mediators of VSG, the specific mechanisms through which BA changes contribute to the metabolic effects of VSG remain poorly understood. Here, we confirm that high fat diet-fed global farnesoid X receptor (Fxr) knockout mice are resistant to the beneficial metabolic effects of VSG. However, the beneficial effects of VSG were retained in high fat diet-fed intestine- or liver-specific Fxr knockouts, and VSG did not result in Fxr activation in the liver or intestine of control mice. Instead, VSG decreased expression of positive hepatic Fxr target genes, including the bile salt export pump (Bsep) that delivers BAs to the biliary pathway. This reduced small intestine BA levels in mice, leading to lower intestinal fat absorption. These findings were verified in sterol 27-hydroxylase (Cyp27a1) knockout mice, which exhibited low intestinal BAs and fat absorption and did not show metabolic improvements following VSG. In addition, restoring small intestinal BA levels by dietary supplementation with taurocholic acid (TCA) partially blocked the beneficial effects of VSG. Altogether, these findings suggest that reductions in intestinal BAs and lipid absorption contribute to the metabolic benefits of VSG.

Overexpression of a nuclear receptor HR96 contributes to spirodiclofen susceptibility in Panonychus citri (McGregor).

The citrus red mite, Panonychus citri, is one of the most notorious and devastating citrus pests around the world that has developed resistance to multiple chemical acaricides. In previous research, we found that spirodiclofen-resistant is related to overexpression of P450, CCE, and ABC transporter genes in P. citri. However, the regulatory mechanisms of these detoxification genes are still elusive. This study identified all hormone receptor 96 genes of P. citri. 8 PcHR96 genes contained highly conserved domains. The expression profiles showed that PcHR96h was significantly upregulated in spirodiclofen resistant strain and after exposure to spirodiclofen. RNA interference of PcHR96h decreased expression of detoxification genes and increased spirodiclofen susceptibility in P. citri. Furthermore, molecular docking, heterologous expression, and drug affinity responsive target stability demonstrated that PcHR96h can interact with spirodiclofen in vitro. Our research results indicate that PcHR96h plays an important role in regulating spirodiclofen susceptibility and provides theoretical support for the resistance management of P. citri.

Retromolar intubation for the general anesthesia of maxillofacial fracture patients.

BACKGROUND: Evaluate the possibility of retromolar intubation for general anesthesia in patients with maxillofacial fractures. METHODS: The medical records of 54 patients with maxillofacial fractures who visited the Oral and Maxillofacial Surgery Department of Nantong First People's Hospital from January 2020 to August 2022 were collected. The retromolar areas of each patient were measured from the coronal CT images, and correlated with the patient's age, sex, type of fracture (i.e., maxillary fracture, mandibular fracture, or complex fracture of multiple maxillofacial bones), and the presence of the third molar (verified from 3D CT). The dimensions of the retromolar areas were finally compared with the outer diameter (OD) of standard endotracheal tubes (ETTs), most importantly the size 7.5 ETT (OD 10.3 mm) for male and the size 7.0 ETT (OD 9.8 mm) for female. RESULTS: The survey included 38 male and 16 female patients, with an average age of 44.1 and 54.3 years, respectively. The dimensions of the retromolar area (height × width) were as follows: male, (9.39 ± 1.77) mm × (12.08 ± 0.98) mm on the left and (9.81 ± 2.23) mm × (11.77 ± 1.08) mm on the right; female, (8.82 ± 1.53) mm × (10.51 ± 1.00) mm on the left and (9.73 ± 1.60) mm × (10.63 ± 1.58) mm on the right. The width was always larger than the OD of the routinely used ETT, but the height could be smaller by less than 1 mm. However, the oral mucosa can be compressed to allow the ETT to fit in the retromolar area. CONCLUSIONS: The retromolar area provided appropriate space to place a reinforced ETT for patients with maxillofacial fractures needing general anesthesia that must not interfere with intermaxillary ligation. Retromolar intubation can help maxillofacial fracture surgeries that focus on occlusal restoration.

Temporal Trends in Public Stroke Knowledge, 1995-2021.

BACKGROUND: Outreach campaigns have sought to reduce the burden of stroke by improving knowledge of stroke risk factors (RF) and warning signs (WS). We describe trends in stroke knowledge from 1995 to 2021. METHODS: From 1995 to 2021, 6 separate surveys were conducted in the Greater Cincinnati Northern Kentucky Region. Temporal trends in RF/WS knowledge were analyzed using logistic regression adjusting for Race, sex, age, and education. RESULTS: In 1995, 28.6% of participants (537/1880) could name ≥2 WS, compared with 50.6% (983/1944) in 2021 (trend P<0.0001 after adjustment). In 1995, 44.5% of participants (836/1880) knew ≥2 RF, compared with 56.7% (1103/1944) in 2021 (trend P<0.0001 after adjustment). Although still improved compared with 1995, fewer participants could identify ≥2 RF in 2021 (1103/1944, 56.7%) when compared with 2011 (1287/2036, 63.2%, pairwise P<0.05). This decline in RF knowledge was disproportionately larger in women (odds ratio of 0.67 for knowledge in 2021 compared with 2011 in females, P=0.047 for the interaction between sex and study year). CONCLUSIONS: Although stroke knowledge has overall improved since 1995, there is evidence for lost gains since 2011, particularly in women. Stroke outreach campaigns need ongoing evaluation.

Ultra-fast Redox Pulse for Stable Electrochemiluminescence on AuNP-Based Biosensors and Mechanism Investigation.

A novel sandwich-type biosensor denoted as "MIP-analyte-Ab" was constructed on a glassy carbon electrode modified with gold nanoparticles (AuNPs@GCE), which is dedicated to explore a general solution for electrochemical tests in a relatively high potential range on Au electrodes. In particular, parasitic reactions of Au oxidation severely hindered the electrochemiluminescence (ECL) reactions of the Ru(bpy)32+/tripropylamine (TPrA) system. In this work, we designed an ultra-fast redox pulse to alleviate reversible oxidation of Au with a potential range of -0.5 to 0.9 V. Stable ECL signals were generated in the last 3 ms of each run (RSD = 5.86%), and interesting mechanisms were revealed. The ultra-high-frequency sampler indicated that free diffusion of TPrA•+ was the rate-determining step at 0.9 V, and it followed a totally different route with ECL at 1.3 V. Furthermore, we proposed a particular ECL reaction route at 0.9 V with C5 desosamine of the analyte, azithromycin, involved for the first time, based on results of radical identification. We believe that our work paved the way for the application of Au-based sandwich-type biosensors in environmental monitoring.

Understanding racial disparities in childhood asthma using individual- and neighborhood-level risk factors.

BACKGROUND: Racial disparities in childhood asthma outcomes result from a complex interplay of individual- and neighborhood-level factors. OBJECTIVES: We sought to examine racial disparities in asthma-related emergency department (ED) visits between African American (AA) and European American (EA) children. METHODS: This is a retrospective study of patients younger than 18 years who visited the ED at Cincinnati Children's for asthma from 2009 to 2018. The outcome was number of ED visits during a year. We assessed 11 social, economic, and environmental variables. Mediation and mixed-effects analyses were used to assess relationships between race, mediators, and number of ED visits. RESULTS: A total of 31,114 children (46.1% AA, 53.9% EA) had 186,779 asthma-related ED visits. AA children had more visits per year than EA children (2.23 vs 2.15; P < .001). Medicaid insurance was associated with a 7% increase in rate of ED visits compared with commercial insurance (1.07; 95% CI, 1.03-1.1). Neighborhood socioeconomic deprivation was associated with an increased rate of ED visits in AA but not in EA children. Area-level particulate matter with diameter less than 2.5 µm, pollen, and outdoor mold were associated with an increased rate of ED visits for both AA and EA children (all P < .001). Associations between race and number of ED visits were mediated by insurance, area-level deprivation, particulate matter with diameter less than 2.5 µm, and outdoor mold (all P < .001), altogether accounting for 55% of the effect of race on ED visits. Race was not associated with number of ED visits (P = .796) after accounting for mediators. CONCLUSIONS: Racial disparities in asthma-related ED visits are mediated by social, economic, and environmental factors, which may be amenable to interventions aimed at improving outcomes and eliminating inequities.

The Protective Effects of Goitrin on LPS-Induced Septic Shock in C57BL/6J Mice via Caspase-11 Non-Canonical Inflammasome Inhibition.

Septic shock is defined as a subset of sepsis, which is associated with a considerably high mortality risk. The caspase-11 non-canonical inflammasome is sensed and activated by intracellular lipopolysaccharide (LPS) leading to pyroptosis, it plays a critical role in septic shock. However, there are few known drugs that can control caspase-11 non-canonical inflammasome activation. We report here that goitrin, an alkaloid from Radix Isatidis, shows protective effects in LPS-induced septic shock and significant inhibitory effect in caspase-11 non-canonical inflammasome pathway. Male C57BL/6J were injected intraperitoneally with LPS (20 mg/kg) to induce experimental septic shock. The results demonstrated that the survival rates of mice pretreated with goitrin or Toll-like receptor 4 (TLR4) inhibitor TKA-242 increased, and LPS-induced hypothermia and lung damage improved by inhibiting inflammatory response. Elucidating the detailed mechanism, we surprisingly found goitrin is really different from TAK-242, it independent of the TLR4 signal activation, but significantly inhibited the activation of caspase-11 non-canonical inflammasome, including cleaved caspase-11 and N-terminal fragment of gasdermin D (GSDMD-NT). Furthermore, with a nonlethal dose of the TLR3 agonist poly(I:C)-primed and subsequently challenged with LPS to induce caspase-11-mediated lethal septic shock, the efficacy of goitrin had been verified. Those results revealed the effect of goitrin in protective against LPS-induced septic shock via inhibiting caspase-11 non-canonical inflammasome, which provided a new therapeutic strategy for clinical treatment of septic shock.

Dump or recycle? Consumer's environmental awareness and express package disposal based on an evolutionary game model.

Along with the rapid development of the express industry and the inevitable trend of sustainable development, the disposal of express packaging is an urgent problem that needs to be solved. With the objective to the effective disposal mode for express packaging, this paper introduces the consumers' environmental awareness into the framework and establishes an evolutionary game model to explore the governing measures of the express packaging recycling industry. It is found that without considering consumers' environmental awareness, the government's reward and punishment mechanism alone cannot restrain the recycler's decision-making effectively, while the participation of the consumers with environmental awareness could drive the strategy of the recycler to converge to the ideal state effectively, which is recycling the express packaging actively. The sensitivity analysis shows that the participation of consumers with environmental awareness significantly weakens the recycling difficulty and reduces the recycling cost of the recycler, which is helpful to improve the willingness of the recycler to recycle the express packaging continually. Thereby, the express packaging recycling industry can be improved better when the consumer's awareness of environmental protection is enhanced.

[Comparison on anti-inflammatory activity of Gynostemma pentaphyllum processed with different methods].

The aim of this study is to investigate the effects of Gynostemma pentaphyllum dried with two different methods(air drying and heating) on inflammation in acute lung injury(ALI) mice in vivo and in vitro. Lipopolysaccharide(LPS) was sprayed into the airway of wild type C57BL/6J male mice to establish the model, and the drug was injected into the tail vein 24 h after modeling. Lung function, lung tissue wet/dry weight(W/D) ratio, the total protein concentration, interleukin 6(IL-6), IL-1ß, and tumor necrosis factor-α(TNF-α) in the bronchoalveolar lavage fluid(BALF), and pathological changes of the lung tissue were used to evaluate the effects of different gypenosides on ALI mice. The results showed that total gypenosides(YGGPs) and the gypenosides substituted with one or two glycosyl(GPs_(1-2)) in the air-dried sample improved the lung function, significantly lowered the levels of IL-1ß and TNF-α in BALF, and alleviated the lung inflammation of ALI mice. Moreover, GPs_(1-2) had a more significant effect on inhibiting NO release in RAW264.7 cells. This study showed that different drying methods affected the anti-inflammatory activity of G. pentaphyllum, and the rare saponins in the air-dried sample without heating had better anti-inflammatory activity.

Novel Strategy to Drive the Intracellular Uptake of Lipid Nanoparticles for Photodynamic Therapy.

Nanoparticles' uptake by cancer cells upon reaching the tumor microenvironment is often the rate-limiting step in cancer nanomedicine. Herein, we report that the inclusion of aminopolycarboxylic acid conjugated lipids, such as EDTA- or DTPA-hexadecylamide lipids in liposome-like porphyrin nanoparticles (PS) enhanced their intracellular uptake by 25-fold, which was attributed to these lipids' ability to fluidize the cell membrane in a detergent-like manner rather than by metal chelation of EDTA or DTPA. EDTA-lipid-incorporated-PS (ePS) take advantage of its unique active uptake mechanism to achieve >95 % photodynamic therapy (PDT) cell killing compared to <5 % cell killing by PS. In multiple tumor models, ePS demonstrated fast fluorescence-enabled tumor delineation within minutes post-injection and increased PDT potency (100 % survival rate) compared to PS (60 %). This study offers a new nanoparticle cellular uptake strategy to overcome challenges associated with conventional drug delivery.

Nanostructure-Driven Indocyanine Green Dimerization Generates Ultra-Stable Phototheranostics Nanoparticles.

Indocyanine green (ICG) is the only near-infrared (NIR) dye approved for clinical use. Despite its versatility in photonic applications and potential for photothermal therapy, its photobleaching hinders its application. Here we discovered a nanostructure of dimeric ICG (Nano-dICG) generated by using ICG to stabilize nanoemulsions, after which ICG enabled complete dimerization on the nanoemulsion shell, followed by J-aggregation of ICG-dimer, resulting in a narrow, red-shifted (780 nm→894 nm) and intense (≈2-fold) absorbance. Compared to ICG, Nano-dICG demonstrated superior photothermal conversion (2-fold higher), significantly reduced photodegradation (-9.6 % vs. -46.3 %), and undiminished photothermal effect (7 vs. 2 cycles) under repeated irradiations, in addition to excellent colloidal and structural stabilities. Following intravenous injection, Nano-dICG enabled real-time tracking of its delivery to mouse tumors within 24 h by photoacoustic imaging at NIR wavelength (890 nm) distinct from the endogenous signal to guide effective photothermal therapy. The unprecedented finding of nanostructure-driven ICG dimerization leads to an ultra-stable phototheranostic platform.

Association Between Maternal Adverse Childhood Experiences and Neonatal SCG5 DNA Methylation-Effect Modification by Prenatal Home Visiting.

Maternal childhood adversity and trauma may elicit biological changes that impact the next generation through epigenetic responses measured in DNA methylation (DNAm). These epigenetic associations could be modified by the early postnatal environment through protective factors, such as early childhood home visiting (HV) programs that aim to mitigate deleterious intergenerational effects of adversity. In a cohort of 53 mother-child pairs recruited in 2015-2016 for the Pregnancy and Infant Development Study (Cincinnati, Ohio), we examined the association between maternal adverse childhood experiences (ACEs) and neonatal DNAm in the secretogranin V gene (SCG5), which is important in neuroendocrine function. We examined prenatal HV as an effect modifier. Mothers completed a questionnaire on ACEs during pregnancy, and infant buccal samples were collected 1 month postpartum. Multivariable linear regression was used to examine the association between maternal ACEs and neonatal DNAm expressed as M-values averaged across 4 cytosine-phosphate-guanine dinucleotide sites. A higher number of maternal ACEs (>3) was associated with a 5.79-percentage-point lower offspring DNAm (95% confidence interval: -10.44, -1.14), and the association was modified by the number of home visits received during pregnancy. In a population of at-risk mother-child dyads, preliminary evidence suggests that maternal ACEs have a relationship with offspring SCG5 DNAm that differs by the amount of prenatal HV.

Prolonged Circulating Lipid Nanoparticles Enabled by High-Density Gd-DTPA-Bis(stearylamide) for Long-Lasting Enhanced Tumor Magnetic Resonance Imaging.

Porphysomes (PS) were explored to incorporate different types of diethylenetriaminepentaacetic-acid-gadolinium-(III) (Gd-DTPA)-lipids into their bilayer membrane to assess PS potential as an MRI contrast agent. The Gd-dPS-BSA by integration of over 30% Gd-DTPA-bis(stearylamide) (Gd-DTPA-BSA)-lipids in PS construction resulted in exceptional serum stability and T1 and T2 relaxivity measurements of 13 mM-1 s-1 and 19 mM-1 s-1, respectively. The Gd-dPS-BSA demonstrated significantly enhanced retention in blood circulation with a half-life of 13.6 h and high tumor accumulation up to 19.5%ID/g at 72 h post-injection in select cancer mouse models. Additionally, Gd-dPS-BSA displayed excellent MRI tumor enhancement over 24, 48, and 72 h with contrast enhancements from the baseline of 35.8%, 38.2%, and 38.3%, respectively. Results reported here highlight a high-density incorporation of Gd-DTPA-BSA-lipids within PS, and other liposome formulations can enhance circulatory longevity, independently of particles' concentration, suggesting effective MRI contrast agent potential for Gd-dPS-BSA and potential utility of Gd-DTPA-BSA-lipids to enhance other liposomal-influenced diagnostic and therapeutic functions.

Partner-Level and Sexual Networking Factors Are Associated With Vaccine-Type and Nonvaccine-Type Human Papillomavirus Infection After Vaccine Introduction in Young Women.

BACKGROUND: The aim of this study was to determine individual-level, partner-level, and sexual networking factors associated with vaccine- and non-vaccine-type human papillomavirus (HPV) in young women, by vaccination status. METHODS: Sexually experienced women 13 to 26 years old (n = 784) completed a survey and were tested for 36 HPV genotypes. We determined factors associated with 4-valent vaccine-type HPV (HPV-6, HPV-11, HPV-16, HPV-18) and non-vaccine-type HPV among vaccinated and unvaccinated women, using univariable and multivariable logistic regression models. RESULTS: Participants' mean age was 19.2 years, 77.7% had received ≥1 vaccine dose, and 7.7% were positive for vaccine-type HPV (HPV-6, HPV-11, HPV-16, and/or HPV-18). Factors associated with vaccine-type HPV in vaccinated women included gonorrhea history (adjusted odds ratio [AOR], 2.71), new female sex partner(s) (AOR, 4.79), age at vaccination (≥15 vs. <15 years; AOR, 2.47), and age discordance with most recent partner (don't know vs. discordant; AOR, 9.17). Factors associated with non-vaccine-type HPV in vaccinated women included history of sexually transmitted infection (AOR, 2.69), male most recent partner (AOR, 2.85), age of first sex (AOR, 1.15), and partner concurrency (don't know vs. 1 other partner; AOR, 2.03). Factors associated with vaccine-type HPV in unvaccinated women included new female sex partner(s) (AOR, 7.45) and partner concurrency (don't know vs. no; AOR, 2.95). Factors associated with non-vaccine-type HPV in unvaccinated women included race (White vs. multiracial; AOR, 4.10) and partner concurrency (don't know vs. 0; AOR, 4.65). CONCLUSIONS: Novel findings of this study, including associations between female sex partners and HPV, and between not knowing about partner concurrency and HPV, have implications for sexual education, clinical counseling, and public health interventions.

The role of immobilized quorum sensing strain in promoting biofilm formation of Moving Bed Biofilm Reactor during long-term stable operation.

Quorum sensing (QS) signaling plays a significant role in the natural regulation of biofilm formation. Multiple species QS systems in wastewater treatment processes have received significant attention in recent years and this study presents a long-term analysis of QS signaling, bacterial structures and extracellular polymeric substance (EPS) during biofilm formation, detachment and reformation processes. Six types of Acyl homoserine lactones (AHLs) were found to be closely related to different phases of biofilm development, with both QS and quorum quenching (QQ) strains being identified as drivers of various biofilm phases and 10 strains presenting a close relationship with AHLs (p < 0.05). Meanwhile, QS strain Sphingomonas rubra was immobilized and added into reactor systems, resulting in significant increase in AHL content, EPS production, and adhesion strength of biofilm (p < 0.05), which might promote biofilm formation processes during long-term stable operation. This study provides a potentially simple and economical way to improve activity and stability of MBBR in complex wastewater systems.

Prognostic significance of visit-to-visit variability, and maximum and minimum LDL cholesterol in diabetes mellitus.

BACKGROUND: Current guidelines for dyslipidemia management recommend that the LDL-C goal be lower than 70 mg/dL. The present study investigated the prognostic significance of visit-to-visit variability in LDL-C, and minimum and maximum LDL-C during follow-up in diabetes mellitus. METHODS: The risk of outcomes in relation to visit-to-visit LDL-C variability was investigated in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Lipid trial. LDL-C variability indices were coefficient of variation (CV), variability independent of the mean (VIM), and average real variability (ARV). Multivariable Cox proportional hazards models were employed to estimate the adjusted hazard ratio (HR) and 95% confidence interval (CI). RESULTS: Compared with the placebo group (n=2667), the fenofibrate therapy group (n=2673) had a significantly (P<0.01) lower mean plasma triglyceride (152.5 vs. 178.6 mg/dL), and total cholesterol (158.3 vs.162.9 mg/dL) but a similar mean LDL-C during follow-up (88.2 vs. 88.6 mg/dL, P>0.05). All three variability indices were associated with primary outcome, total mortality and cardiovascular mortality both in the total population and in the fenofibrate therapy group but only with primary outcome in the placebo group. The minimum LDL-C but not the maximum during follow-up was significantly associated with various outcomes in the total population, fenofibrate therapy and placebo group. The minimum LDL-C during follow-up ≥70 mg/dL was associated with an increased risk for various outcomes. CONCLUSIONS: Visit-to-visit variability in LDL-C was a strong predictor of outcomes, independent of mean LDL-C. Patients with LDL-C controlled to less than 70 mg/dL during follow-up might have a benign prognosis. ClinicalTrials.gov number: NCT00000620.

Feasibility study of cumulative sum (CUSUM) analysis as a competency assessment tool for ultrasound-guided venous access procedures.

PURPOSE: Typically, physician training programs use a self-reported case-log competency assessment that does not measure procedure success or objectively assess competency. Cumulative sum (CUSUM) analysis could provide objective assessments of competency and progress over the training period. Our study objective was to determine the feasibility of CUSUM analysis to assess competency of ultrasound-guided peripheral intravenous (USG-PIV) line placement in pediatric anesthesiology fellows. METHODS: We applied a CUSUM analysis to assess competency in USG-PIV placement in three consecutive pediatric anesthesia fellowship classes. After a didactic and hands-on training session, fellows placed a USG-PIV line and self-reported the outcomes via a web-based application. Fellows were deemed competent if the CUSUM curve crossed two consecutive boundary lines from above. RESULTS: Twenty-nine fellows reported 1,388 USG-PIV attempts, with 74% success. Most fellows (26/29; 90%) achieved competency by the end of the fellowship. Two fellows identified in the mid-year CUSUM as not progressing towards competency achieved competency after targeted interventions. Fellows achieving competency (11/29 vs 25/29; odds ratio, 15; 95% confidence interval [CI], 1.98 to 113.56; P = 0.01) and attempts needed to achieve competency (19 vs 11; mean difference, 8.5; 95% CI, 3.3 to 13.7; P = 0.002) were significantly lower in younger patients and significantly higher in older patients. CONCLUSION: Our study showed that CUSUM can be used to assess competence in USG-PIV procedures performed by pediatric anesthesia fellows and to identify learners not progressing toward competency in procedural skills. Ultrasound-guided venous access required more attempts to achieve competency in younger patients.

RéSUMé: OBJECTIF: En règle générale, les programmes de formation des médecins se fondent sur une évaluation autodéclarée des compétences dans un registre des cas qui ne mesure pas la réussite de l'intervention et n'évalue pas objectivement la compétence. L'analyse du cumul des écarts (CUSUM - pour CUmulative SUM) pourrait fournir des évaluations objectives des compétences et des progrès au cours de la période de formation. L'objectif de notre étude était de déterminer la faisabilité d'une analyse CUSUM pour évaluer la compétence pour le positionnement du cathéter intraveineux périphérique échoguidé (CIP-écho) des fellows en anesthésiologie pédiatrique. MéTHODE: Nous avons appliqué une analyse CUSUM pour évaluer la compétence pour le positionnement du CIP-écho de trois classes consécutives de fellows en anesthésie pédiatrique. Après une séance de formation didactique et pratique, les fellows ont placé un cathéter CIP-écho et ont déclaré eux-même les résultats via une application Web. Les fellows étaient jugés compétents si la courbe CUSUM franchissait deux lignes de démarcation consécutives à partir du haut. RéSULTATS: Vingt-neuf fellows ont rapporté 1388 tentatives de CIP-écho, avec un taux de réussite de 74 %. La plupart des fellows (26/29; 90 %) ont acquis la compétence à la fin de leur fellowship. Deux fellows identifiés dans l'analyse CUSUM de mi-année comme ne progressant pas vers la compétence sont parvenus à l'acquérir après des interventions ciblées. Les fellows acquérant cette compétence (11/29 vs 25/29; rapport de cotes, 15; intervalle de confiance [IC] à 95 %, 1,98 à 113,56; P = 0,01) et les tentatives nécessaires pour acquérir la compétence (19 vs 11; différence moyenne, 8,5; IC 95 %, 3,3 à 13,7; P = 0,002) étaient significativement plus basses avec des patients plus jeunes et significativement plus élevés chez les patients plus âgés. CONCLUSION: Notre étude a montré qu'une analyse CUSUM pouvait être utilisée pour évaluer la compétence pour les procédures de CIP-écho réalisées par des fellows en anesthésie pédiatrique et pour identifier les apprenants qui ne progressent pas vers la compétence en habiletés opératoires. L'accès veineux échoguidé a nécessité davantage de tentatives pour atteindre la compétence chez les patients plus jeunes.