Search

Background Hospital-acquired pressure injuries, including those related to airway devices, are a significant source of morbidity in critically ill patients. Objective To determine the incidence of endotracheal tube–related pressure injuries in critically ill patients and to evaluate the effectiveness of interventions designed to prevent injury. Methods MEDLINE, Embase, CINAHL, and the Cochrane Library were searched for studies of pediatric or adult patients in intensive care units that evaluated interventions to reduce endotracheal tube–related pressure injury. Reviewers extracted data on study and patient characteristics, incidence of pressure injury, type and duration of intervention, and outcomes. Risk of bias assessment followed the Cochrane Collaboration’s criteria. Results Twelve studies (5 randomized clinical trials, 3 quasi-experimental, 4 observational) representing 9611 adult and 152 pediatric patients met eligibility criteria. The incidence of pressure injury was 4.2% for orotracheal tubes and 21.1% for nasotracheal tubes. Interventions included anchor devices, serial endotracheal tube assessment or repositioning, and barrier dressings for nasotracheal tubes. Meta-analysis revealed that endotracheal tube stabilization was the most effective individual intervention for preventing pressure injury. Nasal alar barrier dressings decreased the incidence of skin or mucosal injury in patients undergoing nasotracheal intubation, and data on effectiveness of serial assessment and repositioning were inconclusive. Conclusions Airway device–related pressure injuries are common in critically ill patients, and patients with nasotracheal tubes are particularly susceptible to iatrogenic harm. Fastening devices and barrier dressings decrease the incidence of injury. Evidence regarding interventions is limited by lack of standardized assessments.

Background In the critical care environment, individuals who undergo tracheostomy are highly susceptible to tracheostomy-related pressure injuries. Objective To evaluate the effectiveness of interventions to reduce tracheostomy-related pressure injury in the critical care setting. Methods MEDLINE, Embase, CINAHL, and the Cochrane Library were searched for studies of pediatric or adult patients in intensive care units conducted to evaluate interventions to reduce tracheostomy-related pressure injury. Reviewers independently extracted data on study and patient characteristics, incidence of tracheostomy-related pressure injury, characteristics of the interventions, and outcomes. Study quality was assessed using the Cochrane Collaboration’s risk-of-bias criteria. Results Ten studies (2 randomized clinical trials, 5 quasi-experimental, 3 observational) involving 2023 critically ill adult and pediatric patients met eligibility criteria. The incidence of tracheostomy-related pressure injury was 17.0% before intervention and 3.5% after intervention, a 79% decrease. Pressure injury most commonly involved skin in the peristomal area and under tracheostomy ties and flanges. Interventions to mitigate risk of tracheostomy-related pressure injury included modifications to tracheostomy flange securement with foam collars, hydrophilic dressings, and extended-length tracheostomy tubes. Interventions were often investigated as part of care bundles, and there was limited standardization of interventions between studies. Meta-analysis supported the benefit of hydrophilic dressings under tracheostomy flanges for decreasing tracheostomy-related pressure injury. Conclusions Use of hydrophilic dressings and foam collars decreases the incidence of tracheostomy-related pressure injury in critically ill patients. Evidence regarding individual interventions is limited by lack of sensitive measurement tools and by use of bundled interventions. Further research is necessary to delineate optimal interventions for preventing tracheostomy-related pressure injury.

Tracheostomy dislodgment can lead to catastrophic neurological injury or death. A fresh tracheostomy amplifies the risk of such events, where an immature tract predisposes to false passage. Unfortunately, few resources exist to prepare healthcare professionals to manage this airway emergency.To create and implement an accidental tracheostomy dislodgement (ATD) bundle to improve knowledge and comfort when responding to ATD.A multidisciplinary team with expertise in tracheostomy developed a 3-part ATD bundle including (1) Tracheostomy Dislodgement Algorithm, (2) Head of Bed Tracheostomy Communication Tool and (3) Emergency Tracheostomy Kit. The team tested the bundle during the COVID-19 pandemic in a community hospital critical care unit with the engagement of nurses and Respiratory Care Practitioners. Baseline and post-implementation knowledge and comfort levels were measured using Dorton's Tracheotomy Education Self-Assessment Questionnaire, and adherence to protocol was assessed. Reporting follows the revised Standards for Quality Improvement Reporting Excellence (SQUIRE).Twenty-four participants completed pre-test and post-test questionnaires. The median knowledge score on the Likert scale increased from 4.0 (IQR = 1.0) pre-test to 5.0 (IQR = 1.0) post-test. The median comfort level score increased from 38.0 (IQR = 7.0) pre-test to 40.0 (IQR = 5.0) post-test). In patient rooms, adherence was 100% for the Head of Bed Tracheostomy Communication Tool and Emergency Tracheostomy Kit. The adherence rate for using the Dislodgement Algorithm was 55% in ICU and 40% in SCU.This study addresses the void of tracheostomy research conducted in local community hospitals. The improvement in knowledge and comfort in managing ATD is reassuring, given the knowledge gap among practitioners demonstrated in prior literature. The ATD bundle assessed in this study represents a streamlined approach for bedside clinicians - definitive management of ATD should adhere to comprehensive multidisciplinary guidelines.ATD bundle implementation increased knowledge and comfort levels with managing ATD. Further studies must assess whether ATD bundles and other standardised approaches to airway emergencies reduce adverse events. Relevance to Clinical Practice A streamlined intervention bundle employed at the unit level can significantly improve knowledge and comfort in managing ATD, which may reduce morbidity and mortality in critically ill patients with tracheostomy.

ObjectivesFrailty is a syndrome characterized by increased vulnerability and reduced ability to maintain homeostasis after stressful events that results in an increased risk for poor outcomes. Frailty screening could potentially be valuable in cardiac surgery risk assessment. The purpose of this review is to evaluate the current literature linking multicomponent frailty assessment and invasive cardiac surgery outcomes.MethodsWe searched PubMed, EMBASE, and CINAHL; 1887 articles met the search criteria, and each was independently reviewed by 2 reviewers.ResultsThe 19 eligible studies assessed 52 291 subjects using 17 different frailty measurements. The most commonly used instruments were the Fried Frailty Phenotype and the Clinical Frailty Scale. Between 9% and 61% of participants were found to be frail in each study. All 19 studies included mortality as an outcome, 12 included surgical complications, 12 included hospital length of stay, 3 included quality of life, and 2 included functional status. Nine found statistically significant differences in survival between frail and nonfrail patients, 6 of 12 found that frail patients had a longer length of stay, 4 of 12 found that frail patients were more likely to experience major complications, and 2 of 2 found that frail patients were more likely to have a decrease in functional status.ConclusionAlthough some studies lacked power, the majority confirmed that frail patients are more likely to experience poor outcomes. Further research is needed to determine which frailty measure provides the best predictive validity and to identify interventions to mitigate the risks that major cardiac surgery poses to frail patients.

OBJECTIVE: Investigate healthcare providers, caregivers, and patient perspectives on tracheostomy care barriers during COVID-19. STUDY DESIGN: Cross-sectional anonymous survey SETTING: Global Tracheostomy Collaborative Learning Community METHODS: A 17-item questionnaire was electronically distributed, assessing demographic and occupational data; challenges in ten domains of tracheostomy care; and perceptions regarding knowledge and preparedness for navigating the COVID-19 pandemic. RESULTS: Respondents (n = 115) were from 20 countries, consisting of patients/caregivers (10.4%) and healthcare professionals (87.0%), including primarily otolaryngologists (20.9%), nurses (24.3%), speech-language pathologists (18.3%), respiratory therapists (11.3%), and other physicians (12.2%). The most common tracheostomy care problem was inability to communicate (33.9%), followed by mucus plugging and wound care. Need for information on how to manage cuffs and initiate speech trials was rated highly by most respondents, along with other technical and knowledge areas. Access to care and disposable supplies were also prominent concerns, reflecting competition between community needs for routine tracheostomy supplies and shortages in intensive care units. Integrated teamwork was reported in 40 to 67% of respondents, depending on geography. Forty percent of respondents reported concern regarding personal protective equipment (PPE), and 70% emphasized proper PPE use. CONCLUSION: While safety concerns, centering on personal protective equipment and pandemic resources are prominent concerns in COVID-19 tracheostomy care, patient-centered concerns must also be prioritized. Communication and speech, adequate supplies, and care standards are critical considerations in tracheostomy. Stakeholders in tracheostomy care can partner to identify creative solutions for delays in restoring communication, supply disruptions, and reduced access to tracheostomy care in both inpatient and community settings.

The high design luminosity of the SuperKEKB electron-positron collider will result in challenging levels of beam-induced backgro\ unds in the interaction region. Understanding and mitigating these backgrounds is critical to the success of the Belle~II experi\ ment. We report on the first background measurements performed after roll-in of the Belle II detector, a period known as SuperKE\ KB Phase 2, utilizing both the BEAST II system of dedicated background detectors and the Belle II detector itself. We also repor\ t on first revisions to the background simulation made in response to our findings. Backgrounds measured include contributions f\ rom synchrotron radiation, beam-gas, Touschek, and injection backgrounds. At the end of Phase 2, single-beam backgrounds origina\ ting from the 4 GeV positron Low Energy Ring (LER) agree reasonably well with simulation, while backgrounds from the 7 GeV elect\ ron High Energy Ring (HER) are approximately one order of magnitude higher than simulation. We extrapolate these backgrounds for\ ward and conclude it is safe to install the Belle II vertex detector., Comment: 22 Pages, 33 figures

The Convective Precipitation Experiment (COPE) documented the dynamical and microphysical evolution of convection in southwestern England for testing and improving quantitative precipitation forecasting. A strong warm rain process was hypothesized to produce graupel quickly, initiating ice production by rime splintering earlier to increase graupel production and, ultimately, produce heavy rainfall. Here, convection observed on two subsequent days (2 and 3 August 2013) is used to test this hypothesis and illustrate how environmental factors may alter the microphysical progression. The vertical wind shear and cloud droplet number concentrations on 2 August were 2 times those observed on 3 August. Convection on both days produced comparable maximum radar-estimated rain rates, but in situ microphysical measurements indicated much less ice in the clouds on 2 August, despite having maximum cloud tops that were nearly 2 km higher than on 3 August. Idealized 3D numerical simulations of the convection in their respective environments suggest that the relative importance of particular microphysical processes differed. Higher (lower) cloud droplet number concentrations slow (accelerate) the warm rain process as expected, which in turn slows (accelerates) graupel formation. Rime splintering can explain the abundance of ice observed on 3 August, but it was hampered by strong vertical wind shear on 2 August. In the model, the additional ice produced by rime splintering was ineffective in enhancing surface rainfall; strong updrafts on both days lofted supercooled raindrops well above the 0°C level where they froze to become graupel. The results illustrate the complexity of dynamical–microphysical interactions in producing convective rainfall and highlight unresolved issues in understanding and modeling the competing microphysical processes.

Cumulus clouds modify their immediate surroundings by detraining their warm, humid updrafts. When clouds are closely spaced, this conditioning of the local environment may alter the properties of the air entrained by neighboring clouds and slow their dilution. This effect has not been quantified, nor has its importance been determined for influencing the amount of convective rainfall from a system of neighboring clouds. Here, a series of idealized numerical simulations, which are based on an observed line of precipitating cumulus congestus clouds, is performed using increasingly smaller cloud spacing to investigate how cloud proximity may alter entrainment, cloud development, and convective rainfall. For clouds of radius R, which is approximately 1 km in these simulations, distances between updraft centers from 4R through 9R are tested. Over this range, the initial clouds all exhibit negligible differences in the directly calculated entrainment rates and in the thermodynamic characteristics of the entrained air. Instead, for cloud separation distances of less than 6R, the subcloud inflow is increasingly disturbed, limiting initial cloud depths and slowing updraft speeds and precipitation onset. Ultimately, however, these same cases produce a new generation of clouds that are stronger and produce more rainfall than for all other cases. The smaller cloud separation distance allows precipitation outflows from the initial clouds to meet and force new, stronger cloud updrafts. For this second generation of clouds, their entrained air is slightly more humid, but the stronger updrafts and ingestion of residual ice and precipitation from earlier clouds appear to be most important for enhancing their rainfall.

In der vorliegenden Studie wird das Management von Patienten mit Hamorrhoiden Grad 3–4 in einer deutschen Tagesklinik beschrieben. Es werden 3 Operationsmethoden untersucht: Hamorrhoidektomie nach Milligan-Morgan/Ferguson mit Thermokoagulationsklemmen, dopplergesteuerte Hamorrhoidenarterienligatur (DGHAL) mit Mukopexie und die Hamorrhoidektomie nach Fansler-Arnold. Die Analyse der prospektiven Daten von 332 Patienten zeigte, dass diese Operationsmethoden im ambulanten Bereich sicher durchgefuhrt werden konnen. Da der postoperative Verlauf sich im ambulanten vom stationaren Bereich unterscheidet, musste die multimodale Schmerztherapie entsprechend angepasst werden. Um einen postoperativen Harnverhalt zu vermeiden, erhielten die Patienten keine Spinalanasthesie oder Analtamponaden. Keiner der Patienten musste wegen postoperativer Blutung, Schmerz oder Harnverhalt stationar aufgenommen werden.

In this study, we performed a survey of infantile and late-onset Pompe disease (IOPD and LOPD) in Austria. Paediatric and neuromuscular centres were contacted to provide a set of anonymized clinical and genetic data of patients with IOPD and LOPD. The number of patients receiving enzyme replacement therapy (ERT) was obtained from the pharmaceutical company providing alglucosidase alfa. We found 25 patients in 24 families, 4 IOPD and 21 LOPD with a resulting prevalence of 1:350,914. The most frequent clinical manifestation in LOPD was a lower limb-girdle phenotype combined with axial weakness. Three patients were clinically pauci- or asymptomatic and were diagnosed because of persistent hyperCKemia. Diagnostic delay in LOPD was 7.4 ± 9.7 years. The most common mutation was c.-32-13T > G. All IOPD and 17 symptomatic LOPD patients are receiving ERT. Standardized follow-up was only available in six LOPD patients for the 6-min walk test (6minWT) and in ten for the forced vital capacity (FVC). Mean FVC did not decline (before ERT; 63.6 ± 39.7%; last evaluation during ERT: 61.9 ± 26.9%; P = 0.5) while there was a trend to decline in the mean distance covered by the 6minWT (before ERT: 373.5 ± 117.9 m; last evaluation during ERT: 308.5 ± 120.8 m; P = 0.077). The study shows a lower prevalence of Pompe disease in Austria than in other European countries and corroborates a limb-girdle phenotype with axial weakness as the most common clinical presentation, although asymptomatic hyperCKemia may be the first indication of LOPD.

In this study, we examine the notion of homeland among Syrian-Lebanese immigrants and their descendants in Brazil, a community that for almost one hundred years has established a prominent presence in the host country and has undergone significant social, political, and economic transformation. As we investigate the representations of the homeland in the realms of literature and music across several generations, we seek a better understanding of how this community has perceived and interpreted the concepts of roots, or place of origin. While exploring Syrian-Lebanese cultural production in light of the broader discourses on immigration/diaspora, our research addresses the position of the homeland in the immigrants’ experience, as well as their own history and life in the new world.

Cumulus clouds are frequently observed as comprising multiple successive thermals, yet numerical simulations of entrainment have not investigated this level of detail. Here, an idealized simulated cumulus congestus consisting of three successive thermals is used to analyze and understand their role in maintaining the high liquid water content in the core of the cloud, which past 1D modeling studies have suggested can ultimately determine its ability to precipitate. Entrainment and detrainment are calculated directly at the edge of the cloud core at frequent time intervals. Entrainment maxima occur at the rear of the toroidal circulation associated with each thermal and thus are transient features in the lifetime of multithermal clouds. The evolution of the least diluted parcels within each thermal shows that the entrainment rates alone cannot predict the erosion of the high liquid water content cores. A novel analysis of samples of entrained and detrained air within each successive thermal illustrates tendencies for even positively buoyant air, containing condensate, to be entrained by later thermals that rise in the wakes of their predecessors, limiting their dilution. The later thermals can achieve greater depths and produce precipitation when a single thermal could not. Future work is yet needed to evaluate the generality of these results using multiple clouds simulated in different environments with less-idealized modeling frameworks. Implications for current cumulus parameterizations are briefly discussed.

The Convective Precipitation Experiment (COPE) was a joint U.K.–U.S. field campaign held during the summer of 2013 in the southwest peninsula of England, designed to study convective clouds that produce heavy rain leading to flash floods. The clouds form along convergence lines that develop regularly as a result of the topography. Major flash floods have occurred in the past, most famously at Boscastle in 2004. It has been suggested that much of the rain was produced by warm rain processes, similar to some flash floods that have occurred in the United States. The overarching goal of COPE is to improve quantitative convective precipitation forecasting by understanding the interactions of the cloud microphysics and dynamics and thereby to improve numerical weather prediction (NWP) model skill for forecasts of flash floods. Two research aircraft, the University of Wyoming King Air and the U.K. BAe 146, obtained detailed in situ and remote sensing measurements in, around, and below storms on several days. A new fast-scanning X-band dual-polarization Doppler radar made 360° volume scans over 10 elevation angles approximately every 5 min and was augmented by two Met Office C-band radars and the Chilbolton S-band radar. Detailed aerosol measurements were made on the aircraft and on the ground. This paper i) provides an overview of the COPE field campaign and the resulting dataset, ii) presents examples of heavy convective rainfall in clouds containing ice and also in relatively shallow clouds through the warm rain process alone, and iii) explains how COPE data will be used to improve high-resolution NWP models for operational use.

Three flights from the Ice in Clouds Experiment–Tropical (ICE-T) field campaign examined the onset of ice near the ascending cloud tops of tropical maritime cumuli as they cooled from 0° to −14°C. Careful quantitative analysis of ice number concentrations included manual scrutiny of particle images and corrections for possible particle-shattering artifacts. The novel use of the Wyoming Cloud Radar documented the stage of cloud development and tops relative to the aircraft sampling, complemented the manual estimates of graupel concentrations, and provided new clear evidence of graupel movement through the rime-splintering zone. Measurements of ice-nucleating particles (INPs) provided an estimate of primary initiated ice. The data portray a dynamically complex picture of hydrometeor transport contributing to, and likely resulting from, the rime-splintering process. Hundreds per liter of supercooled raindrops ascended within the updrafts as the cloud tops reached 0°C and contributed in part to the 0.1 L−1 graupel detected soon after the cloud tops cooled to −5°C. Rime splintering could thus be initiated upon first ascent of the cloud top through that zone and arguably contributed to the 1 L−1 or more graupel observed above it. Graupel ascending/descending into, or balanced within, the rime-splintering zone were found. In wider, less isolated clouds with dying updrafts and tops near −14°C, ice particle concentrations sometimes reached 100 L−1. Future 3D numerical modeling will be required to evaluate if rime splintering alone can explain the difference of three to four orders of magnitude in the observed INPs and the graupel observed at −5°C and colder.

INTRODUCTION: Childhood thalamic gliomas are rare cancers, accounting for 5% of all pediatric brain tumors and are of glial origin. The recent WHO classification places thalamic tumors in the category of midline gliomas based on discoveries that indicate histone 3 mutations as the driver genomic aberration of these cancers. Thalamic lesions may be confined to one side, spread to both thalami or to the brainstem. Despite variations in anatomical manifestation, the molecular events dictating tumor spread and pathogenesis are not well defined. METHODS: A cohort of 294 specimens representing 207 subjects diagnosed gliomas with involvement of thalamus, were selected for methylation and whole genome sequencing using Illumina HIseq and EPIC bead array chips. Histological and clinical characterizations were correlated with molecular data to define unique pathways associated with tumor anatomical manifestation. RESULTS: Histological analysis indicated the presence of histone mutation in 46% of specimens. IHC based WHO grading indicated 44% (91/207) of patients with Grade 4, 21% (44/207) were Grade 3, 3% (6/207) were Grade 2, 22% (45/207) were Grade 1 and 10% were other types (e.g. ganglioglioma). Methylation studies conferred hypomethylation to be associated with H3 mutation status. Median age at diagnosis was 9.8 years and 56% of the cohort was male. The presence of the H3K27M mutation was associated with lower survival despite tumor grade. Molecular studies are underway to decipher specific pathways associated with LGG, HGG and TGs.

Diffuse intrinsic pontine glioma (DIPG) is a tumor of the brainstem, specifically in the pons, accounting for 10–20% of all of central nervous system (CNS) tumors in children. Unfortunately, DIPG is the leading cause of death in children with CNS cancers. Clinical interventions trying to effectively treat children with DIPG have failed despite 40 years of clinical trials. The critical location of these tumors eliminates extensive surgical resection as an option. Radiation therapy (RT) is the standard of care, and although it improves the clinical symptoms of most patients, the results are temporary, with tumor progression typically occurring months post radiation. Given the dismal prognosis associated with this disease and the challenge to find chemotherapeutic agents, especially molecularly targeted drugs that improve the survival of the patients, there is a strong incentive to move new treatments forward into clinical trials. The more effective treatment would potentially involve combinatory therapeutic regimens with new epigenetic drugs that can offer synergistic benefits and potentially increase therapeu‐ tic efficacy. The increasing knowledge of genomic, epigenomic, and proteomic characteristics of DIPG is opening doors to new therapeutic avenues and provides hope and promise for this devastating childhood cancer.

TLR activation by multiple pathways leads to triglyceride accumulation in macrophages that could contribute to the accelerated atherosclerosis seen in chronic infections and inflammatory diseases. LPS treatment of macrophages induces TG accumulation, which is accentuated by TG-rich lipoproteins or FFA. We defined pathways altered during macrophage activation that contribute to TG accumulation. Glucose uptake increased with activation, accompanied by increased GLUT1. Oxidation of glucose markedly decreased, whereas incorporation of glucose-derived carbon into FA and sterols increased. Macrophage activation also increased uptake of FFA, associated with an increase in CD36. Oxidation of FA was markedly reduced, whereas the incorporation of FA into TGs increased, associated with increased GPAT3 and DGAT2. Additionally, macrophage activation decreased TG lipolysis; however, expression of ATGL or HSL was not altered. Macrophage activation altered gene expression similarly when incubated with exogenous FA or AcLDL. Whereas activation with ligands of TLR2 (zymosan), TLR3 (poly I:C), or TLR4 (LPS) induced alterations in macrophage gene expression, leading to TG accumulation, treatment of macrophages with cytokines had minimal effects. Thus, activation of TLRs leads to accumulation of TG in macrophages by multiple pathways that may have beneficial effects in host defense but could contribute to the accelerated atherosclerosis in chronic infections and inflammatory diseases.

The incidence of chronic post-surgical pain (CPSP) after various common operations is 10% to 50%. Identification of patients at risk of developing chronic pain, and the management and prevention of CPSP remains inadequate. The aim of this study was to develop an easily applicable risk index for the detection of high-risk patients that takes into account the multifactorial aetiology of CPSP. A comprehensive item pool was derived from a systematic literature search. Items that turned out significant in bivariate analyses were then analysed multivariately, using logistic regression analyses. The items that yielded significant predictors in the multivariate analyses were compiled into an index. The cut-off score for a high risk of developing CPSP with an optimal trade-off between sensitivity and specificity was identified. The data of 150 patients who underwent different types of surgery were included in the analyses. Six months after surgery, 43.3% of the patients reported CPSP. Five predictors multivariately contributed to the prediction of CPSP: capacity overload, preoperative pain in the operating field, other chronic preoperative pain, post-surgical acute pain and co-morbid stress symptoms. These results suggest that several easily assessable preoperative and perioperative patient characteristics can predict a patient's risk of developing CPSP. The risk index may help caregivers to tailor individual pain management and to assist high-risk patients with pain coping.

This paper reports on the thermal Johnson-Nyquist noise of the quantum Hall and longitudinal resistances, which were measured both without an applied current and with an externally applied alternating or direct current. The results verify expected behavior and give interesting insights into the quantum Hall effect. They also demonstrate that ac measuring techniques commonly used in impedance metrology can take noise as a signal, reliably measuring tiny effects with a resolution of 10 pV.

Phospholipids are required for epidermal lamellar body formation. Glycerol 3-phosphate acyltransferases (GPATs) catalyze the initial step in the biosynthesis of glycerolipids. Little is known about the expression and regulation of GPATs in epidermis/keratinocytes. Here, we demonstrate that GPAT 1, 3, and 4 are expressed in epidermis/keratinocytes, whereas GPAT2 is not detected. In mouse epidermis, GPAT 3 and 4 are mainly localized to the upper layers whereas GPAT1 is found in both the upper and lower layers. GPAT1 and 3 mRNA increase during fetal rat epidermal development. No change in GPAT expression was observed in adult mice following acute permeability barrier disruption. Calcium-induced human keratinocyte differentiation increased GPAT3 mRNA whereas both GPAT1 and 4 mRNA levels decreased. In parallel, total GPAT activity increased 2-fold in differentiated keratinocytes attributable to an increase in N-ethylmaleimide (NEM) sensitive GPAT activity localized to microsomes with little change in NEM resistant activity, consistent with an increase in GPAT3. Furthermore, PPARγ or PPARδ activators increased GPAT3 mRNA, microsomal GPAT activity, and glycerol lipid synthesis without affecting the expression of GPAT1 or 4. Finally, both PPARγ and PPARδ activators increased GPAT3 mRNA via increasing its transcription. Thus, multiple isoforms of GPAT are expressed and differentially regulated in epidermis/keratinocytes.

The acute phase response is characterized by elevations in serum triglyceride levels due to both an increase in hepatic VLDL production and a delay in the clearance of triglyceride rich lipoproteins secondary to a decrease in lipoprotein lipase (LPL) activity. Recently there has been a marked increase in our understanding of factors that regulate LPL activity. GPIHBP1 facilitates the interaction of LPL and lipoproteins thereby allowing lipolysis to occur. Angiopoietin like proteins (ANGPTL) 3 and 4 inhibit LPL activity. In the present study, treatment of mice with LPS, an activator of TLR4 and a model of Gram-negative infections, did not alter the expression of GPIHBP1 in heart or adipose tissue. However, LPS decreased the expression of ANGPTL3 in liver and increased the expression of ANGPTL4 in heart, muscle, and adipose tissue. Serum ANGPTL4 protein levels were markedly increased at 8 and 16h following LPS treatment. Administration of zymosan, an activator of TLR2 and a model of fungal infections, also increased serum ANGPTL4 protein and mRNA levels in liver, heart, muscle, and adipose tissue. Finally, treatment of 3T3-L1 adipocytes with LPS or cytokines (TNF alpha, IL-1 beta, and interferon gamma) stimulated ANGPTL4 expression. These studies demonstrate that ANGPTL4 is a positive acute phase protein and the increase in ANGPTL4 could contribute to the hypertriglyceridemia that characteristically occurs during the acute phase response by inhibiting LPL activity.

In the European Waste List (2000/532/EC as amended) the ash of municipal waste incineration is defined as a so called mirror entry. This waste can be classified as hazardous or non-hazardous depending on the content of hazardous substances and other risk properties. For the assignment of waste in mirror entries, 14 criteria are defined. One of the criteria is H14 "ecotoxic". In the presented study, the ecotoxicological potential of 12 ashes from different incineration plants has been assessed using biological test systems. The test battery included aquatic tests with eluates (algae, daphnids, and luminescent bacteria) and terrestrial tests with solid waste (plants, earthworms and bacteria). The test results revealed a clear ecotoxicological hazard potential for some of the MWI ashes. Despite the fact that fresh ashes were several times more toxic than aged ashes both groups did not differ consistently in terms of toxicity. The results show also that there is no correlation between the biological effects and the analyzed chemical compounds of the ash samples.