Basidiobolomycosis in Togo: clinico-pathological study of a series of 12 presumed cases

The purpose of our study was to describe the histological diagnosed of the Basidiobolomycosis cases from 1990 to 2017 (28 years) in the only Pathology Anatomy Laboratory in Togo.

https://ift.tt/2NaDiqp

The State of the States: Growing PhysiatryAssociation of Academic Physiatrists Position Statement Addressing Academic Physiatry and PM&R Growth

The growth of physiatry in the United States is dependent upon academic exposure at both the undergraduate and graduate medical education levels. Undergraduate medical education provides students with knowledge of physiatry, as well as proper understanding of human function, medical rehabilitation treatments, and of physiatrists as consultants. Graduate medical education contributes more directly to the total number of practicing physiatrists. This paper presents disparities in medical student exposure to physiatry, PM&R residency positions, the number of practicing physiatrists, and PM&R-relevant patient care needs, by state. In the model, these disparities are highlighted to provide guidance and expose gaps/opportunities for targeted physiatric growth. Correspondence: Danielle Perret Karimi, Associate Clinical Professor, Department of Physical Medicine and Rehabilitation, University of California, Irvine, 101 The City Drive South, Orange, CA 92868 Author Disclosures: All authors state no competing interests, funding, grants or equipment provided for the project from any source; nor financial benefits to the authors. There are no previous presentations or submissions of this research. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2p9uyCB

Effects of Doxorubicin on the Liquid-Liquid Phase Change Properties of Elastin-Like Polypeptides

The Lower Critical Solution Temperature (LCST) of the thermo-responsive engineered Elastin-Like Polypeptides (ELP) biopolymer is being exploited for the thermal targeted delivery of Doxorubicin (Dox) to solid tumors. We examine the impact of Dox labeling on the thermodynamic and hydrodynamic behavior of an ELP drug carrier and how Dox influences the liquid-liquid phase change. Turbidity, Dynamic Light Scattering (DLS) and Differential Scanning Calorimetry (DSC) measurements show that ELP undergoes a cooperative liquid-liquid phase separation (LLPS) from a soluble to insoluble coacervated state that is enhanced by Dox labeling.

https://ift.tt/2xrxZZ9

Accurate in silico modeling of asymmetric bilayers based on biophysical principles

Technological advances in the last decade have enabled the study of ever more complex and physiologically relevant model membranes to help dispel the mystery surrounding the role of plasma membrane asymmetry in various cellular processes. The slowly accumulating body of experimental data is fueling renewed interest in, and the need for, computational methods to support interpretations and address a wide range of problems that are still not amenable to direct experimental study. The specific appeal of molecular dynamics (MD) simulations for this purpose lies in their ability to access information at atomic resolution, which is useful for the formulation of testable mechanistic hypotheses.

https://ift.tt/2xhrxDW

Diffusion of exit sites on the endoplasmic reticulum – a random walk on a shivering backbone

Major parts of the endoplasmic reticulum (ER) in eukaryotic cells are organized as a dynamic network of membrane tubules connected by three-way junctions. On this network, self-assembled membrane domains, called ER exit sites (ERES), provide platforms at which nascent cargo proteins are packaged into vesicular carriers for subsequent transport along the secretory pathway. While ERES appear stationary and spatially confined on long time scales, we show here via single-particle tracking that they exhibit a microtubule-dependent and heterogeneous anomalous diffusion behavior on short and intermediate time scales.

https://ift.tt/2NeUbjT

Body ownership and the absence of touch: approaching the rubber hand inside and outside peri-hand space

Abstract

It is widely accepted that the integration of visual and tactile information is a necessity to induce ownership over a rubber hand. This idea has recently been challenged by Ferri et al. (Proc R Soc B 280:1–7, 2013), as they found that sense of ownership was evident by mere expectation of touch. In our study, we aimed to further investigate this finding, by studying whether the mere potential for touch yields a sense of ownership similar in magnitude to that resulting from actually being touched. We conducted two experiments. In the first experiment, our set-up was the classical horizontal set-up (similar to Botvinick and Cohen, Nature 391:756, 1998). Sixty-three individuals were included and performed the classical conditions (synchronous, asynchronous), an approached but not touched (potential for touch), and a 'visual only' condition. In the second experiment, we controlled for differences between the current set-up and the vertical set-up used by Ferri et al. (Proc R Soc B 280:1–7, 2013). Fifteen individuals were included and performed a synchronous and various approaching conditions [i.e., vertical approach, horizontal approach, and a control approach (no hands)]. In our first experiment, we found that approaching the rubber hand neither induced a larger proprioceptive drift nor a stronger subjective sense of ownership than asynchronous stimulation did. Generally, our participants gained most sense of ownership in the synchronous condition, followed by the visual only condition. When using a vertical set-up (second experiment), we confirmed previous suggestions that tactile expectation was able to induce embodiment over a foreign hand, similar in magnitude to actual touch, but only when the real and rubber hand were aligned on the vertical axis, thus along the trajectory of the approaching stimulus. These results indicate that our brain uses bottom-up sensory information, as well as top-down predictions for building a representation of our body.

https://ift.tt/2xbpphN

A High-throughput Quantitative Expression Analysis of Cancer-related Genes in Human HepG2 Cells in Response to Limonene, a Potential Anticancer Agent

Background: Citrus bioactive compounds, as active anticancer agents, have been under focus by several studies worldwide. However, the underlying genes responsible for the anticancer potential have not been sufficiently highlighted.

Objectives: The current study investigated the gene expression profile of hepatocellular carcinoma, HepG2, cells after treatment with Limonene.

Methods: The concentration that killed 50% of HepG2 cells was used to elucidate the genetic mechanisms of limonene anticancer activity. The apoptotic induction was detected by flow cytometry and confocal fluorescence microscope. Two of the pro-apoptotic events, caspase-3 activation and phosphatidylserine translocation were manifested by confocal fluorescence microscopy. Highthroughput real-time PCR was used to profile 1023 cancer-related genes in 16 different gene families related to the cancer development.

Results: In comparison to untreated cells, limonene increased the percentage of apoptotic cells up to 89.61%, by flow cytometry, and 48.2% by fluorescence microscopy. There was a significant limonene- driven differential gene expression of HepG2 cells in 15 different gene families. Limonene was shown to significantly (>2log) up-regulate and down-regulate 14 and 59 genes, respectively. The affected gene families, from the most to the least affected, were apoptosis induction, signal transduction, cancer genes augmentation, alteration in kinases expression, inflammation, DNA damage repair, and cell cycle proteins.

Conclusion: The current study reveals that limonene could be a promising, cheap, and effective anticancer compound. The broad spectrum of limonene anticancer activity is interesting for anticancer drug development. Further research is needed to confirm the current findings and to examine the anticancer potential of limonene along with underlying mechanisms on different cell lines.

https://ift.tt/2NIoKOe

Therapeutic Approaches for the Treatment of Epidermal Growth Factor Receptor Mutated Lung Cancer

Lung cancer surfaces to be the predominant determinant of mortality worldwide constituting 13% and 19% of all new cancer cases and deaths related to cancer respectively. Molecular profiling has now become a regular trend in lung cancer to identify the driver mutations. Epidermal Growth Factor Receptor (EGFR) is the most regular driver mutation encountered in Non-Small Cell Lung Cancer (NSCLC). Targeted therapies are now available for the treatment of EGFR mutant NSCLC. EGFR mutation is more frequently expressed in adenocarcinoma than squamous cell carcinoma. This article presents a detailed molecular insight of the therapeutic approaches for the treatment of EGFR mutant lung cancer. The article delineates molecular mechanism of the drugs that are approved, the drugs that are in clinical trial and the drugs that have not entered a clinical trial but shows promising future in the treatment of EGFR mutant lung cancer. Furthermore, this article provides concise information on relevant combinational or monotherapy clinical trials that have been completed for various approaches.

https://ift.tt/2Ooj8pp

The Safety, Efficacy and Therapeutic Potential of Histone Deacetylase Inhibitors with Special Reference to Panobinostat in Gastrointestinal Tumors: A Review of Preclinical and Clinical Studies

Histone deacetylase inhibitors (HDACi) have been demonstrated as an emerging class of anticancer drugs involved in regulation of gene expression and chromatin remodeling thus indicating valid targets for different types of cancer therapeutics. The pan-deacetylase inhibitor panobinostat (Farydac®, LBH589) is developed by Novartis Pharmaceuticals and a newly US FDA approved drug for the multiple myeloma. It is under clinical investigation for a range of hematological and solid tumors worldwide in both oral and intravenous formulations. Panobinostat inhibits tumor cell growth by interacting with acetylation of histones and nonhistone proteins as well as various apoptotic, autophagy-mediated targets and various tumorigenesis pathways involved in the development of cancer. The current article summarizes the status of panobinostat in gastrointestinal cancers. Preclinical and clinical data suggest that panobinostat has potential inhibitory activity in hepatocellular, pancreatic, colorectal, gastric and gastrointestinal stromal tumors. Clinical evaluations of panobinostat are currently underway. Herein, we have also reviewed the rationale behind the combination therapy under the trials and possible future prospective for the treatment of GI tumors.

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Meet Our Editorial Board Member

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Significant Role of MUC1 in Development of Resistance to Currently Existing Anti-cancer Therapeutic Agents

As an extensively glycosylated transmembrane protein of epithelium, Mucin1 (MUC1) mostly protects cells from tensions induced by external milieu. Physiologically, during stress condition, MUC1 separates into MUC1-N and MUC1-C moieties, resulting in transduction of inward survival signals, essential for maintaining cell's functionality. Recent studies have proposed a significant correlation between MUC1 overexpression and amplification of cancer cell's proliferation and metastasis through modulation of multiple signaling pathways and cell-cell and cell-matrix interactions. It has been shown that MUC1- Cytoplasmic Domain (MUC1-CD) accelerates development of resistance to several anti-cancer therapeutic agents including bortezomib, trastuzumab and tamoxifen. Furthermore, MUC1-CD is also involved in promoting expression of multi drug resistance (MDR) genes and finally, silencing MUC1 expression was together with resensitization of human epidermal growth factor receptor 2 positive (HER2+) and/or estrogen receptor (ER+) positive breast cancer cells to bortezomib, trastuzumab and tamoxifen respectively. In this review, we briefly describe the role of MUC1 proto-oncogene in cancer cell's survival, tumor progression and metastasis and then continue with mentioning the mechanisms through which MUC1 induce resistance to various currently existing therapeutic agents in market including bortezomib, trastuzumab and tamoxifen.

https://ift.tt/2NQXWeV

Development of Drug Targeting and Delivery in Cervical Cancer

Cervical cancer is the second most common cancer in women. Standard treatment options available for cervical cancer include chemotherapy, surgery and radiation therapy associated with their own side effects and toxicities. Tumor-targeted delivery of anticancer drugs is perhaps one of the most appropriate strategies to achieve optimal outcomes from the treatment and improve the quality of life. Recently nanocarriers based drug delivery systems owing to their unique properties have been extensively investigated for anticancer drug delivery. In addition to that addressing the anatomical significance of cervical cancer, various local drug delivery strategies for the cancer treatment are introduced like: gels, nanoparticles, polymeric films, rods and wafers, lipid based nanocarrier. Localized drug delivery systems allow passive drug targeting results in high drug concentration at the target site. Further they can be tailor made to achieve both sustained and controlled release behavior, substantially improving therapeutic outcomes and minimizing side effects. This review summarizes the meaningful advances in drug delivery strategies to treat cervical cancer.

https://ift.tt/2OjCV9s

p53-Mdm2 Interaction Inhibitors as Novel Nongenotoxic Anticancer Agents

Background: Cancer is a major global health problem with high mortality rate. Most of the clinically used anticancer agents induce apoptosis through genotoxic stress at various stages of cell cycle and activation of p53. Acting as a tumor suppressor, p53 plays a vital role in preventing tumor development. Tumor suppressor function of p53 is effectively antagonized by its direct interaction with murine double minute 2 (Mdm2) proteins via multiple mechanisms. Thus, p53-Mdm2 interaction has been found to be an important target for the development of novel anticancer agents. Currently, nutlin, spirooxindole, isoquilinone and piperidinone analogues inhibiting p53-Mdm2 interaction are found to be promising in the treatment of cancer.

Objective: The current review focused to scrutinize the structural aspects of p53-Mdm2 interaction inhibitors.

Methods: The present study provides a detailed collection of published information on different classes of inhibitors of p53-Mdm2 interaction as potential anticancer agents. The review highlighted the structural aspects of various reported p53-Mdm2 inhibitors for optimization.

Results: In the last few years, different classes of inhibitors of p53-Mdm2 have been designed and developed, and seven such compounds are being evaluated in clinical trials as new anticancer drugs. Further, to explore the role of p53 protein as a potential target for anticancer drug development, in this review, the mechanism of Mdm2 mediated inactivation of p53 and recent developments on p53- Mdm2 interactions inhibitors are discussed.

Conclusion: Agents designed to block the p53-Mdm2 interaction may have a therapeutic potential for the treatment of a subset of human cancers retaining wild-type p53. We review herein the recent advances in the design and development of potent small molecules as p53-Mdm2 inhibitors.

https://ift.tt/2NK7fgx

JQ1, a BET Inhibitor, Synergizes with Cisplatin and Induces Apoptosis in Highly Chemoresistant Malignant Pleural Mesothelioma Cells

Background: Malignant Pleural Mesothelioma (MPM) is an asbestos-associated tumor with poor prognosis and few therapeutic options. JQ1, a selective antagonist of BRD4, modulates transcription of oncogenes, including MPM chemoresistance-associated c-Myc and Fra-1.

Objective: We investigated if JQ1 could enhance the efficacy of cisplatin against MPM.

Methods: The antiproliferative activity of cisplatin in combination with JQ1 was assessed on MPM cell lines representative of the cellular phenotypes of this tumor (epithelioid, sarcomatoid and biphasic), and on one cisplatin resistant sub-line. The combination schedule was optimized adopting a 3Dspheroid model. Drug combination effects were correlated with cell cycle distribution and senescence- associated β-galactosidase positive cells. The expression of c-Myc and Fra-1 proteins and some apoptosis markers was assessed by immunoblotting and RT-qPCR. DNA damage and repair were evaluated by means of alkaline comet assay.

Results: JQ1 in combination with cisplatin elicited additive or synergistic (superadditive) antiproliferative effects on MPM cells, depending on the cell line. The combination showed tumor regression on the 3D-spheroid model. It induced increased apoptosis, along with decreased c-Myc and, sometimes, Fra-1 expression. JQ1 decreased cisplatin-induced DNA breaks in all MPM cells and increased senescence even in less proficient cells, thus enhancing the DNA Damage Response (DDR).

Conclusion: The superadditive effect is due to c-Myc repression. The consequent DDR enhancement triggers to apoptosis induction and/or permanent growth arrest (senescence), depending on the MPM cellular context, leading to tumor regression. Thus, the pharmacological modulation of BET activity could represent a promising tool for future MPM therapy.

https://ift.tt/2On78o5

FDA Alerts Consumers of BioLyte Laboratories Voluntary Recall of NeoRelief

Audience: Consumer [9/14/2018] The Food and Drug Administration is alerting consumers and health care professionals about a voluntary recall of certain lots (1138, 1139, 1146, and 1160) of NeoRelief distributed by BioLyte Laboratories (Grand Rapids,...

https://ift.tt/2NLKHfl

Surgical treatment and perioperative management of intracranial aneurysms in Chinese patients with ischemic cerebrovascular diseases: a case series

Patients with ischemic cerebrovascular diseases are more likely to suffer from intracranial aneurysms, and their surgical treatment has a growing controversy in this condition. The current case series was aime...

https://ift.tt/2xkeGAQ

Effect of interferon beta-1a subcutaneously three times weekly on clinical and radiological measures and no evidence of disease activity status in patients with relapsing–remitting multiple sclerosis at year 1

In the PRISMS study, interferon beta-1a subcutaneously (IFN β-1a SC) reduced clinical and radiological disease burden at 2 years in patients with relapsing–remitting multiple sclerosis. The study aimed to char...

https://ift.tt/2NFVebZ

Predictive factors for multidrug-resistant gram-negative bacteria among hospitalised patients with complicated urinary tract infections

Patients with complicated urinary tract infections (cUTIs) frequently receive broad-spectrum antibiotics. We aimed to determine the prevalence and predictive factors of multidrug-resistant gram-negative bacter...

https://ift.tt/2xfFhzH

Higher HbA1c Measurement Quality Standards are Needed for Follow-Up and Diagnosis: Experience and Analyses from Germany

Horm Metab Res
DOI: 10.1055/a-0721-2273

Measurement of HbA1c is an essential laboratory measure for the follow-up and therapy decision-making in patients with diabetes. HbA1c is one of the measurands in laboratory medicine that have to be successfully checked according to the criteria of the guidelines of the German Medical Association (Rili-BAEK) in external quality assurance using the reference method value concept, when applied in patient care. The allowed deviation of ±18% in external quality assessment (EQA) and ± 10% in internal quality control has been ultimately met by virtually all the different manufacturers and methods. However, such broad limits for permissible deviations are not suitable in view of medical requirements in patient care. The low-level acceptance criteria also depends on the previously used EQA materials used in Germany. In fact, HbA1c measurement results that are imprecisely measured or come from incorrectly calibrated devices are difficult to identify. With implementation of unprocessed fresh EDTA blood, the situation has changed. Until now systems with unit use reagents for point-of-care testing (POCT) of HbA1c are not mandatory to participate in EQA schemes in Germany. This paper outlines why there was a need to narrow the acceptance limits listed within the Rili-BAEK for HbA1c's internal (to ± 3%) and external (to ± 8%) quality controls in EQA schemes for Germany, which will take place after a transition period in the next years. Higher quality in HbA1c measurements will help to avoid misdiagnosis of diabetes as well as potential over- or undertreatment of patients at risk for diabetes.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

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Primary Tumor Driver Mutations Also Drive Metastases [Research Watch]

The large majority of driver mutations were shared within all metastases from each patient.

https://ift.tt/2OlcNLy

Multiplexed Imaging Characterizes the Tumor-Immune Microenvironment [Research Watch]

TNBCs could be characterized as immune cold, compartmentalized, or mixed based on immune infiltration.

https://ift.tt/2p82NtZ

TXNIP-Dependent Extracellular Matrix Remodeling Drives Glycolysis [Research Watch]

Remodeling of the extracellular matrix promotes glycolysis-dependent breast cancer migration.

https://ift.tt/2OmRVmZ

Illuminating Aberrant mRNA Events in CLL [News in Brief]

Intronic polyadenylation is prevalent, generating truncated proteins that lack tumor-suppressive functions.

https://ift.tt/2p95R9n

PDAC Can Arise from PanINs via Multiple Evolutionary Routes [Research Watch]

Phylogenetic analysis of PanINs and PDACs reveals evolutionary relationships between coexisting lesions.

https://ift.tt/2Oo6aYL

Neurog3-dependent pancreas dysgenesis causes ectopic pancreas in Hes1 mutant mice [RESEARCH ARTICLE]

Mette C. Jorgensen, Kristian H. de Lichtenberg, Caitlin A. Collin, Rasmus Klinck, Jeppe H. Ekberg, Maja S. Engelstoft, Heiko Lickert, and Palle Serup

Mutations in Hes1, a target gene of the Notch signalling pathway, lead to ectopic pancreas by a poorly described mechanism. Here, we use genetic inactivation of Hes1 combined with lineage tracing and live imaging to reveal an endodermal requirement for Hes1, and show that ectopic pancreas tissue is derived from the dorsal pancreas primordium. RNA-seq analysis of sorted E10.5 Hes1^+/+ and Hes1^–/– Pdx1-GFP⁺ cells suggested that upregulation of endocrine lineage genes in Hes1^–/– embryos was the major defect and, accordingly, early pancreas morphogenesis was normalized, and the ectopic pancreas phenotype suppressed, in Hes1^–/–Neurog3^–/– embryos. In Mib1 mutants, we found a near total depletion of dorsal progenitors, which was replaced by an anterior Gcg⁺ extension. Together, our results demonstrate that aberrant morphogenesis is the cause of ectopic pancreas and that a part of the endocrine differentiation program is mechanistically involved in the dysgenesis. Our results suggest that the ratio of endocrine lineage to progenitor cells is important for morphogenesis and that a strong endocrinogenic phenotype without complete progenitor depletion, as seen in Hes1 mutants, provokes an extreme dysgenesis that causes ectopic pancreas.

https://ift.tt/2xj2Yq3

Rasip1 controls lymphatic vessel lumen maintenance by regulating endothelial cell junctions [RESEARCH ARTICLE]

Xiaolei Liu, Xiaowu Gu, Wanshu Ma, Michael Oxendine, Hyea Jin Gil, George E. Davis, Ondine Cleaver, and Guillermo Oliver

Although major progress in our understanding of the genes and mechanisms that regulate lymphatic vasculature development has been made, we still do not know how lumen formation and maintenance occurs. Here, we identify the Ras-interacting protein Rasip1 as a key player in this process. We show that lymphatic endothelial cell-specific Rasip1-deficient mouse embryos exhibit enlarged and blood-filled lymphatics at embryonic day 14.5. These vessels have patent lumens with disorganized junctions. Later on, as those vessels become fragmented and lumens collapse, cell junctions become irregular. In addition, Rasip1 deletion at later stages impairs lymphatic valve formation. We determined that Rasip1 is essential for lymphatic lumen maintenance during embryonic development by regulating junction integrity, as Rasip1 loss results in reduced levels of junction molecules and defective cytoskeleton organization in vitro and in vivo. We determined that Rasip1 regulates Cdc42 activity, as deletion of Cdc42 results in similar phenotypes to those seen following the loss of Rasip1. Furthermore, ectopic Cdc42 expression rescues the phenotypes in Rasip1-deficient lymphatic endothelial cells, supporting the suggestion that Rasip1 regulates Cdc42 activity to regulate cell junctions and cytoskeleton organization, which are both activities required for lymphatic lumen maintenance.

https://ift.tt/2xj2CzJ

A Novel Approach to Serial Amnioinfusion in a Case of Premature Rupture of Membranes Near the Limit of Viability

AJP Rep 2018; 08: e180-e183
DOI: 10.1055/s-0038-1669964

Prelabor rupture of the membranes (PROM) near the limit of viability is associated with significant risks for both mother and fetus. Preterm labor, intra-amniotic infection, and placental abruption are the immediate risks to the pregnancy; however, the fetus incurs additional risks related to the sequela of persistent oligohydramnios. Transabdominal intra-amniotic infusions have been studied. Results, suggesting that this intervention may prolong the latency period, and potentially, decrease pulmonary hypoplasia in surviving neonates without evidence of increasing risk of intra-amniotic infection. To our knowledge, the use of antibiotic-infused fluid has not been reported in this clinical scenario. Therefore, we present a case of a patient with PROM before the limit of viability who underwent serial transabdominal amnioinfusions with oxacillin-containing normal saline, which resulted in membrane resealing and neonatal survival with no additional maternal morbidity.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
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Uterine Monitoring Techniques from Patients' and Users' Perspectives

AJP Rep 2018; 08: e184-e191
DOI: 10.1055/s-0038-1669409

Objective To evaluate preferences from patients and users on 3 uterine monitoring techniques, during labor. Study Design Women in term labor were simultaneously monitored with the intrauterine pressure catheter, the external tocodynamometer, and the electrohysterograph. Postpartum, these women filled out a questionnaire evaluating their preferences and important aspects. Nurses completed a questionnaire evaluating users' preferences. Results Of all 52 participating women, 80.8% preferred the electrohysterograph, 17.3% the intrauterine pressure catheter and 1.9% the external tocodynamometer. For these women, the electrohysterograph scored best regarding application and presence during labor (p < 0.001). Most important aspects were "least likely to harm" and "least discomfort". Of 57 nurses, 40.4% preferred the electrohysterograph, 35.1% the external tocodynamometer, and 24.6% had no preference, or replied that their preference is subject to situation and patient. Conclusion Patients prefer the electrohysterograph over the external tocodynamometer and the intrauterine pressure catheter, while healthcare providers report ambiguous results.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Abstract  |  open access Full text

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Cardiothoracic Area Ratio Predicts Lethal Pulmonary Venous Obstruction in Patients with Single Ventricle and Total Anomalous Pulmonary Venous Connection

AJP Rep 2018; 08: e174-e179
DOI: 10.1055/s-0038-1669429

Background and Objectives When single ventricle (SV) is complicated with total anomalous pulmonary venous connection (TAPVC), the pulmonary vein obstruction (PVO) occurs at a high rate.There are some patients who died from the lethal PVO (l-PVO) which needed PVO release dead due to severe desaturation within 24 hours after birth. The purpose of this study was to find a predictive marker for l-PVO during the fetal period. Methods We enrolled 21 patients diagnosed with SV associated with TAPVC in the antenatal period. Ten patients had supracardiac, five had cardiac, five had infracardiac, and one had mixed TAPVC. We reviewed fetal echocardiography and measured cardiothoracic area ratio (CTAR) and total cardiac dimension (TCD). We divided 21 cases into l-PVO group (6) and non-l-PVO group (15) and compared the fetal echocardiography findings and postnatal prognoses between the groups. Results CTAR at the final fetal echocardiography was 16 to 29% (median: 21) in the l-PVO group and 22 to 38% (median: 28) in the non-l-PVO group (p = 0.01). TCD/week at the final echocardiography was 0.67 to 1.0 (median: 0.77) in the l-PVO group and 0.78 to 1.2 (median: 0.96) in the non-l-PVO group (p = 0.02). Conclusion Reduced CTAR in the antenatal period is a good predictor of l-PVO after birth.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Abstract  |  open access Full text

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Coupling of apical-basal polarity and planar cell polarity to interpret the Wnt signaling gradient in feather development [RESEARCH REPORT]

Jianqiong Lin and Zhicao Yue

Sensing a global directional cue to orient cell growth is crucial in tissue morphogenesis. An anterior-posterior gradient of Wnt signaling controls the helical growth of feather branches (barbs), and thus the formation of bilateral feathers. However, it remains unclear how the keratinocytes sense this gradient and orient barb growth. Here, we show that in chicken, owing to feather branching, the global Wnt gradient is subdivided into periodic barbs. Within each barb, the anterior barbule plate cells tilt before the posterior cells. The core planar cell polarity gene Prickle1 is involved, as knockdown of its expression resulted in no cell shape change and no barb tilting. Furthermore, perturbation of the Wnt gradient leads to diffusive Prickle1 expression and loss of barb orientation. Finally, the asymmetric distribution of Wnt6/Fzd10 is coordinated by the apical-basal polarity of the barbule plate keratinocytes, which is in turn regulated by the Par3/aPKC machinery. Our data elucidate a new mechanism through which the global Wnt signaling gradient is interpreted locally to construct complex spatial forms.

https://ift.tt/2xlXXNk

The LPA-LPA4 axis is required for establishment of bipolar morphology and radial migration of newborn cortical neurons [RESEARCH ARTICLE]

Nobuhiro Kurabayashi, Aiki Tanaka, Minh Dang Nguyen, and Kamon Sanada

Newborn neurons in the developing neocortex undergo radial migration, a process that is coupled with their precise passage from multipolar to bipolar shape. The cell-extrinsic signals that govern this transition are, however, poorly understood. Here, we find that lysophosphatidic acid (LPA) signaling contributes to the establishment of a bipolar shape in mouse migratory neurons through LPA receptor 4 (LPA4). LPA4 is robustly expressed in migratory neurons. LPA4-depleted neurons show impaired multipolar-to-bipolar transition and become arrested in their migration. Further, LPA4-mediated LPA signaling promotes formation of the pia-directed process in primary neurons overlaid on neocortical slices. In addition, LPA4 depletion is coupled with altered actin organization as well as with destabilization of the F-actin-binding protein filamin A (FlnA). Finally, overexpression of FlnA rescues the morphology and migration defects of LPA4-depleted neurons. Thus, the LPA-LPA4 axis regulates bipolar morphogenesis and radial migration of newborn cortical neurons via remodeling of the actin cytoskeleton.

https://ift.tt/2xdoopo

Nodal signaling has dual roles in fate specification and directed migration during germ layer segregation in zebrafish [RESEARCH ARTICLE]

Zairan Liu, Stephanie Woo, and Orion D. Weiner

During gastrulation, endodermal cells actively migrate to the interior of the embryo, but the signals that initiate and coordinate this migration are poorly understood. By transplanting ectopically induced endodermal cells far from the normal location of endoderm specification, we identified the inputs that drive internalization without the confounding influences of fate specification and global morphogenic movements. We find that Nodal signaling triggers an autocrine circuit for initiating endodermal internalization. Activation of the Nodal receptor directs endodermal specification through sox32 and also induces expression of more Nodal ligands. These ligands act in an autocrine fashion to initiate endodermal cell sorting. Our work defines an 'AND' gate consisting of sox32-dependent endodermal specification and Nodal ligand reception controlling endodermal cell sorting to the inner layer of the embryo at the onset of gastrulation.

https://ift.tt/2xlXZ7U

The cytochrome P450 CYP77A4 is involved in auxin-mediated patterning of the Arabidopsis thaliana embryo [RESEARCH ARTICLE]

Kensuke Kawade, Yimeng Li, Hiroyuki Koga, Yuji Sawada, Mami Okamoto, Ayuko Kuwahara, Hirokazu Tsukaya, and Masami Yokota Hirai

Metabolism often plays an important role in developmental control, in addition to supporting basal physiological requirements. However, our understanding of this interaction remains limited. Here, we performed quantitative phenome analysis of Arabidopsis thaliana cytochrome P450 mutants to identify a novel interaction between development and metabolism. We found that cyp77a4 mutants exhibit specific defects in cotyledon development, including asymmetric positioning and cup-shaped morphology, which could be rescued by introducing the CYP77A4 gene. Microscopy revealed that the abnormal patterning was detected at least from the 8-cell stage of the cyp77a4 embryos. We next analysed auxin distribution in mutant embryos, as the phenotypes resembled those of auxin-related mutants. We found that the auxin response pattern was severely perturbed in the cyp77a4 embryos owing to an aberrant distribution of the auxin efflux carrier PIN1. CYP77A4 intracellularly localised to the endoplasmic reticulum, which is consistent with the notion that this enzyme acts as an epoxidase of unsaturated fatty acids in the microsomal fraction. We propose that the CYP77A4-dependent metabolic pathway is an essential element for the establishment of polarity in plant embryos.

https://ift.tt/2xe4TwT

BMP- and neuropilin 1-mediated motor axon navigation relies on spastin alternative translation [RESEARCH ARTICLE]

Nicolas Jardin, Francois Giudicelli, Daniel Ten Martin, Anaïs Vitrac, Stephanie De Gois, Rachel Allison, Corinne Houart, Evan Reid, Jamile Hazan, and Coralie Fassier

Functional analyses of genes responsible for neurodegenerative disorders have unveiled crucial links between neurodegenerative processes and key developmental signalling pathways. Mutations in SPG4-encoding spastin cause hereditary spastic paraplegia (HSP). Spastin is involved in diverse cellular processes that couple microtubule severing to membrane remodelling. Two main spastin isoforms are synthesised from alternative translational start sites (M1 and M87). However, their specific roles in neuronal development and homeostasis remain largely unknown. To selectively unravel their neuronal function, we blocked spastin synthesis from each initiation codon during zebrafish development and performed rescue analyses. The knockdown of each isoform led to different motor neuron and locomotion defects, which were not rescued by the selective expression of the other isoform. Notably, both morphant neuronal phenotypes were observed in a CRISPR/Cas9 spastin mutant. We next showed that M1 spastin, together with HSP proteins atlastin 1 and NIPA1, drives motor axon targeting by repressing BMP signalling, whereas M87 spastin acts downstream of neuropilin 1 to control motor neuron migration. Our data therefore suggest that defective BMP and neuropilin 1 signalling may contribute to the motor phenotype in a vertebrate model of spastin depletion.

https://ift.tt/2xlbgxs

piRNAs and PIWI proteins: regulators of gene expression in development and stem cells [REVIEW]

Patricia Rojas-Rios and Martine Simonelig

PIWI proteins and Piwi-interacting RNAs (piRNAs) have established and conserved roles in repressing transposable elements (TEs) in the germline of animals. However, in several biological contexts, a large proportion of piRNAs are not related to TE sequences and, accordingly, functions for piRNAs and PIWI proteins that are independent of TE regulation have been identified. This aspect of piRNA biology is expanding rapidly. Indeed, recent reports have revealed the role of piRNAs in the regulation of endogenous gene expression programs in germ cells, as well as in somatic tissues, challenging dogma in the piRNA field. In this Review, we focus on recent data addressing the biological and developmental functions of piRNAs, highlighting their roles in embryonic patterning, germ cell specification, stem cell biology, neuronal activity and metabolism.

https://ift.tt/2xdofSS

Embryonic Tbx3+ cardiomyocytes form the mature cardiac conduction system by progressive fate restriction [RESEARCH ARTICLE]

Rajiv A. Mohan, Mathilda T. M. Mommersteeg, Jorge N. Dominguez, Caroline Choquet, Vincent Wakker, Corrie de Gier-de Vries, Gerard J. J. Boink, Bastiaan J. Boukens, Lucile Miquerol, Arie O. Verkerk, and Vincent M. Christoffels

A small network of spontaneously active Tbx3⁺ cardiomyocytes forms the cardiac conduction system (CCS) in adults. Understanding the origin and mechanism of development of the CCS network are important steps towards disease modeling and the development of biological pacemakers to treat arrhythmias. We found that Tbx3 expression in the embryonic mouse heart is associated with automaticity. Genetic inducible fate mapping revealed that Tbx3⁺ cells in the early heart tube are fated to form the definitive CCS components, except the Purkinje fiber network. At mid-fetal stages, contribution of Tbx3⁺ cells was restricted to the definitive CCS. We identified a Tbx3⁺ population in the outflow tract of the early heart tube that formed the atrioventricular bundle. Whereas Tbx3⁺ cardiomyocytes also contributed to the adjacent Gja5⁺ atrial and ventricular chamber myocardium, embryonic Gja5⁺ chamber cardiomyocytes did not contribute to the Tbx3⁺ sinus node or to atrioventricular ring bundles. In conclusion, the CCS is established by progressive fate restriction of a Tbx3⁺ cell population in the early developing heart, which implicates Tbx3 as a useful tool for developing strategies to study and treat CCS diseases.

https://ift.tt/2xk0Ka0

Rnf220 cooperates with Zc4h2 to specify spinal progenitor domains [RESEARCH ARTICLE]

Jumee Kim, Tae-Ik Choi, Shinhye Park, Myung Hee Kim, Cheol-Hee Kim, and Seunghee Lee

During early embryonic development of the spinal cord, graded sonic hedgehog signaling establishes distinct ventral progenitor domains by regulating the spatiotemporal expression of fate-specifying transcription factors. However, regulation of their protein stability remains incompletely understood. Here, we show that RNF220, an E3 ubiquitin ligase, plays crucial roles in the generation of the ventral progenitor domains, which produce ventral interneurons and motor neurons, by targeting key transcription factors including Dbx1/2 and Nkx2.2 for degradation. Surprisingly, RNF220 interacts with, and is co-expressed with, a zinc-finger protein ZC4H2, and they cooperate to degrade Dbx1/2 and Nkx2.2. RNF220-null mice show widespread alterations of ventral progenitor domains, including the loss of the p2 domain that produces V2 interneurons. Knockdown of RNF220 and ZC4H2 in the chick spinal cord downregulates expression of the V2 interneuronal marker Chx10. Co-expression of RNF220 and ZC4H2 further promotes the ability of Nkx6.1 to induce ectopic Chx10⁺ V2 interneurons. Our results uncover a novel regulatory pathway in establishing distinct progenitor domains through modulating the protein stability of transcription factors. Our results provide insights into the molecular mechanism by which ZC4H2 mutations lead to human syndromes characterized by delayed motor development.

https://ift.tt/2xdoc9E

Sidestep-induced neuromuscular miswiring causes severe locomotion defects in Drosophila larvae [RESEARCH ARTICLE]

Jaqueline C. Kinold, Carsten Pfarr, and Hermann Aberle

Mutations in motor axon guidance molecules cause aberrant projection patterns of motor nerves. As most studies in Drosophila have analysed these molecules in fixed embryos, the consequences for larval locomotion are entirely unexplored. Here, we took advantage of sidestep (side)-mutant larvae that display severe locomotion defects because of irreparable innervation errors. Mutations in side affected all motor nerve branches and all body wall regions. Innervation defects were non-stereotypical, showing unique innervation patterns in each hemisegment. Premature activation of Side in muscle precursors abrogated dorsal migration of motor nerves, resulting in larvae with a complete loss of neuromuscular junctions on dorsal-most muscles. High-speed videography showed that these larvae failed to maintain substrate contact and inappropriately raised both head and tail segments above the substrate, resulting in unique 'arching' and 'lifting' phenotypes. These results show that guidance errors in side mutants are maintained throughout larval life and are asymmetrical with respect to the bilateral body axis. Together with similar findings in mice, this study also suggests that miswiring could be an underlying cause of inherited movement disorders.

https://ift.tt/2xdo5Lg

Ma2/d promotes myonuclear positioning and association with the sarcoplasmic reticulum [RESEARCH ARTICLE]

Adriana Reuveny, Marina Shnayder, Dana Lorber, Shuoshuo Wang, and Talila Volk

The cytoplasm of striated myofibers contains a large number of membrane organelles, including sarcoplasmic reticulum (SR), T-tubules and the nuclear membrane. These organelles maintain a characteristic juxtaposition that appears to be essential for efficient inter-membranous exchange of RNA, proteins and ions. We found that the membrane-associated Muscle-specific α2/ (Ma2/d) subunit of the Ca²⁺ channel complex localizes to the SR and T-tubules, and accumulates at the myonuclear surfaces. Furthermore, Ma2/d mutant larval muscles exhibit nuclear positioning defects, disruption of the nuclear-SR juxtapositioning, as well as impaired larval locomotion. Ma2/d localization at the nuclear membrane depends on the proper function of the nesprin ortholog Msp300 and the BAR domain protein Amphiphysin (Amph). Importantly, live imaging of muscle contraction in intact Drosophila larvae indicated altered distribution of Sarco/Endoplamic Reticulum Ca²⁺-ATPase (SERCA) around the myonuclei of Ma2/d mutant larvae. Co-immunoprecipitation analysis supports association between Ma2/d and Amph, and indirectly with Msp300. We therefore suggest that Ma2/d, in association with Msp300 and Amph, mediates interactions between the SR and the nuclear membrane.

https://ift.tt/2xj2O1V

Glypican 4 and Mmp14 interact in regulating the migration of anterior endodermal cells by limiting extracellular matrix deposition [RESEARCH ARTICLE]

Bo Hu, Yuanyuan Gao, Lauren Davies, Stephanie Woo, Jacek Topczewski, Jason R. Jessen, and Fang Lin

During embryogenesis, the germ layers, including the endoderm, undergo convergence and extension movements to narrow and elongate the body plan. In zebrafish, the dorsal migration of endodermal cells during gastrulation is controlled by chemokine signaling, but little is known about how they migrate during segmentation. Here, we show that glypican 4 (Gpc4), a member of the heparin sulfate proteoglycan family, is required for efficient migration of anterior endodermal cells during early segmentation, regulating Rac activation to maintain polarized actin-rich lamellipodia. An endoderm transplantation assay showed that Gpc4 regulates endoderm migration in a non-cell-autonomous fashion. Further analyses revealed that the impaired endoderm migration in gpc4 mutants results from increases in the expression and assembly of fibronectin and laminin, major components of the extracellular matrix (ECM). Notably, we found that matrix metalloproteinase 14 (Mmp14a/b) is required for the control of ECM expression during endoderm migration, with Gpc4 acting through Mmp14a/b to limit ECM expression. Our results suggest that Gpc4 is crucial for generating the environment required for efficient migration of endodermal cells, uncovering a novel function of Gpc4 during development.

https://ift.tt/2xe4A5d

A mesodermal fate map for adipose tissue [RESEARCH ARTICLE]

Zachary L. Sebo, Elise Jeffery, Brandon Holtrup, and Matthew S. Rodeheffer

The embryonic origin of distinct fat depots and the role for ontogeny in specifying the functional differences among adipocyte lineages between and within depots is unclear. Using a Cre/Lox-based strategy to track the fate of major mesodermal subcompartments in mice we present evidence that <50% of interscapular brown adipocytes are derived from progenitors of the central dermomyotome. Furthermore, we demonstrate that depot-specific adipocyte lineages spatially diverge as early as gastrulation, and that perigonadal adipocytes arise from separate mesodermal subcompartments in males and females. Last, we show adipocyte precursors (APs) of distinct lineages within the same depot exhibit indistinguishable responses to a high fat diet, indicating that ontogenetic differences between APs do not necessarily correspond to functional differences in this context. Altogether, these findings shed light on adipose tissue patterning and suggest that the behavior of adipocyte lineage cells is not strictly determined by developmental history.

https://ift.tt/2xdnWHI

The endoderm from a diverse perspective [MEETING REVIEW]

N. Ray Dunn and Brigid L. M. Hogan

The historic town of Taos, New Mexico, with its rich multicultural history of art and craft, was the site of the second Keystone Symposium on 'Endoderm Development and Disease', which was held in February 2018. The theme of the meeting was 'Cross-Organ Comparison and Interplay', emphasizing an integrative and multisystem approach to the broad topics of organ physiology, homeostasis, repair, regeneration and disease. As we review here, participants shared their recent discoveries and discussed how new technologies developed in one organ system might be applied to answer crucial questions in another. Other integrative themes were how agents such as parasites, microbes, immune cells, physical forces and innervation can affect tissue organization and progenitor cell dynamics, and how defects in the development of an organ can impact its adult function. Participants came away with a broader vision of their field and a renewed sense of collective energy empowered by novel tools and fresh ideas.

https://ift.tt/2xihpuC

Association between semi-quantitative microbial load and respiratory symptoms among Thai military recruits: a prospective cohort study

Multiplex real-time polymerase chain reaction assays have improved diagnostic sensitivity for a wide range of pathogens. However, co-detection of multiple agents and bacterial colonization make it difficult to...

https://ift.tt/2pa0VRE

Hepatitis virus (HCV) diagnosis and access to treatment in a UK cohort

As direct acting antiviral (DAA) therapy is progressively rolled out for patients with hepatitis C virus (HCV) infection, careful scrutiny of HCV epidemiology, diagnostic testing, and access to care is crucial...

https://ift.tt/2OoxaaK

Poor Maternal Bonding for Women Denied Abortion

FRIDAY, Sept. 14, 2018 -- Poor maternal bonding is more common for children born to women who are denied access to abortion, according to a study published online Sept. 4 in JAMA Pediatrics. Diana Greene Foster, Ph.D., from the University of...

https://ift.tt/2MxvGsF

Patrons of 'Vampire Facial' Spa May Have Been Exposed to HIV

FRIDAY, Sept. 14, 2018 -- Customers of an Albuquerque spa who received a "vampire facial" are being warned that they may have been exposed to HIV, hepatitis B and hepatitis C through human blood used in the controversial procedure. In a vampire...

https://ift.tt/2NDFB4T

FDA Approves Novel Treatment for Hairy Cell Leukemia

FRIDAY, Sept. 14, 2018 -- Lumoxiti (moxetumomab pasudotox-tdfk) injection has been approved to treat certain instances of relapsed or refractory hairy cell leukemia (HCL), the U.S. Food and Drug Administration said yesterday. Lumoxiti, a...

https://ift.tt/2MrqJSp

Final CDC Update on Salmonella Linked to Backyard Poultry

FRIDAY, Sept. 14, 2018 -- At least 334 people in 47 states have been sickened in Salmonella outbreaks linked to contact with live poultry in backyard flocks, according to the U.S. Centers for Disease Control and Prevention. Twenty-one percent of the...

https://ift.tt/2NDFAOn

FDA Finds Another Carcinogen in Certain Valsartan Heart Meds

FRIDAY, Sept. 14, 2018 -- The U.S. Food and Drug Administration warns that it has found a second impurity in three lots of Torrent Pharmaceuticals' valsartan drug products. The FDA first recalled valsartan medicines back in July, after the Chinese...

https://ift.tt/2MtbtEA

The emerging role of lncRNAs in the regulation of cancer stem cells

Abstract

Background

Tumors contain a functional subpopulation of cells that exhibit stem cell properties. These cells, named cancer stem cells (CSCs), play significant roles in the initiation and progression of cancer. Long non-coding RNAs (lncRNAs) can act at the transcriptional, posttranscriptional and translational level. As such, they may be involved in various biological processes such as DNA damage repair, inflammation, metabolism, cell survival, cell signaling, cell growth and differentiation. Accumulating evidence indicates that lncRNAs are key regulators of the CSC subpopulation, thereby contributing to cancer progression. The aim of this review is to overview current knowledge about the functional role and the mechanisms of action of lncRNAs in the initiation, maintenance and regulation of CSCs derived from different neoplasms. These lncRNAs include CTCF7, ROR, DILC, HOTAIR, H19, HOTTIP, ATB, HIF2PUT, SOX2OT, MALAT-1, CUDR, Lnc34a, Linc00617, DYNC2H1–4, PVT1, SOX4 and ARSR Uc.283-plus. Furthermore, we will illustrate how lncRNAs may regulate asymmetric CSC division and contribute to self-renewal, drug resistance and EMT, thus affecting the metastasis and recurrence of different cancers. In addition, we will highlight the implications of targeting lncRNAs to improve the efficacy of conventional drug therapies and to hamper CSC survival and proliferation.

Conclusions

lncRNAs are valuable tools in the search for new targets to selectively eliminate CSCs and improve clinical outcomes. LncRNAs may serve as excellent therapeutic targets because they are stable, easily detectable and expressed in tissue-specific contexts.

https://ift.tt/2NJf3za

Reply to “Reconsidering Sham in Transcutaneous Vagus Nerve Stimulation studies”

We thank Rangon (2018) for her critical remarks sparked by the design of our recent study (Keute et al. 2018). Specifically, Rangon (2018) questions the widespread use of earlobe stimulation as a sham condition in transcutaneous vagus nerve stimulation (tVNS) studies. She argues that the unexpected results in our study – an increased behavioral effect, even though we expected a decreased one – might be a consequence of the earlobe-sham stimulation, which implies that the earlobe stimulation would have had a stronger effect than tVNS on GABA transmission and, subsequently, on our parameters of interest.

https://ift.tt/2p8cTel

Increasing adenoma detection rates in the right side of the colon comparing retroflexion or a second forward view: a systematic review

Right-sided lesions are often missed during standard colonoscopy (SC). A second forward view examination or retroflexion in the right side of the colon, have both been proposed as techniques to improve ADR in the right side of the colon. Comparative data of examining the right side of the colon with a second forward view or retroflexion is not known in a pooled analysis. We performed a systematic review of the literature to assess the yield of a second forward view compared with retroflexion examination for the detection of right-sided adenomas.

https://ift.tt/2xaM9hV

Phase I Study of EUS-guided Photodynamic Therapy for Locally Advanced Pancreatic Cancer

Locally advanced pancreatic cancer (LAPC) has a poor prognosis. There are limited data describing the use of photodynamic therapy (PDT) for pancreatic cancer in humans. We hypothesized that EUS-guided PDT for LAPC is safe, technically feasible and produces a dose- and time-dependent increasing degree of image-defined tumor necrosis.

https://ift.tt/2Mu2suN

Colonic microRNA Profiles, Identified by a Deep-learning Algorithm, That Predict Responses of Patients With Acute Severe Ulcerative Colitis to Therapy

Acute severe ulcerative colitis (ASUC) is a life-threatening condition managed with intravenous steroids followed by infliximab, cyclosporine, or colectomy (for patients with steroid resistance). There are no biomarkers to identify patients most likely to respond to therapy; ineffective medical treatment can delay colectomy and increase morbidity and mortality. We aimed to identify biomarkers of response to medical therapy for patients with ASUC.

https://ift.tt/2CXuLCv

Characteristics and Response to Crizotinib in ALK-Rearranged, Advanced Non-Adenocarcinoma, Non-Small Cell Lung Cancer (NA-NSCLC) Patients: a Retrospective Study and Literature Review

Abstract

Background

Oncogenic fusion genes consisting of echinoderm microtubule-associated protein-like 4 (EML4) and anaplastic lymphoma kinase (ALK) can be detected in 5–7% of lung adenocarcinoma cases. The prevalence of ALK rearrangement in non-adenocarcinoma, non-small cell lung cancers (NA-NSCLC) is currently unknown. In addition, the efficacy of crizotinib in these patients has not been well established.

Objectives

The aim of this study was to investigate the prevalence of ALK rearrangement in NA-NSCLC patients and the therapeutic efficacy of crizotinib in these patients.

Methods

We included NA-NSCLC patients who were tested for the presence of ALK rearrangement in our institution from January 2013 to May 2018. The effectiveness of crizotinib in ALK-positive patients was retrospectively analyzed. A literature review was performed and eligible previously published cases were analyzed in combination with our data.

Results

A total of 4662 patients were screened and 1696 NA-NSCLC patients were tested for the presence of ALK rearrangement during the study period. Thirty-two positive patients were identified (1.9%, 95% CI, 1.2–2.5%). A statistically higher percentage of younger (58.0 vs. 63.0, p = 0.01), female patients (53.1% vs. 10.8%, p < 0.01) who were non-smokers (71.9% vs. 40.6%, p < 0.01) and whose tumors contained adenocarcinoma components (34.4% vs. 6.1%, p < 0.01) were observed in the ALK-positive group. Eighteen patients were excluded from the study and 14 eligible patients were included for survival analysis. The median duration of crizotinib treatment (MDT) as a proxy for progression-free survival of the 14 eligible patients in our institution was 6.0 months (95% CI, 1.2–10.8 months). We combined our data with sporadic cases from 16 previous publications (total n = 37) and found that the MDT was 7.0 months (95% CI, 6.0–8.0 months).

Conclusions

Our study suggests the opportunity to test ALK rearrangement in NA-NSCLC patients, especially in younger, female, non-smoking patients containing adenocarcinoma components. Crizotinib provides an option for the treatment of NA-NSCLC patients who have an ALK rearrangement.

https://ift.tt/2xhuHYi

How becoming a mother shapes implicit and explicit responses to infant cues

Developmental Psychobiology, EarlyView.


https://ift.tt/2OnKzQn

Transcranial Doppler Ultrasonography Provides Insights into Neurovascular Changes in Children with Cerebral Malaria

To evaluate neurovascular changes in pediatric patients with cerebral malaria.

https://ift.tt/2xfa93j

Morphine vs Methadone Treatment for Infants with Neonatal Abstinence Syndrome

To estimate the relationship of initial pharmacotherapy with methadone or morphine and length of stay (LOS) in infants with neonatal abstinence syndrome (NAS) admitted to the neonatal intensive care unit (NICU).

https://ift.tt/2xpKKn1

Adverse Childhood Experiences Are Associated with Unmet Healthcare Needs among Children with Autism Spectrum Disorder

To explore associations between level of adverse childhood experiences (ACEs) and unmet healthcare needs among children with autism spectrum disorder (ASD) using a population-based sample.

https://ift.tt/2xfa7sd

An Update of Efficacy and Safety of Cetuximab in Metastatic Colorectal Cancer: A Narrative Review

Abstract

Colorectal cancer is the second most common cancer, representing 13% of all diagnosed cancers. Cetuximab is a recombinant chimeric monoclonal IgG1 antibody and epidermal growth factor receptor (EGFR) inhibitor. Cetuximab is approved for the first-line treatment in combination with chemotherapy or as a single agent in patients who have failed or are intolerant to chemotherapy in patients with EGFR-expressing, RAS wild-type metastatic colorectal cancer. Cetuximab efficacy emerged from studies that were conducted to approve the drug. Cetuximab is well tolerated; its toxicities are caused by its mechanism of action and the most common adverse reaction is skin toxicity. The main purpose of this manuscript is to present an update on the evidence-based summary of efficacy and safety and on the cost-effectiveness of cetuximab. Furthermore, it suggests a management of adverse drug reactions to improve the tolerability of the drug.

https://ift.tt/2p8ymE9

A previously unrecognized 22q13.2 microdeletion syndrome that encompasses TCF20 and TNFRSF13C

American Journal of Medical Genetics Part A, EarlyView.


https://ift.tt/2NIliTL

Warsaw breakage syndrome: Further clinical and genetic delineation

American Journal of Medical Genetics Part A, EarlyView.


https://ift.tt/2xiCswP

Dietary intake in youth with prader‐willi syndrome

American Journal of Medical Genetics Part A, EarlyView.


https://ift.tt/2NLSw4s

Improved Automatic Morphology-Based Classification of Parkinson’s Disease and Progressive Supranuclear Palsy

Abstract

Objectives

The overlapping symptoms of Parkinson's disease (PD) and progressive supranuclear palsy—Richardson's syndrome (PSP-RS) often make a correct clinical diagnosis difficult. The volume of subcortical brain structures derived from high-resolution T1-weighted magnetic resonance imaging (MRI) datasets is frequently used for individual level classification of PD and PSP-RS patients. The aim of this study was to evaluate the benefit of including additional morphological features beyond the simple regional volume, as well as clinical features, and morphological features of cortical structures for an automatic classification of PD and PSP-RS patients.

Material and Methods

A total of 98 high-resolution T1-weighted MRI datasets from 76 PD patients, and 22 PSP-RS patients were available for this study. Using an atlas-based approach, the volume, surface area, and surface-area-to-volume ratio (SA:V) of 21 subcortical and 48 cortical brain regions were calculated and used as features for a support vector machine classification after application of a RELIEF feature selection method.

Results

The comparison of the classification results suggests that including all three morphological parameters (volume, surface area and SA:V) can considerably improve classification accuracy compared to using volume or surface area alone. Likewise, including clinical patient features in addition to morphological parameters also considerably increases the classification accuracy. In contrast to this, integrating morphological features of other cortical structures did not lead to improved classification accuracy. Using this optimal set-up, an accuracy of 98% was achieved with only one falsely classified PD and one falsely classified PSP-RS patient.

Conclusion

The results of this study suggest that clinical features as well as more advanced morphological features should be used for future computer-aided diagnosis systems to differentiate PD and PSP-RS patients based on morphological parameters.

https://ift.tt/2p9rfLI

Imatinib and Everolimus in Patients With Progressing Advanced Chordoma: A Phase 2 Clinical Study

Cancer, EarlyView.


https://ift.tt/2p5Ot54

Oncologist Volume and Outcomes in Older Adults Diagnosed With Diffuse Large B Cell Lymphoma

Cancer, EarlyView.


https://ift.tt/2CVzK6w

MELAS: Monitoring treatment with Magnetic Resonance Spectroscopy

Acta Neurologica Scandinavica, Volume 0, Issue ja, -Not available-.


https://ift.tt/2OjXFhh

Reverse Transcription-Loop-mediated Isothermal Amplification (RT-LAMP) Assay for Zika Virus and Housekeeping Genes in Urine, Serum, and Mosquito Samples

This protocol provides an efficient and low-cost method to detect Zika virus or control targets in human urine and serum samples or in mosquitoes by reverse transcription loop-mediated isothermal amplification (RT-LAMP). This method does not require RNA isolation and can be done within 30 min.

https://ift.tt/2MvWWYL

Mouse Body Temperature Measurement Using Infrared Thermometer During Passive Systemic Anaphylaxis and Food Allergy Evaluation

Here we present a new method to accurately measure body temperature differences in passive systemic anaphylaxis (PSA) and food allergy mouse models using an infrared thermometer. This procedure has been accurately duplicated in previous PSA results.

https://ift.tt/2xaKlp6

Single-Digit Nanometer Electron-Beam Lithography with an Aberration-Corrected Scanning Transmission Electron Microscope

We use an aberration-corrected scanning transmission electron microscope to define single-digit nanometer patterns in two widely-used electron-beam resists: poly (methyl methacrylate) and hydrogen silsesquioxane. Resist patterns can be replicated in target materials of choice with single-digit nanometer fidelity using liftoff, plasma etching, and resist infiltration by organometallics.

https://ift.tt/2MxxcuT

Genetic Testing Recommended for Familial Hypercholesterolemia

FRIDAY, Sept. 14, 2018 -- Genetic testing should become the standard of care for patients with definite or probable familial hypercholesterolemia (FH), according to a statement published in the Aug. 7 issue of the Journal of the American College of...

https://ift.tt/2xgfart

Many Older Adults Transition to Long-Term Benzodiazepine Use

FRIDAY, Sept. 14, 2018 -- More than one-quarter of older adults newly prescribed benzodiazepine by an non-psychiatric clinician transition to long-term use, according to a research letter published online Sept. 10 in JAMA Internal Medicine. Lauren...

https://ift.tt/2NM4sDA

Opioid Refills Rare After Rhinoplasty

FRIDAY, Sept. 14, 2018 -- For patients undergoing rhinoplasty, postoperative opioid refills are extremely rare, according to a research letter published online Sept. 6 in JAMA Facial Plastic Surgery. Rosh K.V. Sethi, M.D., M.P.H., from Harvard...

https://ift.tt/2xgoWtK

CDC: Some Sexual Minorities Have Higher Sexual Risk Behaviors

FRIDAY, Sept. 14, 2018 -- Bisexual females and "not sure" male students report higher prevalences for many sexual risk behaviors than heterosexual students, according to research published in the Sept. 14 issue of the U.S. Centers for Disease...

https://ift.tt/2NIIaSZ

Extreme Flooding Can Up Exposure to Pathogens

FRIDAY, Sept. 14, 2018 -- Extreme flooding, such as was seen in Hurricane Harvey, can increase exposure to pathogens, according to a research letter published recently in Environmental Science & Technology. Pingfeng Yu, Ph.D., from Rice...

https://ift.tt/2xgf3Mz

Recommendations Issued for Enhancing ICU Diagnostic Safety

FRIDAY, Sept. 14, 2018 -- Identifying and reducing diagnostic errors in the intensive care unit (ICU) should be a top priority, according to a perspective article published in the Aug. 1 issue of the Annals of the American Thoracic Society. Paul A....

https://ift.tt/2NII7GN

Small Reduction in Lung Function With Tx De-Escalation in COPD

FRIDAY, Sept. 14, 2018 -- A de-escalation from triple therapy to indacaterol/glycopyrronium may lead to a small reduction in lung function in non-frequently exacerbating patients with chronic obstructive pulmonary disease (COPD) but no difference in...

https://ift.tt/2xgf17p

Situation Framing, Language Can Influence Decision-Making

FRIDAY, Sept. 14, 2018 -- How a situation is framed and the language used to describe risks can influence patients' decision-making, according to an article published in Physicians Practice. Patients tend to focus more strongly on the potential risk...

https://ift.tt/2NM4qvs

Sales of Flavored E-Cigarette Products Up Since 2012

FRIDAY, Sept. 14, 2018 -- Sales of flavored electronic cigarette products have increased dramatically since 2012, according to a study published online Aug. 23 in the U.S. Centers for Disease Control and Prevention's Preventing Chronic...

https://ift.tt/2xiy7tP

Folic Acid Past First Trimester Doesn't Prevent Preeclampsia

FRIDAY, Sept. 14, 2018 -- Supplementation with folic acid beyond the first trimester does not prevent preeclampsia among high-risk women, according to a study published online Sept. 12 in The BMJ. Shi Wu Wen, Ph.D., from the Ottawa Research...

https://ift.tt/2NII5yF

[18F]AV‐1451 binding is increased in frontotemporal dementia due to C9orf72 expansion

Annals of Clinical and Translational Neurology, EarlyView.


https://ift.tt/2xcEnEa

Burden of cardiovascular disease in Japanese cancer patients and survivors: a single cancer-center study in Niigata City

Abstract

Background

Cardiovascular disease (CVD) and cancer are major causes of death in Japan. As most CVDs are chronic and often aggravate, long-term follow-up is necessary. Although some cancer patients and survivors have CVD, its prognostic significance and prevalence are unknown. Therefore, we conducted a retrospective study at our center to determine the prevalence of cancer patients with CVD.

Methods

In 2015, our 10-year (2005–2014) cancer registry was summarized. Comorbidities including left ventricular dysfunction, atrial fibrillation (AF), ischemic heart disease, aortic stenosis, venous thromboembolism (VTE), and elevation of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) were examined.

Results

In total, 26,235 de novo cancer patients were registered and 16,130 survived until January 1, 2015. The 5-year survival rate was 64.0% for all cancer patients and 44.2% for cancer patients with CVD. Cox proportional hazards analysis adjusting for age, cancer stage, and body mass index revealed that AF [hazard ratio (HR) 1.219, male; P = 0.038], VTE (HR 1.517, male; P = 0.003 and HR 2.089, female; P < 0.001), and NT-proBNP elevation (HR 1.861, female; P = 0.002) were significantly associated with death. The CVD prevalence among cancer survivors in 2015 was 8.7% vs 3.5% for males vs females. AF was the most common CVD (prevalence: male, 4.0%; female, 1.0%). The prevalence of most CVD in adults increased progressively with age, with male predominance (12.1% for male and 7.5% for female patients in the 80 s age group).

Conclusions

One in 10 elderly cancer survivors has serious CVD. AF, VTE, and heart failure were critical comorbidities. Cardiologists and cancer-care providers should recognize CVD presence and monitor patients closely, providing medications or interventions concurrently with cancer therapy.

https://ift.tt/2OmvTRt

Measuring Hypopharyngeal Gland Acinus Size in Honey Bee (Apis mellifera) Workers

Hypopharyngeal gland acinus size is a robust measure of nurse honey bee nutrition. Here, we provide a detailed protocol for dissecting, staining, imaging, and measuring nurse bee hypopharyngeal gland acini.

https://ift.tt/2CWths2

Detection of Phospholipase C Activity in the Brain Homogenate from the Honeybee

To test the inhibitory effects of pharmacologic agents on phospholipase C (PLC) in different regions of the honeybee brain, we present a biochemical assay to measure PLC activity in those regions. This assay could be useful for comparing PLC activity among tissues, as well as among bees exhibiting different behaviors.

https://ift.tt/2xcVYvv

Ohio family boasts 3 generations of EMS providers

Bob Smith, owner of Smith Ambulance, jokes that if someone in his family isn't an EMT, "we can't use you"

https://ift.tt/2MwB8Mr

Genetic Encoding of a Non-Canonical Amino Acid for the Generation of Antibody-Drug Conjugates Through a Fast Bioorthogonal Reaction

Incorporating a cyclopropene derivative of lysine into antibodies allows the site-specific, rapid and efficient linkage of tetrazine-bearing molecules to generate antibody-drug conjugates.

https://ift.tt/2Mx89rR

CRISPR-Mediated Reorganization of Chromatin Loop Structure

Chromatin looping plays a significant role in gene regulation; however, there have been no technological advances that allow for selective and reversible modification of chromatin loops. Here we describe a powerful system for chromatin loop re-organization using CRISPR-dCas9 (CLOuD9), demonstrated to selectively and reversibly modulate gene expression at targeted loci.

https://ift.tt/2QqeAAe

Dynamical Ventral Tegmental Area Circuit Mechanisms of Alcohol‐Dependent Dopamine Release

European Journal of Neuroscience, Volume 0, Issue ja, -Not available-.


https://ift.tt/2MyOo3v

AR–PDEF pathway promotes tumour proliferation and upregulates MYC-mediated gene transcription by promoting MAD1 degradation in ER-negative breast cancer

Abstract

Background

Androgen receptor (AR) is expressed in 60%~ 70% oestrogen receptor (ER)-negative breast cancer (BC) cases and promotes the growth of this cancer subtype. Expression of prostate-derived Ets factor (PDEF), a transcription factor, is highly restricted to epithelial cells in hormone-regulated tissues. MYC and its negative regulator MAD1 play an important role in BC progression. Previously, we found that PDEF expression is strongly correlated with AR expression. However, the relationship between AR and PDEF and the function of PDEF in ER-negative BC proliferation are unclear.

Methods

AR and PDEF expression in ER-negative BC tissues and cell lines was determined by performing immunohistochemistry or western blotting. Protein expression levels and location were analysed by performing western blotting, RT-qPCR and immunofluorescence staining. Co-immunoprecipitation and chromatin immunoprecipitation assays were performed to validate the regulation of AR–PDEF–MAD1–MYC axis. Moreover, the effect of AR and PDEF on BC progression was investigated both in vitro and in vivo.

Results

We found that PDEF was overexpressed in ER-negative BC tissues and cell lines and appeared to function as an oncogene. PDEF expression levels were strongly correlated with AR expression in ER-negative BC, and PDEF transcription was positively regulated by AR. PDEF upregulated MYC-mediated gene transcription by promoting MAD1 degradation in ER-negative BC. Finally, we found that compared with the inhibition of AR expression alone, simultaneous inhibition of AR and PDEF expression further suppressed tumour proliferation both in vitro and in vivo.

Conclusions

Our data highlight the role of the AR–PDEF–MAD1–MYC axis in BC progression and suggest that PDEF can be used as a new clinical therapeutic target for treating ER-negative BC.

https://ift.tt/2Mx0N7Q

The precision prevention and therapy of HPV‐related cervical cancer: new concepts and clinical implications

Cancer Medicine, EarlyView.


https://ift.tt/2p6Zcwf

Effects of age and extraction solvent on phytochemical content and antioxidant activity of fresh Moringa oleifera L. leaves

Food Science &Nutrition, EarlyView.


https://ift.tt/2MyJgfL

Anticancer, antithrombotic, antityrosinase, and anti‐α‐glucosidase activities of selected wild and commercial mushrooms from Pakistan

Food Science &Nutrition, EarlyView.


https://ift.tt/2QvKrQg

Cancers, Vol. 10, Pages 332: Clonal Heterogeneity Reflected by PI3K-AKT-mTOR Signaling in Human Acute Myeloid Leukemia Cells and Its Association with Adverse Prognosis

Cancers, Vol. 10, Pages 332: Clonal Heterogeneity Reflected by PI3K-AKT-mTOR Signaling in Human Acute Myeloid Leukemia Cells and Its Association with Adverse Prognosis

Cancers doi: 10.3390/cancers10090332

Authors: Ina Nepstad Kimberley Joanne Hatfield Tor Henrik Anderson Tvedt Håkon Reikvam Øystein Bruserud

Clonal heterogeneity detected by karyotyping is a biomarker associated with adverse prognosis in acute myeloid leukemia (AML). Constitutive activation of the phosphatidylinositol-3-kinase-Akt-mechanistic target of rapamycin (PI3K-Akt-mTOR) pathway is present in AML cells, and this pathway integrates signaling from several upstream receptors/mediators. We suggest that this pathway reflects biologically important clonal heterogeneity. We investigated constitutive PI3K-Akt-mTOR pathway activation in primary human AML cells derived from 114 patients, together with 18 pathway mediators. The cohort included patients with normal karyotype or single karyotype abnormalities and with an expected heterogeneity of molecular genetic abnormalities. Clonal heterogeneity reflected as pathway mediator heterogeneity was detected for 49 patients. Global gene expression profiles of AML cell populations with and without clonal heterogeneity differed with regard to expression of ectopic olfactory receptors (a subset of G-protein coupled receptors) and proteins involved in G-protein coupled receptor signaling. Finally, the presence of clonal heterogeneity was associated with adverse prognosis for patients receiving intensive antileukemic treatment. The clonal heterogeneity as reflected in the activation status of selected mediators in the PI3K-Akt-mTOR pathway was associated with a different gene expression profile and had an independent prognostic impact. Biological heterogeneity reflected in the intracellular signaling status should be further investigated as a prognostic biomarker in human AML.

https://ift.tt/2QsVnxX

Diversity of Adipose Tissue Immune Cells: Are All Eosinophils Created Equal?

BioEssays, EarlyView.


https://ift.tt/2CVn5k8

It is Neither Frankenstein Nor a Submarine Alkaline Vent, It is Just the Second Law

BioEssays, EarlyView.


https://ift.tt/2QvlWTa

Antibiotic resistance genes show enhanced mobilization through suspended growth and biofilm-based wastewater treatment processes

In the original version of this article the SRA accession number was incorrect. The correct number, SRP107015, is now displayed.

https://ift.tt/2MtakN7

Bacterial bioclusters relate to hydrochemistry in New Zealand groundwater

ABSTRACT

Groundwater is a major source of New Zealand's water supply and supports base flows in rivers. Microbial communities in groundwater ecosystems mediate biogeochemical processes, and it is therefore crucial to understand microbial diversity in these ecosystems. We analysed bacterial assemblages from 35 New Zealand groundwater monitoring sites with varying hydrogeochemical conditions across the country. Proteobacteria was the most abundant phylum, and Variovorax represented the most common taxon. Pseudomonas, Burkholderia, Acidovorax, Janthinobacterium, Polaromonas and Caulobacter were the other common taxa. There was no Operational Taxonomic Unit (OTU) that was found in every one of the 35 samples. Here, we introduce a framework that has potential utility for groundwater ecosystem management, where the samples with similar microbial communities are grouped together into 'bioclusters'. Metabolic inferences derived from the taxonomic data were used to predict the oxygen requirements, metabolic potential and bacterial energy sources of each biocluster. Groundwater chemistry explains 59% of the variation in the relative abundance of all OTUs, with NO₃-N, pH, DO, NH₄-N, Fe, Br and SO₄ displaying the strongest relationships to bioclusters. We propose that the biocluster framework, coupled with metabolic inferences derived from the taxonomic data, may have application outside New Zealand for on-going monitoring of the health of groundwater ecosystems.

https://ift.tt/2xd6R0F

Molecular characterization of plasmid-mediated AmpC beta-lactamase- and extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae among corvids (Corvus brachyrhynchos and Corvus corax) roosting in Canada

ABSTRACT

This study evaluated the carriage of AmpC and extended-spectrum beta-lactamase (ESBL) genes and associated plasmids in faecal bacteria of Canadian corvids. Faecal samples from 449 birds in five roosting sites across Canada were analyzed using selective media, screening for AmpC and ESBL genes by PCR, and sequencing. Genomic relatedness was determined by PFGE and MLST. Plasmid mobility was studied by conjugation and transformation experiments, followed by plasmid typing. In total, 96 (21%, n = 449) cefotaxime-resistant Escherichia coli and three (0.7%) Klebsiella pneumoniae isolates were identified. ESBL genes bla_CTX-M-1 (n = 3), bla_CTX-M-14 (n = 2), bla_CTX-M-32 (n = 2) and bla_CTX-M-124 (n = 1) were detected in eight E. coli isolates, whereas bla_SHV-2 (2) was found in two K. pneumoniae. E. coli isolates contained bla_CMY-2 (n = 83) and bla_CMY-42 (n = 1). The high genetic diversity of the isolates and presence of clinically important E. coli ST69 (n = 1), ST117 (n = 7) and ST131 (n = 1) was revealed. AmpC genes were predominantly carried by plasmids of incompatibility groups I1 (45 plasmids), A/C (10) and K (7). The plasmid IncI1/ST12 was most common and found in diverse E. coli STs in all sites. Highly diverse E. coli isolates containing AmpC and ESBL genes, including clinically important clones and emerging plasmids, are in circulation throughout Canadian wildlife.

https://ift.tt/2MtaeFf

Incorporating molecular-based functional and co-occurrence network properties into benthic marine impact assessments

Abstract

Taxonomic and functional community structures may respond differently to anthropogenic stressors. Used in combination they can provide an estimate of functional redundancy, a key component of ecosystem resilience. In this study, the utility of incorporating functional community structure and co-occurrence network properties into impact assessments of offshore oil and gas (O&G) operations on benthic bacterial communities was investigated. Sediment samples and physico-chemical data were collected along a transect at increasing distances from one exploratory drilling (ED), and one gas production and drilling (GPD) field. Bacterial community composition was determined by 16S rRNA metabarcoding. A hidden-state prediction method (PAPRICA) was used to characterize bacterial metabolic community functions. At both sites, diversity differed significantly between near-field (impacted) and far-field (non-impacted) stations, with both taxonomic and functional alpha-diversity positively affected in near-field stations at the GPD site. The opposite pattern was observed in the near-field samples of ED with lower and higher values respectively. Overall, impacted stations displayed a distinct network signature, with a lower ratio of positive interactions and signs of higher community cohesion. Community profiles from metabolic inference and co-occurrence network topology provided complementary information to taxonomic indices, which may assist with assessing the effects of O&G activities on benthic communities.

https://ift.tt/2xd6PG5

Infection dynamics of endosymbionts reveal three novel localization patterns of Rickettsia during the development of whitefly Bemisia tabaci

ABSTRACT

The whitefly Bemisia tabaci (Hemiptera: Aleyrodidae) is a severe agricultural pest that harbors at least seven endosymbionts. Many important aspects of the symbiosis mechanism between these bacterial endosymbionts and their hosts are poorly understood, such as endosymbiont proliferation dynamics, spatial distribution and titer regulation during host development. In this study, infection by bacterial endosymbionts in the whitefly B. tabaci Middle East-Asia Minor-1 (MEAM1, formerly B biotype) South China population, their infection titers in various stages of whitefly host development and their spatial localization were investigated. Results revealed that the MEAM1 B. tabaci harbors the primary symbiont Portiera and secondary symbionts Rickettsia and Hamiltonella. The titers of these three endosymbionts increased with the development of their B. tabaci host. Significant proliferation of Portiera and Hamiltonella mainly occurred during the second to fourth instar nymphal stages, while Rickettsia proliferated mainly during adult eclosion. Fluorescence in situ hybridization analysis of B. tabaci adults revealed three novel infection patterns of Rickettsia: assemblage in the bacteriocytes that scattered through the entire abdomen of the female host, localization in wax glands and localization in the colleterial gland. These novel infection patterns may help to uncover the function of Rickettsia in its insect hosts.

https://ift.tt/2Mw2PFp

Growth promotion and inhibition induced by interactions of groundwater bacteria

ABSTRACT

Microorganisms can produce a plethora of secondary metabolites, some acting as signaling compounds and others as suppressing agents. As yet, the potential of groundwater microbes to produce antimicrobial compounds to increase their competitiveness against other bacteria has not been examined. In this study, we developed an AlamarBlue® based high-throughput screening method that allowed for a fast and highly standardized evaluation of both growth-inhibiting and -promoting metabolites. With this technique, 149 screened bacterial isolates were grown in monocultures and in 1402 co-cultures. Co-cultivation did not increase the frequency of growth inhibition against the two tested model organisms (Staphylococcus aureus 533R4 and Escherichia coli WA321) compared to monocultures. Mainly co-cultivation of Proteobacteria induced growth inhibition of both model organisms. Only slightly increased growth promotion of S. aureus 533R4 was observed. Growth-promoting effects on E. coli WA321 were observed by supernatants from co-cultures between Bacteroidetes and Firmicutes. With the standardized screening for both growth-inhibiting and -promoting effects, this method will enable further studies to elaborate and better understand complex inter-specific interactions and networks in aquatic communities as well as in other environments.

https://ift.tt/2xd3uGT

Epithelial membrane protein 2: a novel biomarker for circulating tumor cell recovery in breast cancer

Abstract

Purpose

EpCAM is a common marker used in the detection of circulating tumor cells (CTC). Disseminated cancer cells display the characteristics of epithelial-to-mesenchymal transition events. The purpose of this study was to assess the potential of epithelial membrane protein 2 (EMP2) as a novel biomarker for CTC retrieval in breast cancer.

Methods

MCF7 and MDA-MB-231 cells were stained with either anti-EpCAM or anti-EMP2 mAbs, respectively, followed by flow cytometric assay to measure their expression levels. PBMCs isolated from healthy donors were used for breast cancer cell spiking. CD45-depleted PBMCs from breast cancer patients' blood were used for CTC capturing. Immunomagnetic separation was used to enrich breast cancer cells. Cytospin centrifugation was performed to concentrate the captured cells, followed by immunofluorescence staining with anti-CD45 mAb, anti-pan cytokeratin mAb and DAPI. Fluorescent images were taken using a confocal microscope for CTC counts.

Result

MDA-MB-231 cells had 2.56 times higher EMP2 expression than MCF7 cells, and EMP2 had a significantly higher capture efficiency than EpCAM for MCF7 cells. Furthermore, anti-EMP2 was capable of capturing MCF7 cells that escaped in the flow-through of anti-EpCAM. Likewise, EMP2 had a significantly higher capture efficiency on MDA-MB-231 cells when compared to MCF7 cells. Most importantly, EMP2 biomarker was successfully used for CTC capture in patients with primary breast cancer.

Conclusions

EMP2 is superior to EpCAM for capturing both MCF7 and MDA-MB-231 cells. Additionally, EMP2 is a novel biomarker and capable of capturing breast cancer cells in patient blood samples.

https://ift.tt/2x9cXyY

Goal-directed therapy in cytoreductive surgery with hyperthermic intraperitoneal chemotherapy: a prospective observational study

Abstract

Background

Cytoreductive surgery (CRS) with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in peritoneal carcinomatosis treatment causes significant hemodynamic, metabolic, and hematological alterations. Studies on the anesthetic intraoperative management are heterogeneous and scarce. There is a great heterogeneity in the anesthetic management of CRS and HIPEC. The aim of this study is to analyze perioperative hemodynamic goal-directed management and to evaluate the complications arisen until the seventh postoperative day.

Methods

Prospective, observational study of all CRS and HIPEC patients from March 2014 to May 2017. Hemodynamic and clinical parameters were registered during surgery and the first 3 postoperative days. We correlated intraoperative data with the postoperative course until the seventh day.

Results

A total of 92 patients were included in the study (age 58.5 ± 10.9 years, 47% colorectal carcinoma, and 38% ovarian carcinoma). Peritoneal Carcinomatosis Index (PCI) (median and ranges) was 10 [0–39]. Cardiac Index (CI) 3.15 l/min⁻¹/m⁻² [1.79–5.60]) and Systolic Volume Variation (SVV) (10% [3%–17%]) remained within the values of normality in all surgery phases. A large difference was observed between the minimum and maximum ranges of fluid therapy administered (median 9.8 ml/kg/h [5.3–24.3]), showing a great interindividual variation in the fluids requirement. A direct relationship was observed between PCI and surgery duration, fluid therapy, and intraoperative transfusion percentage (p < 0.02).

Conclusions

There is a great variability in the intraoperative fluid therapy needs of the patients. SVV monitoring makes it possible to adjust the fluid therapy needs in each surgery phase. The use of a hemodynamic goal-directed anesthetic protocol in CRS and HIPEC enables to individually adjust the fluid therapy, avoiding over-hydration and ensuring hemodynamic stability in all surgery phases.

https://ift.tt/2OqYMfq

Molecular Pathways in Melanomagenesis: What We Learned from Next-Generation Sequencing Approaches

Abstract

Purpose of Review

Conventional clinico-pathological features in melanoma patients should be integrated with new molecular diagnostic, predictive, and prognostic factors coming from the expanding genomic profiles. Cutaneous melanoma (CM), even differing in biological behavior according to sun-exposure levels on the skin areas where it arises, is molecularly heterogeneous. The next-generation sequencing (NGS) approaches are providing data on mutation landscapes in driver genes that may account for distinct pathogenetic mechanisms and pathways. The purpose was to group and classify all somatic driver mutations observed in the main NGS-based studies.

Recent Findings

Whole exome and whole genome sequencing approaches have provided data on spectrum and distribution of genetic and genomic alterations as well as allowed to discover new cancer genes underlying CM pathogenesis.

Summary

After evaluating the mutational status in a cohort of 686 CM cases from the most representative NGS studies, three molecular CM subtypes were proposed: BRAF^mut, RAS^mut, and non-BRAF^mut/non-RAS^mut.

https://ift.tt/2xhPHhy

Jack of many trades: Multifaceted role of neuropilins in pancreatic cancer

Cancer Medicine, EarlyView.


https://ift.tt/2xbPYTP

Protracted Bacterial Bronchitis (PBB) in Children

American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 6, Page P11-P12, September 15, 2018.


https://ift.tt/2xb1m2f

Short-Term Elevation of Fine Particulate Matter Air Pollution and Acute Lower Respiratory Infection

American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 6, Page 759-766, September 15, 2018.


https://ift.tt/2xewCwB

Opsonic Phagocytosis in Chronic Obstructive Pulmonary Disease Is Enhanced by Nrf2 Agonists

American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 6, Page 739-750, September 15, 2018.


https://ift.tt/2x86m7S

Evolving Challenges in Pediatric Pulmonary Medicine. New Opportunities to Reinvigorate the Field

American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 6, Page 724-729, September 15, 2018.


https://ift.tt/2xi35lP

Know Your Limitations: Assumptions in the Single-Beat Method for Estimating Right Ventricular–Pulmonary Vascular Coupling

American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 6, Page 707-709, September 15, 2018.


https://ift.tt/2xeeHa4

Circulating and Tumor Myeloid-derived Suppressor Cells in Resectable Non–Small Cell Lung Cancer

American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 6, Page 777-787, September 15, 2018.


https://ift.tt/2xc0edS

Reply to Voelkel and Newman: The Light at the End of the Long Pulmonary Hypertension Tunnel Brightens

American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 6, Page 820-821, September 15, 2018.


https://ift.tt/2xbLqgl

Chronic Obstructive Pulmonary Disease: Abandoning the “Streetlight Effect”

American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 6, Page 697-698, September 15, 2018.


https://ift.tt/2xoLEAb

Consider Using Attributable Fraction of Mortality from Acute Respiratory Distress Syndrome to Guide Sample Size Estimates

American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 6, Page 821-822, September 15, 2018.


https://ift.tt/2xc2fb4

Nintedanib in Severe Pulmonary Arterial Hypertension

American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 6, Page 808-810, September 15, 2018.


https://ift.tt/2xfOPK7

How Many FOXs Are There on The Road to Pulmonary Hypertension?

American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 6, Page 704-707, September 15, 2018.


https://ift.tt/2xaKYyS

Erratum: Galectin-3 Promotes Vascular Remodeling and Contributes to Pulmonary Hypertension

American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 6, Page 824-824, September 15, 2018.


https://ift.tt/2xfOFlZ

Expression of IL-33 and TSLP and Their Receptors in Asthmatic Airways after Inhaled Allergen Challenge

American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 6, Page 805-807, September 15, 2018.


https://ift.tt/2xbLpJj

Erratum: Skeletal Muscle Dysfunction in Chronic Obstructive Pulmonary Disease: What We Know and Can Do for Our Patients

American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 6, Page 824-825, September 15, 2018.


https://ift.tt/2xgg5IG

Reply to Tremlett and Kanthimathinathan and to Koopman and Kneyber

American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 6, Page 823-824, September 15, 2018.


https://ift.tt/2xaXRJc

New Insights into Complicated Grief in Bereaved Family Members Approached for Organ Donation

American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 6, Page 698-700, September 15, 2018.


https://ift.tt/2xgfJlk

Myeloid Regulatory Cells: New and Exciting Players in the Immunology of Lung Cancer

American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 6, Page 703-704, September 15, 2018.


https://ift.tt/2xeeC6g

Mycobacterial Lipids Induce Calcium Mobilization and Degranulation of Mast Cells

American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 6, Page 813-816, September 15, 2018.


https://ift.tt/2xeuLId

More on Single-Beat Estimation of Right Ventriculoarterial Coupling in Pulmonary Arterial Hypertension

American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 6, Page 816-818, September 15, 2018.


https://ift.tt/2xeevrm

Endothelial and Smooth Muscle Cell Interaction via FoxM1 Signaling Mediates Vascular Remodeling and Pulmonary Hypertension

American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 6, Page 788-802, September 15, 2018.


https://ift.tt/2xewugB

Regulation of PTEN expression by noncoding RNAs

Abstract

Phosphatase and tensin homologue (PTEN) triggers a battery of intracellular signaling pathways, especially PI3K/Akt, playing important roles in the pathogenesis of multiple diseases, such as cancer, neurodevelopmental disorders, cardiovascular dysfunction and so on. Therefore PTEN might be a biomarker for various diseases, and targeting the abnormal expression level of PTEN is anticipated to offer novel therapeutic avenues. Recently, noncoding RNAs (ncRNAs) have been reported to regulate protein expression, and it is definite that PTEN expression is controlled by ncRNAs epigenetically or posttranscriptionally as well. Herein, we provide a review on current understandings of the regulation of PTEN by ncRNAs, which could contribute to the development of novel approaches to the diseases with abnormal expression of PTEN.

https://ift.tt/2CWmjn1

The association of sleep-disordered breathing and white matter hyperintensities in heart failure patients

Abstract

Heart failure patients often manifest white matter hyperintensites on brain magnetic resonance imaging (MRI). White matter hyperintnsities have also been linked with cognitive problems in patients with heart failure. Sleep disordered breathing may contribute to structural brain changes in heart failure. The purpose of this study was to test the extent to which the apnea hypopnea index is associated with global and regional white matter hyperintensities, and is a moderating factor in the relationship between age and white matter hyperintensites. A total of 28 HF patients [mean age (SD) = 67.89 (5.8)] underwent T1-weighted and T2FLAIR MRI and a home sleep monitoring study. The apnea hypopnea index cut off of 10 was used to compare between higher and lower risks of sleep disordered breathing. Regression analysis was used to test the association between apnea hypopnea index and both global and regional white matter hyperintensities. The interaction term was entered to identify the moderation effect. Apnea hypopnea index was associated with higher regional white matter hyperintensities but not global white matter hyperintensities. There was a significant interaction between the apnea hypopnea index and age, such that older participants with the apnea hypopnea index ≥10 showed greater regional white matter hyperintensities than those with the apnea hypopnea index <10. The results of this preliminary study indicate that a higher apnea hypopnea index is associated with more white matter hyperintensities. The age-related white matter hyperintensities appear to be exacerbated by apnea hypopnea index in our individuals with heart failure. Future studies are needed to further investigate the underlying mechanisms.

https://ift.tt/2Mq1ekp

Pineoblastoma in a child with 22q11.2 deletion syndrome

Description 

A 4-year-old girl with a history of chromosome 22q11.2 deletion syndrome presented to the emergency department with 2–3 weeks of worsening emesis. CT of the head revealed a large pineal region calcified tumour with associated hydrocephalus. Contrast-enhanced MRI of the brain and spine status postexternal ventricular drain placement confirmed a pineal tumour with diffuse metastatic leptomeningeal spinal spread (figure 1A,B). The child had a normal MRI of the brain 2 years prior (figure 1C) as work-up for her developmental delay. The diagnosis of 22q11.2 deletion syndrome was made by chromosomal microarray testing, which revealed a 2.5 MB deletion of 22q11.2 that included the TBX1 gene. Neuropathology on a subtotal resection showed clusters and sheets of tightly packed, small, blue cells with oval or slightly angulated nuclei and scant cytoplasm, consistent with a primitive neuroectodermal tumour. The tumour showed no loss of expression of INI...

https://ift.tt/2MvHxra

Coronary artery ectasia: a rare cause of acute coronary syndrome

Coronary artery ectasia (CAE) is defined as a localised or diffuse dilatation of coronary artery lumen more than 1.5 times that of an adjacent normal segment. CAE may present with or without functionally significant stenosis. Such patients may manifest with stable angina or with acute coronary syndrome. Ectasia may serve as a nidus for thrombus formation with likelihood of distal embolisation or it may lead to dissection or spasm. This condition presents a challenge for an interventionist. Should we intervene or manage it medically. We describe a case of CAE where all the vessels were diffusely ectatic with variable degree of stenosis. In brief we discuss the causes and management issues in ectasia.

https://ift.tt/2Qvj60h

Uncommon cause of chest pain in a postoperative spinal patient

An 84-year-old woman with previous spinal operations including vertebroplasty and lumbar decompressions was admitted electively under the spinal team for right-sided L4/5 decompression for worsening back pain which she undergoes using a posterior approach. Postoperatively, she develops stabbing upper central chest pain and given unremarkable chest X-ray, ECG and cardiac troponin, she undergoes a CT pulmonary angiogram which shows a fracture of the upper part of sternum but no pulmonary embolism. There is no history of recent trauma and this is deemed to be secondary to prolonged spinal surgery in the prone position in a patient with osteopenic bones. To date, we have not come across a case of spontaneous sternal fracture as a complication of spinal surgery at our regional spinal unit. Most cases of sternal fractures are secondary to blunt anterior chest wall trauma with spontaneous fractures and stress fractures being rare.

https://ift.tt/2MvHmfu

Spin-top-like encrustation of suprapubic cystostomy catheter: when proper counselling is all that it takes!

Description 

A 25-year-old man from a rural background and suffering from psychiatric illness had complaints of acute urinary retention 1 year ago for which trocar-guided suprapubic cystostomy (SPC) Foley catheter placement was done elsewhere after failed attempt of per-urethral catheterisation.

There was no history of haematuria, lithuria, catheterisation and endourological intervention in the past. On further eliciting the history, there was a retrograde urethrogram film taken 1 year back which revealed a short segment (1.0 cm) bulbar urethral stricture. He had undergone optical internal urethrotomy with Foley catheter placement (14F) under regional anaesthesia for his urethral stricture. Per-urethral catheter was removed after 7 days and he voided well with good urinary stream. He was sent back home and instructed to follow-up after 3 days for removal of SPC catheter and need of de-clamping SPC catheter in case of urinary retention again.

However, a thorough counselling about catheter's care and related complications was not...

https://ift.tt/2QviVlD

A rare case of cellular angiofibroma affecting the periurethral region in a 38-year-old woman

Cellular angiofibroma (CAF) is a rare, site-specific, benign mesenchymal tumour affecting both women and men in the genitourinary region. The tumour usually presents as a small, asymptomatic lesion involving the vulvovaginal regions in women and inguinoscrotal regions in men. We report the case of a 38-year-old woman presenting with a painless mass in the vulval region, especially on the right side of urethral meatus for 8 years with progressively increasing lower abdominal discomfort. A simple excision was performed. The diagnosis of CAF was confirmed histopathologically.

https://ift.tt/2MvGd7Z

Cervical tuberculous lymphadenitis in an elderly adult

Description 

A 94-year-old man presented with complaints of increasing fatigue and generalised weakness for 1 month's duration. On admission, the patient had tachycardia of 112 bpm and fever of 101.1 °F. His initial physical examination was otherwise normal. Lactic acid was elevated (4.13 pg/mL), but other laboratory markers were within normal limits. No apparent source of infection was identified by initial urinalysis, chest radiography or CT of the abdomen without contrast. The lactic acidosis resolved after administration of normal saline, but he continued to have fever, which prompted more thorough physical examination that revealed a painless right-sided neck mass. CT of the neck without contrast confirmed a low-density neck mass in the right posterior cervical region measuring 7 cm in the maximum diameter (figures 1 and 2), suspicious for necrotic tumour or an abscess. Ultrasound-guided drainage of the mass recovered 50 mL of purulent material that was submitted for...

https://ift.tt/2QstE0d

Cytomegalovirus-associated haemophagocytic lymphohistiocytosis: a rare cause of febrile neutropenia during cancer chemotherapy

Febrile neutropenia (FN) is a common complication in patients with cancer during treatment with antineoplastic drugs. The initial cause is usually bacterial, and treatment of FN follows well-defined algorithms. We report a case of a 62-year-old patient with chronic lymphocytic leukaemia (CLL), who developed FN, which was unresponsive to both empirical antibacterial and empirical antifungal therapy. Surprisingly, a diagnosis of the life-threatening condition haemophagocytic lymphohistiocytosis (HLH) associated with cytomegalovirus (CMV) infection was made and treated successfully. CMV-associated HLH has not previously been described in patients with CLL treated with rituximab and bendamustine. It is concluded that HLH should be considered in patients with cancer with FN not responding to conventional antibiotic therapy.

https://ift.tt/2MvH2NO