LPS promotes HBO1 stability via USP25 to modulate inflammatory gene transcription in THP-1 cells

Publication date: Available online 4 August 2018

Source: Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms

Author(s): Chen Long, Yandong Lai, Jin Li, Jiangsheng Huang, Chunbin Zou

Abstract

The histone acetyltransferase HBO1 (Histone acetyltransferase binding to origin recognition complex 1, Myst2/Kat7) participates in a range of life processes including DNA replication and tumorigenesis. Recent studies revealed that HBO1 is involved in gene transcriptional activation. However, the molecular behavior of HBO1 in inflammation is yet to be studied. Here we report that endotoxin lipopolysaccharide (LPS) elevates HBO1 protein level via up-regulating UPS25 (ubiquitin specific peptidase 25) and alters inflammatory gene transcription in THP-1 monocytes and in human primary macrophages. LPS protects HBO1 from ubiquitin proteasomal degradation without significantly altering its transcription. By immunoprecipitation, we identified that HBO1 associates with a deubiquitinating enzyme USP25 in THP-1 cells. LPS increases protein level of USP25 resulting in accumulation of HBO1 by suppression of HBO1 ubiquitination. Stabilized-HBO1 modulates inflammatory gene transcription in THP-1 cells. These findings indicate that USP25 promotes stability of HBO1 in bacterial infection thereby enhances HBO1-mediated inflammatory gene transcription.

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Quercetin Attenuates Adhesion Molecule Expression in Intestinal Microvascular Endothelial Cells by Modulating Multiple Pathways

Abstract

Background

In inflammatory bowel disease, activation of microvascular endothelial cells and adhesion of immune cells are required for the initiation and maintenance of inflammation. We evaluated the effects and mechanisms of quercetin, a flavone identified in a wide variety of dietary sources, in LPS-induced rat intestinal microvascular endothelial cells (RIMVECs).

Methods

RIMVECs were pretreated with quercetin of various concentrations (20, 40 and 80 μM) followed by LPS (10 μg/ml) stimulation. ELISA was used to examine protein levels of intercellular adhesion molecules-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in the supernatant. Protein levels of Toll-like receptor 4 (TLR4), nuclear transcription factor kappa B (NF-κB) p65, inhibitors of NF-κB (IκB-α), extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase (JNK), mitogen-activated protein kinase (MAPK) p38 and signal transducer and activator of transcription (STAT) in cells were measured by Western blot.

Results

Quercetin significantly suppressed protein levels of ICAM-1 and VCAM-1 induced by LPS. Quercetin also inhibited TLR4 expression, NF-κB p65, ERK, JNK and STAT phosphorylation and decreased IκB-α degradation. Moreover, the MAPK p38 signal does not contribute to the anti-inflammatory effects on RIMVECs, although LPS significantly increases its phosphorylation.

Conclusions

These results indicate that quercetin may have an anti-inflammatory effect by inhibiting expression of ICAM-1 and VCAM-1 in RIMVECs by suppressing TLR4, NF-κB, ERK, JNK and STAT but not the p38 signaling pathway.

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Influence of mineral dust on changes of 7Be concentrations in air as measured by CTBTO global monitoring system

Publication date: December 2018

Source: Journal of Environmental Radioactivity, Volume 192

Author(s): J. Kuśmierczyk-Michulec, P. Bourgouin

Abstract

Atmospheric Transport Modelling (ATM) results were combined with ⁷Be observations collected during the 2009–2015 period by the three radionuclide stations from the International Monitoring System (IMS), located in Mauritania (18.1 N, 15.9 W), Kuwait (29.3 N, 47.9 E) and Panama (9.0 N, 79.5 W), to study the influence of Saharan dust on changes in ⁷Be surface concentrations. It is demonstrated that for long-range transport (>3000 km), the overall impact of Sahara can be reproduced using a single point source located in the Bodélé depression (17.0 N, 18.0 E). To monitor the arrival time of dust plumes at the IMS stations, a series of 14-day forward simulations with daily releases from the Bodélé, during dusty episodes between 2009 and 2015, were generated. In total 1020 simulations with the output at the surface level (0–150 m) and 420 simulations with the output at 9 vertical layers ranging from the surface up to 10 km, were analysed. In the simulations, the analysed meteorological input data provided by the European Centre for Medium-Range Weather Forecasts (ECMWF) were used. It is demonstrated that an influx of dust at high levels (3–10 km) tends to locally increase surface ⁷Be concentrations in area under the influence of subsiding dust plume. It is also shown that an influx of dust at lower altitudes (up to 1 km) will have the opposite effect on surface concentrations. In case dust is present in the whole column of atmosphere, its final impact depends on the ratio between its amount in the upper layers (3–10 km) and lower layers (0–1 km). In consequence an increase up to 30% or a decrease up 20% in daily ⁷Be surface values may be observed during such an episode. On a monthly scale a few episodes related to an increase of ⁷Be values or its decrease may follow each other. It was estimated that on average the presence of dust leads to the increase of ⁷Be mean monthly surface values. The largest increase was noted at the station MRP43, of about 4.1 ± 1.3%; and the smallest at the stations KWP40, of about 2.0 ± 1.6% and PAP50, of about 2.0 ± 1.0%, respectively.

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Contents

Publication date: September 2018

Source: Clinical Neurophysiology, Volume 129, Issue 9

Author(s):

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Editorial Board

Publication date: September 2018

Source: Clinical Neurophysiology, Volume 129, Issue 9

Author(s):

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Specific EEG markers in POLG1 Alpers’ syndrome

Publication date: Available online 4 August 2018

Source: Clinical Neurophysiology

Author(s): Anouk van Westrhenen, Elisabeth A. Cats, Bart van den Munckhof, Sandra M.A. van der Salm, Nico W. Teunissen, Cyrille H. Ferrier, Frans S.S. Leijten, Karin P.W. Geleijns

Abstract

Objective

To examine whether rhythmic high-amplitude delta with superimposed (poly)spikes (RHADS) in EEG allow a reliable early diagnosis of Alpers-Huttenlocher syndrome (AHS) and contribute to recognition of this disease.

Methods

EEGs of nine patients with DNA-proven AHS and fifty age-matched patients with status epilepticus were retrospectively examined by experts for the presence of RHADS and for accompanying clinical signs and high-frequency ripples. Reproducibility of RHADS identification was tested in a blinded panel.

Results

Expert defined RHADS were found in at least one EEG of all AHS patients and none of the control group. RHADS were present at first status epilepticus in six AHS patients (67%). Sometimes they appeared 5-10 weeks later and disappeared over time. RHADS were symptomatic in three AHS patients and five AHS patients showed distinct ripples on the (poly)spikes of RHADS. Independent RHADS identification by the blinded panel resulted in a sensitivity of 87.5% (95% CI 47-100) and a specificity of 87.5% (95% CI 77-94) as compared to the experts' reporting.

Conclusion

RHADS are a highly specific EEG phenomenon for diagnosis of AHS and can be reliably recognized. Clinical expression and EEG ripples suggest that they signify an epileptic phenomenon.

Significance

RHADS provide a specific tool for AHS diagnosis.

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Contents

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Editorial Board

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Electrical activity of the human amygdala during all-night sleep and wakefulness

Several studies have established a close relationship between sleep and emotion (Deliens et al., 2014). In particular, rapid eye movement (REM) sleep has been implicated in emotion during dreams and nightmares (Desseilles et al., 2011; Ross et al., 1994), also in posttraumatic sleep disorder (Mellman et al., 2002), and in next day emotional regulation. For example, emotional reactivity to threatening images is exacerbated after selective REM sleep deprivation (Rosales-Lagarde et al., 2012), as are fear responses to previously extinguished stimuli (Spoormaker et al., 2012).

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Heart rate variability and impact of central pacemaker on cardiac activity

The study of heart rate variability (HRV) has become increasingly popular in the last decade, spanning from basic physiological mechanisms to psychosocial correlates and clinical applications. In this issue of Clinical Neurophysiology, Hamasaki et al. (2018) report on the coincidence of hemifacial spasm (HFS) and significant HRV increase in the low frequency (LF) band around 0.1 Hz and acceleration of heart rate. HFS caused by arterial compression of the facial nerve may be explained by various possible causes.

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Ultrasound-guided, open-source microneurography: Approaches to improve recordings from peripheral nerves in man

Microneurography is an established technique that allows recordings to be made from peripheral nerves in humans (Vallbo and Hagbarth, 1968, Vallbo et al. , 2004). This includes the ability to record from afferent neurones conducting in the C-fibre range (Torebjork and Hallin, 1974), which are predominantly nociceptors. In the pain field, the normal response characteristics of several classes of nociceptors have been defined and a growing body of work is now identifying pathophysiological changes in human disease (Donadio and Liguori, 2015).

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Auditory N100 gating in patients with schizophrenia: A systematic meta-analysis

Several event-related potential (ERP) components have been considered as biological markers for schizophrenia, such as the auditory mismatch negativity (MMN), auditory P50 gating, or P3 (Thibaut et al., 2015). For these ERP components, there has been decade-long clinical research, with first reports of deficiencies in schizophrenia dating back more than 45 years (Roth and Cannon, 1972). Recent meta-analyses suggest relatively large, trait-related deficits in schizophrenia patients, with patients showing smaller MMN and P3 amplitudes, a delayed P3 response, and less efficient P50 gating, as compared to healthy controls (MMN: Erickson et al., 2016; P3: Jeon and Polich, 2003; P50 gating: de Wilde et al., 2007; Patterson et al., 2008).

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A glimpse into the future of clinical neurophysiology: Can we use machines to interpret EEG?

To help diagnose epilepsy, the clinical neurophysiologist reviews and analyzes EEG recordings, a subtle and time-consuming skill. Historically, researchers have improved this diagnostic process by identifying epileptiform markers and by automating their detection (e.g. Gibbs and Gibbs, 1952; Kellaway et al., 1959; Gotman and Gloor, 1976; Gotman, 1982). One recently developed approach that can extract and classify signal features is deep learning, an application based on artificial neural nets with the neural elements arranged in multiple layers.

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Spasticity in adults with cerebral palsy and multiple sclerosis measured by objective clinically applicable technique

Spasticity occurs frequently following lesions of central motor pathways in neurological disorders such as stroke (Malhotra et al., 2009; Sommerfeld et al., 2012), spinal cord injury (Sheean, 2002), multiple sclerosis (MS) (Sinkjaer et al., 1993; Mayer, 1997) and cerebral palsy (CP) (Gracies, 2005). Spasticity is most commonly defined as a velocity dependent increase in muscle tone with exaggeration of the stretch reflex circuitry (Lance, 1980). However, in the clinic a somewhat broader understanding of spasticity, which also includes sustained muscle contractions such as spasms and spastic dystonia as well as alterations in muscle properties, prevails (Malhotra et al., 2009).

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Inhibition and attentional control in pedophilic child sexual offenders – An event-related potential study

Deficits in response inhibition and attentional control as impairment of executive functions have been presumed to play a role in child sexual abuse by pedophiles, as primarily revealed by neuropsychological testing of such individuals (Eastvold et al., 2011; Joyal et al., 2014; Schiffer and Vonlaufen, 2011; Suchy et al., 2009). Pedophilic and non-pedophilic child molesters showed e.g. increased false alarm rates in a Go/Nogo-task, as compared to both healthy and forensic controls (Schiffer and Vonlaufen, 2011).

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Reply to “Work-up for mitochondrial small fiber neuropathy requires application of skin biopsies”

In reply to the letter of Finsterer (2018) we further analyzed our cohort of patients with mitochondrial diseases (MDs), in order to confirm our results.

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Physical activity effects on the individual alpha peak frequency of older adults with and without genetic risk factors for Alzheimer’s Disease: A MEG study

For more than two decades, an enormous effort has been devoted to the search for pharmacological therapies that could palliate the devastating effects of Alzheimer's Disease (AD). Most of these therapies relied on the so-called "amyloid hypothesis" (Hardy and Higgins, 1992), that is considered the leading explanation for the disease. Unfortunately, clinical trials testing agents that interfere with amyloid production failed to improve cognition or to slow down the deterioration process, while produced substantial side effects (Drachman, 2014; Intlekofer and Cotman, 2013).

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Normative values for sleep parameters in pre-schoolers using actigraphy

Sleep disturbances are relatively common in children. Primary care providers have reported that approximately 20% of their 0-to-4-year-old patients had sleeping difficulties (Honaker and Meltzer, 2016). The prevalence of manifest sleep problems reported by parents range between 11 and 12% (Honaker and Meltzer, 2016), and at least one symptom of insomnia is reported in approximately 40% of children (Archbold et al., 2002). The high prevalence of sleeping problems in children calls for reliable diagnostic tools for the clinicians.

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Work-up for mitochondrial small fiber neuropathy requires application of skin biopsies

With interest, I read the article from Luigetti et al. about the work-up for small fiber neuropathy in genetically confirmed patients with a mitochondrial disorder (MID) (m.3243A > G (n = 7), m.8344A > G (n = 4), single mtDNA deletion (n = 9), multiple mtDNA deletions (n = 7)) (Luigetti et al., 2018). By application of the Sudoscan, the sympathetic skin response (SSR), and laser-evoked potentials (LEP), the authors found that 33% of the 27 patients had autonomic small fiber dysfunction by application of the Sudoscan, that only 3/27 patients had an abnormal SSR, and that LEP confirmed the Sudocan findings.

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Is hemifacial spasm affected by changes in the heart rate? A study using heart rate variability analysis

Hemifacial spasm (HFS), a movement disorder characterized by involuntary muscle contraction of one side of the face. HFS impairs not only daily activities but also social activities of patients. Because the central etiology of HFS is mechanical compression by offending arteries to the root exit zone (REZ) of the facial nerve (Campbell and Keedy, 1947; Gardner, 1962; McLaughlin et al., 1999), microvascular decompression is a standard surgical treatment, in which the arteries are microsurgically separated from the facial nerve REZ, and provides favorable outcome (Barker et al., 1995; Chung et al., 2000; Samii et al., 2002).

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Neuromodulation of lower limb motor responses with transcutaneous lumbar spinal cord direct current stimulation

The spinal cord (SC) is a complex structure that contains its own neuronal circuits modulated by higher encephalic function. The motor information descends via the corticospinal tracts to synapse with the alpha and gamma motor neurons located in the anterior horns, directly or via spinal interneurons. SC is not only a bidirectional communication pathway between brain and the periphery, but it also contains local circuits known to permit locomotion movements and segmental spinal reflexes (Iglesias et al., 2008).

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Specific EEG markers in POLG1 Alpers’ syndrome

Alpers-Huttenlocher syndrome (AHS) is a rare, mitochondrial disease with high mortality.(Cohen and Naviaux 2010) It is characterized by refractory seizures, episodic psychomotor regression, ataxia, cortical blindness and liver failure.(Saneto and Naviaux 2010; Harding 1990) Disease onset is often during childhood, but can range from three months to 36 years of age.(Cohen and Naviaux 2010; Tzoulis et al. 2006) Epilepsy is an important diagnostic factor in AHS and has a focal onset with occipital lobe predeliction.(Engelsen et al.

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Measurement of cervical multifidus and longus colli muscles dimensions in patients with cervical radiculopathy and healthy controls using ultrasonography: A reliability study

Cervical radiculopathy is an increasing musculoskeletal disorder, with high prevalence in the office workers. In recent years, ultrasonography (US) is reported to be a valid, non-expensive and non-invasive technique for the objective evaluation of the morphology of muscles. However, measuring deep cervical paraspinal muscle dimensions using US in patients with cervical radiculopathy has not yet been demonstrated.

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Outcomes of Multi-Level Vertebrectomy for Spondylodiscitis

The incidence of pyogenic vertebral osteomyelitis (PVO) continues to increase in the United States, highlighting the need to recognize unique challenges presented by these cases and develop effective methods of surgical management. To date, no prior research has focused on the outcomes of PVO requiring two or more contiguous corpectomies.

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Allometric relationship in the bioaccumulation of radionuclides (134Cs & 241Am) and delineation of contamination pathways (food and seawater) in bloody cockle Anadara senilis using radiotracer techniques

Publication date: December 2018

Source: Journal of Environmental Radioactivity, Volume 192

Author(s): Harriet Kuranchie-Mensah, Simon Pouil, Jean-Louis Teyssié, François Oberhänsli, Michel Warnau, Marc Metian

Abstract

The uptake and depuration kinetics of ¹³⁴Cs and ²⁴¹Am were investigated in the bloody cockle Anadara senilis exposed via seawater and food in controlled conditions, using animals of different weight groups in order to assess how their bioaccumulation is affected by allometry and, hence, the individual's age. This study is one of the few experiments investigating bioaccumulation capacities of radionuclides in a West-African bivalve. Results showed that allometric relationships were mainly dependent on the exposure pathway considered. Significant relationships with body weight of bloody cockles were found during the uptake from dissolved phase for both radionuclides; they followed inverse power functions: smaller cockles concentrated both radionuclides more than larger ones. In contrast, radionuclide absorption and assimilation efficiencies from water and food, respectively, did not show any significant relationship with weight: only slight variation was observed between small and large organisms for the retention of ²⁴¹Am accumulated from food. A bioaccumulation model was used to assess the contribution of each pathway of exposure (food vs. water) in organisms grouped in small and large individuals. We found that, regardless of the size, ¹³⁴Cs was mainly bioaccumulated through the dietary pathway. In the case of ²⁴¹Am, the relative contribution of each pathway is weight-dependent: major contribution of dissolved pathway in smaller organisms and the major dietary contribution in larger organisms.

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Assessment of driver drowsiness using electroencephalogram signals based on multiple functional brain networks

Publication date: Available online 3 August 2018

Source: International Journal of Psychophysiology

Author(s): Jichi Chen, Hong Wang, Chengcheng Hua

Abstract

This paper proposes a comprehensive approach to explore whether functional brain network (FBN) changes from the alert state to the drowsy state and to find out ideal neurophysiology indicators able to detect driver drowsiness in terms of FBN. A driving simulation experiment consisting of two driving tasks is designed and conducted using fifteen participant drivers. Collected EEG signals are then decomposed into multiple frequency bands by wavelet packet transform (WPT). Based on this, two novel FBN approaches, synchronization likelihood (SL) and minimum spanning tree (MST) are combined and applied to feature recognition and classification system. Unlike other methods, our approaches focus on the interaction and correlation between different brain regions. Statistical analysis of network features indicates that the difference between alert state and drowsy state are significant and further confirmed that brain network configuration should be related to drowsiness. For classification, these brain network features are selected and then fed into four classifiers considered namely Support Vector Machines (SVM), K Nearest Neighbors classifier (KNN), Logistic Regression (LR) and Decision Trees (DT). It is found that combining MST method and SL method is actually increasing the classification accuracy with all classifiers considered in this work especially the KNN classifier from 95.4% to 98.6%. Moreover, KNN classifier also gives the highest precision of 98.3%, sensitivity of 98.8% and specificity of 98.9%. Thus this kind of methodology might be a useful tool for further understanding the neurophysiology mechanisms of driver drowsiness, and as a reference work for future studies or future 'systems'.

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PEDIATRIC AUTOIMMUNE LIVER DISEASE AND EXTRA-HEPATIC IMMUNE-MEDIATED COMORBIDITIES

Autoimmune liver disease (AILD) includes autoimmune hepatitis (AIH) and autoimmune sclerosing cholangitis (ASC). AILD is often associated with other extra-hepatic immune-mediated disorders (EDs), but there are few pediatric studies available to date. In this study we evaluated the association between AILD and EDs in our pediatric series.

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Quiz: 4 things EMS providers need to know about pulmonary embolism

When a patient's life is in your hands, you need to know the risk factors, signs and symptoms of PE

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Prolonged standing increases lower limb arterial stiffness

Abstract

Purpose

Standing workstations have recently been promoted as a healthy alternative to sitting. However, it is unknown how prolonged standing affects arterial stiffness, a prognostic indicator of cardiovascular health. The purpose of this study was twofold: to observe changes in arterial stiffness, as assessed by pulse wave velocity (PWV), with a 2-h bout of standing, and to determine if short, intermittent walking bouts provide a comparative advantage to standing alone.

Methods

Nineteen adults had arterial stiffness assessed by pulse wave velocity. Central (C_PWV), upper peripheral (U_PWV), and lower peripheral (L_PWV) PWV were assessed before (supine), during standing (min 10, 60, and 120), and after (supine) the 2-h standing bout. In one trial, the participants stood at a standing desk immobile for 2 h. In the other trial, participants performed 5-min walking breaks after every 25 min of standing.

Results

After 2-h of standing, supine (85.8 ± 90.1 cm/s) and standing (303.4 ± 390.2 cm/s), L_PWV increased independent of trial (i.e., main effect of time; p < 0.001). Walking breaks during 2 h of standing did not significantly attenuate these changes. In addition, standing C_PWV decreased over time (− 38.5 ± 61.5 cm/s; p = 0.04). Yet, U_PWV, standing or supine, did not change over the course of standing (p > 0.05).

Conclusions

These findings indicate that prolonged standing increases the measures of arterial stiffness and there is no evidence that walk breaks attenuate this response.

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Joint Nordic nuclear research to strengthen nuclear emergency preparedness after the Fukushima accident

Publication date: December 2018

Source: Journal of Environmental Radioactivity, Volume 192

Author(s): Kasper G. Andersson, Christian Linde, Sigurður M. Magnússon, Finn Physant

Abstract

Contrary to most areas of Europe, the Nordic countries (Denmark, Finland, Iceland, Norway, Sweden, and the Faroe Islands) have for many years shared a regional research and development program on nuclear reactor safety and emergency preparedness - NKS. In spite of its project results having received great recognition and having been integrated in state-of-the-art emergency preparedness tools over the world, NKS as an organization does not seem well known outside the Nordic countries. Although the Fukushima accident had no health impact at all in Nordic areas, it taught a number of lessons of generic nature with respect to new R&D tasks that could further strengthen and secure future maintenance of the Nordic region's capability to effectively respond to such events. For broader inspiration, this paper briefly introduces the Nordic nuclear emergency preparedness cooperation channels and outlines the related NKS R&D project initiatives launched after the Fukushima accident, many of which should be of general interest also far outside the region. The paper is intended as an introduction to NKS with an invitation to explore its results. All project results are available cost-free on the NKS website.

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United Kingdom: transfers of genomic data to third countries

Abstract

In the United Kingdom (UK), transfer of genomic data to third countries is regulated by data protection legislation. This is a composite of domestic and European Union (EU) law, with EU law to be adopted as domestic law when Brexit takes place. In this paper we consider the content of data protection legislation and the likely impact of Brexit on transfers of genomic data from the UK to other countries. We examine the advice by regulators not to rely upon consent as a lawful basis for processing under data protection law, at least not when personal data are used for research purposes, and consider some of the other ways in which the research context can qualify an individual's ability to exercise control over processing operations. We explain how the process of pseudonymization is to be understood in the context of transfer of genomic data to third parties, as well as how adequacy of data protection in a third country is to be determined in general terms. We conclude with reflections on the future direction of UK data protection law post Brexit with the reclassification of the UK itself as a third country.

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RedSky Emergency Vehicles to handle Braun Ambulance sales in California

VAN WERT, OH — Braun Ambulances is proud to welcome RedSky Emergency Vehicles to the Braun family. Effective July 16, 2018, RedSky became an official dealer partner with Braun Industries. This partnership recognizes RedSky as the Authorized Sales and Service Center for Braun ambulances in the state of California. "We are beyond excited to welcome RedSky Emergency Vehicles to the Braun...

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Braun Industries expands new ambulance sales territory for Autotronics, LLC

VAN WERT, OH — Braun Ambulances is proud to announce a territory expansion for Autotronics, LLC. Starting July 31, 2018, Autotronics began serving customers located in New Hampshire and Maine; they previously covered the state of Maine only. The expansion is a testament to the great work Autotronics is doing for Braun Industries in the New England region. Additionally, Autotronics has added...

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Braun Industries welcomes back Bulldog Fire & Emergency Apparatus for new ambulance sales

VAN WERT, OH — Braun Ambulances is proud to welcome back Bulldog Fire Apparatus to the Braun family. Effective July 31, 2018, Bulldog Fire Apparatus rejoined Braun's national dealer network as an Authorized Sales and Service Center. They will provide Braun ambulance sales and service to customers in Massachusetts, Rhode Island, and Connecticut. "We are pleased to have Jeff Mazza...

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Immediate loading at single crowns and 2‐unit bridges supported by implants installed in a healed alveolar bony ridge or immediately after tooth extraction. An experimental study in dogs

Journal of Oral Rehabilitation, Volume 0, Issue ja, -Not available-.


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Clinicopathological differences in signet ring cell adenocarcinoma between early and advanced gastric cancer

Gastric Cancer

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Extended release bupivacaine formulations for postoperative analgesia: an update

Purpose of review New formulations of local anesthetics with sustained release and longer duration of action are being developed to improve patient outcomes following surgery. This review summarizes the efficacy and safety of the three most recently developed extended-release formulations of the local anesthetic, bupivacaine. Recent findings Bupivacaine liposome injectable suspension (EXPAREL) encapsulates bupivacaine in biodegradable liposomes. It is currently the only extended-release formulation of bupivacaine approved by the FDA for infiltration of the tissues during surgery and for interscalene nerve block analgesia following shoulder surgery. SABER-Bupivacaine and HTX-011, are extended-release bupivacaine products in active development. Available data suggest relative safety and efficacy of all three formulations, although more data are needed to define their indications and dosing. Summary Extended-release bupivacaine formulations are promising alternatives to prolong duration of analgesia. To date, only EXPAREL has been approved by the FDA for tissue infiltration during surgery and for interscalene nerve block. Correspondence to Admir Hadzic, MD, PhD, Professor, Department of Anesthesiology, Ziekenhuis Oost-Limburg (ZOL), Schiepse bos 6, 3600 Genk, Belgium. E-mail: admir@nysora.com Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Macrophage Markers are Poorly Associated with Liver Histology in Children with Non-Alcoholic Fatty Liver Disease

Objectives: We have previously demonstrated associations between the macrophage activation marker soluble (s)CD163 and histology of non-alcoholic fatty liver disease (NAFLD) in adults, and elevated sCD163 levels in obese children with NAFLD. However, macrophage activation has not been investigated in children with biopsy-proven NAFLD, which was the objective of the present study. Methods: We used in-house ELISAs to measure sCD163 and the novel macrophage marker soluble mannose receptor (sMR) in a cross-sectional (n = 155) pediatric NAFLD cohort, and a cohort of NAFLD children (n = 36) undergoing a randomized trial by the probiotic VSL#3. We included 56 healthy non-obese children for comparison. Results: Levels of sCD163 and sMR were higher in both of the NAFLD cohorts compared with controls (p 

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Absorption and Safety with Sustained Use of RELiZORB Evaluation (ASSURE) Study in Patients with Cystic Fibrosis Receiving Enteral Feeding

Objectives: Pancreatic insufficiency (PI) and malabsorption of fats lead to reduced caloric intake, inability to maintain weight, and increased gastrointestinal symptoms. Thus, Enteral Nutrition (EN) is used in patients with cystic fibrosis (CF) and poor nutritional status. The current study evaluated safety, tolerability and improvement of fatty acid (FA) status in Red Blood Cell (RBC) membranes, a marker of long term FA absorption, with an in-line digestive cartridge (RELiZORB®) that hydrolyzes fat in enteral formula. Methods: Patients with CF receiving EN participated in a multicenter, 90-day open label study during which RELiZORB was used with overnight EN. The primary endpoint was change over time in RBC uptake of DHA+EPA. Gastrointestinal symptoms were collected to evaluate safety and tolerability. Several clinical and anthropometric parameters were also assessed throughout the study. Results: 36 subjects completed the study with a mean age of 13.6 years, BMI of 17.7 and 6.2 years mean use of overnight EN. Fat absorption significantly improved as shown by increased RBC levels of DHA+EPA, improved ω-6/ω-3 ratio, and increased plasma levels of DHA+EPA. RELiZORB use was not associated with any unanticipated adverse events. Conclusions: RELiZORB use was found to be safe, well tolerated and resulted in increased levels of FAs in RBCs and plasma. This is the first prospective study to show EN can improve FA abnormalities in CF. Since improvement in omega-3 levels has been shown to help pulmonary and inflammatory status as well as anthropometric parameters in CF, RELiZORB may have important long term therapeutic benefits in patients with CF. This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. https://ift.tt/1eRPUFd Address correspondence and reprint requests to Steven D. Freedman, MD, PhD, Beth Israel Deaconess Medical Center, 330 Brookline Ave., Dana 501, Boston, MA 02215 (e-mail: sfreedma@bidmc.harvard.edu). Received 10 March, 2018 Accepted 22 June, 2018 Trial identification number and URL: NCT02750501 https://ift.tt/2n6nbL1 Source of Support: This study was funded by Alcresta Therapeutics, Inc. ClinicalTrials.gov Identifier: NCT02750501 - https://ift.tt/2n6nbL1 Authors roles in the submitted manuscript: Steven Freedman, MD, PhD: substantial contribution to the design of the study and the analysis and interpretation of the data, as well as critical review and revision of the manuscript Colby Wyatt, MD: substantial contribution to the acquisition of the data, as well as critical review and revision of the manuscript Perry Brown, MD: substantial contribution to the acquisition of the data, as well as critical review and revision of the manuscript John Stevens, MD: substantial contribution to the acquisition of the data, as well as critical review and revision of the manuscript Dhiren Patel, MD: substantial contribution to the acquisition of the data, as well as critical review and revision of the manuscript Danica Grujic, PhD: substantial contribution to the conception and design of the study and the analysis and interpretation of the data, as well as critical review and revision of the manuscript All authors have reviewed and approved the submitted manuscript and agree to be accountable for all aspects of the work and will participate in addressing any questions related to the accuracy and integrity of the research and results presented in the manuscript. Conflicts of Interest: Dr. Grujic is an employee of Alcresta Therapeutics, Inc.; Dr. Freedman has received research support from Alcresta Therapeutics, Inc. For the remaining authors, none is declared. Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal's Web site (www.jpgn.org). Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (www.jpgn.org). © 2018 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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Impaired Quality of Life, Work, and Activities Among Adults with Clostridium difficile Infection: A Multinational Survey

Abstract

Background

Evidence of humanistic detriments of Clostridium difficile infection (CDI) remains limited.

Aims

To assess humanistic burden associated with CDI.

Methods

Self-reported National Health and Wellness Survey data between 2013 and 2016 were analyzed for the USA, five European countries, China, and Brazil. Outcome measures included SF-36v2^® for health-related quality of life (HRQoL) and Work Productivity and Activity Impairment questionnaire. Respondents (≥ 18 years old) were classified as (1) currently treated doctor-diagnosed CDI (C-CDI), (2) doctor-diagnosed prior CDI (P-CDI), or (3) never experienced CDI (NO-CDI). Regression modeling assessed the association between CDI status and outcomes, adjusting for potential confounders.

Results

Of 352,780 respondents, 299, 2111, and 350,370 met the criteria for C-CDI, P-CDI, and NO-CDI, respectively, with 45% of the total from the USA. C-CDI and P-CDI respondents were older, were less often employed and had more comorbidities than those with NO-CDI. After adjustment for covariates, C-CDI and P-CDI had significantly lower HRQoL relative to NO-CDI for mental (MCS 39, 43 vs. 46) and physical (PCS 39, 41 vs. 46) component summary scores, and health utility (SF-6D 0.58, 0.64 vs. 0.71) (all p < 0.05), meeting common thresholds for minimally important differences. Those with C-CDI and P-CDI reported missing more work (21, 16 vs. 8%), greater impairment while working (43, 34 vs. 22%), and more activity impairment (61, 49 vs. 34%) than those with NO-CDI (all p < 0.05), respectively.

Conclusions

CDI is associated with meaningfully worse HRQoL and greater impairment to work and activities compared with NO-CDI. The impairment directly attributable to CDI requires further evaluation.

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