Decreased Mortality in Patients with Isolated Severe Blunt Traumatic Brain Injury Receiving Higher Plasma to Packed Red Blood Cells Transfusion Ratios

Publication date: Available online 5 August 2017
Source:Injury
Author(s): Tobias Haltmeier, Elizabeth Benjamin, John Peter Gruen, Ira A. Shulman, Lydia Lam, Kenji Inaba, Demetrios Demetriades
IntroductionHigher transfusion ratios of plasma to packed red blood cells (PRBC) and platelets (PLT) to PRBC have been shown to be associated with decreased mortality in major trauma patients. However, little is known about the effect of transfusion ratios on mortality in patients with isolated severe traumatic brain injury (TBI). The aim of this study was to investigate the effect of transfusion ratios on mortality in patients with isolated severe blunt TBI. We hypothesized that higher transfusion ratios of plasma to PRBC and PLT to PRBC are associated with a lower mortality rate in these patients.MethodsRetrospective observational study. Patients with isolated severe blunt TBI (AIS head≥3, AIS extracranial <3) admitted to an urban level I trauma centre were included. Clinical data were extracted from the institution's trauma registry, blood transfusion data from the blood bank database. The effect of higher transfusion ratios on in-hospital mortality was analysed using univariate and multivariable regression analysis.ResultsA total of 385 patients were included. Median age was 32 years (IQR 2-50), 71.4% were male, and 76.6% had an ISS≥16. Plasma:PRBC transfusion ratios≥1 were identified as an independent predictor for decreased in-hospital mortality (adjusted OR 0.43 [CI 0.22-0.81]). PLT:PRBC transfusion ratios≥1 were not significantly associated with mortality (adjusted OR 0.39 [CI 0.08-1.92]).ConclusionThis study revealed plasma to PRBC transfusion ratios≥1 as an independent predictor for decreased in-hospital mortality in patients with isolated severe blunt TBI.



http://ift.tt/2ud14EJ

Women’s and men’s negative experience of child birth—A cross-sectional survey

Publication date: Available online 5 August 2017
Source:Women and Birth
Author(s): Astrid Nystedt, Ingegerd Hildingsson
BackgroundA negative birth experience may influence both women and men and can limit their process of becoming a parent.AimsThis study aimed to analyze and describe women's and men's perceptions and experiences of childbirth.DesignA cross-sectional study of women and their partners living in one Swedish county were recruited in mid pregnancy and followed up two months after birth. Women (n=928) and men (n=818) completed the same questionnaire that investigated new parents' birth experiences in relation to socio-demographic background and birth related variables.ResultsWomen (6%) and men (3%) with a negative birth experiences, experienced longer labours and more often emergency caesarean section compared to women (94%) and men (97%) with a positive birth experience. The obstetric factors that contributed most strongly to a negative birth experience were emergency caesarean and was found in women (OR 4.7, 95% CI 2.0–10.8) and men (OR 4.5, Cl 95% 1.4–17.3). In addition, pain intensity and elective caesarean section were also associated with a negative birth experiences in women. Feelings during birth such as agreeing with the statement; 'It was a pain to give birth' were a strong contributing factor for both women and men.ConclusionsA negative birth experience is associated with obstetric factors such as emergency caesarean section and negative feelings. The content of negative feelings differed between women and men. It is important to take into account that their feelings differ in order to facilitate the processing of the negative birth experience for both partners.



http://ift.tt/2hyb4GH

The Anti-Inflammatory Effect of Guchangzhixie-Pill by Reducing Colonic EC Cell Hyperplasia and Serotonin Availability in an Ulcerative Colitis Rat Model

Ulcerative colitis (UC) is one of the major types of inflammatory bowel diseases (IBD). Abnormal colonic enterochromaffin (EC) cell hyperplasia and serotonin availability have been described in UC. Guchangzhixie-pill (GCZX-pill), a Chinese herbal formula composed of six herbs, is modified based on a traditional formula (Jiechangyan-pill) for inflammatory and ulcerative gastrointestinal disorders. This study aims to investigate the anti-inflammatory effect and the underlying mechanisms of GCZX-pill on trinitrobenzene sulfonic acid- (TNBS-) induced UC in rats. After orally administrating a GCZX-pill to UC rats for 14 days, the results of the inflammation evaluation, such as disease activity index (DAI), macroscopic score (MS), myeloperoxidase (MPO) activity, and other methods, suggested that the GCZX-pill showed remarkable anti-inflammatory results in UC rats. In addition, the abnormal EC cell numbers, colonic tryptophan hydroxylase (TPH) expression, and serotonin (5-HT) contents in TNBS-induced UC rats were significantly reduced by the GCZX-pill. This data demonstrates that the GCZX-pill can attenuate the inflammation in UC rats and the anti-inflammatory effect of the GCZX-pill may be medicated by reducing colonic EC cell hyperplasia and 5-HT availability.

http://ift.tt/2uctH4Y

Urinary Neutrophil Gelatinase-Associated Lipocalin Is Complementary to Albuminuria in Diagnosis of Early-Stage Diabetic Kidney Disease in Type 2 Diabetes

Background. Two clinical phenotypes of diabetic kidney disease (DKD) have been reported, that is, with or without increased albuminuria. The aim of study was to assess the usefulness of urinary neutrophil gelatinase-associated lipocalin (uNGAL) for the early diagnosis of DKD in the type 2 diabetes mellitus (T2DM). Methods. The study group consisted of 123 patients with T2DM (mean age 62 ± 14 years), with urine albumin/creatinine ratio (uACR) 39.64 µg/g, 13 (54%) did not have markedly increased albuminuria. Women with T2DM had higher uNCR than men (), without difference in uACR (). uNCR in T2DM patients correlated significantly with HbA1c. Sex, total cholesterol, and uACR were independent predictors of uNCR above 39.64 µg/g. Conclusions. Increased uNGAL and uNCR may indicate early tubular damage, associated with dyslipidemia and worse diabetes control, especially in females with T2DM.

http://ift.tt/2vBfMJ7

Overweight or Obesity, Gender, and Age Influence on High School Students of the City of Toluca’s Physical Fitness

Material and Method. This is a prospective, cross-sectional, and correlational study with a probabilistic sampling in which 150 teenagers from three different high schools from the city of Toluca, Mexico, aged 15–17, were assessed. Objective. To determine if weight, age, and gender have an influence on physical fitness evaluated with the EUROFIT and ALPHA-FITNESS batteries. Results. Women have a higher overweight and obesity rate than men (3 : 1). Adolescents who have normal weight have regular physical fitness (74.9%). When comparing genders we found that men have a higher mean than women in the tests, except for skinfold thickness and waist circumference. Age was only correlated with the plate tapping test . There are significant differences in the standing broad jump test and the Course-Navette of the EUROFIT and ALPHA-FITNESS batteries . Conclusions. It is likely that regular physical activity, and not normal weight, helps generate healthy physical fitness. Male subjects had a higher mean than women, reporting a better physical fitness and more frequent physical activity.

http://ift.tt/2vBfUIB

Histologic and Histomorphometric Comparison between Sintered Nanohydroxyapatite and Anorganic Bovine Xenograft in Maxillary Sinus Grafting: A Split-Mouth Randomized Controlled Clinical Trial

The presence of vital bone after maxillary sinus augmentation is crucial to enhance the quality of bone-implant interface, ensuring predictable long-term results. The aims of this RCT with split-mouth design were the histologic and histomorphometric comparison of two different biomaterials in sinus elevation after 6 months of healing and the evaluation of the clinical outcomes of implants inserted in the augmented areas after 12 months of prosthetic loading. Twenty-eight patients (10 females, 18 males) were treated with bilateral sinus floor elevation with lateral approach. Pure sintered nanohydroxyapatite (NHA) and anorganic bovine bone (ABB) were used as test and active control, respectively. After six months, 52 bone biopsies were harvested from 26 patients, and 107 implants were inserted in the augmented areas. Histomorphometry showed that, in the two groups, vital bone percentages were % (NHA) and % (ABB) (), marrow spaces percentages were % (NHA) and % (ABB) (), and residual graft percentages were % (NHA) and % (ABB) (). After 6 months of healing, no statistically significant difference was present in histomorphometric outcomes between NHA and ABB groups. Implant survival rate in NHA group after 12 months of loading was 96.4%, showing no statistically significant differences with ABB group.

http://ift.tt/2vBy5xE

Vitamin D Receptor Gene Polymorphism: Association with Susceptibility to Early-Onset Breast Cancer in Iranian, BRCA1/2 -Mutation Carrier and non-carrier Patients

Abstract

Mounting evidences support that vitamin D insufficiency or deficiency is a risk factor of breast cancer. Vitamin D receptor (VDR) is expressed in more than 36 cell types in different organs as in cancerous cells. Numerous allelic variants of VDR gene have been identified in human populations. Association of FokI (rs2228570) and BsmI (rs1544410) single nucleotide polymorphisms (SNPs) in VDR gene with the risk of breast cancer have been investigated in several studies, however, the published data are still inconsistent. Here, we investigated BsmI and FokI polymorphisms in Iranian young (≤ 35 years old) breast cancer patient with known BRCA1/2 germline mutations. VDR gene polymorphisms were detected by restriction fragment length polymorphism (RFLP) analysis in a cohort of 203 breast cancer patients and 214 controls from Iran. There was a significant association between the bb and Bb genotypes of the BsmI and the increased risk of breast cancer (OR 1.74, CI 1.06–2.87 and OR 2.08, CI 1.31–3.29, respectively). This association was maintained in the subgroup of BRCA1/2 mutation non carriers (OR 1.90, CI 1.15–3.20 and OR 1.75, CI 1.07–2.87 for bb and Bb genotypes respectively) and in the subgroup of BRCA1/2 mutation non-carriers with a family history of breast and/or ovarian cancer (OR 1.81, CI 1.08–3.05 and OR 1.65, CI 1.00–2.70 for bb and Bb genotypes respectively). None of the FokI homozygous or heterozygous genotypes were associated with the risk of breast cancer. In summary, the BsmI polymorphism of VDR gene may be associated with the risk of breast cancer in Iranian women.

http://ift.tt/2whVpyx

All-Cause Hospital Admissions Among Older Adults After a Natural Disaster

We characterize hospital admissions among older adults for any cause in the 30 days after a significant natural disaster in the United States. The main outcome was all-cause hospital admissions in the 30 days after natural disaster. Separate analyses were conducted to examine all-cause hospital admissions excluding the 72 hours after the disaster, ICU admissions, all-cause inhospital mortality, and admissions by state.

http://ift.tt/2ueKMzd

Preliminary Performance on the New CMS Sepsis-1 National Quality Measure: Early Insights From the Emergency Quality Network (E-QUAL)

We describe current hospital-level performance for the Centers for Medicare & Medicaid Services' Severe Sepsis/Septic Shock Early Management Bundle (SEP-1) quality measure and qualitatively assess emergency department (ED) sepsis quality improvement best practice implementation.

http://ift.tt/2uvlLLj

Frontmatter

Journal Name: Biological Chemistry
Volume: 398
Issue: 9
Pages: i-iii

http://ift.tt/2v9IxKz

The role of sirtuins in mitochondrial function and doxorubicin-induced cardiac dysfunction

Journal Name: Biological Chemistry
Volume: 398
Issue: 9
Pages: 955-974

http://ift.tt/2vsNmBp

Structural and functional insight into pan-endopeptidase inhibition by α2-macroglobulins

Journal Name: Biological Chemistry
Volume: 398
Issue: 9
Pages: 975-994

http://ift.tt/2v9WBnq

Iron overload and altered iron metabolism in ovarian cancer

Journal Name: Biological Chemistry
Volume: 398
Issue: 9
Pages: 995-1007

http://ift.tt/2vsNkth

Shared function and moonlighting proteins in molybdenum cofactor biosynthesis

Journal Name: Biological Chemistry
Volume: 398
Issue: 9
Pages: 1009-1026

http://ift.tt/2v9UbFz

Molecular challenges imposed by MHC-I restricted long epitopes on T cell immunity

Journal Name: Biological Chemistry
Volume: 398
Issue: 9
Pages: 1027-1036

http://ift.tt/2vt0gPS

The monoheme cytochrome c subunit of Alternative Complex III is a direct electron donor to caa3 oxygen reductase in Rhodothermus marinus

Journal Name: Biological Chemistry
Volume: 398
Issue: 9
Pages: 1037-1044

http://ift.tt/2va8oC4

β-NGF and β-NGF receptor upregulation in blood and synovial fluid in osteoarthritis

Journal Name: Biological Chemistry
Volume: 398
Issue: 9
Pages: 1045-1054

http://ift.tt/2vt0V3Y

Idiopathic intracranial hypertension: ocular vestibular evoked myogenic potentials as a new evaluation tool

Patients with idiopathic intracranial hypertension (IIH) have an elevated intracranial pressure (ICP) in absence of any tumor or venous drain disorders. Diagnosis is based on the symptoms of elevated intracranial pressure (ICP) such as papillary edema, elevated cerebrospinal fluid (CSF) pressure in the spinal tap test of >25 cmH2O in absence of pathologic cellular or biochemical results in the spinal tap test, or structural or vascular abnormalities on cerebral MRI. For the clinical management and follow-up of patients with IIH, the possibility of non-invasively monitoring changes in ICP over time could potentially reduce the need for invasive diagnostic lumbar drainages (LD).

http://ift.tt/2uePlJJ

New Recommendations of the IFCN: from scalp EEG to electrical brain imaging

The importance of a standardized electrode placement (1) based on specific measurements of skull landmarks, (2) labeled according to a universal designation, and (3) offering adequate coverage of all parts of the head, was proposed by Dr. Jasper a few years after the first scalp EEG recordings and readily adopted by the Second International EEG Congress (Second International EEG congress, 1950). The 10-20 electrode system was born (Klem et al., 1999)! This electrode placement system was so clinically and physiologically relevant that it has been used without any significant change ever since.

http://ift.tt/2uvgNOI

A smoking-related background helps moderate smokers to focus: An Event-Related Potential study using a Go-NoGo Task

Smoking tobacco is known as being one of the most common health-damaging behaviors, which seems to persist, despite awareness of its negative consequences on health and intensive prevention and treatment efforts (Le Faou and Scemama, 2005). Indeed, tobacco seems to be the most addictive substance among addictive drugs (32% of users become dependent; Inserm, 2015) and a smoker dies, on average, 15 years earlier than a non-smoker (U.S. Department of Health and Human Services, 2010).

http://ift.tt/2ueIrEA

Clinical diagnostic value of simultaneous amplification and testing for the diagnosis of sputum-scarce pulmonary tuberculosis

Since 20% of pulmonary tuberculosis (PTB) patients are asymptomatic, the early detection of PTB is a challenge particularly in sputum-scarce patients and diagnostic accuracy based solely on clinical characteri...

http://ift.tt/2ueGNT7

Selenium Deficiency Augments the Levels of Inflammatory Factors and Heat Shock Proteins via the Redox Regulatory Pathway in the Skeletal Muscles of Mice

Abstract

Dietary selenium (Se) deficiency is known to cause myodynia syndrome and Se influences immune responses by changing the expression of inflammatory cytokines and heat shock proteins (Hsps), but the details are not completely elucidated. In the present study, 72 1-day-old mice were divided into two groups; the first group was fed a Se-sufficient diet, while the second group was fed a Se-deficient diet. Skeletal muscles and blood samples were taken from all mice after 42 days of treatment. The activities of glutathione peroxidase (GPX) and glutathione (GSH), mRNA and protein expression levels of inflammatory cytokines (including TNF-α, inducible NO synthase, cyclooxygenase-2, and prostaglandin E synthases), protein expression levels of NF-κB, and the mRNA expression levels of Hsps in the skeletal muscles of mice were examined. The results showed that GPX and GSH activities were decreased, while the mRNA and protein expression levels of inflammatory cytokines and the mRNA levels of Hsps were increased by Se deficiency in mouse skeletal muscles. In the present study, the protective role of Se in oxidative stress, inflammatory cytokines, and Hsps in the skeletal muscles of mice was summarized.

http://ift.tt/2v9urZT

Comparison of the RECIST and EORTC PET criteria in the tumor response assessment: a pooled analysis and review

Abstract

Purpose

The EORTC PET criteria (EORTC criteria) are used to assess metabolic tumor response in patients with solid tumors. We conducted this pooled study to compare tumor responses according to the RECIST and EORTC criteria.

Methods

Electronic databases were searched for eligible articles with the terms of "RECIST" or "EORTC criteria". We found seven articles with the data on the comparison of tumor responses by the RECIST and EORTC criteria.

Results

A total of 181 patients were recruited from the seven studies. Ninety-two patients (50.8%) received cytotoxic chemotherapy and 89 were treated with targeted agents. The agreement of tumor responses between the RECIST and EORTC criteria was moderate (k = 0.493). Of 181 patients, 66 (36.5%) showed disagreement in the tumor responses: tumor response was upgraded in 54 patients and downgraded in 12 when adopting the EORTC criteria. The estimated overall response rates were significantly different between the two criteria (52.5% by the EORTC vs. 29.8% by the RECIST, P < 0.0001). When comparing the two criteria according to the anti-cancer treatments (chemotherapy or targeted therapy), the levels of agreement in tumor responses were not excellent (k = 0.461 for chemotherapy and k = 0.524 for targeted therapy, respectively) regardless of therapeutic types.

Conclusion

This pooled study indicates that the concordance of tumor responses between the RECIST and EORTC criteria is not excellent. When adopting the EORTC criteria instead of the RECIST, the overall response rate was significantly increased.

http://ift.tt/2udP9KF

Signatures in the gut microbiota of Japanese infants who developed food allergies in early childhood

Abstract

Bacterial colonization in infancy is considered crucial for the development of the immune system. Recently, there has been a drastic increase in childhood allergies in Japan. Therefore, we conducted a prospective study with 56 infants on the relationship between gut microbiota in the first year of life and the development of allergies during the first 3 years. In the lactation period, organic acid producers such as Leuconostoc, Weissella, and Veillonella tended to be underrepresented in subjects who developed food allergies (FA, n = 14) within the first two years. In the weaning period, children in the FA group were highly colonized by unclassified Enterobacteriaceae and two Clostridium species closely related to Clostridium paraputrificum and Clostridium tertium, and the whole tree phylogenetic diversity (PD) index was significantly lower in the FA group. All of these differences in the weaning period were statistically significant, even after adjusting for potential confounding factors. A higher abundance of unclassified Enterobacteriaceae was also found in the other allergic group (n = 15), whereas the two Clostridium species were highly specific to the FA group. The mode of action of these Clostridium species in childhood food allergies remains unknown, warranting further investigation.

http://ift.tt/2vsozNS

Changes in fibre-adherent and fluid-associated microbial communities and fermentation profiles in the rumen of cattle fed diets differing in hay quality and concentrate amount

Abstract

The rumen microbiota enable important metabolic functions to the host cattle. Feeding of starch-rich concentrate feedstuffs to cattle has been demonstrated to increase the risk of metabolic disorders and to significantly alter the rumen microbiome. Thus, alternative feeding strategies like the use of high-quality hay, rich in sugars, as an alternative energy source need to be explored. The aim of this study was to investigate changes in rumen microbial abundances in the liquid and solid-associated fraction of cattle fed two hay qualities differing in sugar content with graded amounts of starchy concentrate feeds using Illumina MiSeq sequencing and quantitative polymerase chain reaction (qPCR). Operational taxonomic units (OTU) clustered separately between the liquid and the solid-associated fraction. Phyla in the liquid fraction were identified as mainly Firmicutes, Proteobacteria and Bacteroidetes, whereas main phyla of the fibre-associated fraction were Bacteroidetes, Fibrobacteres and Firmicutes. Significant alterations in the rumen bacterial communities at all taxonomic levels as a result of changing the hay quality and concentrate proportions were observed. Several inter-microbial correlations were found. Genera Ruminobacter and Fibrobacter were significantly suppressed by feeding sugar-rich hay, whereas others like Selenomonas and Prevotella proliferated. This study extends the knowledge about diet-induced changes in ruminal microbiome of cattle.

http://ift.tt/2v9rvwt

The Use of Trace Eyeblink Classical Conditioning to Assess Hippocampal Dysfunction in a Rat Model of Fetal Alcohol Spectrum Disorders

Trace eyeblink classical conditioning (ECC) was used to assess hippocampal-dependent associative learning in adult rats that were administered a high concentration (11.9% v/v) of alcohol during early neonatal brain development. In general, ECC procedures are sound diagnostic tools for detecting brain dysfunction across many psychological and biomedical settings.

http://ift.tt/2vsh0qi

First description of a new uncultured epsilon sulfur bacterium colonizing marine mangrove sediment in the Caribbean: Thiovulum sp. strain karukerense

Abstract

Here, the first description of an epsilon sulfur-oxidizing bacterium from sulfide-rich sediments of marine mangrove in Caribbean is reported. According to TEM, this new strain contains intracytoplasmic large internal sulfur granules as confirmed by EDXS analyses performed using ESEM. The sulfur distribution obtained for this sulfur-oxidizing bacterial strain allows to conclude that elemental sulfur is formed as an intermediate oxidation product and stored intracellularly. According to conventional SEM observations, bacterial cells are ovoid, extremely motile by lophotrichous flagella. Phylogenetic analyses based on the analysis of partial sequence of 16S rDNA confirm that such bacterial strain belongs to the Thiovulum cluster and could be a representative of a new species in this poorly studied genus of sulfur-oxidizing free-living bacteria. Thus, reduced sediment of marine mangrove represents sulfide-rich environment sustaining development of both gamma and epsilon sulfur-oxidizing Proteobacteria.

http://ift.tt/2uus9T9

Doxycycline enhances adsorption and inhibits early-stage replication of porcine reproductive and respiratory syndrome virus in vitro

Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV) has an important impact on the pig industry. Doxycycline (Dox) is a second-generation tetracycline widely used for treating bacterial infections. We evaluated the antiviral effect of Dox against PRRSV infection in Marc-145 cells that was susceptible to PRRSV infection. Dox significantly reduced the PRRSV-induced cytopathic effect and effectively restrained PRRSV replication in a dose-dependent manner. The 50% effective concentration of Dox was approximately 0.25 ± 0.05 μg/ml. We also determined the stage at which Dox influenced PRRSV replication, and showed that Dox enhanced PRRSV adsorption and inhibited the early stage of PRRSV replication after viral entry into host cells. These observations demonstrate that Dox is able to restrain PRRSV infection in cultured cells.

http://ift.tt/2udJqF1

Role of host cell integrins in the microsporidium Encephalitozoon intestinalis adherence and infection in vitro

Abstract

Microsporidia are obligate intracellular, spore-forming, fungal-related pathogens that employ a unique organelle, the polar tube, to transfer infectious spore contents into host cells to initiate infection. Spore adherence to host cells may provide the proximity required for polar tube/host cell interaction during in vivo infection. In previous in vitro studies, host sulfated glycosaminoglycans (GAGs) or recombinant microsporidia endospore protein (EnP1) were implicated in the pathogen adherence and infection process; however, complete ablation of spore adherence and infection could not be achieved, suggesting that additional or alternative spore and host cell determinants of adherence and infection may exist. Analysis of the E. intestinalis genome revealed about 100 predicted proteins containing the canonical integrin-binding motif Arginine-Glycine-Aspartic Acid (RGD). And, many pathogens have been shown to engage integrin molecules on cell surfaces. We hypothesized that host cell integrins play a role in microsporidia adherence and infection. In this study, we demonstrated that addition of exogenous integrin ligands or recombinant Alpha 3 Beta 1 integrin or Alpha 5 Beta1 integrin to assays of E. intestinalis adherence and infection significantly reduced spore adherence and infection of host cells, supporting our hypothesis and implicating these specific integrins as putative host cell receptors for E. intestinalis spores.

http://ift.tt/2uu7zlM

First report of sasX -positive methicillin-resistant Staphylococcus aureus in Japan

Abstract

SasX is a known virulence factor of Staphylococcus aureus involved in colonisation and immune evasion of the bacterium. The sasX gene, which is located on the ϕSPβ prophage, is frequently found in the sequence type (ST) 239 S. aureus lineage, which is the predominant healthcare-associated clone in Asian countries. In Japan, ST239 clones have rarely been identified, and sasX-positive strains have not been reported to date. Here, we report the first identification of 18 sasX-positive methicillin-resistant S. aureus (MRSA) strains in Japanese hospitals between 2009 and 2011. All sasX-positive isolates belonged to a ST239-staphylococcal cassette chromosome mec type III (ST239-III) lineage. However, we were unable to identify additional sasX-positive MRSA strains from 2012 to 2016, indicating that the small epidemic of sasX-positive isolates observed in this study was temporary. The sequence surrounding sasX in the strain TOHH628 lacked 51 genes that encode phage packaging and structural proteins, and no bacteriophage was induced by mitomycin C. Additionally, in the TOHH628 strain, the region (64.6 kb) containing sasX showed high identity to the ϕSPβ-like element (71.3 kb) of the Taiwanese MRSA strain Z172. The data strongly suggest that the present sasX-positive isolates found in Japanese hospitals were transmitted incidentally from other countries.

http://ift.tt/2udKybn

Unlicensed and off-label uses of medicines: definitions and clarification of terminology

Abstract

The terms "licensed", "unlicensed", and "off-label", often used in relation to marketing and prescribing medicinal products, may confuse UK prescribers.

To markset a medicinal product in the UK requires a Marketing Authorisation ("product licence") for specified indications under specified conditions, regulated by the Medicines and Healthcare products Regulatory Agency (MHRA). The Marketing Authorisation includes the product's agreed terms of use (the "label"), described in the Summary of Product Characteristics (SmPC). Prescribing a licensed product outside those terms is called "off-label" prescribing. Products for which no-one holds a UK Marketing Authorisation are unlicensed.

Prescribers can prescribe authorised products according to the conditions described in the SmPC ("on-label") or outside those conditions ("off-label"). They can also prescribe unauthorised products, unlicensed in the UK, if they are licensed elsewhere or if they have been manufactured in the UK by a licensed manufacturer as a "special".

The complexities of this system can be understood by considering the status of the manufacturer of the product, the company that markets it (which may or may not be the same), the product itself, and its modes of use, and by emphasizing the word "authorised".

If a Marketing Authorisation is granted to the supplier of a product, it will specify the authorised modes of use; the product will be prescribable as authorised (i.e. "on-label") or in other modes of use, which will all be off-label. Unlicensed products with no authorised modes of use can be regarded as "unauthorised products". All "specials" can be regarded as authorised products lacking authorised modes of use.

http://ift.tt/2ubG4hD

EM Nerd-An Addendum to the Case of the Tarnished Standard

In a previous post we discussed the use of IVC variation and the concept of fluid responsiveness. Despite a strong physiological basis, no studies examining the use of fluid responsiveness to guide resuscitative efforts in patients with septic shock have been shown to improve patient important outcomes. Shortly after this post was released, Critical Care […]

EMCrit by Rory Spiegel.

http://ift.tt/2v7eg0K

Oncostatin M causes liver fibrosis by regulating cooperation between hepatic stellate cells and macrophages in mice

Abstract

Fibrosis is an important wound-healing process in injured tissues, but excessive fibrosis is often observed in patients with chronic inflammation. While Oncostatin M (OSM) has been reported to play crucial roles for the recovery from acute liver injury by inducing tissue inhibitor of metalloproteinase 1 (Timp1) expression, the role of OSM in chronic liver injury is yet to be elucidated. Here we show that OSM exerts powerful fibrogenic activity by regulating macrophage activation during chronic liver injury. Genetic ablation of the OSM gene alleviated fibrosis in a mouse model of chronic hepatitis. Conversely, continuous expression of OSM in a normal mouse liver by hydrodynamic tail vein injection (HTVi) induced severe fibrosis without necrotic damage of hepatocytes, indicating that OSM is involved in the fundamental process of liver fibrosis after hepatitis. In a primary co-culture of hepatic stellate cells (HSCs) and hepatic macrophages (HMs), OSM up-regulated the expression of fibrogenic factors such as TGF-ß and PDGF in HMs, while inducing Timp1 expression in HSCs, suggesting the synergistic roles of OSM for collagen deposition in the liver. FACS analyses using OSM-HTVi and OSM KO mice have revealed that bone marrow derived monocyte/macrophage are responsive to OSM for pro-fibrotic activation. Furthermore, depletion or blocking of HMs by administration of clodronate liposome or chemokine inhibitor prevented OSM-induced fibrosis. Conclusion: OSM plays a crucial role in liver fibrosis by coordinating the phenotypic change of HMs and HSCs. Our data suggest that OSM is a promising therapeutic target for liver fibrosis. This article is protected by copyright. All rights reserved.

http://ift.tt/2hxn37y

Brexanolone as Adjunctive Therapy in Super-Refractory Status Epilepticus

ABSTRACT

Objective: Super-refractory status epilepticus (SRSE) is a life-threatening form of status epilepticus that continues or recurs despite 24 hours or more of anesthetic treatment. We conducted a multi-center, phase 1/2 study in SRSE patients to evaluate the safety and tolerability of brexanolone (USAN; formerly SAGE-547 Injection), a proprietary, aqueous formulation of the neuroactive steroid allopregnanolone. Secondary objectives included pharmacokinetic assessment and open-label evaluation of brexanolone response during and after anesthetic third-line agent (TLA) weaning.

Methods: Patients receiving TLAs for SRSE control were eligible for open-label, one-hour brexanolone loading infusions, followed by maintenance infusion. After 48 hours of brexanolone infusion, TLAs were weaned during brexanolone maintenance. After four days, the brexanolone dose was tapered. Safety and functional status were assessed over 3-weeks of follow-up.

Results: Twenty-five patients received open-label study drug. No serious adverse events (SAEs) were attributable to study drug, as determined by the Safety Review Committee. Sixteen patients (64%) experienced ≥1 SAE. Six patient deaths occurred, all deemed related to underlying medical conditions. Twenty-two patients underwent ≥1 TLA wean attempt. Seventeen (77%) met the response endpoint of weaning successfully off TLAs before tapering brexanolone. Sixteen (73%) were successfully weaned off TLAs within five days of initiating brexanolone infusion without anesthetic agent reinstatement in the following 24-hours.

Interpretation: In an open-label cohort of limited size, brexanolone demonstrated tolerability among SRSE patients of heterogeneous etiologies and was associated with a high rate of successful TLA weaning. The results suggest the possible development of brexanolone as an adjunctive therapy for SRSE requiring pharmacologic coma for seizure control. This article is protected by copyright. All rights reserved.

http://ift.tt/2v72vaJ

Very high frequency oscillations: Novel biomarkers of the epileptogenic zone

Abstract

Objective: In the present study, we aimed to investigate depth EEG recordings in a large cohort of patients with drug resistant epilepsy and to focus on interictal very high frequency oscillations (VHFOs) between 500 Hz and 2 kHz. We hypothesized that interictal VHFOs are more specific biomarkers for epileptogenic zone compared to traditional HFOs.

Methods: Forty patients with focal epilepsy who underwent presurgical stereo-electroencephalography (SEEG) were included in the study. SEEG data have been recorded with sampling rate of 25 kHz and 30 minutes of resting period was analyzed for each patient. Ten patients met selected criteria for analyses of correlations with surgical outcome - detection of interictal ripples (R), fast ripples (FR) and VHFOs, resective surgery, and at least one-year post-operative follow-up. Using power envelope computation and visual inspection of power distribution matrixes, electrode contacts with HFOs and VHFOs were detected and analyzed.

Results: Interictal very fast ripples (VFR; 500-1000 Hz) were detected in 23 out of 40 patients and ultra fast ripples (UFR; 1000-2000 Hz) in almost half of investigated subjects (N=19). VFR and UFR were observed only in patients with temporal lobe epilepsy and were recorded exclusively from mesiotemporal structures. The UFR were more spatially restricted in the brain then lower frequency HFOs. When compared to R oscillations, significantly better outcomes were observed in patients with higher percentage of removed contacts containing FR, VFR, and UFR.

Interpretation:

Interictal VHFOs are relatively frequent abnormal phenomena in patients with epilepsy, and appear to be more specific biomarkers for epileptogenic zone when compared to traditional HFOs. This article is protected by copyright. All rights reserved.

http://ift.tt/2whdxbV

Body weight is a robust predictor of clinical progression in Huntington disease

Abstract

Unintended weight loss is a hallmark of Huntington disease (HD), but it is unknown to what extent weight loss impacts the rate of disease progression. Therefore, using longitudinal data from the Enroll-HD study, we assessed the association between baseline body mass index (BMI) and the rate of clinical progression in 5821 HD mutation carriers. We found that high baseline BMI was associated with a significantly slower rate of functional, motor and cognitive deterioration (all p < 0.001), independent of mutant HTT CAG repeat size. Our findings provide strong rationale for exploration of systemic metabolism as a therapeutic target in HD. This article is protected by copyright. All rights reserved.

http://ift.tt/2v7gCg3

The clonal evolution of two distinct T315I-positive BCR-ABL1 subclones in a Philadelphia-positive acute lymphoblastic leukemia failing multiple lines of therapy: a case report

Abstract

Background

The treatment of Philadelphia chromosome-positive Acute Lymphoblastic Leukemia (Ph+ ALL) patients who harbor the T315I BCR-ABL1 mutation or who have two or more mutations in the same BCR-ABL1 molecule is particularly challenging since first and second-generation Tyrosine Kinase Inhibitors (TKIs) are ineffective. Ponatinib, blinatumomab, chemotherapy and transplant are the currently available options in these cases.

Case presentation

We here report the case of a young Ph+ ALL patient who relapsed on front-line dasatinib therapy because of two independent T315I-positive subclones, resulting from different nucleotide substitutions -one of whom never reported previously- and where additional mutant clones outgrew and persisted despite ponatinib, transplant, blinatumomab and conventional chemotherapy. Deep Sequencing (DS) was used to dissect the complexity of BCR-ABL1 kinase domain (KD) mutation status and follow the kinetics of different mutant clones across the sequential therapeutic approaches.

Conclusions

This case presents several peculiar and remarkable aspects: i) distinct clones may acquire the same amino acid substitution via different nucleotide changes; ii) the T315I mutation may arise also from an 'act' to 'atc' codon change; iii) the strategy of temporarily replacing TKI therapy with chemo or immunotherapy, in order to remove the selective pressure and deselect aggressive mutant clones, cannot always be expected to be effective; iv) BCR-ABL1-mutated sub-clones may persist at very low levels (undetectable even by Deep Sequencing) for long time and then outcompete BCR-ABL1-unmutated ones becoming dominant even in the absence of any TKI selective pressure.

http://ift.tt/2vC7gub

Development of Novel Faster-Dissolving Microneedle Patches for Transcutaneous Vaccine Delivery.

Related Articles

Development of Novel Faster-Dissolving Microneedle Patches for Transcutaneous Vaccine Delivery.

Pharmaceutics. 2017 Aug 03;9(3):

Authors: Ono A, Ito S, Sakagami S, Asada H, Saito M, Quan YS, Kamiyama F, Hirobe S, Okada N

Abstract
Microneedle (MN) patches are promising for transcutaneous vaccination because they enable vaccine antigens to physically penetrate the stratum corneum via low-invasive skin puncturing, and to be effectively delivered to antigen-presenting cells in the skin. In second-generation MN patches, the dissolving MNs release the loaded vaccine antigen into the skin. To shorten skin application time for clinical practice, this study aims to develop novel faster-dissolving MNs. We designed two types of MNs made from a single thickening agent, carboxymethylcellulose (CMC) or hyaluronan (HN). Both CMC-MN and HN-MN completely dissolved in rat skin after a 5-min application. In pre-clinical studies, both MNs could demonstrably increase antigen-specific IgG levels after vaccination and prolong antigen deposition compared with conventional injections, and deliver antigens into resected human dermal tissue. In clinical research, we demonstrated that both MNs could reliably and safely puncture human skin without any significant skin irritation from transepidermal water loss measurements and ICDRG (International Contact Dermatitis Research Group) evaluation results.

PMID: 28771172 [PubMed]

http://ift.tt/2v8mUul

Oral vaccination of fish: Lessons from humans and veterinary species.

Related Articles

Oral vaccination of fish: Lessons from humans and veterinary species.

Dev Comp Immunol. 2016 Nov;64:118-37

Authors: Embregts CW, Forlenza M

Abstract
The limited number of oral vaccines currently approved for use in humans and veterinary species clearly illustrates that development of efficacious and safe oral vaccines has been a challenge not only for fish immunologists. The insufficient efficacy of oral vaccines is partly due to antigen breakdown in the harsh gastric environment, but also to the high tolerogenic gut environment and to inadequate vaccine design. In this review we discuss current approaches used to develop oral vaccines for mass vaccination of farmed fish species. Furthermore, using various examples from the human and veterinary vaccine development, we propose additional approaches to fish vaccine design also considering recent advances in fish mucosal immunology and novel molecular tools. Finally, we discuss the pros and cons of using the zebrafish as a pre-screening animal model to potentially speed up vaccine design and testing for aquaculture fish species.

PMID: 27018298 [PubMed - indexed for MEDLINE]

http://ift.tt/2v8KIhu

Treatment with antioxidants ameliorates oxidative damage in a mouse model of propionic acidemia.

Related Articles

Treatment with antioxidants ameliorates oxidative damage in a mouse model of propionic acidemia.

Mol Genet Metab. 2017 Jul 25;:

Authors: Rivera-Barahona A, Alonso-Barroso E, Pérez B, Murphy MP, Richard E, Desviat LR

Abstract
Oxidative stress contributes to the pathogenesis of propionic acidemia (PA), a life threatening disease caused by the deficiency of propionyl CoA-carboxylase, in the catabolic pathway of branched-chain amino acids, odd-number chain fatty acids and cholesterol. Patients develop multisystemic complications including seizures, extrapyramidal symptoms, basal ganglia deterioration, pancreatitis and cardiomyopathy. The accumulation of toxic metabolites results in mitochondrial dysfunction, increased reactive oxygen species and oxidative damage, all of which have been documented in patients' samples and in a hypomorphic mouse model. Here we set out to investigate whether treatment with a mitochondria-targeted antioxidant, MitoQ, or with the natural polyphenol resveratrol, which is reported to have antioxidant and mitochondrial activation properties, could ameliorate the altered redox status and its functional consequences in the PA mouse model. The results show that oral treatment with MitoQ or resveratrol decreases lipid peroxidation and the expression levels of DNA repair enzyme OGG1 in PA mouse liver, as well as inducing tissue-specific changes in the expression of antioxidant enzymes. Notably, treatment decreased the cardiac hypertrophy marker BNP that is found upregulated in the PA mouse heart. Overall, the results provide in vivo evidence to justify more in depth investigations of antioxidants as adjuvant therapy in PA.

PMID: 28774709 [PubMed - as supplied by publisher]

http://ift.tt/2vrU9ev

Cross-reactive influenza-specific antibody-dependent cellular cytotoxicity-mediating antibodies in HIV-infected Indian individuals

.


http://ift.tt/2vBQZWc

Pneumonia in mechanically ventilated patients: no diagnostic and prognostic value of different quantitative tracheal aspirates thresholds

.


http://ift.tt/2wumqy8

Trends in cervical cancer incidence and mortality in Poland: is there an impact of the introduction of the organised screening?

Abstract

Aside from existing opportunistic screening, an organised screening programme (OSP) for cervical cancer (CC) was implemented in 2006/2007 in Poland. We applied joinpoint regression and age-period-cohort model to look for the impact of the OSP on CC incidence/mortality trends. Decline of age-standardised incidence rates (ASIRs) in the screening-age group (25–59 years) accelerated from −2.2% (95% CI −2.7 to −1.7%) between 1993 and 2008 to −6.1% (95% CI −7.7 to −4.4%) annually after 2008. In women aged 60+ years, ASIRs declined from 1986 until 2005 [annual percent change (APC) = −2.6%, 95% CI −2.9 to −2.4%] and stabilised thereafter. Decline of age-standardised mortality rates (ASMRs) in the screening-age group accelerated from −1.3% (95% CI −1.5 to −1.1%) between 1980 and 2005 to −4.7% (95% CI −5.6 to −3.8%) annually after 2005. In women aged 60+ ASMR declined between 1991 and 2004 (APC = −2.9%, 95% CI −3.5 to −2.3%) and stabilised thereafter. Relative risks of CC diagnosis and death were 0.63 (95% CI 0.62–0.65) and 0.61 (95% CI 0.59–0.63), respectively, for the most recent period compared to the reference around 1982. Implementation of the OSP possibly accelerated downward trends in the burden of CC in Polish women under the age of 60, but recent stabilisation of trends in older women requires actions.

http://ift.tt/2v5RIxd

Defective splicing of the RB1 transcript is the dominant cause of retinoblastomas

Abstract

Defective splicing is a common cause of genetic diseases. On average, 13.4% of all hereditary disease alleles are classified as splicing mutations with most mapping to the critical GT or AG nucleotides within the 5′ and 3′ splice sites. However, splicing mutations are underreported and the fraction of splicing mutations that compose all disease alleles varies greatly across disease gene. For example, there is a great excess (46%; ~threefold) of hereditary disease alleles that map to splice sites in RB1 that cause retinoblastoma. Furthermore, mutations in the exons and deeper intronic position may also affect splicing. We recently developed a high-throughput method that assays reported disease mutations for their ability to disrupt pre-mRNA splicing. Surprisingly, 27% of RB1-coding mutations tested also disrupt splicing. High-throughput in vitro spliceosomal assembly assay reveals heterogeneity in which stage of spliceosomal assembly is affected by splicing mutations. 58% of exonic splicing mutations were primarily blocked at the A complex in transition to the B complex and 33% were blocked at the B complex. Several mutants appear to reduce more than one step in the assembly. As RB1 splicing mutants are enriched in retinoblastoma disease alleles, additional priority should be allocated to this class of allele while interpreting clinical sequencing experiments. Analysis of the spectrum of RB1 variants observed in 60,706 exomes identifies 197 variants that have enough potential to disrupt splicing to warrant further consideration.

http://ift.tt/2vzeU7S

Investigating the genetic relationship between Alzheimer’s disease and cancer using GWAS summary statistics

Abstract

Growing evidence from both epidemiology and basic science suggest an inverse association between Alzheimer's disease (AD) and cancer. We examined the genetic relationship between AD and various cancer types using GWAS summary statistics from the IGAP and GAME-ON consortia. Sample size ranged from 9931 to 54,162; SNPs were imputed to the 1000 Genomes European panel. Our results based on cross-trait LD Score regression showed a significant positive genetic correlation between AD and five cancers combined (colon, breast, prostate, ovarian, lung; r _g = 0.17, P = 0.04), and specifically with breast cancer (ER-negative and overall; r _g = 0.21 and 0.18, P = 0.035 and 0.034) and lung cancer (adenocarcinoma, squamous cell carcinoma and overall; r _g = 0.31, 0.38 and 0.30, P = 0.029, 0.016, and 0.006). Estimating the genetic correlation in specific functional categories revealed mixed positive and negative signals, notably stronger at annotations associated with increased enhancer activity. This suggests a role of gene expression regulators in the shared genetic etiology between AD and cancer, and that some shared variants modulate disease risk concordantly while others have effects in opposite directions. Due to power issues, we did not detect cross-phenotype associations at individual SNPs. This genetic overlap is not likely driven by a handful of major loci. Our study is the first to examine the co-heritability of AD and cancer leveraging large-scale GWAS results. The functional categories highlighted in this study need further investigation to illustrate the details of the genetic sharing and to bridge between different levels of associations.

http://ift.tt/2uaGuou

Targeting Immune System Alterations in Hodgkin Lymphoma

Abstract

Purpose of Review

This review discusses novel immunotherapeutic approaches to treat Hodgkin lymphoma (HL), specifically PD-1 inhibitors and cellular immunotherapy.

Recent Findings

PD-1 inhibitors have shown promising results in the treatment of relapsed or refractory HL, leading to FDA approval of nivolumab and pembrolizumab, although complete remissions are rare. Chimeric antigen receptor T cells directed against CD30 have been investigated with preliminary clinical trials showing minimal toxicities and some responses in heavily pre-treated patients with HL.

Summary

HL is unique as it consists of a small percentage of malignant cells (Hodgkin Reed Sternberg cells) surrounded by an inflammatory microenvironment which promotes tumor growth and suppresses immune responses, making it an ideal target for immunotherapeutic approaches, such as PD-1 inhibitors and cellular immunotherapy. Current research is focused on overcoming barriers to efficacy via rational combinations that overcome resistance to therapy.

http://ift.tt/2vzuZKJ

A review of oral cannabinoids and medical marijuana for the treatment of chemotherapy-induced nausea and vomiting: a focus on pharmacokinetic variability and pharmacodynamics

Abstract

Purpose

Oral cannabinoids (i.e., dronabinol, nabilone) containing the active component of marijuana, delta(Δ)9-tetrahydrocannabinol (THC), are available for the treatment of chemotherapy-induced nausea and vomiting (CINV) in patients with cancer who have failed to adequately respond to conventional antiemetic therapy. The aim of this article is to provide an overview of the efficacy, pharmacokinetics (PK), pharmacodynamics (PD), and safety of oral cannabinoids for patients with CINV.

Methods

A PubMed search of the English-language literature available through 4 January 2017 was conducted to identify relevant articles for inclusion in the review.

Results

Oral cannabinoids have been shown to have similar or improved efficacy compared with conventional antiemetics for the resolution of nausea and/or vomiting in patients with cancer. However, oral THC has high PK variability, with variability in oral dronabinol peak plasma concentrations (C _max) estimated between 150 and 200%. A new oral dronabinol solution has decreased intraindividual variability (area under the curve) vs oral dronabinol capsules. Further, oral THC has a slower time to C _max compared with THC administered intravenously (IV) or by smoking, and a lower systemic availability than IV or smoked THC. The PD profile (e.g., "high") of oral THC differs from that of IV or smoked THC in healthy individuals. Oral cannabinoids are associated with greater incidence of adverse effects compared with conventional antiemetic therapy or placebo (e.g., dizziness, hypotension, and dysphoria or depression).

Conclusions

A new formulation of oral cannabinoids (i.e., dronabinol oral solution) minimized the PK/PD variability currently observed with capsule formulations.

http://ift.tt/2hvO3UK

Clinical Value of Mammography in the Evaluation of Palpable Breast Lumps in Women 30 Years Old and Older

American Journal of Roentgenology, Ahead of Print.


http://ift.tt/2v6kAWp

Frondlike Synovitis on MRI and Correlation With Polyethylene Surface Damage of Total Knee Arthroplasty

American Journal of Roentgenology, Ahead of Print.


http://ift.tt/2wgooTz

Combined Hepatocellular Cholang iocarcinoma (Biphenotypic) Tumors: Potential Role of Contrast-Enhanced Ultrasound in Diagnosis

American Journal of Roentgenology, Ahead of Print.


http://ift.tt/2v6L61P

Semiquantitative Assessment of 18F-FDG Uptake in the Normal Skeleton: Comparison Between PET/CT and Time-of-Flight Simultaneous PET/MRI

American Journal of Roentgenology, Ahead of Print.


http://ift.tt/2wgNl14

Safety-Net Academic Hospital Experience in Following Up Noncritical Yet Potentially Significant Radiologist Recommendations

American Journal of Roentgenology, Ahead of Print.


http://ift.tt/2v6aDrT

Trainees May Add Value to Patient Care by Decreasing Addendum Utilization in Radiology Reports

American Journal of Roentgenology, Ahead of Print.


http://ift.tt/2wgGnJu

Changing Musculoskeletal Extremity Imaging Utilization From 1994 Through 2013: A Medicare Beneficiary Perspective

American Journal of Roentgenology, Ahead of Print.


http://ift.tt/2v6aBjL

Ablation of Musculoskeletal Metastases

American Journal of Roentgenology, Ahead of Print.


http://ift.tt/2wgsdrD

Utility of CT Findings in the Diagnosis of Cecal Volvulus

American Journal of Roentgenology, Ahead of Print.


http://ift.tt/2v6Dmgo

The European society of regional anesthesia and pain therapy and the American society of regional anesthesia and pain medicine joint committee practice advisory on controversial topics in pediatric regional anesthesia I and II: what do they tell us?.

Purpose of review: To summarize the two recent sets of European and American Societies of Regional Anesthesia (ESRA-ASRA) Practice Advisory Guidelines for the performance of pediatric regional anesthesia (PRA). Recent findings: Owing to the still ongoing debate regarding crucial issues concerning the effective and safe conduct of PRA and because of the lack of any generally accepted guidelines regarding PRA the (ESRA-ASRA) have addressed these in two topical publications. Summary: Following an extensive literature search and an evidence-based approach the ESRA-ASRA task force have now provided a practice advisory on the following hot topics in PRA: the safety and appropriateness of placing block during general anesthesia or deep sedation, the use of test dosing, whether to use air or saline when performing loss-of-resistance, the risk of masking an acute compartment syndrome by use of PRA, dosing of local anesthetics for neuroaxial nerve blocks as well as peripheral nerve blocks, and finally the use of various drugs as adjuncts to local anesthetics. Copyright (C) 2017 YEAR Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2hvRjzE

Current Status of Gender and Racial/ Ethnic Disparities Among Academic Emergency Medicine Physicians

Abstract

Objective

A 2010 survey identified disparities in salaries by gender and underrepresented minorities (URM). With an increase in the EM workforce since, we aimed to 1) Describe the current status of academic EM workforce by gender, race and rank, and 2) Evaluate if disparities still exist in salary or rank by gender.

Methods

Information on demographics, rank, clinical commitment, and base and total annual salary for full-time faculty members in U.S. academic EDs were collected in 2015 via the Academy of Administrators in Academic Emergency Medicine (AAAEM) Salary Survey. Multiple linear regression was used to compare salary by gender while controlling for confounders.

Results

Response rate was 47% (47/101), yielding data on 1371 full-time faculty; 33% women, 78% white, 4% black, 5% Asian, 3% Asian Indian, 4% other, and 7% unknown race. Comparing white race to nonwhite, 62% vs. 69% were instructor/assistant, 23% vs. 20% were associate, and 15% vs. 10% were full professors. Comparing women to men, 74% vs. 59% were instructor/assistant, 19% vs. 24% were associate, and 7% vs. 17% were full professors. Of 113 Chair/Vice-Chair positions, only 15% were women, and 18% were nonwhite. Women were more often fellowship trained (37% vs. 31%), less often core-faculty (59% vs. 64%), with fewer administrative roles (47% vs. 57%) (all p<0.05) but worked similar clinical hours (mean 1069 vs. 1051 hours). Mean overall salary was $278,631 (SD ± 68,003). The salary of women was $19,418 (SD ± 3,736) less than men (p < 0.001), even after adjusting for race, region, rank, years of experience, clinical hours, core faculty status, administrative roles, board certification, and fellowship training.

Conclusions

In 2015, disparities in salary and rank persist among full-time U.S. academic EM faculty. There were gender and URM disparities in rank and leadership positions. Women earned less than men regardless of rank, clinical hours, or training. Future efforts should focus on evaluating salary data by race and developing system-wide practices to eliminate disparities.

This article is protected by copyright. All rights reserved.

http://ift.tt/2fh9IQ5

A knock-in/knock-out mouse model of HSPB8-associated distal hereditary motor neuropathy and myopathy reveals toxic gain-of-function of mutant Hspb8

Abstract

Mutations in the small heat shock protein B8 gene (HSPB8/HSP22) have been associated with distal hereditary motor neuropathy, Charcot–Marie–Tooth disease, and recently distal myopathy. It is so far not clear how mutant HSPB8 induces the neuronal and muscular phenotypes and if a common pathogenesis lies behind these diseases. Growing evidence points towards a role of HSPB8 in chaperone-associated autophagy, which has been shown to be a determinant for the clearance of poly-glutamine aggregates in neurodegenerative diseases but also for the maintenance of skeletal muscle myofibrils. To test this hypothesis and better dissect the pathomechanism of mutant HSPB8, we generated a new transgenic mouse model leading to the expression of the mutant protein (knock-in lines) or the loss-of-function (functional knock-out lines) of the endogenous protein Hspb8. While the homozygous knock-in mice developed motor deficits associated with degeneration of peripheral nerves and severe muscle atrophy corroborating patient data, homozygous knock-out mice had locomotor performances equivalent to those of wild-type animals. The distal skeletal muscles of the post-symptomatic homozygous knock-in displayed Z-disk disorganisation, granulofilamentous material accumulation along with Hspb8, αB-crystallin (HSPB5/CRYAB), and desmin aggregates. The presence of the aggregates correlated with reduced markers of effective autophagy. The sciatic nerve of the homozygous knock-in mice was characterized by low autophagy potential in pre-symptomatic and Hspb8 aggregates in post-symptomatic animals. On the other hand, the sciatic nerve of the homozygous knock-out mice presented a normal morphology and their distal muscle displayed accumulation of abnormal mitochondria but intact myofiber and Z-line organisation. Our data, therefore, suggest that toxic gain-of-function of mutant Hspb8 aggregates is a major contributor to the peripheral neuropathy and the myopathy. In addition, mutant Hspb8 induces impairments in autophagy that may aggravate the phenotype.

http://ift.tt/2v6gduf

Reducing Circumduction and Hip Hiking During Hemiparetic Walking Through Targeted Assistance of the Paretic Limb Using a Soft Robotic Exosuit.

Objective: The aim of the study was to evaluate the effects on common poststroke gait compensations of a soft wearable robot (exosuit) designed to assist the paretic limb during hemiparetic walking. Design: A single-session study of eight individuals in the chronic phase of stroke recovery was conducted. Two testing conditions were compared: walking with the exosuit powered versus walking with the exosuit unpowered. Each condition was 8 minutes in duration. Results: Compared with walking with the exosuit unpowered, walking with the exosuit powered resulted in reductions in hip hiking (27 [6%], P = 0.004) and circumduction (20 [5%], P = 0.004). A relationship between changes in knee flexion and changes in hip hiking was observed (Pearson r = -0.913, P

http://ift.tt/2utiyvU

Lower Selenoprotein T Expression and Immune Response in the Immune Organs of Broilers with Exudative Diathesis Due to Selenium Deficiency

Abstract

The objective of the present study was to investigate whether dietary selenium (Se) deficiency would affect the expression of selenoprotein T (SelT) and immune response in the immune organs of broilers. Changes in expression of inflammatory cytokines and oxidative stress response caused by Se deficiency can lead to organism damage, which in turn leads to immune response. Sixty (1-day-old) broilers were divided into the control group and Se-deficiency group. Animal models with exudative diathesis were duplicated in the broilers by feeding them Se-deficient diet for 20 days. After the Se-deficient group exhibited symptoms of exudative diathesis, all the broilers were euthanized, and their immune organs were taken for analysis. The tissues including spleen, bursa of Fabricius, and thymus were treated to determine the pathological changes (including microscopic and ultramicroscopic), the messenger RNA (mRNA) expression levels of SelT and its synthetase (SecS and SPS1), cytokine mRNA expression levels, and antioxidant status. The microscopic and ultramicroscopic analyses showed that immune tissues were obviously injured in the Se-deficient group. The mRNA expression of SelT was decreased compared with that in the control group. Meanwhile, the mRNA expression levels of SecS and SPS1 were downregulated. In the Se-deficient group, the mRNA expression levels of IL-1R and IL-1β were higher than those of three control organs. Additionally, the IL-2 and INF-γ mRNA expression levels were lower than those of the control group. The activity of CAT was decreased, and the contents of H₂O₂ and •OH were increased due to Se deficiency. Pearson method analysis showed that the expression of SelT had a positive correlation with IL-2, INF-γ, SecS, and SPS1 and a negative correlation with IL-1R and IL-1β. In summary, these data indicated that Se-deficient diet decreased the SelT expression and its regulation of oxidative stress, and it inhibited a pleiotropic mechanism of the immune response.

http://ift.tt/2wgG9C6

Adaptation of the Acute Organ Failure Score for Use in a Medicare Population.

Objectives: Without widely available physiologic data, a need exists for ICU risk adjustment methods that can be applied to administrative data. We sought to expand the generalizability of the Acute Organ Failure Score by adapting it to a commonly used administrative database. Design: Retrospective cohort study. Setting: One hundred fifty-one hospitals in Pennsylvania. Patients: A total of 90,733 ICU admissions among 77,040 unique patients between January 1, 2009, and December 1, 2009, in the Medicare Provider Analysis and Review database. Measurements and Main Results: We used multivariable logistic regression on a random split cohort to predict 30-day mortality, and to examine the impact of using different comorbidity measures in the model and adding historical claims data. Overall 30-day mortality was 17.6%. In the validation cohort, using the original Acute Organ Failure Score model's [beta] coefficients resulted in poor discrimination (C-statistic, 0.644; 95% CI, 0.639-0.649). The model's C-statistic improved to 0.721 (95% CI, 0.711-0.730) when the Medicare cohort was used to recalibrate the [beta] coefficients. Model discrimination improved further when comorbidity was expressed as the COmorbidity Point Score 2 (C-statistic, 0.737; 95% CI, 0.728-0.747; p

http://ift.tt/2ffS0wh

ELABELA Improves Cardio-Renal Outcome in Fatal Experimental Septic Shock.

Objectives: Apelin-13 was recently proposed as an alternative to the recommended [beta]-adrenergic drugs for supporting endotoxin-induced myocardial dysfunction. Since Apelin-13 signals through its receptor (Apelin peptide jejunum) to exert singular inotropic/vasotropic actions and to optimize body fluid balance, this candidate pathway might benefit septic shock management. Whether the newly discovered ELABELA (ELA), a second endogenous ligand of the Apelin peptide jejunum receptor highly expressed in the kidney, further improves cardio-renal impairment remains unknown. Design, Setting, and Subjects: Interventional study in a rat model of septic shock (128 adult males) to assess the effects of ELA and Apelin-13 on vascular and cardio-renal function. Experiments were performed in a tertiary care University-based research institute. Interventions: Polymicrobial sepsis-induced cardiac dysfunction was produced by cecal ligation puncture to assess hemodynamic efficacy, cardioprotection, and biomechanics under acute or continuous infusions of the apelinergic agonists ELA or Apelin-13 (39 and 15 [micro]g/kg/hr, respectively) versus normal saline. Measurements and Main Results: Apelinergic agonists improved 72-hour survival after sepsis induction, with ELA providing the best clinical outcome after 24 hours. Apelinergic agonist infusion counteracted cecal ligation puncture-induced myocardial dysfunction by improving left ventricular pressure-volume relationship. ELA-treated cecal ligation puncture rats were the only group to 1) display a significant improvement in left ventricular filling as shown by increased E-wave velocity and left ventricular end-diastolic volume, 2) exhibit a higher plasma volume, and 3) limit kidney injury and free-water clearance. These beneficial renal effects were superior to Apelin-13, likely because full-length ELA enabled a distinctive regulation of pituitary vasopressin release. Conclusions: Activation of the apelinergic system by exogenous ELA or Apelin-13 infusion improves cardiovascular function and survival after cecal ligation puncture-induced sepsis. However, ELA proved better than Apelin-13 by improving fluid homeostasis, cardiovascular hemodynamics recovery, and limiting kidney dysfunction in a vasopressinergic-dependent manner. Copyright (C) by 2017 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

http://ift.tt/2hvYeZw

Nosocomial Infections During Extracorporeal Membrane Oxygenation: Incidence, Etiology, and Impacton Patients' Outcome.

Objective: To study incidence, type, etiology, risk factors, and impact on outcome of nosocomial infections during extracorporeal membrane oxygenation. Design: Retrospective analysis of prospectively collected data. Setting: Italian tertiary referral center medical-surgical ICU. Patients: One hundred five consecutive patients who were treated with extracorporeal membrane oxygenation from January 2010 to November 2015. Interventions: None. Measurements and Main Results: Ninety-two patients were included in the analysis (48.5 [37-56] years old, simplified acute physiology score II 37 [32-47]) who underwent peripheral extracorporeal membrane oxygenation (87% veno-venous) for medical indications (78% acute respiratory distress syndrome). Fifty-two patients (55%) were infected (50.4 infections/1,000 person-days of extracorporeal membrane oxygenation). We identified 32 ventilator-associated pneumonia, eight urinary tract infections, five blood stream infections, three catheter-related blood stream infections, two colitis, one extracorporeal membrane oxygenation cannula infection, and one pulmonary-catheter infection. G+ infections (35%) occurred earlier compared with G- (48%) (4 [2-10] vs. 13 [7-23] days from extracorporeal membrane oxygenation initiation; p 50 years old), reason for connection different from acute respiratory distress syndrome, higher simplified acute physiology score II, diagnosis of ventilator-associated pneumonia, and infection by multidrug-resistant bacteria were independently associated to increased death rate. Conclusions: Infections (especially ventilator-associated pneumonia) during extracorporeal membrane oxygenation therapy are common and frequently involve multidrug-resistant organisms. In addition, they have a negative impact on patients' outcomes. Copyright (C) by 2017 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

http://ift.tt/2fgispe

Alterations in Spanish Language Interpretation During Pediatric Critical Care Family Meetings.

Objectives: To characterize alterations in Spanish language medical interpretation during pediatric critical care family meetings. Design: Descriptive, observational study using verbatim transcripts of nine PICU family meetings conducted with in-person, hospital-employed interpreters. Setting: A single, university-based, tertiary children's hospital. Subjects: Medical staff, family members, ancillary staff, and interpreters. Interventions: None. Measurements and Main Results: Interpreted speech was compared with original clinician or family speech using the qualitative research methods of directed content analysis and thematic analysis. Alterations occurred in 56% of interpreted utterances and included additions, omissions, substitutions, editorializations, answering for the patient/clinician, confessions, and patient advocacy. Longer utterances were associated with more alterations. Conclusions: To minimize interpreter alterations during family meetings, physicians should speak in short utterances (fewer than 20 words) and ask interpreters to interrupt in order to facilitate accurate interpretation. Because alterations occur, physicians may also regularly attempt to assess the family's understanding. Copyright (C) by 2017 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

http://ift.tt/2hvE4Pg

Prevalence and Prognostic Association of Circulating Troponin in the Acute Respiratory Distress Syndrome.

Objective: Circulating cardiac troponin has been associated with adverse prognosis in the acute respiratory distress syndrome in small and single-center studies; however, comprehensive studies of myocardial injury in acute respiratory distress syndrome using modern high-sensitivity troponin assays, which can detect troponin at much lower circulating concentrations, have not been performed. Design: We performed a prospective cohort study. Setting: We included patients enrolled in previously completed trials of acute respiratory distress syndrome. Patients: One thousand fifty-seven acute respiratory distress syndrome patients were included. Interventions: To determine the association of circulating high-sensitivity troponin I (Abbott ARCHITECT), with acute respiratory distress syndrome outcomes, we measured high-sensitivity troponin I within 24 hours of intubation. The primary outcome was 60-day mortality. Measurements and Main Results: Detectable high-sensitivity troponin I was present in 94% of patients; 38% of patients had detectable levels below the 99th percentile of a healthy reference population (26 ng/L), whereas 56% of patients had levels above the 99th percentile cut point. After multivariable adjustment, age, cause of acute respiratory distress syndrome, temperature, heart rate, vasopressor use, Sequential Organ Failure Assessment score, creatinine, and PCO2 were associated with higher high-sensitivity troponin I concentration. After adjustment for age, sex, and randomized trial assignment, the hazard ratio for 60-day mortality comparing the fifth to the first quintiles of high-sensitivity troponin I was 1.61 (95% CI, 1.11-2.32; p trend = 0.003). Adjusting for Sequential Organ Failure Assessment score suggested that this association was not independent of disease severity (hazard ratio, 0.95; 95% CI, 0.64-1.39; p = 0.93). Conclusions: Circulating troponin is detectable in over 90% of patients with acute respiratory distress syndrome and is associated with degree of critical illness. The magnitude of myocardial injury correlated with mortality. Copyright (C) by 2017 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

http://ift.tt/2fgSS3y

Bacteria-induced morphogenesis of Ulva intestinalis and Ulva mutabilis (Chlorophyta): a contribution to the lottery theory

Abstract

The green marine macroalgae of the class Ulvophyceae (Ulvophytes) are common algae distributed worldwide particularly in intertidal areas, which play a key role in aquatic ecosystems. They are potentially valuable resources for food, animal feed and fuel but can also cause massive nuisance blooms. Members of Ulvaceae, like many other seaweeds, harbour a rich diversity of epiphytic bacteria with functions related to host growth and morphological development. In the absence of appropriate bacterially derived signals, germ cells of the genus Ulva develop into 'atypical' colonies consisting of undifferentiated cells with abnormal cell walls. This paper examines the specificity of bacteria-induced morphogenesis in Ulva, by cross-testing bacteria isolated from several Ulva species on two Ulva species, the emerging model system Ulva mutabilis and the prominent biofouler species Ulva intestinalis. We show that pairs of bacterial strains isolated from species other than U. mutabilis and U. intestinalis can fully rescue axenic plantlets generated either from U. mutabilis or U. intestinalis gametes. This laboratory-based study demonstrates that different compositions of microbial communities with similar functional characteristics can enable complete algal morphogenesis and thus supports the 'competitive lottery' theory for how symbiotic bacteria drive algal development.

http://ift.tt/2to3gb7

Seasonal and spatial variations of prokaryoplankton communities in a salinity-influenced watershed, China

Abstract

Prokaryotes represent the largest biodiversity pool and drive the biogeochemical cycles in fluvial environments. However, the mechanisms underlying the assembly of prokaryotic communities are largely unexplored at taxonomic and functional levels, simultaneously. Here, we investigated the spatio-seasonal distribution of prokaryoplankton communities in a salinity-influenced watershed, China using 16S rRNA gene amplicon sequencing. The OTUs were divided into core and satellite, based on a statistical approach. Our results indicated that the core taxa accounted for 87.4% of all the communities, predominantly including Betaproteobacteria, Actinobacteria and Thaumarchaeota. Whereas 10 of 22 metabolic phenotypes annotated using METAGENassist had significantly higher relative abundances in the core than satellite communities. Temporal variations in the composition of ammonia-oxidizing prokaryotes could be attributed to the seasonal nutrient concentrations. Multivariate statistical analysis indicated that environmental filtering rather than dispersal limitation is the primary mechanism driving the assembly of the whole, core and satellite communities at both taxonomic and functional levels. Network analysis revealed that the mutualistic interactions might also have certain roles in the assembly of the core taxonomic community. However, taxonomic community fluctuations can only partially reflect the functional community variations. Collectively, this study significantly advanced our understanding of the biogeographic pattern of the fluvial prokaryotic communities.

http://ift.tt/2tRaPus

Effect of dietary nucleosides and yeast extracts on composition and metabolic activity of infant gut microbiota in PolyFermS colonic fermentation models

Abstract

Nucleotides (NT) and nucleosides (NS) are added to infant formula to mimic the content of breast milk, but little is known about their impact on infant gut microbiota. In this study, we tested the effect of NS and of yeast extracts (YE) with different NT content using PolyFermS continuous fermentation models mimicking formula-fed, healthy and enteropathogen-contaminated infant gut microbiota. Microbiota composition, short-chain fatty acid (SCFA) formation and gene expression were determined. NS, and to a larger extend YE modulated microbiota composition and increased metabolic activity in both models. Anaerococcus, Peptoniphilus, Fusobacterium, Lactobacillus/Pediococcus/Leuconostoc and Veillonella were enhanced when YE and/or NS were added. The production of SCFA increased with the level of supplied NT equivalents. Addition of NS and YE reduced colonization of Salmonella compared to control periods. Gene expression analysis confirmed taxonomical changes and indicated functional responses to YE. Transcripts related to NT and sulfur metabolism and iron acquisition increased while biosynthesis of co-factors and vitamins decreased after YE addition. Elevated butyrate formation correlated with increased transcripts encoding key enzymes of the two major butyrate synthesis pathways. Our results uncover a strong dose-dependent modulation of NS and YE on infant gut microbiota composition and metabolic activity.

http://ift.tt/2utEdUE

High-throughput sequencing of microbial eukaryotes in Lake Baikal reveals ecologically differentiated communities and novel evolutionary radiations

Abstract

We performed high-throughput 18S rDNA V9 region sequencing analyses of microeukaryote (protist) communities at seven sites with depths ranging from 0 to 1450 m in the southern part of Lake Baikal. We show that microeukaryotic diversity differed according to water column depth and sediment depth. Chrysophytes and perkinsids were diverse in subsurface samples, novel radiations of petalomonads and Ichthyobodo relatives were found in benthic samples, and a broad range of divergent OTUs were detected in deep subbenthic samples. Members of clades usually associated with marine habitats were also detected, including syndineans for the first time in freshwater systems. Fungal- and cercozoan-specific c. 1200 bp amplicon clone libraries also revealed many novel lineages in both planktonic and sediment samples at all depths, a novel radiation of aphelids in shallower benthic samples, and partitioning of sarcomonad lineages in shallow vs deep benthic samples. Putative parasitic lineages accounted for 12.4% of overall reads, including a novel radiation of Ichthyobodo (fish parasite) relatives. Micrometazoans were also analysed, including crustaceans, rotifers and nematodes. The deepest (>1000 m) subsurface sediment samples harboured some highly divergent sequence types, including heterotrophic flagellates, parasites, putative metazoans and sequences likely representing organisms originating from higher up in the water column.

http://ift.tt/2ud4Wtm

Rapamycin prolongs graft survival and induces CD4+IFN-[gamma]+IL-10+ regulatory type 1 cells in old recipient mice.

Background: Although the elderly represents a rapidly growing population among transplant recipients, age-specific aspects have not been considered sufficiently in clinical trials. Moreover, age-specific effects of immunosuppressive therapies remain poorly understood. Methods: Here, we assessed the impact of Rapamycin on alloimmune responses in old recipients using a fully MHC-mismatched murine transplantation model. Results: Old untreated recipients displayed a prolonged skin graft survival compared to their young counterparts, an observation that confirmed data of our previous experiments. Rapamycin led to a significant prolongation of graft survival in both, young and old recipients. However, graft survival was age-dependent and extended in old vs. young recipients (19 days vs. 12 days, p=0.004). This age-specific effect was not linked to changes in frequencies or subset composition of either CD8+ or CD4+ T cells. Moreover, antiproliferative effects of Rapamycin on CD8+ and CD4+ T cells as assessed by in vivo BrdU-incorporation were comparable and age-independent. In contrast, the systemic production of IL-10 was markedly elevated in old recipients treated with Rapamycin. In parallel to this shift in cytokine balance, IFN-[gamma]/IL-10 double-positive regulatory type 1 cells emerged during Th1-differentiation of old T helper cells in presence of Rapamycin. Similarly, CD4+IFN-[gamma]+IL-10+ cells expanded among Foxp3-negative cells after in vivo treatment of old recipients with Rapamycin. Conclusions: Our results highlight novel aspects of age-dependent immunosuppressive effects of Rapamycin, with relevance for age-specific immunosuppressive regimens. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2fh0tPT