P-316Is there any association of dose received by pelvic bone marrow in preoperative radiotherapy in rectal cancer with hematological toxicity of subsequent oxaliplatin-based chemotherapy?

Introduction: Preoperative radio(chemo)therapy in rectal cancer may irreversibly damage pelvic bone marrow (PBM) and impair the tolerance of subsequent chemotherapy. The aim of the study was to assess the association between irradiated volume of PBM and the tolerance of subsequent FOLFOX-4 chemotherapy in rectal cancer.

https://ift.tt/2K6cJBe

LBA-002Overall survival results from a phase III trial of trifluridine/tipiracil versus placebo in patients with metastatic gastric cancer refractory to standard therapies (TAGS)

Background: Trifluridine/tipiracil (FTD/TPI), an orally administered combination agent approved for patients with refractory metastatic colorectal cancer, demonstrated promising clinical activity in a refractory gastric cancer Japanese Phase II trial. Therefore, we initiated the TAGS study (NCT02500043) to evaluate the efficacy and safety of FTD/TPI in patients with heavily pretreated metastatic gastric cancer (mGC).

https://ift.tt/2K4hKdA

LBA-004Efficacy and safety results from IMblaze370, a randomised Phase III study comparing atezolizumab+cobimetinib and atezolizumab monotherapy vs regorafenib in chemotherapy-refractory metastatic colorectal cancer

Background: Patients with chemotherapy-refractory microsatellite stable (MSS) metastatic colorectal cancer (CRC) are a population with limited treatment options and relatively short survival. Atezolizumab (an anti–PD-L1 mAb) inhibits the binding of PD-L1 to its receptors PD-1 and B7.1, leading to the re-invigoration of tumour-specific T-cell immunity. Cobimetinib inhibits MEK1/MEK2 in the MAPK pathway, and blocking the MAPK pathway has been shown to favourably alter the tumour, tumour microenvironment and T-cell responses to promote anti-tumour immune activity. We hypothesized that combining atezolizumab with cobimetinib may allow better immune recognition and generate greater anti-tumour effects than either agent alone in MSS/microsatellite instability-low (MSI-L) metastatic CRC. Here we report the primary analysis results from IMblaze370 (NCT02788279), a global, multi-centre, open-label, randomised Phase III trial comparing atezolizumab+cobimetinib and atezolizumab monotherapy with standard-of-care regorafenib in patients with previously treated, unresectable locally advanced or metastatic CRC.

https://ift.tt/2Mlku2N

LBA-001Ramucirumab as second-line treatment in patients with advanced hepatocellular carcinoma (HCC) and elevated alpha-fetoprotein (AFP) following first-line sorafenib: Pooled efficacy and safety across two global randomized Phase 3 studies (REACH-2 and REACH)

Background: Ramucirumab (RAM), a human IgG1 monoclonal antibody, inhibits ligand activation of VEGFR2. REACH and REACH-2 were two global, randomized, double-blind, placebo (PBO)-controlled multicenter, phase 3 studies of RAM vs PBO in patients with HCC after prior sorafenib. REACH-2 was designed to confirm the ramucirumab treatment benefit for patients with baseline AFP ≥400 ng/mL first observed in the prespecified subgroup of patients in REACH with AFP ≥400 ng/mL. The primary endpoint of REACH-2 was met demonstrating an improved overall survival (OS) compared to PBO, a result consistent with that in patients with AFP ≥400 ng/mL in REACH. Pooled analyses of patients from REACH-2 and REACH with baseline AFP ≥400 ng/mL was performed.

https://ift.tt/2K2QU5n

LBA-003Withdrawn

https://ift.tt/2Meh0io

LBA-005KEYNOTE-061: Phase 3 study of pembrolizumab vs paclitaxel for previously treated advanced gastric or gastroesophageal junction (G/GEJ) cancer

Background: Pembrolizumab showed promising antitumor activity and a manageable safety profile in patients with pretreated G/GEJ cancer in KEYNOTE-012 and KEYNOTE-059. KEYNOTE-061 (NCT02370498) was a global, open-label phase 3 study of pembrolizumab vs paclitaxel for previously treated advanced G/GEJ adenocarcinoma that progressed after first-line chemotherapy containing platinum and fluoropyrimidine.

https://ift.tt/2KguY6g

Author Index

Abada, Paolo   LBA-001

https://ift.tt/2InosFJ

P-200Risk factors of colorectal cancer in Linxian, China: A nutrition intervention trial with 30 years follow-up

Introduction: Colorectal cancer (CRC) is one of the most common cancers in the world. Epidemiological and experimental studies have shown that some dietary factors and vitamins/minerals are associated with the risk of CRC. The Nutrition Intervention Trial (NIT) tested whether daily multivitamin/mineral supplements could reduce the incidence and mortality rate of esophageal/gastric cardia cancer. The current study evaluated the CRC risk factors at the NIT population.

https://ift.tt/2Km3jAG

P-233Trifluridine/tipiracil vs regorafenib as salvage-line treatment in patients with metastatic colorectal cancer: A multicenter retrospective study

Introduction: Trifluridine/tipiracil (TAS-102) and Regorafenib (REG) have shown promising activity in patients with heavily pretreated metastatic colorectal cancer (mCRC). The aim of this study was to compare the efficacy and safety of TAS-102 and REG alone in patients with mCRC refractory to standard chemotherapies.

https://ift.tt/2ImWBW8

P-267The prognostic impact of sidedness in RAS wild-type colorectal cancer

Introduction: Colorectal cancer (CRC) is a heterogeneous disease and sidedness [right colon (RC) vs. left colon (LC)] reflects different clinical, biological and molecular behaviors, which could have a significant prognostic impact. This study tried to evaluate the impact of sidedness on overall survival (OS) and progression-free survival (PFS) in RAS wild-type (RAS-WT) CRC patients treated with anti-EGFR antibodies in first line palliative chemotherapy.

https://ift.tt/2Km3g7Y

PD-008Molecular characterization of immune microenvironment in colorectal cancers with microsatellite instability by digital RNA counting

Introduction: Alterations in the mismatch repair (MMR) mechanism in colorectal cancers (CRCs) lead to high levels of microsatellite instability (MSI-h) causing considerable endogenous immune anti-tumor response, counterbalanced by immune inhibitory signals. We evaluated the mRNA immune-profile of a series of MSI-h CRCs to identify new potential targets for future CRC immunotherapy trials by combining an extensive gene expression analysis and the clinicopathological characteristics such as presence of metastases, staging, genotype and primary tumor sidedness.

https://ift.tt/2IndMGZ

P-300Predictive value of circulating tumor-derived DNA (ctDNA) in patients with locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiotherapy (CT-RT): Preliminary results

Introduction: In patients with LARC, neoadjuvant CT-RT followed by curative surgery is the standard of care. Risk-adopted treatment is based on MRI-predicting local T and N stage, radial margins and vascular involvement while no molecular predictive markers are available. In the present prospective study, we investigated the predictive role of serum ctDNA in patients with LARC.

https://ift.tt/2Km3cVM

P-217ABCG2 and TOP-1 as predictive biomarkers and targets for therapy in colon cancer

Introduction: There is a need for new and innovative solutions in the medical treatment of colon cancer since many of these patients eventually develop resistance to currently used drugs leading to untreatable cancer disease and death of the patients. We have by using our DEN50-R cell line based screening platform (isogenic pairs of drug sensitive and drug resistant human cancer cell lines), followed by testing in the PETACC-3 prospective randomized clinical study, identified ABCG2 and TOP1 mRNA expression as significant predictive biomarkers for irinotecan (a topoisomerase 1 inhibitor) resistance in the adjuvant treatment of colon cancer. Moreover, we have identified a new drug (SCO-101) that reverses irinotecan resistance in preclinical experiments (the DEN50-R platform). Here we present the clinical data with the biomarkers and data on SCO-101 including the clinical development plans for the drug.

https://ift.tt/2MkEPW6

P-251The prognostic ad predictive value of primary tumor sidedness in the mCRC pts

Introduction: The prognostic and predictive value of primary tumor sidedness in the pts with metastatic colorectal cancer (mCRC) is well known today. Right-sided primary was associated with high mutational burden, microsatellite instability, worse prognosis, more BRAF mutation rates and poor anti-EGFR response. We aimed to investigate the effects of tumor sidedness on survival, RAS-RAF mutation rates and responses to biologic agents in the pts with mCRC.

https://ift.tt/2Km3ax8

P-284Characteristics of colorectal cancer in the elderly patients about 60 cases

Introduction: Older people constitute a heterogeneous population, according to World Health Organization, the elderly person is defined as any individual with a chronological age equal to or higher than 60 years. In most cases, colorectal carcinoma is a disease of the elderly. Occurs mostly in the elderly people of more than 65 years and it poses public health problem. For several years geriatric evaluation has shown multiple benefits and we are witnessing a significant improvement in the oncological management of these patients.

https://ift.tt/2IjJjJX

WITHDRAWN

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O-001Efficacy of TAS-120, an irreversible fibroblast growth factor receptor (FGFR) inhibitor, in cholangiocarcinoma patients with FGFR pathway alterations who were previously treated with chemotherapy and other FGFR inhibitors

Introduction: TAS-120, an oral and highly selective, irreversible FGFR1-4 tyrosine kinase inhibitor, has demonstrated inhibition of cancer cell growth in human xenografts of tumors bearing FGFR aberrations. TAS-120 inhibited mutant and wild-type FGFR2 with similar IC50 (wild-type FGFR2, 0.9 nM; V5651, 1-3 nM; N550H, 3.6 nM; E566G, 2.4 nM) and has shown efficacy in cell lines with acquired resistance to FGFR inhibitors. In this Phase I study in patients with advanced solid tumors, TAS-120 was evaluated at 8-24 mg once daily (QD). 20 mg QD was determined as the maximum tolerated dose/recommended Phase II dose, while 24 mg QD had dose-limiting toxicity. Here we report results from cholangiocarcinoma (CCA) patients enrolled in this Phase I study.

https://ift.tt/2K3lnQR

P-191Combined analysis of KRAS, NRAS, BRAF mutations and mismatch repair deficiency testing in Indian patients with metastatic colorectal carcinoma: A single centre experience

Introduction: Molecular evaluation of KRAS, NRAS and BRAF mutation has become an important part in colorectal carcinoma evaluation as their alterations determine the therapeutic response to anti-EGFR therapy and prognosis. MMR deficiency is important for identification of Lynch syndrome families and it has now become an important biomarker of response to immunotherapy in metastatic CRC. The aim of this study is to investigate the distribution of these mutations by tumor localization and to determine the prevalence of MMR deficiency in metastatic colorectal cancer.

https://ift.tt/2IiR2Ip

P-208Autophagy (A) related proteins evaluation represents an independent survival factor of colorectal cancer (CRC) patients (pts)

Introduction: A holds a bimodal role during carcinogenesis. Before tumorigenesis, A promotes normal cells survival and suppress carcinogenesis, while after cancer development A induces cancer cells survival. The aim of this study is to assess the impact of A related proteins in the survival of CRC pts.

https://ift.tt/2K2iqQs

P-225The role of maintenance therapy in the first line treatment of metastatic colorectal cancer

Introduction: The first line of chemotherapy is decisive in the treatment of colorectal cancer. Choosing the right one allows you to increase PFS and improve long-term results. Surgical treatment and maintenance therapy (MT) increase PFS and OS, as they can be prescribed at any stage of treatment.

https://ift.tt/2Mh1rqq

Management of the Critically Ill Adult Chimeric Antigen Receptor-T Cell Therapy Patient: A Critical Care Perspective

Objectives: Chimeric antigen receptor T-cell therapy, a type of immune effector therapy for cancer, has demonstrated encouraging results in clinical trials for the treatment of patients with refractory hematologic malignancies. Nevertheless, there are toxicities specific to these treatments that, if not recognized and treated appropriately, can lead to multiple organ failure and death. This article is a comprehensive review of the available literature and provides, from a critical care perspective, recommendations by experienced intensivists in the care of critically ill adult chimeric antigen receptor T-cell patients. Data Sources: PubMed and Medline search of articles published from 2006 to date. Study Selection: Clinical studies, reviews, or guidelines were selected and reviewed by the authors. Data Extraction: Not available . Data Synthesis: Not available. Conclusions: Until modifications in chimeric antigen receptor T-cell therapy decrease their toxicities, the intensivist will play a leading role in the management of critically ill chimeric antigen receptor T-cell patients. As this novel immunotherapeutic approach becomes widely available, all critical care clinicians need to be familiar with the recognition and management of complications associated with this treatment. Drs. Gutierrez, McEvoy, Mead, Stephens, and Pastores disclosed off-label product use of siltuximab for use in cytokine release syndrome and neurotoxicity related to chimeric antigen receptor T cells. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: cgutierrez4@mdanderson.org Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

https://ift.tt/2IkW3Ah

Molecular cloning, expression and adhesion analysis of silent slpB of Lactobacillus acidophilus NCFM

The slpB gene of Lactobacillus acidophilus NCFM, which differs from the slpA gene and is silent under normal conditions, was successfully amplified and ligated to the corresponding available sites on a recombinan...

https://ift.tt/2K2KeEC

Similarities and differences in gut microbiome composition correlate with dietary patterns of Indian and Chinese adults

The interaction between diet and gut microbiota, and ultimately their link to health, has turned into the concentration of huge research. However, this relationship still needs to be fully characterized, parti...

https://ift.tt/2IoY7Y4

Clinical, genetic and neuropathological characterization of spinocerebellar ataxia type 37

Abstract

The autosomal dominant spinocerebellar ataxias (SCAs) consist of a highly heterogeneous group of rare movement disorders characterized by progressive cerebellar ataxia variably associated with ophthalmoplegia, pyramidal and extrapyramidal signs, dementia, pigmentary retinopathy, seizures, lower motor neuron signs, or peripheral neuropathy. Over 41 different SCA subtypes have been described evidencing the high clinical and genetic heterogeneity. We previously reported a novel spinocerebellar ataxia type subtype, SCA37, linked to an 11-Mb genomic region on 1p32, in a large Spanish ataxia pedigree characterized by ataxia and a pure cerebellar syndrome distinctively presenting with early-altered vertical eye movements. Here we demonstrate the segregation of an unstable intronic ATTTC pentanucleotide repeat mutation within the 1p32 5′ non-coding regulatory region of the gene encoding the reelin adaptor protein DAB1, implicated in neuronal migration, as the causative genetic defect of the disease in four Spanish SCA37 families. We describe the clinical-genetic correlation and the first SCA37 neuropathological findings caused by dysregulation of cerebellar DAB1 expression. Post-mortem neuropathology of two patients with SCA37 revealed severe loss of Purkinje cells with abundant astrogliosis, empty baskets, occasional axonal spheroids, and hypertrophic fibres by phosphorylated neurofilament immunostaining in the cerebellar cortex. The remaining cerebellar Purkinje neurons showed loss of calbindin immunoreactivity, aberrant dendrite arborization, nuclear pathology including lobulation, irregularity, and hyperchromatism, and multiple ubiquitinated perisomatic granules immunostained for DAB1. A subpopulation of Purkinje cells was found ectopically mispositioned within the cerebellar cortex. No significant neuropathological alterations were identified in other brain regions in agreement with a pure cerebellar syndrome. Importantly, we found that the ATTTC repeat mutation dysregulated DAB1 expression and induced an RNA switch resulting in the upregulation of reelin-DAB1 and PI3K/AKT signalling in the SCA37 cerebellum. This study reveals the unstable ATTTC repeat mutation within the DAB1 gene as the underlying genetic cause and provides evidence of reelin-DAB1 signalling dysregulation in the spinocerebellar ataxia type 37.

https://ift.tt/2MTGa7s

The structural basis for filovirus neutralization by monoclonal antibodies

Liam B King | Brandyn R West | Sharon L Schendel | Erica Ollmann Saphire

https://ift.tt/2KfK4ZH

Inference of Crosstalk Effects between DNA Methylation and lncRNA Regulation in NSCLC

Intercellular crosstalk effects between DNA methylation and lncRNA regulation remain elusive in lung carcinoma epigenetics. We present an application toolkit MetLnc in integration and annotation for group-wise NSCLC tissue-based DNA methylation and lncRNA profiling resources, to comprehensively analyze differentially methylated loci and lncRNAs through genome-wide analysis. Together with multiple analytic functions, MetLnc acts as an efficient approach on epigenetic omics integration and interrogation. Via the benchmark with group-wise NSCLC tissue profiling and TCGA cohort resources, we study differentially methylated CpG loci and lncRNAs as meaningful clues for inferring crosstalk effects between DNA methylation and lncRNA regulation; together we conclude with investigated biomarkers for further epigenetics and clinical trial research.

https://ift.tt/2lw6QOS

Selective Progesterone Receptor Modulators for the Medical Treatment of Uterine Fibroids with a Focus on Ulipristal Acetate

Uterine fibroids are the most frequent benign tumours in women of child-bearing age. Their symptoms are diverse and the quality of life of the women affected can be significantly impaired. While treatment to date has been primarily by means of surgical intervention, selective progesterone receptor modulators (SPRMs) open up new medication-based treatment options. EMA's Pharmacovigilance Risk Assessment Committee (PRAC) has recently completed its review of ESMYA® (ulipristal acetate, 5 mg), following reports of serious liver injury, including liver failure leading to transplantation in postmarketing settings. We will provide some information on the PRAC's recommendations to minimize this risk. Nevertheless, the effectiveness and safety of the SPRM ulipristal acetate (UPA), both with regard to preoperative administration and with regard to an intermittent administration as long-term treatment for patients with symptomatic uterine fibroids, have been shown in several clinical studies (PEARL I–IV).

https://ift.tt/2tuJGw0

Advances in Microbial and Nucleic Acids Biotechnology

https://ift.tt/2luJqJK

Molecular Imaging in Gastroenterology: a route for personalized endoscopy

With the rapid expansion and diversification of the repertoire of biological agents utilized in inflammatory bowel diseases and cancer and the increase in oncological patients in gastroenterology, visualization of single receptor or molecular target expression and the subsequent initiation of expression tailored therapy are gaining increasing attention. Through the combination of utilizing fluorescently labelled probes with high specificity towards defined molecular targets and their subsequent detection and visualisation with endoscopic devices, molecular imaging is a new emerging field focussing on the receptor expression within the mucosa on a cellular level rather than on macroscopic changes.

https://ift.tt/2yEme5a

Impact of radiotracer injection latency and seizure duration on subtraction ictal SPECT co-registered to MRI (SISCOM) performance in children

Localization of the epileptogenic zone (EZ) in patients with drug-resistant epilepsy undergoing presurgical evaluation is crucial for successful outcome and usually requires multiple investigations. It has been described that seizure activity is associated with transient focal increased cerebral blood flow in the involved cortical region (Horsley, 1892, Penfield, 1939). Subtraction ictal single-photon emission computed tomography (SPECT) co-registered to magnetic resonance imaging (SISCOM), which demonstrates regional differences in cerebral blood flow based on a differential between ictal and interictal perfusion imaging, has been shown to help improve the accuracy of epileptic focus localization, particularly in adult population (O'Brien et al., 1998b, O'Brien et al., 1999, Spanaki et al., 1999b, Kaiboriboon et al., 2002, O'Brien et al., 2004).

https://ift.tt/2ttTeHq

Effect of Accelerated infliximab induction on short- and long-term outcomes of acute severe ulcerative colitis: A retrospective multi-center study and meta-analysis

In patients with acute severe ulcerative colitis (ASUC), standard infliximab induction therapy has modest efficacy. There are limited data on the short-term or long-term efficacy of accelerated infliximab induction therapy for these patients.

https://ift.tt/2Ij9LUc

NF2 and ATRX gene copy number losses on a case of ovarian ependymoma

Ovarian ependymomas are rare glial neoplasms that typically occur in females on their 3rd to 4th decade of life. They are histologically similar to ependymomas of the central nervous system (CNS) but may have a broader immunophenotype. We describe a 27year old female who presented to the emergency room with a 3week history of cough and shortness of breath. Further workup disclosed a left pelvic mass and extensive intra-abdominal metastases. Pathology revealed sheets of monomorphic cells within a fibrillary stroma, papillary projections, true ependymal rosettes, and pseudorosettes consistent with an ependymoma of ovarian origin.

https://ift.tt/2IkAZK4

MED12 is frequently mutated in ovarian and other adnexal Leiomyomas

In the female genital tract, extra-uterine leiomyomas such as those that arise in the ovary and paraovarian/paratubal regions are rare. Currently, little is known about the background genetic changes in such adnexal leiomyomas. Recent studies have found that the MED12 mutation is common in uterine leiomyomas, which suggests that such mutations may play an oncogenic role in smooth muscle neoplasms in females. Herein, we examined a series of ovarian and other adnexal leiomyomas in terms of MED12 mutational status to investigate possible MED12 involvement in the pathogenesis of extra-uterine smooth muscle tumors.

https://ift.tt/2KcNSuG

Overexpression of signal sequence receptor γ (SSR3) predicts poor survival in patients with hepatocellular carcinoma

Signal sequence receptor subunit γ (SSR3), an SSR family member, is heavily involved in cell growth and differentiation and closely associated with many tumor types. However, the role of this protein in hepatocellular carcinoma (HCC) remains unknown. In this study, we used data from public databases to analyze SSR3 expression in HCC. We subjected 20 pairs of fresh-frozen tissues to quantitative real-time polymerase chain reaction (qRT-PCR) to investigate SSR3 expression. We also subjected 95 formalin-fixed, paraffin-embedded HCC tissues to immunohistochemistry to detect SSR3 expression and determine the clinical significance of SSR3 expression in HCC.

https://ift.tt/2KeY6aF

Ovarian carcinomas: at least five different diseases with distinct histological features and molecular genetics

Based on histopathology and molecular genetics, ovarian carcinomas are divided into five main types: high-grade serous (70%), endometrioid (10%), clear cell (10%), mucinous (3%), and low-grade serous (<5%) carcinomas. These tumors, which account for over 95% of cases, represent distinct diseases with different prognosis and treatments. TP53 mutations are identified in almost all (96%) high-grade serous carcinomas (HGSCs). Early p53 loss followed by BRCA loss leads to deficiency in homologous recombination (DHR) repair, which in turn triggers chromosomal instability and widespread somatic copy number changes.

https://ift.tt/2KdOOPn

Giant cell tumor of bone: updated molecular pathogenesis and tumor biology

GCTB-related clonal aberrations occur in a background of epigenetic histone modifications (especially, the G34 W mutation of H3F3A gene) that induce cytogenetic abnormalities. Clonal aberrations are closely linked to the aggressiveness of GCTB. The "neoplastic" mononuclear stromal cells in GCTB express fundamental RANKLs and various chemokines and cytokines associated with monocyte recruitment and "reactive" multinucleated giant cells (osteoclastogenesis). The reciprocal and orchestrated actions between mononuclear stromal cells and multinucleated giant cells helps in the understanding of the molecular pathogenesis and tumor biology of GCTB.

https://ift.tt/2IkwUFy

Low-grade dysplasia diagnosis ratio and progression metrics identify variable Barrett’s esophagus risk stratification proficiency in independent pathology practices

The diagnosis of low-grade dysplasia (LGD) in Barrett's esophagus (BE) is subject to substantial interobserver variation. Our central aim in this study is to compare independent pathology practices using objective measures of BE risk stratification proficiency, including frequency of diagnosis and rate of progression to high-grade dysplasia (HGD) or adenocarcinoma (EAC) after the first diagnosis of LGD.

https://ift.tt/2ImuiHp

Single Sensillum Recordings for Locust Palp Sensilla Basiconica

This paper describes a detailed and highly effective protocol for single sensillum recordings from the sensilla basiconica on the palps of insect mouthparts.

https://ift.tt/2KbXmDm

Fabrication of Flexible Image Sensor Based on Lateral NIPIN Phototransistors

We present a detailed method to fabricate a deformable lateral NIPIN phototransistor array for curved image sensors. The phototransistor array with an open mesh form, which is composed of thin silicon islands and stretchable metal interconnectors, provides flexibility and stretchability. The parameter analyzer characterizes the electrical property of the fabricated phototransistor.

https://ift.tt/2KfdZ4m

Evaluation of the Impact of Protein Aggregation on Cellular Oxidative Stress in Yeast

Protein aggregation elicits cellular oxidative stress. This protocol describes a method for monitoring the intracellular states of amyloidogenic proteins and the oxidative stress associated with them, using flow cytometry. The approach is used to study the behavior of soluble and aggregation-prone variants of the amyloid-β peptide.

https://ift.tt/2MiFYgN

Surface Engineering of Pancreatic Islets with a Heparinized StarPEG Nanocoating

This protocol aims to achieve surface engineering of pancreatic islets using a heparin-incorporated starPEG nanocoating via pseudo-bioorthogonal chemistry between the N-hydroxysuccinimide groups of the nanocoating and the amine groups of islet cell membrane.

https://ift.tt/2K6EBoH

Evolution in the dark: unifying our understanding of eye loss

Abstract

The evolution of eye loss in subterranean, deep sea and nocturnal habitats has fascinated biologists since Darwin wrestled with it in On the Origin of Species. This phenomenon appears consistently throughout the animal kingdom, in groups as diverse as crustaceans, salamanders, gastropods, spiders and the well-known Mexican cave fish, but the nature, extent and evolutionary processes behind eye loss remain elusive. With the advantage of new imaging, molecular, and developmental tools, eye loss has once again become the subject of intense research focus. To advance our understanding of eye loss as a taxonomically widespread and repeated evolutionary trajectory, we organized a cross-disciplinary group of researchers working on the historic question, 'how does eye loss evolve in the dark?'. The resulting set of papers showcase new progress made in understanding eye loss from the diverse fields of molecular biology, phylogenetics, development, comparative anatomy, paleontology, ecology and behaviour in a wide range of study organisms and habitats. Through the integration of these approaches, methods and results, common themes begin to emerge across the field. For the first time, we hope researchers can exploit this new synthesis to identify the broader challenges and key evolutionary questions surrounding eye evolution and so-called regressive evolution and collectively work to address them in future research.

https://ift.tt/2yA8c4x

Dim light at night: physiological effects and ecological consequences for infectious disease

Abstract

Light pollution has emerged as a pervasive component of land development over the past century. Several detrimental impacts of this anthropogenic influence have been identified in night shift workers, laboratory rodents, and a plethora of wildlife species. Circadian, or daily, patterns are interrupted by the presence of light at night and have the capacity to alter rhythmic physiological or behavioral characteristics. Indeed, biorhythm disruption can lead to metabolic, reproductive, and immunological dysfunction depending on the intensity, timing, duration and wavelength of light exposure. Light pollution, in many forms and by many pathways, is thus apt to affect the nature of host-pathogen interactions. However, no research has yet investigated this possibility. The goal of this manuscript is to outline how dim light at night (dLAN), a relevant and common form of light pollution, may affect disease dynamics by interrupting circadian rhythms and regulation of immune responses as well as opportunities for host-parasite interactions and subsequent transmission risk including spillover into humans. We close by proposing some promising interventions including alternative lighting methods or vector control efforts.

https://ift.tt/2lsixpR

Science in the Public Eye: Leveraging Partnerships—An Introduction

Abstract

With stories of struggle and dramatic breakthroughs, science has incredible potential to interest the public. However, as the rhetoric of outrage surrounds controversies over science policy there is an urgent need for credible, trusted voices that frame science issues in a way that resonates with a diverse public. A network of informal educators, park rangers, museum docents and designers, and zoo and aquarium interpreters are prepared to do so during millions of visits a year; just where science stories are most meaningfully told—in the places where members of the public are open to learning. Scientific researchers can benefit from partnerships with these intermediaries who are accorded status for their trustworthiness and good will, who have expertise in translating the science using language, metaphors, encounters, and experiences that are appropriate for non-experts. In this volume, we describe and probe examples wherein scientists work productively with informal educators and designers, artists, staff of federal agencies, citizen scientists, and volunteers who bring science into the public eye.

https://ift.tt/2yDlSMg

PET imaging of cardiomyocyte apoptosis in a rat myocardial infarction model

Abstract

Cardiomyocyte apoptosis has been observed in several cardiovascular diseases and contributes to the subsequent cardiac remodeling processes and progression to heart failure. Consequently, apoptosis imaging is helpful for noninvasively detecting the disease progression and providing treatment guidance. Here, we tested ¹⁸F-labeled 2-(5-fluoropentyl)-2-methyl-malonic acid (¹⁸F-ML-10) and ¹⁸F-labeled 2-(3-fluoropropyl)-2-methyl-malonic acid (¹⁸F-ML-8) for apoptosis imaging in rat models of myocardial infarction (MI) and compared them with ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG). MI was induced in Sprague-Dawley rats by permanent left coronary artery ligation. Procedural success was confirmed by echocardiography and positron emission tomography (PET) imaging with ¹⁸F-FDG. In vivo PET imaging with ¹⁸F-ML-10 and ¹⁸F-ML-8 was performed in the MI models at different time points after operation. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assays and immunohistochemical analyses were used to evaluate myocardial apoptosis. In vitro cell binding assays were performed to validate ¹⁸F-ML-8 binding to apoptotic cardiomyocytes. PET imaging demonstrated high ¹⁸F-ML-10 and ¹⁸F-ML-8 uptake where ¹⁸F-FDG uptake was absent. The focal accumulation of the two tracers was high on days 1 and 3 but was not notable on days 5 and 7 after surgery. The infarct-to-lung uptake ratio was 4.29 ± 0.30 for ¹⁸F-ML-10 and 3.51 ± 0.18 for ¹⁸F-ML-8 (n = 6, analyzed by averaging the uptake ratios on postoperative days 1 and 3, P < 0.05). The TUNEL results showed that myocardial cell apoptosis was closely related to the focal uptake of the apoptotic tracers in the infarct area. In addition, the apoptosis rates calculated from the TUNEL results were better correlated with ¹⁸F-ML-8 uptake than with ¹⁸F-ML-10 uptake. Ex vivo cell binding assays demonstrated that ¹⁸F-ML-8 accumulated in apoptotic cells but not in necrotic or normal cells. PET imaging using ¹⁸F-ML-10 or ¹⁸F-ML-8 allows the noninvasive detection of myocardial apoptosis in the early phase. In addition, ¹⁸F-ML-8 may be better than ¹⁸F-ML-10 for apoptosis imaging. We propose that PET imaging with ¹⁸F-ML-10 or ¹⁸F-ML-8 combined with ¹⁸F-FDG is an alternative for detecting and assessing MI.

https://ift.tt/2Kgf8oO

Nursing care of fragility fracture patients

Publication date: Available online 22 June 2018
Source:Injury
Author(s): Louise Brent, Ami Hommel, Ann Butler Maher, Karen Hertz, Anita J. Meehan, Julie Santy-Tomlinson
The challenge of caring for patients with fragility fractures is particularly acute for nursing teams who are in short supply and work with patients following fracture on a 24 h basis, coordinating as well as providing complex care. This paper considers the role of nurses within the orthogeriatric team and highlights the value of effective nursing care in patient outcomes. It explores the nature of nursing for patients with fragility fracture with a focus on the provision of safe and effective care and the coordination of care across the interdisciplinary team. It also highlights the need for specific skills in orthopaedic and geriatric nursing as well as specialist education.



https://ift.tt/2yxPeM1

Rising to the Challenge of Fragility Fractures

Publication date: Available online 22 June 2018
Source:Injury
Author(s): David Marsh, Henrik Palm




https://ift.tt/2MSlcFZ

Volar Plating in Distal Radius Fractures: A Prospective Clinical Study on Efficacy of Dorsal Tangential Views to Avoid Screw Penetration

Publication date: Available online 22 June 2018
Source:Injury
Author(s): Minke Bergsma, Job N. Doornberg, Robin Duit, Aimane Saarig, David Worsley, Ruurd Jaarsma
PurposeThe purpose of this prospective cohort study of patients treated with volar plating for distal radius fractures is to evaluate the efficacy (defined as detection rate, or the ability to detect dorsally protruding screws) of additional dorsal tangential views (DTV) after obtaining standard anteroposterior (AP) and elevated lateral views by evaluating the change in intraoperative strategy in 100 patients.Materials and Methods100 patients aged 18 years and older undergoing volar plating for acute extra- or intra- articular distal radius fractures were prospectively enrolled. Intraoperative fluoroscopy views, including AP, elevated lateral and DTV were obtained. Intraoperative –screw– revision frequency for dorsal screw protrusion, screw position relative to volar plate and to dorsal compartment, and screw lengths were evaluated.ResultsAdditional DTV led to a change of intraoperative management in 31 of 100 (31%) of patients. A total of 35 out of 504 screws (6.9%) were changed. Screws in the two most radial screws in the plate were at the highest risk of being revised; 16 (46%) screws in most radial position and nine (26%) screws in the 2nd from radial position were revised. Furthermore, five (14%) screws in both the 2nd from ulnar and most ulnar screw holes were revised after DTV. No screws were revised in the central hole. The average length of revised screws was 21 mm (range, 12 to 26 mm), and these were changed to an average length of 18 mm (range, 10 to 22 mm).ConclusionIn this prospective series of 100 patients, obtaining additional DTV is found to be efficient as it led to change in intraoperative strategy in one-third of patients. We concur with previous pilot studies that DTV, after obtaining conventional AP and elevated lateral views, is advised to avoid dorsally protruding screws, which could minimize the potential for iatrogenic extensor tendon rupture after volar plating for distal radius fractures. Diagnostic accuracy of DTV is subject of a subsequent prospective cohort study with post-operative CT to serve as the reference standard.Level of EvidenceDiagnostic II



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Clinical Research in Fragility Fractures

Publication date: Available online 22 June 2018
Source:Injury
Author(s): M A Fernandez, M L Costa
The Fragility Fracture Network is coordinating international initiatives to promote collaborative research, multidisciplinary care, and the secondary prevention of fragility fractures. This review discusses the use of national audit processes and the collection of common outcomes to facilitate research, as well as the key role played by patient and public involvement, and strategies to overcome research barriers.



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Anaesthetic aspects in the treatment of fragility fracture patients

Publication date: Available online 22 June 2018
Source:Injury
Author(s): S.M. White, N.B. Foss, R Griffiths
As longevity increases globally, the number of older, frailer, comorbid patients requiring fragility fracture surgery will increase. Fundamentally, anaesthesia should aim to maintain these patients' pre-fracture cognitive and physiological trajectories and facilitate early (ie day 1) postoperative recovery. This review describes the 10 general principles of anaesthesia for fragility fracture surgery that best achieve these aims: multidisciplinary care, 'getting it right first time', timely surgery, standardisation, sympathetic anaesthesia, avoiding ischaemia, sympathetic analgesia, re-enablement, data collection and training.



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Letter to the editor regarding “Minimally invasive plate osteosynthesis has equal safety to reamed intramedullary nails in treating Gustilo-Anderson type I, II and III-A open tibial shaft fractures”

Publication date: Available online 22 June 2018
Source:Injury
Author(s): Ahmet Imerci, Nevres Hurriyet Aydogan




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Macrocephaly, epilepsy and intracranial cysts: an image to remember

Description  

An 11-year-old, developmentally normal girl presented with recurrent seizures for the past 2 years. She was also noted to have progressively increasing head size since early infancy. She was born to non-consanguineous parents from the Aggarwal community in India and had a 7-year-old younger sister with similar problems. There was no associated history of vision impairment, tone abnormalities, cognitive or behavioural problems, extrapyramidal movements or gait changes. Examination showed head circumference of 58 cm (>3 z-scores), a single café-au-lait macule and normal bilateral fundi. The rest of the systemic examination was unremarkable. Parental head circumference was normal. She was evaluated for familial macrocephaly with epilepsy. MRI brain showed diffuse involvement of the subcortical and periventricular white matter with sparing of corpus callosum and formation of subcortical cysts (figure 1A–D). Electroencephalogram showed intermittent spike-slow waves from left temporal and right centroparietal areas and bilateral frontal intermittent rhythmic delta activity. Targeted...

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Pyrexia of unknown origin: inferior vena cava agenesis

A 26-year-old woman presented with a 5-day history of fever after returning from Bali. She denied sexual contact abroad. On examination, there was suprapubic tenderness and a widespread maculopapular rash. Malaria serology was negative and blood tests were normal except for an elevated C reactive protein. Treatment was initially with ceftriaxone, metronidazole and doxycycline, but her symptoms failed to improve. A CT pelvis suggested a possible tubo-ovarian abscess, a suspected inferior vena cava (IVC) anomaly and left internal iliac/femoral venous thrombosis. A gynaecology review demonstrated left tubo-ovarian tenderness and fullness. An MRI suggested pelvic inflammatory disease and thrombophlebitis affecting the pelvic veins; deep vein thrombosis (DVT) treatment was commenced. Further family history revealed thrombosis throughout multiple generations. Further imaging analysis demonstrated agenesis of the IVC with compensatory dilation of pelvic collaterals and an acute DVT of the deep pelvic venous system. The patient was discharged with direct oral anticoagulant therapy.

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Pregnancy and gastric cancer: diagnostic and treatment dilemma

Gastric cancer in pregnancy is an extremely rare entity. The incidence of gastric cancer is more in elderly patients and higher in the male population. Gastric cancer symptoms can be nausea, vomiting and epigastric discomfort which is similar to early pregnancy symptoms. This leads to a misinterpretation and delay in the diagnosis during pregnancy. Gastric cancer in pregnancy is associated with poor prognosis because of its delayed diagnosis at an advance stage. We present our patient here, with this rare clinical diagnosis and with no suspicion in a young healthy woman.

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Delayed leucoencephalopathy after coil embolisation of unruptured cerebral aneurysm

A 56-year-old right-handed woman was successfully treated by coil embolisation for a large unruptured paraclinoid aneurysm of the left internal carotid artery. Though she was discharged on day 3 after the intervention with uneventful clinical course, she was rehospitalised for continuous headache and right upper limb weakness 2 weeks after the treatment. Subsequent progression of cognitive dysfunction and right hemiparesis were observed. Repeated MRI revealed diffuse leucoencephalopathy within the ipsilateral brain hemisphere. Clinical course, serological examination, and radiological findings were consistent with localised hypocomplemental vasculitis caused by delayed hypersensitivity reaction. Immunosuppressive treatments using prednisolone successfully improved her symptoms. After a washout period for immunosuppressant, skin reaction test was performed and revealed polyglycolic-polylactic acid, coating material of the coil, positive for delayed allergic reaction. Given the increased frequency of endovascular treatment for unruptured aneurysms, even such a rare complication should be recognised and treated properly to avoid neurological sequelae.

https://ift.tt/2IngrRm

Pancreatic intraepithelial neoplasia in heterotopic pancreas: incidentally diagnosed on endoscopic mucosal resection of a duodenal polyp

Heterotopic pancreas is the presence of pancreatic tissue outside its normal location. It can develop similar pathological conditions that develop in the normal pancreas, including adenocarcinoma and its precursor lesions. Due to the rarity of the condition, the diagnosis can be challenging, and treatment is not well established. We present a 47-year-old female patient referred for endoscopic resection of a 2 cm polyp in the second part of her duodenum. Complete endoscopic mucosal resection (EMR) was performed, with pathology revealing low-grade pancreatic intraepithelial neoplasia (PanIN) in heterotopic pancreatic tissue. To the best of our knowledge, this is the first case of heterotopic pancreas with low-grade PanIN in the duodenum to be incidentally diagnosed and treated with EMR.

https://ift.tt/2Kfcgfi

Involvement of bilateral posterior limb of internal capsule in hypernatraemic dehydration

Description 

A 3-month-old male infant presented with loose stools and vomiting for the past 2 weeks and altered sensorium for the past 5 days. He was being administered inadequately diluted oral rehydration solution. On examination, he had moderate encephalopathy, depressed anterior fontanel and doughy skin. Laboratory investigations showed serum sodium 200 mEq/L, potassium 6.1 mEq/L, chloride 129 mEq/L, urea 136 mg/dL and creatinine 0.7 mg/dL. MRI of the brain showed predominant involvement of bilateral posterior limbs of internal capsule and genu with diffusion restriction (figure 1A–F). The baby improved with administration of free water, supportive care and gradual reduction of serum sodium. There were no seizures, and encephalopathy improved by day 3 of hospitalisation. At 3-month follow-up, he has normal development, absence of seizures or focal motor deficits.

Figure 1

(A–F) MRI brain on day 4 of illness, axial T2 (A and D), diffusion-weighted (B and E, b...

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Spontaneous intracerebral haemorrhage: a rare complication of aortic aneurysm endoleak

We present a rare case of intracerebral haemorrhage secondary to consumptive coagulopathy in relation to ongoing endoleak after thoracic endovascular aneurysm repair (TEVAR). A 68-year-old man underwent elective TEVAR for an 18 cm diameter Crawford type II thoracoabdominal aneurysm. He was subsequently shown to have a type 1b endoleak and a short episode of disseminated intravascularcoagulation (DIC) perioperatively. Two months after the procedure, he experienced a consumptive coagulopathy leading to intracerebral haemorrhage and ultimately his death. Endoleak-related DIC is an underappreciated phenomenon within the medical literature. Currently, management is reliant on general DIC principles and anecdotal experiences of others within the case report literature.

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A migratory shark bone

Fish bone ingestion is a common presentation in ENT. If not managed correctly, it can cause serious complications for the patient and dilemmas for the clinician. A 49-year-old Sri Lankan woman presented to the emergency department following shark bone ingestion with a 'pricking' sensation in her throat. After initial investigation, the bone migrated through to the sternocleidomastoid muscle. After surgical removal of the shark bone she went on to develop a large neck collection, which required surgical drainage. The careful attention to the patient's history and use of imaging facilitated treatment in this case of fish bone ingestion and management of the sequelae.

https://ift.tt/2twIZ5s

Antibody-dependent cell-mediated cytotoxicity induced by active immunotherapy based on racotumomab in non-small cell lung cancer patients

Abstract

Antitumor strategies based on positive modulation of the immune system currently represent therapeutic options with prominent acceptance for cancer patients' treatment due to its selectivity and higher tolerance compared to chemotherapy. Racotumomab is an anti-idiotype (anti-Id) monoclonal antibody (mAb) directed to NeuGc-containing gangliosides such as NeuGcGM3, a widely reported tumor-specific neoantigen in many human cancers. Racotumomab has been approved in Latin American countries as an active immunotherapy for advanced non-small cell lung cancer (NSCLC) treatment. In this work, we evaluated the induction of Ab-dependent cell-mediated cytotoxicity (ADCC) in NSCLC patients included in a phase III clinical trial, in response to vaccination with racotumomab. The development of anti-NeuGcGM3 antibodies (Abs) in serum samples of immunized patients was first evaluated using the NeuGcGM3-expressing X63 cells, showing that racotumomab vaccination developed antigen-specific Abs that are able to recognize NeuGcGM3 expressed in tumor cell membranes. ADCC response against NeuGcGM3-expressing X63 (target) was observed in racotumomab-treated- but not in control group patients. When target cells were depleted of gangliosides by treatment with a glucosylceramide synthase inhibitor, we observed a significant reduction of the ADCC activity developed by sera from racotumomab-vaccinated patients, suggesting a target-specific response. Our data demonstrate that anti-NeuGcGM3 Abs induced by racotumomab vaccination are able to mediate an antigen-specific ADCC response against tumor cells in NSCLC patients.

https://ift.tt/2K0xzlr

Antiplatelet Agents in Secondary Stroke Prevention: Selection, Timing, and Dose

Abstract

Purpose of review

This narrative review critically evaluated the published studies regarding the systematic use of antiplatelet agents for secondary stroke prevention.

Recent findings

Stroke is a leading cause of morbidity and mortality around the world. Multimodal prevention is the most viable strategy for reducing the societal burden of stroke recurrence. For secondary stroke prevention, antiplatelet therapy is at the core of effective long-term vascular risk reduction among survivors of an ischemic stroke or transient ischemic attack (TIA). In addition to aspirin, there are several antiplatelet agents proven to be efficacious in averting recurrent vascular events after an index ischemic stroke or TIA. However, beyond the challenges of keeping up with recent advances in antiplatelet drug options for secondary stroke prevention, questions linger about the most appropriate selection, timing, and dosing of antiplatelet treatment for a given patient.

Summary

We narratively summarized the pharmacological properties of key antiplatelet drugs; discussed the evidence regarding efficacy, selection, timing, and dosing of various antiplatelet treatment regimens; and highlighted ongoing clinical trials identifying novel therapies with more favorable risk-benefit profiles than currently available antiplatelet agents for patients with a recent history of ischemic or TIA stroke. Finally, we reviewed published data on antiplatelet therapies that could potentially be applied in the management of commonly encountered challenging clinical scenarios.

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Current and Emerging Therapies for Duchenne Muscular Dystrophy

Abstract

Purpose of review

The purpose of this review is to summarize the current and emerging therapies for Duchenne muscular dystrophy (DMD).

Recent findings

Coinciding with new standardized care guidelines, there are a growing number of therapeutic options to treat males with DMD. Treatment of the underlying pathobiology, such as micro-dystrophin gene replacement, exon skipping, stop codon read-through agents, and utrophin modulators showed variable success in animal and human studies. Symptomatic therapies to target muscle ischemia, enhance muscle regeneration, prevent muscle fibrosis, inhibit myostatin, and reduce inflammation are also under investigation.

Summary

DMD is a complex, heterogeneous degenerative disease. The pharmacological and technological achievements made in recent years, plus timely supportive interventions will likely lead to an improved quality of life for many individuals with DMD.

https://ift.tt/2lsylJ7

Treatment of Visual Disorders in Parkinson Disease

Abstract

Purpose of review

This article discusses visual disorders in both Parkinson disease (PD) and other Parkinsonian disorders. It is organized largely by the anatomical site of pathology and emphasizes practical treatments. Targeted treatment options include medications, surgery, occupational, and physical therapies as well as optical aids.

Recent findings

The causes of visual complaints in Parkinson disease and other similar disorders are being more clearly identified. A new medication approved specifically to treat hallucinations in PD now is available. There is increased understanding of the important role that an ophthalmologist can play in the care of these patients. Finally, research and therapeutic development are unmet needs in accessing and treating visual complaints in PD and Parkinsonian disorders.

Summary

A better understanding of Parkinson-related visual complaints and of available treatment options is important to optimize patient safety and quality of life. Vision impairment leads to difficulties in many common activities including reading, ambulating, and driving. Falls and injuries, made more likely because of impaired vision, result in an early loss of independence. Awareness of the problem, patient education, ophthalmologic care, selected therapeutics, physical therapy, and occupational therapy are crucial to maximizing quality of life in these patients.

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Management of Subdural Hematomas: Part I. Medical Management of Subdural Hematomas

Abstract

Purpose of review

Subdural hematomas (SDH) represent common neurosurgical problem associated with significant morbidity, mortality, and high recurrence rates. SDH incidence increases with age; numbers of patients affected by SDH continue to rise with our aging population and increasing number of people taking antiplatelet agents or anticoagulation. Medical and surgical SDH management remains a subject of investigation.

Recent findings

Initial management of patients with concern for altered mental status with or without trauma starts with Emergency Neurological Life Support (ENLS) guidelines, with a focus on maintaining ICP < 22 mmHg, CPP > 60 mmHg, MAP 80–110 mmHg, and PaO₂ > 60 mmHg, followed by rapid sequence intubation if necessary, and expedited acquisition of imaging to identify a space-occupying lesion. Patients are administered anti-seizure medications, and their antiplatelet medications or anticoagulation may be reversed if neurosurgical interventions are anticipated, or until hemorrhage is stabilized on imaging.

Summary

Medical SDH care focuses on (a) management of intracranial hypertension; (b) maintenance of adequate cerebral perfusion; (c) seizure prevention and treatment; (d) maintenance of normothermia, eucarbia, euglycemia, and euvolemia; and (e) early initiation of enteral feeding, mobilization, and physical therapy. Post-operatively, SDH patients require ICU level care and are co-managed by neurointensivists with expertise in treating increased intracranial pressure, seizures, and status epilepticus, as well as medical complications of critical illness. Here, we review various aspects of medical management with a brief overview of pertinent literature and clinical trials for patients diagnosed with SDH.

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Anti-IgLON 5 Disease

Abstract

Purpose of review

This review aims to give an overview about the current knowledge of this novel neurological disorder associated to IgLON-5 antibodies and its treatment.

Recent findings

Anti-IgLON5 disease was first formally described in 2014. This newly discovered disorder recaps a complex neurological disorder with sleep, movement, and neuroimmunological and neurodegenerative aspects.

Summary

The clinical manifestation of the anti-IgLON5 disease is very heterogeneous mostly including a sleep disorder with non-rapid eye movement (REM) sleep parasomnia and REM behavior disorder besides obstructive sleep apnea syndrome and stridor. Other neurological features (bulbar symptoms, gait abnormalities, cognitive dysfunction) are common. Until today, the mean age of diagnosis was mostly above the age of 60 with a balanced distribution of sex. Neuropathological examination showed neuronal loss and gliosis associated with an atypical tauopathy mainly involving the tegmentum of brainstem and hypothalamus. Although the function of the antibodies stays unclear so far, the evidence for the pathogenetic role of the antibody becomes more evident. Among the association to HLA-DRB1*10:01 and HLA-DQB1*05:01 as a potential factor for susceptibility, immunopathological findings are promising. So far, the pathophysiology of anti-IgLON5 disease is not sufficiently enlightened and needs more interdisciplinary approach to a better understanding of this interesting disorder at the border of autoimmunity and neurodegeneration. Immunotherapy has been frequently used but its therapeutic effect is limited.

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Bacterial and fungal communities in boreal forest soil are insensitive to changes in snow cover conditions

ABSTRACT

The northern regions are experiencing considerable changes in winter climate leading to more frequent warm periods, rain-on-snow events and reduced snow pack diminishing the insulation properties of snow cover and increasing soil frost and freeze-thaw cycles. In this study, we investigated how the lack of snow cover, formation of ice encasement and snow compaction affect the size, structure and activities of soil bacterial and fungal communities. Contrary to our hypotheses, snow manipulation treatments over one winter had limited influence on microbial community structure, bacterial or fungal copy numbers or enzyme activities. However, microbial community structure and activities shifted seasonally among soils sampled before snow melt, in early and late growing season and seemed driven by substrate availability. Bacterial and fungal communities were dominated by stress-resistant taxa such as the orders Acidobacteriales, Chaetothyriales and Helotiales that are likely adapted to adverse winter conditions. This study indicated that microbial communities in acidic northern boreal forest soil may be insensitive to direct effects of changing snow cover. However, in long-term, the detrimental effects of increased ice and frost to plant roots may alter plant derived carbon and nutrient pools to the soil likely leading to stronger microbial responses.

https://ift.tt/2KdQipF

Intronic pentanucleotide TTTCA repeat insertion in the SAMD12 gene causes familial cortical myoclonic tremor with epilepsy type 1

Abstract

Familial cortical myoclonic tremor with epilepsy is an autosomal dominant neurodegenerative disease, characterized by cortical tremor and epileptic seizures. Although four subtypes (types 1–4) mapped on different chromosomes (8q24, 2p11.1-q12.2, 5p15.31-p15.1 and 3q26.32-3q28) have been reported, the causative gene has not yet been identified. Here, we report the genetic study in a cohort of 20 Chinese pedigrees with familial cortical myoclonic tremor with epilepsy. Linkage and haplotype analysis in 11 pedigrees revealed maximum two-point logarithm of the odds (LOD) scores from 1.64 to 3.77 (LOD scores in five pedigrees were >3.0) in chromosomal region 8q24 and narrowed the candidate region to an interval of 4.9 Mb. Using whole-genome sequencing, long-range polymerase chain reaction and repeat-primed polymerase chain reaction, we identified an intronic pentanucleotide (TTTCA)_n insertion in the SAMD12 gene as the cause, which co-segregated with the disease among the 11 pedigrees mapped on 8q24 and additional seven unmapped pedigrees. Only two pedigrees did not contain the (TTTCA)_n insertion. Repeat-primed polymerase chain reaction revealed that the sizes of (TTTCA)_n insertion in all affected members were larger than 105 repeats. The same pentanucleotide insertion (ATTTCATTTC)₅₈ has been reported to form RNA foci resulting in neurotoxicity in spinocerebellar ataxia type 37, which suggests the similar pathogenic process in familial cortical myoclonic tremor with epilepsy type 1.

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Interplay between spinal cord and cerebral cortex metabolism in amyotrophic lateral sclerosis

Abstract

We recently reported the potential of Hough transform in delineating spinal cord metabolism by ¹⁸F-fluorodeoxyglucose PET/CT scanning in amyotrophic lateral sclerosis. The present study aimed to verify the relationship between spinal cord and brain metabolism in 44 prospectively recruited patients affected by amyotrophic lateral sclerosis submitted to ¹⁸F-fluorodeoxyglucose brain and whole-body PET/CT. Patients were studied to highlight the presence of brain hypo- or hypermetabolism with respect to healthy controls, and multiple regression analysis was performed to evaluate the correlation between spinal cord and brain metabolism. Our results confirmed higher ¹⁸F-fluorodeoxyglucose uptake in both cervical and dorsal spinal cord in patients with amyotrophic lateral sclerosis with respect to controls. This finding was paralleled by the opposite pattern in the brain cortex that showed a generalized reduction in tracer uptake. This hypometabolism was particularly evident in wide regions of the frontal-dorsolateral cortex while it did not involve the midbrain. Bulbar and spinal disease onset was associated with similar degree of metabolic activation in the spinal cord. However, among spinal onset patients, upper limb presentation was associated with a more pronounced metabolic activation of cervical segment. Obtained data suggest a differential neuro-pathological state or temporal sequence in disease progression.

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The Suffering of Children

New England Journal of Medicine, Ahead of Print.


https://ift.tt/2tD3GwH

Housing Immigrant Children — The Inhumanity of Constant Illumination

New England Journal of Medicine, Ahead of Print.


https://ift.tt/2MRv1Ea

Rotating Bacteria on Solid Surfaces Without Tethering

Bacterial motion is strongly affected by the presence of a surface. One of the hallmarks of swimming near a surface is a defined curvature of bacterial trajectories, underlining the importance of counter rotations of the cell-body and flagellum for locomotion of the microorganism. We find that there is another mode of bacterial motion on solid surfaces, i.e., self trapping due to fluid flows created by a rotating flagellum perpendicular to the surface. For a rod-like bacterium, such as Escherichia coli, this creates a peculiar situation in that the bacterium appears to swim along a minor axis of the cell body and is pressed against the surface.

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A Changing Landscape in Pancreatic Cancer

No abstract available

https://ift.tt/2l3p2PF

Incisional Hernia After Midline Versus Transverse Specimen Extraction Incision: A Randomized Trial in Patients Undergoing Laparoscopic Colectomy

Objective: To compare the incidence of incisional hernia (IH) between midline and transverse specimen extraction site in patients undergoing laparoscopic colectomy. Background: Midline specimen extraction incision is most commonly used in laparoscopic colectomy, but has high IH risk. IH may be lower for transverse incision. Methods: A single-center superiority trial was conducted. Eligible patients undergoing laparoscopic colectomy were randomly assigned to midline or transverse specimen extraction. Primary outcome was IH incidence at 1 year. Power calculation required 76 patients per group to detect a reduction in IH from 20% to 5%. Secondary outcomes included perioperative outcomes, pain scores, health-related quality of life (SF-36), and cosmesis (Body Image Questionnaire). Results: A total of 165 patients were randomly assigned to transverse (n = 79) or midline (n = 86) specimen extraction site, of which 141 completed 1-year follow-up (68 transverse, 73 midline). Patient, tumor, surgical data, and perioperative morbidity were similar. Pain scores were similar on each postoperative day. On intention-to-treat analysis, there was no difference in the incidence of IH at 1 year (transverse 2% vs midline 8%, P = 0.065) or after mean 30.3 month (standard deviation 9.4) follow-up (6% vs 14%, P = 0.121). On per-protocol analysis there were more IH after midline incision with longer follow-up (15% vs 2%, P = 0.013). On intention-to-treat analysis, SF-36 domains body pain and social functioning were improved after transverse incision. Cosmesis was higher after midline incision on per-protocol analysis, but without affecting body image. Conclusions: Per-protocol analysis of this trial demonstrates that a transverse specimen extraction site has a lower incidence of IH compared to midline with longer follow-up but has worse cosmesis.

https://ift.tt/2l64q9s

Electroencephalographic Arousal Patterns Under Dexmedetomidine Sedation

BACKGROUND: The depth of dexmedetomidine-induced sedation is difficult to assess without arousing the patient. We evaluated frontal electroencephalogram (EEG) as an objective measure of dexmedetomidine-induced sedation. Our aims were to characterize the response patterns of EEG during a wide range of dexmedetomidine-induced sedation and to determine which spectral power best correlated with assessed levels of dexmedetomidine-induced sedation. METHODS: Sedline EEG sensor was positioned on the forehead of 16 volunteers. Frontal EEG data were collected at 250 Hz using the Sedline monitor. A computer-controlled infusion pump was used to infuse dexmedetomidine to four 15-minute target plasma concentrations of 0.3, 0.6, 1.2, and 2.4 ng/mL. Arterial blood samples for dexmedetomidine plasma concentration and sedation (self-reported numerical rating scale) and arousal were measured at baseline and at the end of each infusion step. The EEG signal was used to estimate spectral power in sequential 4-second data segments with 75% overlap for 3 power bands: delta = 0.5–1.5 Hz, alpha = 9–14 Hz, beta = 15–24 Hz. We quantified the relationships among the plasma concentrations of dexmedetomidine, level of sedation, and various EEG parameters. RESULTS: EEG data at the end of the dexmedetomidine infusion steps show progressive loss of high frequencies (beta) and increase in alpha and delta powers, with increasing dexmedetomidine concentrations. Beta prearousal spectral power was best in predicting dexmedetomidine-induced level of sedation (R = −0.60, 95% CI, −0.43 to −0.75). The respective values for delta and alpha powers were R = 0.28 (95% CI, 0.03–0.45) and R = 0.16 (95% CI, −0.09 to 0.38). When the beta power has dropped below −16 dB or the delta power is above 15 dB, the subjects show moderate to deep levels of sedation. When awakening the subject, there is a reduction in power in the delta and alpha bands at the 0.6, 1.2, and 2.4 ng/mL dexmedetomidine target levels (P

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Driving Under the Influence of Cannabis: A Framework for Future Policy

Marijuana is the most widely consumed illicit substance in the United States, and an increasing number of states have legalized it for both medicinal and recreational purposes. As it becomes more readily available, there will be a concurrent rise in the number of users and, consequently, the number of motor vehicle operators driving under the influence. This article examines the cognitive and psychomotor effects of cannabis, as well as current policy concerning driving under the influence of drugs. The authors performed a MEDLINE search on the epidemiology of cannabis use, its cognitive and psychomotor effects, and policies regarding driving under the influence of drugs. Twenty-eight epidemiological studies, 16 acute cognitive and psychomotor studies, 8 chronic cognitive and psychomotor studies, and pertinent state and federal laws and policies were reviewed. These search results revealed that marijuana use is associated with significant cognitive and psychomotor effects. In addition, the legalization of marijuana varies from state to state, as do the laws pertaining to driving under the influence of drugs. Marijuana is a commonly found illicit substance in motor vehicle operators driving under the influence of drugs. Current evidence shows that blood levels of tetrahydrocannabinol do not correlate well with the level of impairment. In addition, although acute infrequent use of cannabis typically leads to cognitive and psychomotor impairment, this is not consistently the case for chronic heavy use. To establish the framework for driving under the influence of cannabis policy, we must review the current published evidence and examine existing policy at state and federal levels. Accepted for publication May 10, 2018. Funding: This study was partially funded by the Centers for Rehabilitation Sciences Research, US Department of Defense. The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/KegmMq). Reprints will not be available from the authors. Address correspondence to Robert M. Chow, MD, Department of Anesthesiology, Yale School of Medicine, 330 Cedar St, TMP-3, New Haven, CT 06520. Address e-mail to Robert.chow@yale.edu. © 2018 International Anesthesia Research Society

https://ift.tt/2tvg0ig

The Suffering of Children

New England Journal of Medicine, Ahead of Print.


https://ift.tt/2tD3GwH

Housing Immigrant Children — The Inhumanity of Constant Illumination

New England Journal of Medicine, Ahead of Print.


https://ift.tt/2MRv1Ea

Perioperative Management in Hepatic Resections: Comparative Effectiveness of Neuraxial Anesthesia and Disparity of Care Patterns

BACKGROUND: Complication rates after hepatic resection can be affected by management decisions of the hospital care team and/or disparities in care. This is true in many other surgical populations, but little study has been done regarding patients undergoing hepatectomy. METHODS: Data from the claims-based national Premier Perspective database were used for 2006 to 2014. The analytical sample consisted of adults undergoing partial hepatectomy and total hepatic lobectomy with anesthesia care consisting of general anesthesia (GA) only or neuraxial and GA (n = 9442). The key independent variable was type of anesthesia that was categorized as GA versus GA + neuraxial. The outcomes examined were clinical complications and health care resource utilization. Unadjusted bivariate and adjusted multivariate analyses were conducted to examine the effects of the different types of anesthesia on clinical complications and health care resource utilization after controlling for patient- and hospital-level characteristics. RESULTS: Approximately 9% of patients were provided with GA + neuraxial anesthesia during hepatic resection. In multivariate analyses, no association was observed between types of anesthesia and clinical complications and/or health care utilization (eg, admission to intensive care unit). However, patients who received blood transfusions were significantly more likely to have complications and intensive care unit stays. In addition, certain disparities of care, including having surgery in a rural hospital, were associated with poorer outcomes. CONCLUSIONS: Neuraxial anesthesia utilization was not associated with improvement in clinical outcome or cost among patients undergoing hepatic resections when compared to patients receiving GA alone. Future research may focus on prospective data sources with more clinical information on such patients and examine the effects of GA + neuraxial anesthesia on various complications and health care resource utilization. Accepted for publication May 14, 2018. Funding: None. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Jeron Zerillo, MD, Department of Anesthesiology, Mount Sinai School of Medicine, 1 Gustave L Levy Pl, New York, NY 10029. Address e-mail to jeron.zerillo@mountsinai.org. © 2018 International Anesthesia Research Society

https://ift.tt/2ltuYSg

High-Fidelity Simulation Nurse Training Reduces Unplanned Interruption of Continuous Renal Replacement Therapy Sessions in Critically Ill Patients: The SimHeR Randomized Controlled Trial

BACKGROUND: Although continuous renal replacement therapy (CRRT) is common, unplanned interruptions (UI) often limit its usefulness. In many units, nurses are responsible for CRRT management. We hypothesized that a nurse training program based on high-fidelity simulation would reduce the rate of interrupted sessions. METHODS: We performed a 2-phase (training and evaluation), randomized, single-center, open study: During the training phase, intensive care unit nurses underwent a 6-hour training program and were randomized to receive (intervention) or not (control) an additional high-fidelity simulation training (6 hours). During the evaluation phase, management of CRRT sessions was randomized to either intervention or control nurses. Sessions were defined as UI if they were interrupted and the interruption was not prescribed in writing more than 3 hours before. RESULTS: Study nurses had experience with hemodialysis, but no experience with CRRT before training. Intervention nurses had higher scores than control nurses on the knowledge tests (grade, median [Q1–Q3], 14 [10.5–15] vs 11 [10–12]/20; P = .044). During a 13-month period, 106 sessions were randomized (n = 53/group) among 50 patients (mean age 70 ± 13 years, mean simplified acute physiology II score 69 [54–96]). Twenty-one sessions were not analyzed (4 were not performed and 17 patients died during sessions). Among the 42 intervention and 43 control sessions analyzed, 25 (59%) and 38 (88%) were labeled as UI (relative risk [95% CI], 0.67 [0.51–0.88]; P = .002). Intervention nurses required help significantly less frequently (0 [0–1] vs 3 [1–4] times/session; P

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Variable Ventilation Associated With Recruitment Maneuver Minimizes Tissue Damage and Pulmonary Inflammation in Anesthetized Lung-Healthy Rats

BACKGROUND: Recruitment maneuver and positive end-expiratory pressure (PEEP) can be used to counteract intraoperative anesthesia-induced atelectasis. Variable ventilation can stabilize lung mechanics by avoiding the monotonic tidal volume and protect lung parenchyma as tidal recruitment is encompassed within the tidal volume variability. METHODS: Forty-nine (7 per group) male Wistar rats were anesthetized, paralyzed, and mechanically ventilated. A recruitment maneuver followed by stepwise decremental PEEP titration was performed while continuously estimating respiratory system mechanics using recursive least squares. After a new recruitment, animals were ventilated for 2 hours in volume-control with monotonic (VCV) or variable (VV) tidal volumes. PEEP was adjusted at a level corresponding to the minimum elastance or 2 cm H2O above or below this level. Lungs were harvested for histologic analysis (left lung) and cytokines measurement (right lung). Seven animals were euthanized before the first recruitment as controls. RESULTS: A time-dependent increase in respiratory system elastance was observed and significantly minimized by PEEP (P

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Perioperative Hydroxyethyl Starch: A Potential Threat to a Patient Safety

No abstract available

https://ift.tt/2yAVCSL

Propofol Attenuates the Myocardial Protection Properties of Desflurane by Modulating Mitochondrial Permeability Transition

BACKGROUND: Desflurane and propofol are cardioprotective, but relative efficacy is unclear. The aim was to compare myocardial protection of single, simultaneous, and serial administration of desflurane and propofol. METHODS: Sixty New Zealand White rabbits and 65 isolated Sprague Dawley rat hearts randomly received desflurane, propofol, simultaneous desflurane and propofol, or sequential desflurane then propofol. Rabbits were subdivided to receive either ischemia-reperfusion with temporary occlusion of the left anterior descending artery or a time-matched, nonischemic perfusion protocol, whereas rat hearts were perfused in a Langendorff model with global ischemia-reperfusion. End points were hemodynamic, functional recovery, and mitochondrial uptake of 3H-2-deoxy-D-glucose as an indicator of mitochondrial permeability transition. RESULTS: In rabbits, there were minimal increases in preload-recruitable stroke-work with propofol(P

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Spinal Activation of Tropomyosin Receptor Kinase-B Recovers the Impaired Endogenous Analgesia in Neuropathic Pain Rats

BACKGROUND: Although endogenous analgesia plays an important role in controlling pain states, chronic pain patients exhibit decreased endogenous analgesia compared to healthy individuals. In rats, noxious stimulus–induced analgesia (NSIA), which is an indicator of endogenous analgesia, diminished 6 weeks after spinal nerve ligation (SNL6W). A recent study in rats with deleted noradrenergic fibers demonstrated that the noradrenergic fibers were essential to NSIA. It has also been reported that brain-derived neurotrophic factor increased spinal noradrenergic fibers. Therefore, this study examined the effect of TrkB activation, which is the receptor for brain-derived neurotrophic factor, on impaired NSIA in SNL6W rats. In addition, we also examined the effect of endogenous analgesia on acute incisional pain. METHODS: After 5 daily intraperitoneal injections of 7,8-dihydroxyflavone (7,8-DHF, TrkB agonist, 5 mg/kg), NSIA was examined by measuring the withdrawal threshold increment in the left (contralateral to nerve ligation) hindpaw at 30 minutes after capsaicin injection (250 μg) in the forepaw. K252a (TrkB antagonist, 2 μg) was administrated intrathecally for 5 days. Idazoxan (α2 adrenoceptor antagonist, 30 μg), atropine (muscarinic antagonist, 30 μg), and propranolol (nonselective β adrenoceptor antagonist, 30 μg) were administered intrathecally for 15 minutes before capsaicin injection. Microdialysis and immunohistochemistry were performed to examine the noradrenergic plasticity in the spinal dorsal horn. A hindpaw incision was performed on the left (contralateral to nerve ligation) hindpaw. Data were analyzed by 1-way analyses of variance or 2-way repeated-measures 1-way analysis of variance followed by a Student t test with Bonferroni correction. RESULTS: Five daily intraperitoneal injections of 7,8-DHF restored the attenuated NSIA in SNL6W rats (n = 7, P = .002; estimated treatment effect [95% CI]: 62.9 [27.0–98.7] g), with this effect blocked by 5 daily intrathecal coadministrations of K252a (n = 6, P

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Incidence of Venous Air Embolism During Endoscopic Retrograde Cholangiopancreatography

BACKGROUND: Known complications of endoscopic retrograde cholangiopancreatography (ERCP) include pancreatitis, bleeding, duodenal perforation, and venous air embolism (VAE). The aim of this study was to determine the incidence of VAE during ERCP and be able to differentiate high-risk versus low-risk ERCP procedures. METHODS: This is a prospective cohort study consisting of patients who underwent ERCP and were monitored with a precordial Doppler ultrasound (PDU) for VAE. PDU monitoring was digitally recorded and analyzed to confirm the suspected VAE. Demographic and clinical data related to the anesthetic care, endoscopic procedure, and intraoperative hemodynamics were analyzed. RESULTS: A total of 843 ERCP procedures were performed over a 15-month period. The incidence of VAE was 2.4% (20 patients). All VAE's occurred during procedures in which stent placement, sphincterotomy, biopsy, duct dilation, gallstone retrieval, cholangioscopy, or necrosectomy occurred. Ten of 20 (50%) of VAEs were associated with hemodynamic alterations. None occurred if the procedure was only diagnostic or for stent removal. Subanalysis for the type of procedure showed that VAE was statistically more frequent when stents were removed and then replaced or if a cholangioscopy was performed. CONCLUSIONS: The high incidence of VAE highlights the need for practitioners to be aware of this potentially serious event. Use of PDU can aid in the detection of VAE during ERCP and should be considered especially during high-risk therapeutic procedures. Detection may allow appropriate interventions before serious adverse events such as cardiovascular collapse occur. Accepted for publication January 19, 2018. Funding: None. The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/KegmMq). Reprints will not be available from the authors. Address correspondence to Ayesha S. Bryant, MSPH, MD, Department of Anesthesiology and Perioperative Medicine, University of Alabama at Birmingham, 625 19th St S, JT 880A, Birmingham, AL 35249. Address e-mail to asbryant@uabmc.edu. © 2018 International Anesthesia Research Society

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Association Between Intraoperative Oliguria and Acute Kidney Injury After Major Noncardiac Surgery

BACKGROUND: Acute kidney injury (AKI) occurs in 6.1%–22.4% of patients undergoing major noncardiac surgery. Previous studies have shown no association between intraoperative urine output and postoperative acute renal failure. However, these studies used various definitions of acute renal failure. We therefore investigated the association between intraoperative oliguria and postoperative AKI defined by the serum creatinine criteria of the Risk, Injury, Failure, Loss, and End-stage kidney disease (RIFLE) classification. METHODS: In this single-center, retrospective, observational study, we screened 26,984 patients undergoing elective or emergency surgery during the period September 1, 2008 to October 31, 2011 at a university hospital. Exclusion criteria were age

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In Response

No abstract available

https://ift.tt/2txuk9Y

Overdiagnosis Should Not Be a Factor in Formulating Age-of-Onset and Screening-Interval Guidelines

American Journal of Roentgenology, Volume 211, Issue 1, Page W79-W79, July 2018.


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Accurate Inputs for Costs and Benefits of Screening Mammography

American Journal of Roentgenology, Volume 211, Issue 1, Page W80-W80, July 2018.


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What Is Benign Posttraumatic Pseudopneumoperitoneum? Where Does the Gas Come From?

American Journal of Roentgenology, Volume 211, Issue 1, Page W77-W77, July 2018.


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Incomplete Assumptions and Treatment Options Affect the Results of a Monte Carlo Simulation of Two Screening Mammography Strategies

American Journal of Roentgenology, Volume 211, Issue 1, Page W81-W81, July 2018.


https://ift.tt/2MS4SoA

On the Importance of Accurate Inputs and Assumptions for Screening Mammography Modeling

American Journal of Roentgenology, Volume 211, Issue 1, Page W82-W83, July 2018.


https://ift.tt/2yAecub

The Origin of Benign Posttraumatic Pseudopneumoperitoneum Is Not Clear

American Journal of Roentgenology, Volume 211, Issue 1, Page W78-W78, July 2018.


https://ift.tt/2tkp0r4

Spectrum of Pitfalls, Pseudolesions, and Misdiagnoses in Noncirrhotic Liver

American Journal of Roentgenology, Volume 211, Issue 1, Page 97-108, July 2018.


https://ift.tt/2yCPnxK

Spectrum of Pitfalls, Pseudolesions, and Potential Misdiagnoses in Cirrhosis

American Journal of Roentgenology, Volume 211, Issue 1, Page 87-96, July 2018.


https://ift.tt/2ttgEhh

ARRS Annual Planning Meeting: Process Challenges and Modifications

American Journal of Roentgenology, Volume 211, Issue 1, Page 1-2, July 2018.


https://ift.tt/2txHZxX