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Κυριακή 29 Ιουλίου 2018

Brine shrimp lethality and acute toxicity tests of different hydro-methanol extracts of Anacardium occidentale using in vitro and in vivo models: a preliminary study

Abstract

The antimicrobial, antifungal, antiprotozoal, anthelminthic, and antiviral activities of various part of Anacardium occidentale have been reported in vitro. However, there are no records or documentation on the potential cytotoxicity and acute toxicity effects of the extracts using in vivo study. The present study was conducted to evaluate the cytotoxicity and acute toxicity effects of stem bark, root, stem, and leave extracts using in vivo and in vitro models. Plant materials were extracted using cold maceration in 70% hydro-methanol, and the extracts were concentrated under hot air oven at 40 °C. In brine shrimp lethality assay, five concentrations of each extract (10, 100, 250, 500, and 1000 ppm) were used. Each of the concentration was tested in triplicate and mortality of Artemia salina was monitored for 24 h post exposure. Sea water was used in control group. Acute toxicity testing was conducted according to the method of Organisation for Economic Co-operation and Development (OECD) using 2-week-old cockerels. Dose-probing tests were used to determine the median lethal dose (LD50). Four measures of acute toxicity tests were used, 3000, 1500, 750 and 375 mg/kg in 2-week-old cockerels. The LC50 was estimated using Fumey probit analysis. The LC50 of the four extracts were 336.34, 338.72, 486.36, and 657.62 ppm for stem bark, roots, stem, and leave, respectively. Acute toxicity tests did not show any sign of toxicity as no mortality was recorded in the four extracts. The treatment with all the plant extracts did not cause any morphological changes in the internal organs of the chickens grossly when compared to the control group. The study showed that the extracts of A. occidentale contain bioactive compounds which may be cytotoxic in vitro and non-toxic in vivo and can be used in ethnomedicine.



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Cancers, Vol. 10, Pages 251: The Role of Inflammation and Inflammatory Mediators in the Development, Progression, Metastasis, and Chemoresistance of Epithelial Ovarian Cancer

Cancers, Vol. 10, Pages 251: The Role of Inflammation and Inflammatory Mediators in the Development, Progression, Metastasis, and Chemoresistance of Epithelial Ovarian Cancer

Cancers doi: 10.3390/cancers10080251

Authors: Sudha S. Savant Shruthi Sriramkumar Heather M. O'Hagan

Inflammation plays a role in the initiation and development of many types of cancers, including epithelial ovarian cancer (EOC) and high grade serous ovarian cancer (HGSC), a type of EOC. There are connections between EOC and both peritoneal and ovulation-induced inflammation. Additionally, EOCs have an inflammatory component that contributes to their progression. At sites of inflammation, epithelial cells are exposed to increased levels of inflammatory mediators such as reactive oxygen species, cytokines, prostaglandins, and growth factors that contribute to increased cell division, and genetic and epigenetic changes. These exposure-induced changes promote excessive cell proliferation, increased survival, malignant transformation, and cancer development. Furthermore, the pro-inflammatory tumor microenvironment environment (TME) contributes to EOC metastasis and chemoresistance. In this review we will discuss the roles inflammation and inflammatory mediators play in the development, progression, metastasis, and chemoresistance of EOC.



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Endoscopic Treatment of Early-Stage Esophageal Cancer

Abstract

Purpose of Review

Esophageal cancer is a leading cause of global cancer-related mortality. Here, we discuss the major endoscopic treatment modalities for management of early esophageal cancer (EEC).

Recent Findings

Advances in endoscopic imaging and therapy have shifted the paradigm of managing early esophageal cancers. Though esophagectomy remains the preferred management for advanced cancers, guidelines now recommend endoscopic resection followed by ablative therapy for early (Tis and T1a) cancers. Available data suggests endoscopic treatment is comparable to surgery with regard to overall and cancer-specific survival with lower procedural morbidity and mortality.

Summary

Endoscopic modalities are emerging as frontline treatment options for patients with early esophageal cancers. Accurate clinical staging with assessment of disease extent, tumor grade, and risk of nodal metastases is crucial when determining eligibility for endoscopic management of EEC. High-quality routine surveillance endoscopy is critical in patients who have undergone resection and/or ablation.



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Poor evidence to guide chronic pain treatment [Letters]



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The association between suicide deaths and putatively harmful and protective factors in media reports [Research]

BACKGROUND:

Exposure to media reporting on suicide can lead to suicide contagion and, in some circumstances, may also lead to help-seeking behaviour. There is limited evidence for which specific characteristics of media reports mediate these phenomena.

METHODS:

This observational study examined associations between putatively harmful and protective elements of media reports about suicide in 13 major publications in the Toronto media market and subsequent suicide deaths in Toronto (2011–2014). We used multivariable logistic regression to determine whether specific article characteristics were associated with increases or decreases in suicide deaths in the 7 days after publication, compared with a control window.

RESULTS:

From 2011 to 2014, there were 6367 articles with suicide as the major focus and 947 suicide deaths. Elements most strongly and independently associated with increased suicides were a statement about the inevitability of suicide (odds ratio [OR] 1.97, confidence interval [CI] 1.07–3.62), about asphyxia by a method other than car exhaust (OR 1.72, CI 1.36–2.18), about suicide by jumping from a building (OR 1.70, CI 1.28–2.26) or about suicide pacts (OR 1.63, CI 1.14–2.35), or a headline that included the suicide method (OR 1.41, CI 1.07–1.86). Elements most strongly and independently associated with decreased suicides were unfavourable characteristics (negative judgments about the deceased; OR 1.85, CI 1.20–2.84), or mentions of railway (OR 1.61, CI 1.10–2.36) and cutting or stabbing (OR 1.59, CI 1.19–2.13) deaths, and individual murder-suicide (OR 1.50, CI 1.23–1.84).

INTERPRETATION:

This large study identified significant associations between several specific elements of media reports and suicide deaths. It suggests that reporting on suicide can have a meaningful impact on suicide deaths and that journalists and media outlets and organizations should carefully consider the specific content of reports before publication.



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Responsible reporting to prevent suicide contagion [Commentary]



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How placebo characteristics can influence estimates of intervention effects in trials [Analysis]



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Doctors increasingly caught in crosshairs of counter-terrorism efforts [News]



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Monilethrix [Practice]



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Look for an underlying cause of headache [Letters]



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It was never about The Cancer It was about Me [Humanities]



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Decisions by new Ontario government worry science and health care communities [News]



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Daily analgesia for nonheadache pain may not lead to daily rebound headaches [Letters]



https://ift.tt/2AjlP9l

Doctors need retraining to keep up with technological change [News]



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The prognostic value of [ 123 I]-vascular endothelial growth factor ([ 123 I]-VEGF) in glioma

Abstract

Purpose

Recent studies have shown that tumor vascular endothelial cells and various tumor cells overexpress receptors for vascular endothelial growth factor (VEGF). The aim of this study was to investigate the prognostic value of [123I]-VEGF scintigraphy in patients with histologically verified brain tumors.

Methods

23 consecutive patients (9 women and 14 men aged 30–83 years, mean age 56.6 ± 14.4 years) with histopathologically-verified primary brain tumors were included in the study. All patients had undergone [123I]-VEGF scintigraphy. SPECT examinations of brain were performed 30 min and 18 h after injection. Additional [11C]-methionine PET ([11C]-MET PET) was performed in eight of the 23 patients. Both [123I]-VEGF and [11C]-MET PET were evaluated visually and semiquantitatively by tumor-to-normal brain uptake ratio (T/N ratio). Thresholds of the T/N ratio were evaluated by analysis of receiver operating characteristics (ROC). Overall survival (OS) was estimated using the Kaplan-Meier method.

Results

World Health Organization (WHO) grade IV glioma lesions showed [123I]-VEGF uptake 18 h after the injection, whereas other brain tumors of grade II or III showed negative results. There was no significant difference in the tumor size between VEGF positive and VEGF negative tumors. Patients with [123I]-VEGF T/N ratio threshold <1.32 showed significantly longer survival than patients with T/N ratio ≥ 1.32 (2680 days vs 295 days; P < 0.05). In the subgroup of 16 grade IV glioma patients, significant OS differences were found using a T/N ratio of 1.75 as threshold (T/N ratio < 1.75: 720 days; T/N ≥ 1.75: 183 days; P < 0.05). Significant difference (P < 0.05) was also found in [11C]-MET PET T/N ratios between the grade IV glioma (mean T/N ratio: 3.71) and the grade II or III glioma (mean T/N ratio: 1.74).

Conclusion

Our results suggest that [123I]-VEGF scintigraphy may be useful for visualization of tumor angiogenesis. In addition, [123I]-VEGF may provide relevant prognostic information in patients with glioma.



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Secondary Headaches in Children and Adolescents: What Not to Miss

Abstract

Introduction

Headaches are a common occurrence in childhood and adolescence. Most children presenting with a chief complaint of headache have a self-limited infectious disorder or primary headache syndrome that should not require extensive workup.

Purpose of Review

Differentiating these conditions from other more serious causes of headache in children can sometimes be difficult. This article aims to provide information regarding "red flags" that should indicate a need for concern for disorders that require more urgent evaluation.

Recent Findings

Long-held beliefs about specific "red flags" that have been analyzed in recent years as to their validity and new criteria for the diagnosis of idiopathic intracranial hypertension have been elaborated based on study. These publications are reviewed in this article.

Summary

Knowledge of past and current literature on secondary headache in children, combined with thorough history taking and examination, should help determine when there is concern for a serious secondary cause for headache in children and adolescents and direct workup.



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Photophobia: When Light Hurts, a Review

Abstract

Purpose of Review

To provide an updated overview of Photophobia with a particular focus on photophobia related to migraine.

Recent Findings

Melanopsin-containing photoreceptors called intrinsically photosensitive retinal ganglion cells (ipRGCs) have been identified in the retina and explain the rational for photophobia in individuals who are blind.

Summary

Photophobia, a sensory disturbance provoked by light, is a common neurological and ophthalmological symptom. Migraine, a common neurological condition, is pathognomonic of photophobia; however, other primary headache conditions, traumatic brain injury, and impairment of the optic pathway can cause photophobia. In addition, anterior and posterior segment ocular pathology, medications, and psychiatric conditions can result in photophobia. At least 2 (possibly three) distinct neural pathways are involved in photophobia. Some of the basic science regarding these pathways is discussed in this review including the role of calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating polypeptide. Management of photophobia includes treatment of the underlying etiology and conservative strategies such as wearing sunglasses.



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89 Zr-trastuzumab PET supports clinical decision making in breast cancer patients, when HER2 status cannot be determined by standard work up

Abstract

Background

Up-to-date information on human epidermal growth factor receptor 2 (HER2) status in breast cancer (BC) is important, as expression can vary during the course of the disease, necessitating anti-HER2 therapy adjustments. Repeat biopsies, however, are not always possible. In this feasibility trial we assessed whether 89Zr-trastuzumab PET could support diagnostic understanding and aid clinical decision making, when HER2 status could not be determined by standard work up. Additionally, HER2 status on circulating tumour cells (CTCs) was assessed.

Patients and methods

89Zr-trastuzumab PET was performed in patients if disease HER2 status remained unclear after standard work up (bone scan, 18F-FDG PET, CT and if feasible a biopsy). PET result and central pathologic revision of available tumour biopsies were reported to the referring physician. CTC HER2 status prior to PET was evaluated afterwards and therefore not reported. Diagnostic understanding and treatment decision questionnaires were completed by the referring physicians before, directly after and ≥ 3 months after 89Zr-trastuzumab PET.

Results

Twenty patients were enrolled: 8 with two primary cancers (HER2-positive and HER2-negative BC or BC and non-BC), 7 with metastases inaccessible for biopsy, 4 with prior HER2-positive and -negative metastases and 1 with primary BC with equivocal HER2 status. 89Zr-trastuzumab PET was positive in 12 patients, negative in 7 and equivocal in 1 patient. In 15/20 patients, 89Zr-trastuzumab PET supported treatment decision. The scan altered treatment of 8 patients, increased physicians' confidence without affecting treatment in 10, and improved physicians' disease understanding in 18 patients. In 10/20 patients CTCs were detected; 6/10 showed HER2 expression. CTC HER2 status was not correlated to 89Zr-trastuzumab PET result or treatment decision.

Conclusion

89Zr-trastuzumab PET supports clinical decision making when HER2 status cannot be determined by standard work up. The impact of CTC HER2 status needs to be further explored.



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The detection and identification of saliva in forensic samples by RT-LAMP

Abstract

We report on a novel method for saliva identification by reverse transcription-loop-mediated isothermal amplification (RT-LAMP). In our previous report, real-time RT-LAMP was used for blood identification by using HBB detection as a model but in this advanced study, this method was refined for the identification of the more challenging body fluid of saliva. Expression of the18S rRNA gene was used as the internal control and the Statherin (STATH) gene as the saliva-specific marker. A turbidimeter was used for real-time detection of the RT-LAMP products, and confirmation was obtained that the real products were generated using: agarose gel electrophoresis, calcein fluorescence detection and/or enzymatic digestion. The specificity of the test was performed using 42 samples including 7 different body fluids, and the expression of STATH was only observed in all the saliva samples (6) with a threshold time of 39.4 ± 2.9 min. Sensitivity testing showed that RT-LAMP products for STATH were stably detected when the RNA template was not less than 6.25 ng. When the primer concentrations for STATH were two times that of 18S rRNA, saliva could be identified in the body fluid mixtures even at a ratio (saliva:semen) of 1:3 (without loop primer)/1:5 (with loop primer). A multiplex RT-LAMP was established to simultaneously amplify the 18S rRNA and STATH genes, and applied to the identification of saliva on ten non-probative cigarette butts. A positive result for saliva was obtained from all ten butts, even for those that returned a negative or ambiguous result using the amylase test. A direct RT-LAMP test is also reported where the RNA extraction step was omitted to speed the collection of data and all tests using either the simplex or multiplex RT-LAMP resulted in a positive response if saliva was present. Our data provide a simple and effective means to detect the presence of saliva.



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Factors influencing job loss and early retirement in working men with prostate cancer—findings from the population-based Life After Prostate Cancer Diagnosis (LAPCD) study

Abstract

Purpose

To investigate factors associated with job loss and early retirement in men diagnosed with prostate cancer (PCa) 18–42 months previously.

Methods

Men ≤ 60 years at diagnosis who completed the Life After Prostate Cancer Diagnosis (LAPCD) survey were identified. Men who moved from employment at diagnosis to unemployment (EtoU) or retirement (EtoR) at survey (18–42 months post-diagnosis) were compared to men remaining in employment (EtoE). Sociodemographic, clinical and patient-reported factors were analysed in univariable and multivariable analysis.

Results

There were 3218 men (81.4%) in the EtoE, 245 (6.2%) in EtoU and 450 (11.4%) in the EtoR groups. Men with stage IV disease (OR = 4.7 95% CI 3.1–7.0, relative to stage I/II) and reporting moderate/big bowel (OR = 2.5, 95% CI 1.6–3.9) or urinary problems (OR = 2.0, 95% CI 1.4–3.0) had greater odds of becoming unemployed. Other clinical (≥ 1 comorbidities, symptomatic at diagnosis) and sociodemographic (higher deprivation, divorced/separated), living in Scotland or Northern Ireland (NI)) factors were predictors of becoming unemployed. Men who were older, from NI, with stage IV disease and with caring responsibilities had greater odds of retiring early. Self-employed and non-white men had lesser odds of retiring early.

Conclusion

PCa survivors who retire early following diagnosis do not report worse urinary or bowel problems compared to men remaining in employment. However, we identified clinical and sociodemographic factors which increased unemployment risk in PCa survivors.

Implications for Cancer Survivors

Targeted support and engagement with PCa survivors at risk of unemployment, including their families and employers, is needed.



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Pathway Network Analysis of Complex Diseases Based on Multiple Biological Networks

Biological pathways play important roles in the development of complex diseases, such as cancers, which are multifactorial complex diseases that are usually caused by multiple disorders gene mutations or pathway. It has become one of the most important issues to analyze pathways combining multiple types of high-throughput data, such as genomics and proteomics, to understand the mechanisms of complex diseases. In this paper, we propose a method for constructing the pathway network of gene phenotype and find out disease pathogenesis pathways through the analysis of the constructed network. The specific process of constructing the network includes, firstly, similarity calculation between genes expressing data combined with phenotypic mutual information and GO ontology information, secondly, calculating the correlation between pathways based on the similarity between differential genes and constructing the pathway network, and, finally, mining critical pathways to identify diseases. Experimental results on Breast Cancer Dataset using this method show that our method is better. In addition, testing on an alternative dataset proved that the key pathways we found were more accurate and reliable as biological markers of disease. These results show that our proposed method is effective.

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Therapeutic Effects of Systemic Administration of the Novel RANKL-Modified Peptide, MHP1, for Ischemic Stroke in Mice

Microglial healing peptide 1, "MHP1", is a newly developed synthetic peptide composed of the DE and a part of the EF loop of the receptor activator of nuclear factor-кB (NFκB) ligand (RANKL). Our previous report demonstrated that MHP1 significantly inhibits Toll-like receptor (TLR) 2- and 4-induced inflammation in microglia/macrophages through RANK signaling without osteoclast activation. However, its inhibitory effects on ischemic stroke when administered intravenously have not been clarified. First, we examined whether MHP1 could penetrate the brain parenchyma. Intravenous injection of FITC-conjugated MHP1 demonstrated that MHP1 could cross the blood-brain-barrier in peri-infarct regions, but not in intact regions. Because MHP1 in the parenchyma was reduced at 60 minutes after injection, we speculated that continuous injection was necessary to achieve the therapeutic effects. To check the possible deactivation of MHP1 by continuous injection, the anti-inflammatory effects were checked in MG6 cells after incubation in 37°C for 24 hours. Although the inhibitory effects for IL6 and TNFα were reduced compared to nonincubated MHP1, its anti-inflammatory efficacy remained, indicating that continuous administration with pump was possible. The single and successive continuous administration of MHP1 starting from 4 or 6 hours after cerebral ischemia successfully reduced infarct volume and prevented the exacerbation of neurological deficits with reduced activation of microglia/macrophages and inflammatory cytokines. Different from recombinant RANKL, MHP1 did not activate osteoclasts in the paralytic arm. Although further modification of MHP1 is necessary for stabilization, the MHP1 could be a novel agent for the treatment ischemic stroke.

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Protein expression of the transcription factors DMRT1, TCLF5, and OCT4 in selected germ cell neoplasms of the testis

In the present study, we investigated protein expression of the transcription factors mammalian doublesex and mab-3 related transcription factor 1 (DMRT1), basic helix–loop–helix transcription factor-like 5 (TCLF5), and octamer-binding transcription factor 4 (OCT4) in normal human spermatogenesis, testicular mixed germ cell-sex cord stromal tumor (MGC-SCST), spermatocytic tumor, and seminoma. In normal human spermatogenesis, DMRT1 is expressed in the nuclei of spermatogonia, but not in those of more mature germ cells.

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Immunohistochemical profiles of different subsets of Merkel cell carcinoma

The literature records many examples of Merkel cell carcinoma (MCC) exhibiting aberrant immunohistochemical profiles. These can lead to diagnostic difficulty. The objectives of the current study were (1) to examine the immunohistochemical profile of different subsets of MCC to determine whether predictable subset-specific patterns exist and (2) to establish whether shared immunophenotypic patterns might reveal links between individual subsets, as demonstrated previously at a genetic level. In 52 cases of MCC, stratified by viral status and morphology, we studied 5 markers commonly used in the diagnostic evaluation of these tumors (CK20, CK7, chromogranin, neurofilament and TTF-1).

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Can tumor-associated macrophages in ductal carcinoma in situ (DCIS) on biopsy predict invasive carcinoma on excision?

Recent trials have explored surveillance of ductal carcinoma in situ (DCIS) without complete excision but it is difficult to fully exclude an associated, un-sampled invasive focus. Tumor microenvironment, including tumor-associated macrophages, may play a role in the transition from in situ to invasive carcinoma and the presence of CD163 positive cells with DCIS has been associated with increased risk of progression to invasive carcinoma. We aimed to evaluate the role of DCIS-associated CD163 positive cells on biopsy in predicting associated invasion on excision.

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Histopathologic findings in lung biopsies from patients with primary biliary cholangitis

Primary biliary cholangitis (PBC) is a progressive autoimmune disease of the liver causing destruction of intrahepatic bile ducts, associated with lymphocytic and granulomatous inflammation. PBC has been associated with many extrahepatic manifestations including interstitial lung disease. However, comprehensive pulmonary histopathology in PBC has not been well documented. Sixteen PBC patients who underwent lung biopsies were identified from surgical pathology files in three institutions. Histopathologic review was performed.

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Epithelial-to-mesenchymal transition related transcription factors are upregulated in ependymomas and correlate with a poor prognosis

Epithelial-to-mesenchymal transition (EMT) plays an important role in invasion and metastasis of various cancers including gliomas. EMT has also been linked to cancer stem cells and resistance to chemotherapy. An initial in-silico data mining in a published ependymoma (EPN) patient series (GSE21687) revealed upregulation of EMT-Transcription factors (EMT-TFs) in tumor samples. Further, quantitative real-time polymerase chain reaction (q-RT-PCR) based gene expression analysis of EMT-TFs in 96 EPNs showed significant up-regulation of SNAI1, SNAI2, ZEB1, and TWIST1 as compared to normal brain, associated with upregulation of CDH2/N-Cadherin and downregulation of CDH1/E-Cadherin.

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Treatment and survival of rectal cancer patients over the age of 80 years: a EURECCA international comparison



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A phase II randomised (calibrated design) study on the activity of the single-agent trabectedin in metastatic or locally relapsed uterine leiomyosarcoma



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Transcription factors WT1 and p53 combined: a prognostic biomarker in ovarian cancer



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Tumour-stroma ratio and prognosis in gastric adenocarcinoma



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Is it time to pull epinephrine from the EMS formulary?

Our co-hosts discuss a recent study out of the UK that puts the use of epinephrine in prehospital cardiac arrest patients into question

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Native hip dislocation at acetabular fracture predicts poor long-term outcome

Publication date: Available online 29 July 2018

Source: Injury

Author(s): J.A. Nicholson, C.E.H. Scott, J. Annan, I. Ahmed, J.F. Keating

Abstract
Aim

The aim of this study was to evaluate the long-term clinical outcomes and complications following an acetabular fracture associated with a posterior hip dislocation compared to those without dislocation.

Patients & Methods

A retrospective cohort study of 113 patients (mean age 42 (14-95), 77% male) with acetabular fracture dislocations compared to 367 patients with acetabular fractures without dislocation (mean age 54 (16-100), 66% male) treated from 1988-2010. Patient characteristics, complications, reoperations, and conversion to total hip arthroplasty (THA) were recorded. Long term patient reported outcomes (Oxford Hip Score and SF-12) were measured at mean follow up 9.7 years (5 to 26).

Results

At long-term follow up 12/113 (11%) patients had died and 22/113 (19%) were lost. Isolated posterior wall fracture was the most common fracture associated with dislocation. Patients with dislocation were more likely to be younger and male with higher Injury Severity Scores (ISS). There was no significant difference in radiographic PTOA development between fractures with and without dislocation (p = 0.246). Sciatic nerve palsy (12% Vs 1%, p < 0.001) and avascular necrosis (AVN) (11% Vs 1%, p < 0.001) were more common when dislocation was present. AVN was associated with increasing age and hypotension on arrival to the emergency department. Ten-year native hip survival was worse following fracture dislocations compared to fractures without dislocation: 75.1% (65.7 to 84.5 95% CI) Vs 90.7% (87.0 to 94.4), p < 0.001. Significant predictors of THA requirement were older age, particularly age >55 years at fracture, and increased ISS. Long-term OHS was worse in fractures with dislocations (33.6 ± 13.1 Vs 37.0 ± 14.0, p = 0.016).

Conclusion

Acetabular fractures with an associated dislocation have worse long-term functional outcomes with higher rates of complications and conversion to late THA compared to acetabular fractures without a dislocation.



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Bilateral Low-Dose Computed Tomography Assessment for Post-Operative Rotational Malalignment after Intramedullary Nailing for Tibial Shaft Fractures: Reliability of a Practical Imaging Technique

Publication date: Available online 29 July 2018

Source: Injury

Author(s): Nils Jan Bleeker, Megan Cain, Mariana Rego, Aimane Saarig, Andrew Chan, Inger Sierevelt, Job N. Doornberg, Ruurd L Jaarsma

Abstract
Introduction

The purpose of this study is to evaluate the intra- and inter-observer reliability of low-dose protocolled bilateral postoperative Computed Tomography (CT)-assessment of rotational malalignment after intramedullary nailing (IMN) of tibial shaft fractures.

Materials and methods

156 patients were prospectively included with tibial shaft fractures that were treated with IMN in a Level-I Trauma Centre. All patients underwent post-operative bilateral low-dose CT-assessment (effective dose of 0.03784 – 0.05768 mGy) as per hospital protocol. Four observers performed the validated reproducible measurements of tibial torsion in degrees, based on standardized techniques. The Intra-Class Coefficient (ICC) was calculated to evaluate intra- and inter-observer reliability. The intra- and inter-observer reliability was categorized according to Landis and Koch.

Results

Intra-observer reliability for quantification of rotational malalignment on post-operative CT after IMN of tibial shaft fractures was excellent with 0.95 (95% CI = 0.92-0.97).

The overall inter-observer reliability was 0.90 (95% CI = 0.87-0.92), also excellent according Landis and Koch.

Conclusion

Firstly, bilateral post-operative low-dose –similar radiation exposure as plain chest radiographs– CT assessment of tibial rotational alignment is a reliable diagnostic imaging modality to assess rotational malalignment in patients following IMN of tibial shaft fractures and it allows for early revision surgery. Secondly, it may contribute to our understanding of the incidence-, predictors- and clinical relevance of post-operative tibial rotational malalignment in patients treated with IMN for a tibial shaft fracture, and facilitates future studies on this topic.



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BIOCHEMICAL ASSESSMENT OF NANOSTRUCTURES IN HUMAN TRABECULAR BONE: PROPOSAL OF A RAMAN MICROSPECTROSCOPY BASED MEASUREMENTS PROTOCOL

Publication date: Available online 29 July 2018

Source: Injury

Author(s): Manuel Toledano, Manuel Toledano-Osorio, Enrique Guerado, Enrique Caso, Fátima S. Aguilera, Raquel Osorio

Abstract
Background

Improvements to the understating of the compositional contributions of bone mineral and organic components to the competence of trabecular bone are crucial. The purpose of this study was to propose a protocol to study biochemical composition of trabecular bone, based on two combined Raman analysis methodologies.

Material and Methods

Both cluster and single point Raman mappings were obtained, in order to assess bone degeneration associated with aging, disease, or injury, and to help in the evaluation and development of successful therapies. In this study, human trabecular bone has been analysed throughout a) Raman cluster analysis: bone mineral content, carbonate-to-phosphate ratio (both from the mineral components), the crosslinking and nature/secondary structure of collagen (both from the organic components); and b) Single point Raman spectra, where Raman points related to the minerals and organic components were also obtained, both techniques were employed in spectra attained at 400 to 1700 cm-1.

Results

Multivariate analysis confirmed: 1) the different spectral composition, 2) the existence of centroids grouped by chemical affinity of the various components of the trabecular bone, and 3) the several traces of centroids and distribution of chemical compositional clusters.

Conclusions

This study is important, because it delivers a study protocol that provides molecular variations information in both mineral and collagen structure of trabecular bone tissue. This will enable clinicians to benefit knowing the microstructural differences in the bone subjected to degeneration of their patients.



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Worsening Head Bleeds in Elderly Blunt Head Trauma Patients Taking Antithrombotics: Delayed CT Head Fails to Change Management

Publication date: Available online 29 July 2018

Source: Injury

Author(s): Dane Scantling, Robert Kucejko, John Williamson, Alvaro Galvez, Amanda Teichman, Ryan Gruner, Nicholas Serniak, Brendan McCracken

Abstract
Background

Most elderly trauma patients suffer blunt head injury and many utilize antithrombotic (AT) medications. The utility of delayed CT-head (D-CTH) in neurologically intact elderly patients using AT who have an intracranial hemorrhage (ICH) on presentation is unknown. We hypothesized that D-CTH would not alter clinical management and aimed to evaluate the role of D-CTH in this population.

Methods

A retrospective cohort study was performed. Patients ≥65 years sustaining blunt head injuries from January 2010-July 2017 were identified using our level 1 trauma center database. AT-patients presenting with ICH who underwent D-CTH were included. Patients with worsened ICH were compared to those with stable to improved ICH on D-CTH. AT-patients were compared to a cohort of non-AT patients. Fisher's Exact and Mann-Whitney U tests were utilized and a power analysis conducted.

Results

137 A T and 34 non-AT patients were identified. There was no difference in hemorrhage progression or appearance of new ICH. No patient had a change in management from D-CTH in either cohort. AT-patients were slightly older (p < 0.001), but cohorts were otherwise similar.

50 AT-patients with worsened ICH were compared to 87 with stable ICH. There was no difference in cohort demographics. Hemorrhage progression did not vary with type of AT used but did increase if multiple types of synchronous ICH were present (p < 0.001).

Conclusions

Our data supports abstaining from routine D-CTH of elderly ICH patients with an intact neurologic examination who are utilizing aspirin, clopidogrel or warfarin. Conclusions cannot be drawn regarding new oral anticoagulants (NOACs) given low enrollment. Further multicenter study is required to provide adequate power and detect small levels of management change.



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Prediction of tibial nonunion at the 6-week time point

Publication date: Available online 29 July 2018

Source: Injury

Author(s): Keir A. Ross, Kevin O'Halloran, Renan C. Castillo, Max Coale, Justin Fowler, Jason W. Nascone, Marcus F. Sciadini, Christopher T. LeBrun, Theodore T. Manson, Robert V. O'Toole

Abstract
Introduction

Intramedullary (IM) nail fixation is a common operative treatment, yet concerns regarding the frequency of complications, such as nonunion, remain. Treatment of tibial shaft fractures remains a challenge, and little evidence of prognostic factors that increase risk of nonunion is available. The aim of this study was to develop a predictive model of tibial shaft fracture nonunion 6 weeks after reamed intramedullary (IM) nail fixation based on commonly collected clinical variables and the radiographic union score for tibial fractures (RUST).

Methods

A retrospective case-control study was conducted. All tibial shaft fractures treated at our level I trauma center from 2007 to 2014 were retrospectively reviewed. Only patients with follow-up until fracture healing or secondary operation for nonunion were included. Fracture gaps ≥3 mm were excluded. A total of 323 patients were included for study.

Results

Infection within 6 weeks of operation, standard RUST, and the Nonunion Risk Determination (NURD) score had statistically significant associations with nonunion (odds ratio > or < 1.0; p < 0.01). The NURD score was increasingly predictive of nonunion with decreasing RUST. All patients in the high RUST group (RUST ≥ 10), achieved union regardless of NURD score. In the medium RUST group (RUST 6–9), 25% of patients with a NURD score ≥7 experienced nonunion. In the low RUST group (RUST <6 or infection within 6 weeks), 69% of patients with a NURD score ≥7 experienced nonunion.

Conclusion

Three variables predicted nonunion. Based on these variables, we created a clinical prediction tool of nonunion that could aid in clinical decision making and discussing prognosis with patients.



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Effect of high frequency electromagnetic wave stimulation on muscle injury in a rat model

Publication date: June 2018

Source: Injury, Volume 49, Issue 6

Author(s): Da Hyun Song, Mi Hwa Kim, Yong-Taek Lee, Jung Hwan Lee, Kyung Ah Kim, Sang Jun Kim

Abstract
Introduction

The aim of this study was to investigate biological changes in tissues with muscle contusion after the application of high frequency (HF) electromagnetic wave.

Methods

An acrylic pipe was placed on the right hind limb and a metallic ball was dropped inside the pipe, which resulted in a muscle contusion. After acquiring the optimal condition for muscle contusion, 20 Sprague-Dawley rats were allocated to the HF treatment (N = 10) and sham groups (N = 10), which then underwent muscle contusion injury at their right thigh. The thickness and circumference of the right thigh and the left thigh (negative control groups) were measured (day 0). HF electromagnetic wave stimulation for three days was performed on the contusion area in the HF group after one day. Thickness was measured at the thickest area of both hind limbs and the circumference was measured every day for three days. The sham group received no treatment, and the circumference and thickness were measured using the same method. After three days, Hematoxylin and eosin and immunohistochemical (IHC) staining for IL-1β were performed and TUNEL assay was conducted for apoptosis in the skin and muscle layers.

Results

The thigh muscle thickness at day 1 was significantly different between groups (P = 0.018) and this difference was observed between both sham and control groups (corrected P = 0.007), and between sham and HF groups (corrected P = 0.043). Thigh circumference was significantly different at day 3 (P = 0.047) and this difference was found between sham and control groups (corrected P = 0.018), and between sham and HF groups (corrected P = 0.032). In the HF group, the inflammatory response was reduced to almost the same level as the control group. Evaluation of IL-1β level, the inflammatory cytokine, through IHC showed marked localization of IL-1β in muscle fibers of the sham group. However, significantly less IL-1β was observed in the muscle of the HF treatment group. There was neither injury nor apoptosis after HF stimulation.

Conclusions

Application of the HF showed therapeutic effect on muscle contusion by reducing muscle swelling. This effect might be caused by the anti-inflammatory action of the HF, which evoked energy into the injured muscle.



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Identification and Isolation of Oligopotent and Lineage-committed Myeloid Progenitors from Mouse Bone Marrow

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We demonstrate how to identify and isolate 6 subsets of myeloid progenitors from murine bone marrow using a combination of magnetic and fluorescence sorting (MACS and FACS). This protocol can be used for in vitro culture assays (methylcellulose or liquid cultures), in vivo adoptive transfer experiments, and RNA/protein analyses.

https://ift.tt/2LH4XOf

Nanoparticle-mediated siRNA Gene-silencing in Adult Zebrafish Heart

It remains a major challenge to develop conditional gene-knockout or effective gene-knockdown in adult zebrafish organs. Here we report a protocol for performing nanoparticle-mediated siRNA gene-silencing in adult zebrafish heart, thus providing a new loss-of-function method for studying adult organs in zebrafish and other model organisms.

https://ift.tt/2veHhGB

A Direct Force Probe for Measuring Mechanical Integration Between the Nucleus and the Cytoskeleton

In this protocol, we describe a micropipette method to directly apply a controlled force to the nucleus in a living cell. This assay allows interrogation of nuclear mechanical properties in the living, adherent cell.

https://ift.tt/2OsggZd

An Efficient Sample Preparation Method to Enhance Carbohydrate Ion Signals in Matrix-assisted Laser Desorption/Ionization Mass Spectrometry

A protocol for enhancing carbohydrate ion signals in MALDI mass spectrometry by reforming crystalline structures during sample preparation processes is demonstrated.

https://ift.tt/2OvmCXM

Establishment of a Valuable Mimic of Alzheimer's Disease in Rat Animal Model by Intracerebroventricular Injection of Composited Amyloid Beta Protein

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This is a protocol to mimic Alzheimer's Disease in rats by evaluation of spatial memory impairment, neuronal pathological changes, neuronal amyloid beta protein (Aβ) burden, and neurofibrillary tangles aggregation, induced by the injection of Aβ25-35 combined with aluminum trichloride and recombinant human transforming growth factor-β1.

https://ift.tt/2AlPA9i

Researchers are first to sequence rare bacteria that causes rampant tooth decay

Little is know about the bacteria Streptococcus sobrinus, which accelerates tooth decay in some people. This will soon change because a team of researchers has now successfully sequenced the complete genomes of three strains of S. sobrinus.

https://ift.tt/2veY3Wb

Prediction of Meniscal and Ligamentous Injuries in Lateral Tibial Plateau Fractures Based on Measurements of Lateral Plateau Widening on Multidetector Computed Tomography Scans

Background. The influence of increasing lateral plateau widening on the frequency of meniscal and ligamentous lesions in lateral tibial plateau fractures has been examined in very few studies using plain radiographs. Because the amount of this parameter cannot be measured accurately on plain radiographs, the purpose of this survey was to look for a possible correlation between the extent of lateral plateau widening, as measured on multidetector CT (MDCT) scans, and different soft-tissue injuries determined from magnetic resonance imaging (MRI). Materials and Methods. 55 patients with a lateral tibial plateau fracture were included in this retrospective case series. Patient age averaged 52.6 years (SD = 18.0). The degree of lateral plateau widening was measured on CT images. MRIs were screened for meniscal and ligamentous injuries. Results. We found a significant effect of increasing lateral plateau widening on the incidence of lateral meniscus lesions (P = 0.021), lateral collateral ligament tears (P = 0.047), and the overall quantity of meniscal and ligamentous lesions (P = 0.001). Discussion. MRIs are not widely used as a diagnostic tool in lateral plateau fractures of the tibia. Reasons might be the costs and the fact that it is a time-consuming examination. The results of this study may help to estimate the probability of specific soft-tissue lesions in lateral tibial plateau fractures based on measurements of lateral plateau widening on MDCT scans, and they may guide the decision for additional MRI and/or arthroscopically assisted repair.

https://ift.tt/2AgbryW

APLP2 Modulates JNK-Dependent Cell Migration in Drosophila

Amyloid precursor-like protein 2 (APLP2) belongs to the APP family and is widely expressed in human cells. Though previous studies have suggested a role of APLP2 in cancer progression, the exact role of APLP2 in cell migration remains elusive. Here in this report, we show that ectopic expression of APLP2 in Drosophila induces cell migration which is mediated by JNK signaling, as loss of JNK suppresses while gain of JNK enhances such phenotype. APLP2 is able to activate JNK signaling by phosphorylation of JNK, which triggers the expression of matrix metalloproteinase MMP1 required for basement membranes degradation to promote cell migration. The data presented here unraveled an in vivo role of APLP2 in JNK-mediated cell migration.

https://ift.tt/2mPYLoX

Adiponectin, Omentin, Ghrelin, and Visfatin Levels in Obese Patients with Severe Obstructive Sleep Apnea

Objectives. Obstructive sleep apnea (OSA) is closely associated with obesity, insulin resistance, and inflammation. Adiponectin, omentin, ghrelin, and visfatin are adipokines involved in insulin sensitivity or regulation of inflammatory disease. This study aims to clarify the relationship between OSA and associated adipokines. Patients and Methods. Thirty overweight male patients with severe OSA and twenty controls underwent standard diagnostic polysomnography (PSG), and 10 patients underwent overnight continuous positive airway pressure (CPAP) treatment. Blood samples were collected in the morning after PSG or CPAP procedures. Results. Among the investigated adipokines, only plasma omentin levels of patients with OSA were significantly lower than those of control subjects (442.94 ± 191.89 ng/ml versus 573.52±228.67 ng/ml, p=0.034) and levels did not change after CPAP treatment. In patients with OSA, omentin levels were positively correlated with high-density lipoprotein cholesterol (HDL) levels (r=0.378, p=0.007), adiponectin levels (r=0.709, p

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Acupuncture and Related Therapies for Treatment of Postoperative Ileus in Colorectal Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Delays in recovery of intestinal function following abdominal surgery are associated with longer hospital stays, increased postoperative complications, and higher costs to the health care system. Studies of acupuncture for postoperative ileus and other postoperative issues have reported improvements. This systematic review and meta-analysis aimed to assess whether acupuncture assisted recovery following surgery for colorectal cancer (CRC). Randomized controlled trials (RCTs) were identified from major English and Chinese language biomedical databases. Participants (aged 18 years plus) had received surgical resection for CRC. 22 studies (1,628 participants) were included. Five were sham-controlled. Outcomes included gastrointestinal function recovery (21 studies), recovery of urinary function (1 study), postoperative abdominal distension (3 studies), and quality of life (1 study). Meta-analyses found significant reductions in time to first bowel sounds, first flatus, and first defecation in both the sham-controlled and nonblinded studies. These results suggested that the addition of acupuncture following CRC surgery improved recovery of gastrointestinal function based on four blinded good quality RCTs (281 participants) and 17 nonblinded lower quality RCTs (1,265 participants). The best available evidence was for interventions that included electroacupuncture at the point ST36 Zusanli and there is supporting evidence for other types of acupuncture therapies that involve stimulation of this point. This review is registered with the following: systematic review registration in PROSPERO: CRD42017079590.

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Russell Bodies and Russell Body Inflammatory Polyp in the Colorectum: A Review of Clinicopathologic Features

Colorectal mucosa with Russell bodies is a reactive inflammatory lesion composed of mature plasma cells, known as Mott cells which contain multiple intracytoplasmic eosinophilic globules. To the best of our knowledge, 3 case reports of colorectal Russell body containing lesions have been reported in the English literature (searched from 1980 to date), including just one case report of Colonic Russell body inflammatory polyp. Their importance lies in being aware of this unusual entity, recognizing it as well as the clinical scenario in which this typically arises and differentiating it from its malignant mimics that come in the histologic differential. This review discusses the clinical and endoscopic presentation, histopathologic features, ancillary studies, pathogenesis, differential diagnosis, prognosis, and treatment of this rare lesion.

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Effect of Coenzyme Q10 on Insulin Resistance in Korean Patients with Prediabetes: A Pilot Single-Center, Randomized, Double-Blind, Placebo-Controlled Study

Introduction. This study aimed to examine whether administration of coenzyme Q10, an antioxidant, improves insulin resistance in patients with prediabetes. The study design was a pilot single-center, randomized, double-blind, placebo-controlled trial. Methods. This pilot single-center, randomized, double-blind, placebo-controlled trial included a total of 80 adults (aged ≥20 years) with impaired glucose tolerance. After the initial screening visit, subjects were assigned to either the experimental (n = 40) or placebo (n = 40) group via simple randomization. Insulin resistance was represented as the insulin resistance index estimated by homeostasis model assessment (HOMA-IR). Results. After the 8-week treatment period, the coenzyme group exhibited a significant decrease in the HOMA-IR (P

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Modified Si-Ni-San Decoction Ameliorates Central Fatigue by Improving Mitochondrial Biogenesis in the Rat Hippocampus

The traditional Chinese medicine (TCM) decoction Si-Ni-San (SNS) has been utilised for millennia to improve physiological coordination of the functions of the liver and spleen, which are regarded as the main pathological organs of central fatigue in TCM. This study evaluates the effect of a modified SNS (MSNS) formula on central fatigue in rats and explores molecular changes associated with hippocampal mitochondrial biogenesis. Central fatigue was induced through a 21-day sleep deprivation protocol. We assessed MSNS's effects on behaviour, blood and liver biomarkers, and mitochondrial ultrastructure. We found that MSNS could reverse various signs of central fatigue such as its effects on hippocampal gene and protein expression levels of sirtuin 1 (SIRT1), peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), and nuclear respiratory factor 1 (NRF1). We also observed evidence of MSNS decreasing central fatigue, such as decreasing creatine kinase activity, decreasing levels of malondialdehyde and blood urea nitrogen, increasing lactate dehydrogenase and superoxide dismutase activities, increasing mitochondrial DNA copy number, and reversing mitochondrial ultrastructure changes. These findings suggest that MSNS can ameliorate central fatigue and that its molecular mechanism involves mitochondrial biogenesis enhancement mediated by hippocampal SIRT1, PGC-1α, and NRF1.

https://ift.tt/2mRkpJD