Αρχειοθήκη ιστολογίου

Αναζήτηση αυτού του ιστολογίου

Κυριακή 25 Φεβρουαρίου 2018

Cervicovaginal microbiota composition correlates with the acquisition of high-risk human papillomavirus types

Abstract

High-risk (hr) human papillomavirus (HPV) infection is closely associated with the clinical conditions of both squamous intraepithelial lesions (SILs) and cervical carcinoma. However, it remains unclear what factors determine the type of hrHPV infection. Here, we have comprehensively investigated the bacterial composition of the cervicovaginal microbiota of 280 women infected with one type of hrHPV (HPV 16, 52, or 58) by the pyrosequencing of barcoded 16S rRNA genes. Differential microbiota composition was observed among various SIL groups and within the subgroups of each group. This result showed that it is not the microbiota diversity or the common microbiota, but rather agents that are specific to each SIL that might have a positive influence on the acquisition of hrHPV types, independent of abundance. Specifically, a composition of Oribacterium, Lachnobacterium and Thermus in the cervicovaginal microbiota is more likely to be associated with HPV 16, while a composition of Motilibacter in the cervicovaginal microbiota is more likely to be associated with HPV 52, and a composition of Litorilinea and Paludibaculum with a concomitant paucity of L. iners in the cervicovaginal microbiota is more likely to be associated with HPV 58. Furthermore, functional predictions regarding infectious diseases and cancer-related genes disclosed significant differences (P < 0.01) among the different (sub)groups. Our study provides an elucidation of the relationship between the composition of the cervicovaginal microbiota and the type of hrHPV acquired. This article is protected by copyright. All rights reserved.



http://ift.tt/2sUCDQ2

Survival of patients with hepatobiliary tract and duodenal cancer sites in Germany and the United States in the early 21st century

Abstract

Hepatobiliary tract cancers (HBTC) are a heterogeneous group of cancers with high mortality. Because most of these cancers, with the exception of hepatocellular carcinoma (HCC) are rare, few data are available concerning the population level survival expectations of patients with HBTC. Here, we describe survival of patients with HBTC in Germany with comparison to survival in the United States (US). Therefore, data were extracted from 12 databases in Germany and the Surveillance, Epidemiology and End Results (SEER13) database in the US. Period analysis and modeled period analysis were used to calculate 5-year relative survival estimates for patients with HBTC diagnosed from 1997-2013. HCC was the most common HBTC in each database, accounting for over 1/3 of HBTC in Germany and about half of cases in the US. Overall age adjusted 5-year relative survival for HBTC in 2006-13 was 19.1% in Germany and 20.6% in the US. Five year relative survival increased by 3.8 percent units in Germany and 4.5 percent units in the US between 2002-05 and 2010-13. Five year relative survival for individual types of HBTC ranged from 9.8% in Germany and 2.9% in the US for not otherwise specified biliary tract cancers to 44.4% and 50.1%, respectively, in Germany and the US for duodenal cancers. In conclusion, survival for HBTC remains poor in both Germany and the US, although a small increase in survival in the past decade was observed. Further work to find better treatment options for HBTC is needed to improve survival. This article is protected by copyright. All rights reserved.



http://ift.tt/2F5jBv9

Prospective study of blood metabolites associated with colorectal cancer risk

Abstract

Few prospective studies, and none in Asians, have systematically evaluated the relationship between blood metabolites and colorectal cancer risk. We conducted a nested case-control study to search for risk-associated metabolite biomarkers for colorectal cancer in an Asian population using blood samples collected prior to cancer diagnosis. Conditional logistic regression was performed to assess associations of metabolites with cancer risk. In the current study, we included 250 incident cases with colorectal cancer and individually matched controls nested within two prospective Shanghai cohorts. We found 35 metabolites associated with risk of colorectal cancer after adjusting for multiple comparisons. Among them, 12 metabolites were glycerophospholipids including nine associated with reduced risk of colorectal cancer and three with increased risk [odds ratios (ORs) per standard deviation (SD) increase of transformed metabolites: 0.31 to 1.98; p values: 0.002 to 1.25 × 10−10]. The other 23 metabolites associated with colorectal cancer risk included nine lipids other than glycerophospholipid, seven aromatic compounds, five organic acids, and four other organic compounds. After mutual adjustment, nine metabolites remained statistically significant for colorectal cancer. Together, these independently associated metabolites can separate cancer cases from controls with an area under the curve of 0.76 for colorectal cancer. We have identified that dysregulation of glycerophospholipids may contribute to risk of colorectal cancer. This article is protected by copyright. All rights reserved.



http://ift.tt/2sYcksm

Blood-Brain Barrier Damage as the Starting Point of Leukoaraiosis Caused by Cerebral Chronic Hypoperfusion and Its Involved Mechanisms: Effect of Agrin and Aquaporin-4

White matter lesion (WML) is popular in the patients aged over 65. Brain edema and blood-brain barrier (BBB) dysfunction due to cerebral chronic hypoperfusion (CCH) contributed to WML. Preserving astrocyte polarity is vital for BBB integrity. In our experiment, CCH model is established by bilateral carotid arteries occlusion (2VO). Leukoaraiosis was verified by fiber density stain, and brain edema was evaluated using brain water content measuring. The expressions of agrin and aquaporin-4 (AQP4) were evaluated, as well as the integrity of BBB. Astrocyte polarity was assessed by visualizing the distribution of AQP4 on astrocyte end-feet membranes. The results showed that expression of AQP4 firstly increased and then decreased, as agrin expression decreased gradually. At 3 days after 2VO, AQP4 and agrin displayed the most opposite expression with the former increasing and the latter decreasing; at the same time, brain edema reached high point as well as BBB permeability, and astrocyte polarity was degeneration. In the later phase, brain edema and BBB permeability were getting recovered, but WML was getting more evident. In accordance with that, agrin and AQP4 expression decreased significantly with astrocyte polarity reducing. We speculated that agrin and AQP4 played key roles in development of WML by mediating BBB damage in CCH, and BBB dysfunction due to reduced astrocyte polarity is the starting point of WMH.

http://ift.tt/2FxbTrs

The expanding neurological phenotype of DNM1L-related disorders

Sir,

http://ift.tt/2EWcK43

Reply: The expanding neurological phenotype of DNM1L-related disorders

Sir,

http://ift.tt/2FxbFk6

Synthesis of Engineered Zeolitic Materials: From Classical Zeolites to Hierarchical Core–Shell Materials

Abstract

The term "engineered zeolitic materials" refers to a class of materials with a rationally designed pore system and active-sites distribution. They are primarily made of crystalline microporous zeolites as the main building blocks, which can be accompanied by other secondary components to form composite materials. These materials are of potential importance in many industrial fields like catalysis or selective adsorption. Herein, critical aspects related to the synthesis and modification of such materials are discussed. The first section provides a short introduction on classical zeolite structures and properties, and their conventional synthesis methods. Then, the motivating rationale behind the growing demand for structural alteration of these zeolitic materials is discussed, with an emphasis on the ongoing struggles regarding mass-transfer issues. The state-of-the-art techniques that are currently available for overcoming these hurdles are reviewed. Following this, the focus is set on core–shell composites as one of the promising pathways toward the creation of a new generation of highly versatile and efficient engineered zeolitic substances. The synthesis approaches developed thus far to make zeolitic core–shell materials and their analogues, yolk–shell, and hollow materials, are also examined and summarized. Finally, the last section concisely reviews the performance of novel core–shell, yolk–shell, and hollow zeolitic materials for some important industrial applications.

Thumbnail image of graphical abstract

Engineered zeolitic materials are of great importance for catalysis or selective adsorption. These modern materials are made by the combination of zeolites as the main building blocks and other secondary components to form composite structures. Herein, critical aspects related to synthesis and modification of zeolitic core–shell materials, yolk–shell, and hollow materials are summarized.



http://ift.tt/2CJIk38

2D GeP: An Unexploited Low-Symmetry Semiconductor with Strong In-Plane Anisotropy

Abstract

Germanium phosphide (GeP), a new member of the Group IV–Group V compounds, is introduced into the fast growing 2D family with experimental and theoretical demonstration of strong anisotropic physical properties. The indirect band gap of GeP can be drastically tuned from 1.68 eV for monolayer to 0.51 eV for bulk, with highly anisotropic dispersions of band structures. Thin GeP shows strong anisotropy of phonon vibrations. Moreover, photodetectors based on GeP flakes show highly anisotropic behavior with anisotropic factors of 1.52 and 1.83 for conductance and photoresponsivity, respectively. This work lays the foundation and ignites future research interests in Group IV–Group V compound 2D materials.

Thumbnail image of graphical abstract

A new in-plane anisotropic 2D material GeP with a tunable bandgap is introduced. Angle-resolved polarized Raman investigations indicate that the GeP flake has a strong anisotropic Raman response. Moreover, a remarkable in-plane anisotropic conductance with the anisotropic factor of 1.52 and an in-plane anisotropic potoresponsivity with an anisotropic factor of 1.83 are realized in GeP flakes.



http://ift.tt/2F72TvC

People Rationalize Policies as Soon as They Take Effect

People express greater approval for political outcomes as soon as those outcomes transition from being anticipated to being actual, according to new research published in Psychological Science, a journal of the Association for Psychological Science. Findings from three field studies indicate that people report more favorable opinions about policies and politicians once they become the status quo.

"When we anticipate that something is going to happen, and then it actually happens, we immediately start to find ways of twisting our perceptions to make ourselves feel better about it, more so than we were doing when we merely anticipated this new thing," says study author Kristin Laurin of The University of British Columbia. "This suggests that public opinion polls about any potential new initiative are going to overestimate how much opposition will actually emerge once the new initiative takes effect."

In previous research, Laurin had found that people rationalize things that they feel stuck with, including situations they cannot physically escape or that are stable.

"It occurred to me that one thing that really makes you feel stuck with a new reality is when it becomes, so to speak, real—when it goes from being something that is hypothetically supposed to happen in the future, to something that is part of the present," she explains.

In one preliminary study, Laurin used Facebook ads to recruit participants in San Francisco and survey them about a citywide ban on selling plastic water bottles. Participants who completed the survey on the Tuesday immediately following the ban reported more positive attitudes toward the policy than did those who completed the survey on the Tuesday preceding the ban.

A second study expanded on these findings, surveying participants in Ontario about a new law that banned smoking in parks and restaurant patios. The participants, all of whom lived in Ontario and smoked, answered questions about their smoking habits and reported the proportion of their smoking that occurred in certain locations. They also saw information from the Ontario government website outlining the new legislation, including the date it would go into effect and the locations where smoking would be prohibited.

Participants who completed a follow-up survey after the new law went into effect changed their estimates: They reported that they had spent less of their time smoking in the prohibited areas than they had reported on the first survey. Participants who completed the follow-up survey just before the law went into effect did not report different smoking behaviors in the initial survey and follow-up.

These findings suggest that participants may have adjusted their reporting after the new law went into effect so as to minimize the extent to which the law affected them.

In a third study, Laurin surveyed Americans twice before Donald Trump's inauguration as President of the United States and once in the three days following it. The participants reported their attitudes toward the Trump presidency and how psychologically real Trump's presidency felt to them.

Once again, participants reported more positive attitudes after the inauguration compared with before, when the inauguration was anticipated but had not yet happened. An increase in how psychologically real the presidency felt seemed to account for this positive shift in attitudes.

Intriguingly, even participants who evaluated Trump's inauguration performance negatively and those who had preferred a different candidate for president showed the same pattern of results – these participants also tended to report more favorable attitudes as soon as Trump took office.

The finding may seem counterintuitive, but they fall in line with Laurin's hypothesis:

"It's hard to understand why seeing someone give what you judge to be a disappointing performance would make you more confident in their abilities to lead the country. It's not rational—it's rationalization: When something becomes a part of the present reality, even when it's something you don't like, you find ways of tricking yourself into thinking it's not quite so bad," she explains.

These studies shed light on how we might feel about new political realities, but they have implications that apply in a variety of scenarios.

"If you're going to have a new boss at work, or if you have to start a new diet for medical reasons, or if you're about to have a new baby—the message is that your 'psychological immune system' will likely kick in and make you feel better about any unpleasant aspect of these new realities once they actually take hold," Laurin concludes.

All data and materials have been made publicly available via the Open Science Framework (OSF). The design and analysis plans for Study 3 were preregistered at OSF. The complete Open Practices Disclosure for this article is available online. This article has received badges for Open Data, Open Materials, and Preregistration.



http://ift.tt/2CmeuGc

An expert consensus for the management of chronic hepatitis B in Asian Americans

Summary

Background

Hepatitis B virus (HBV) infection is common with major clinical consequences. In Asian Americans, the HBsAg carrier rate ranges from 2% to 16% which approximates the rates from their countries of origin. Similarly, HBV is the most important cause of cirrhosis, hepatocellular carcinoma (HCC) and liver related deaths in HBsAg positive Asians worldwide.

Aim

To generate recommendations for the management of Asian Americans infected with HBV.

Methods

These guidelines are based on relevant data derived from medical reports on HBV from Asian countries as well as from studies in the HBsAg positive Asian Americans. The guidelines herein differ from other recommendations in the treatment of both HBeAg positive and negative chronic hepatitis B (CHB), in the approach to HCC surveillance, and in the management of HBV in pregnant women.

Results

Asian American patients, HBeAg positive or negative, with HBV DNA levels >2000 IU/mL (>104 copies/mL) and ALT values above normal are candidates for anti-viral therapy. HBeAg negative patients with HBV DNA >2000 IU/mL and normal ALT levels but who have either serum albumin <3.5 g/dL or platelet count <130 000 mm3, basal core promoter (BCP) mutations, or who have first-degree relatives with HCC should be offered treatment. Patients with cirrhosis and detectable HBV DNA must receive life-long anti-viral therapy. Indications for treatment include pregnant women with high viraemia, coinfected patients, and those requiring immunosuppressive therapy. In HBsAg positive patients with risk factors, life-long surveillance for HCC with alpha-fetoprotein (AFP) testing and abdominal ultrasound examination at 6-month intervals is required. In CHB patients receiving HCC treatments, repeat imaging with contrast CT scan or MRI at 3-month intervals is strongly recommended. These guidelines have been assigned to a Class (reflecting benefit vs. risk) and a Level (assessing strength or certainty) of evidence.

Conclusions

Application of the recommendations made based on a review of the relevant literature and the opinion of a panel of Asian American physicians with expertise in HBV treatment will inform physicians and improve patient outcomes.



http://ift.tt/2Fw2bpx

Relationship between preoperative axial length and myopic shift over 3 years after congenital cataract surgery with primary intraocular lens implantation at the National Institute of Ophthalmology of Peru, 2007–2011



http://ift.tt/2FxxLDg

Sclerosing mucoepidermoid carcinoma with eosinophilia: Cytologic characterization of a rare distinct entity in the thyroid

Sclerosing mucoepidermoid carcinoma with eosinophilia (SMECE) is an extremely rare thyroid carcinoma with limited cytologic descriptions in the literature. Here, we present a 52-year-old woman with a 3.9 cm thyroid nodule. Fine-needle aspiration smears consisted of a highly cellular specimen with tumor cells in isolated patterns and solid squamoid nests. Tumor cells had round to oval nuclei, prominent nucleoli, smooth nuclear contours, and moderate amounts of dense cytoplasm. In addition to the polymorphous population of lymphocytes, the background contained a striking abundance of eosinophils. The subsequent right thyroidectomy showed histologic features diagnostic for SMECE.



http://ift.tt/2FtCSUR

The Yokohama system for reporting directly sampled endometrial cytology: The quest to develop a standardized terminology

Background

The main purpose of directly sampled endometrial cytology is to detect invasive endometrial malignancies. With this principle in mind, The Yokohama System (TYS) Working Group, composed of cytopathologists, surgical pathologists, and gynecologic oncologists met at the 2016 International Congress of Cytology, Yokohama, with the aim to publish a standardized reporting system inclusive of specific diagnostic categories and cytomorphologic criteria for uniform and reliable diagnosis of endometrial malignancies on directly sampled endometrial samples.

Methods

The diagnostic cytopathologic criteria previously published in the literature by the Japanese and Greek working group on endometrial cytology (Yanoh et al. [2012] Acta Cytol. 56:233; Margari et al. [2016] Diagn Cytopathol. 44:888-901) were critically reviewed with the aim of correlating the diagnostic classes to well defined risk categories for endometrial carcinoma (EC). Moreover, two classes of "atypical" endometrial cells were correlated respectively to a low- and high risk group. Some methodological suggestions for the application of ancillary special technologies to liquid based samples were also given.

Results

The TYS group conceived a new Bethesda-style classification for directly sampled endometrial cytology which correlates the cytologic diagnostic classes with definite risk categories. The cytomorphologic findings have been correlated to the molecular pathology of EC, also through the application of ancillary special techniques to liquid-based samples.

Conclusions

The success of TYS will depend on the acceptance of TYS by all the relevant pathology and gynecologic oncology communities who, by their joint efforts, will adopt, critically evaluate, and optimize this method with the only aim of further improving the impact of endometrial cytology on patients' care.



http://ift.tt/2ETkofy

Severe central sleep apnoea associated with nalmefene: a case report

Nalmefene, an opioid antagonist, has recently been approved for the treatment of alcohol dependence. We describe here the first case of a 52-year-old woman who developed a severe central sleep apnoea (CSA) 5 months after initiation of nalmefene. Scoring of ventilation during sleep recording revealed an apnoea-hypopnoea index of 67/h with 98.7% of central events and an apnoea index of 65/h. Nalmefene was withdrawn and a new polysomnography was performed which concluded that CSA has disappeared. Pathophysiology is still unclear but could involve the κ-opioid receptors. Physicians should be aware that CSA might affect patients treated with nalmefene. Further investigations are required to determine the pathophysiology, frequency, and treatment of CSA associated with nalmefene and other therapy for alcohol disorders.



http://ift.tt/2ETXrc0

Role of p62 in the regulation of cell death induction

Abstract

p62 is a multifunctional adaptor protein implicated in various cellular processes. It has been found to regulate selective autophagy, cell survival, cell death, oxidative stress, DNA repair and inflammation, and to play a role in a number of diseases, such as tumourigenesis, Paget's disease of bone, neurodegenerative disease, diabetes, and obesity. Cell death induction is an important cellular process. The dysregulation of cell death induction is involved in the pathogenesis of various diseases, such as cancer, neurodegeneration diseases, and diabetes. In this review, we discuss the functional role of p62 in inducing cell death in response to multiple stimuli, and we summarize the potential signaling pathways that contribute to this regulation. Given the important role of p62 in regulating cell death, p62 is considered to be a reasonable target for managing cell death dysregulation-related pathogenic conditions. A better understanding of the role of p62 and its related mechanisms in regulating cell death is necessary for the more precise utilization of p62 as a target for treating relevant diseases.



http://ift.tt/2CkA11M

End-of-Life Care for Unauthorized Immigrants in the U.S.

The notion of patients' rights is based on the Universal Declaration of Human Rights,1 which recognizes inherent human dignity and the equal and unalienable rights of all members of the human family to be universally protected irrespective of race, color, gender, language, religion, political or other opinion, national or social origin, property, birth, or other status.1 These fundamental human rights become particularly important to seriously ill patients as they are vulnerable due to the limitations imposed by their illness(es).

http://ift.tt/2Fx2NuO

Health on the Hill: Parliament mulls vaping regulations [News]



http://ift.tt/2BQjVvU

Quebec medical residents threaten strike over hours and pay [News]



http://ift.tt/2ESz42m

Do students enter medicine for money and prestige or to be of service? [News]



http://ift.tt/2BOkXsa

Electronic health records: physicians must lead [Letters]



http://ift.tt/2oraSKj

Insurance helps to brush physician depression under the rug [Letters]



http://ift.tt/2BQ3Zd3

Hepatopulmonary syndrome [Practice]



http://ift.tt/2ESySAa

"Is there a doctor on board?": Practical recommendations for managing in-flight medical emergencies [Analysis]



http://ift.tt/2BQyaRu

Demographic predictors of active tuberculosis in people migrating to British Columbia, Canada: a retrospective cohort study [Research]

BACKGROUND:

Canadian tuberculosis (TB) guidelines recommend targeting postlanding screening for and treatment of latent tuberculosis infection (LTBI) in people migrating to Canada who are at increased risk for TB reactivation. Our objectives were to calculate robust longitudinal estimates of TB incidence in a cohort of people migrating to British Columbia, Canada, over a 29-year period, and to identify groups at highest risk of developing TB based on demographic characteristics at time of landing.

METHODS:

We included all individuals (n = 1 080 908) who became permanent residents of Canada between Jan. 1, 1985, and Dec. 31, 2012, and were resident in BC at any time between 1985 and 2013. Multiple administrative databases were linked to the provincial TB registry. We used recursive partitioning models to identify populations with high TB yield.

RESULTS:

Active TB was diagnosed in 2814 individuals (incidence rate 24.2/100 000 person-years). Demographic factors (live-in caregiver, family, refugee immigration classes; higher TB incidence in country of birth; and older age) were strong predictors of TB incidence in BC, with elevated rates continuing many years after entry into the cohort. Recursive partitioning identified refugees 18–64 years of age from countries with a TB incidence greater than 224/100 000 population as a high-yield group, with 1% developing TB within the first 10 years.

INTERPRETATION:

These findings support recommendations in Canadian guidelines to target postlanding screening for and treatment of LTBI in adult refugees from high-incidence countries. Because high-yield populations can be identified at entry via demographic data, screening at this point may be practical and high-impact, particularly if the LTBI care cascade can be optimized.



http://ift.tt/2orkJQe

Comparing Canadian health care to that in other countries: looking beyond the headlines [Commentary]



http://ift.tt/2BPDfJD

Green urine [Practice]



http://ift.tt/2ERgrfx

In the closet, again [Humanities]



http://ift.tt/2BQjRfE

Host cell cytosolic immune response during Plasmodium liver stage development

Abstract
Recent years have witnessed a great gain in knowledge regarding parasite-host cell interactions during Plasmodium liver stage development. It is now an accepted fact that a large percentage of sporozoite invading a hepatocyte fail to form infectious merozoites. There appears to be a delicate balance between parasite survival and elimination and we now start to understand why this is so. Plasmodium liver stages replicate within the parasitophorous vacuole (PV), formed during invasion by invagination of the host cell plasma membrane. The main interface between the parasite and hepatocyte is the parasitophorous vacuole membrane (PVM) that surrounds the PV. Recently, it was shown that autophagy marker proteins decorate the PVM of Plasmodium liver stages and eliminate a proportion of parasites by an autophagy-like mechanism. Successfully developing Plasmodium berghei parasites are initially also labeled but in the course of development, they are able to control this host defense mechanism by shedding PVM material into the tubovesicular network (TVN), an extension of the PVM that releases vesicles into to the host cell cytoplasm. Better understanding of the molecular events at the PVM/TVN during parasite elimination could be the basis of new anti-malarial measures.

http://ift.tt/2ER6Y3x

Strategies of adaptation of microorganisms of the three domains of life to high salt concentrations

Abstract
Hypersaline environments with salt concentrations up to NaCl saturation are inhabited by a great diversity of microorganisms belonging to the three domains of life. They all must cope with the low water activity of their environment, but different strategies exist to provide osmotic balance of the cells' cytoplasm with the salinity of the medium. One option used by many halophilic Archaea and a few representatives of the Bacteria is to accumulate salts, mainly KCl and to adapt the entire intracellular machinery to function in the presence of molar concentrations of salts. A more widespread option is the synthesis or accumulation of organic osmotic, so-called compatible solutes. Here we review the mechanisms of osmotic adaptation in a number of model organisms, including the KCl accumulating Halobacterium salinarum (Archaea) and Salinibacter ruber (Bacteria), Halomonas elongata as a representative of the Bacteria that synthesize organic osmotic solutes, eukaryotic microorganisms including the unicellular green alga Dunaliella salina and the black yeasts Hortaea werneckii and the basidiomycetous Wallemia ichthyophaga, which use glycerol and other compatible solutes. The strategies used by these model organisms and by additional halophilic microorganisms presented are then compared to obtain an integrative picture of the adaptations to life at high salt concentrations in the microbial world.

http://ift.tt/2FwHF83

Yield improvement of epothilones in Burkholderia strain DSM7029 via transporter engineering

Abstract
Transporter engineering has been shown to be a positive approach for enhancing natural product titers in microbial cell factories by expelling target compounds out of feasible hosts. In this work, two multidrug efflux pumps, Orf14 and Orf3, were modulated in the epothilone production strain Burkholderia DSM7029::Tn5-km-epo (named G32) via Red/ET engineering to increase heterologous polyketide epothilone yields. Compared with the prior G32 strain, the total production of several epothilones in the G32::orf14-orf3 mutant was meaningfully doubled according to high-performance liquid chromatography-mass spectrometer (HPLC-MS) analysis. Typically for epothilone B, in simple and clear liquid medium CYMG, the overall productivity in the engineered high-yield producer G32::orf14-orf3 was improved for almost three-fold, from 2.7 to about 8.1 μg/l. Additionally, the ratio of extracellular to intracellular accumulation of epothilone B was raised from 9.3:1 to 13.7:1 in response to expression of two putative transport genes orf14 and orf3. Hence, we strongly recommend that the Orf14 and Orf3 transporters export epothilone, thus promotes the forward reaction of biosynthesis on epothilone manufacture inside the cells. Our results afford a practical stage for yield improvement of other heterologous natural products in broad chassis cells.

http://ift.tt/2ER5RAT

Validation of Reference Genes for RT-qPCR Analysis in the Deep-sea Bacterium Shewanella psychrophila WP2

Abstract
Reference genes are critical to obtain reliable results of RT-qPCR, which is widely used for relative quantification of gene expression. In this study, we evaluated the validity of seven candidate reference genes for normalization in RT-qPCR analysis in the deep-sea bacterium Shewanella psychrophila WP2 under different environmental conditions. Among the set of genes investigated, gyrA, 16S rRNA and rho were identified as the most suitable reference genes for WP2 at different temperatures, hydrostatic pressures and salinities, respectively. Notably, the rho gene is conserved in Shewanella genus and other deep-sea bacteria, thus could be used as a versatile reference gene for RT-qPCR analysis of these microorganisms under extreme environmental conditions.

http://ift.tt/2FvXM5T

Optimization of physicochemical parameters of tannase post-purification and its versatile bioactivity

Abstract
The present study investigates the optimization of tannase production from A. nidulans for various physicochemical parameters and harvests tannase for its chemical characterization. The maximum tannase activity was observed on the third day of incubation at 35°C and the stability was observed at pH 5.5 to 6.0 by holding its 100% activity. The tannase was partially purified from A. nidulans [FT10] by ammonium sulfate precipitation at different concentrations and it was found that at 80% of ammonium sulfate concentration, the precipitate exhibited the maximum activity for tannase of 96 U/ml. LCMS showed its M/Z value as 162.3 which was reconfirmed by SDS-PAGE. The UV spectrum and FTIR confirmed the presence of two oxy- and three hydroxyl groups in the benzene ring structure. The antibacterial activity of tannase was enhanced with antibiotics such as streptomycin and ceftazidime whereas the biofilm formation was significantly inhibited by the purified tannase. The scavenging activity was greatly increased with purified component and when the concentration of the purified tannase, TN09 was increased. To the best of our knowledge, this is one of the few reports where microbial species was used as the source for producing tannase enzyme and its role in various bioactivities such as antibacterial, anti-biofilm and antioxidant activity was evaluated.

http://ift.tt/2EV9XIq

Exploratory analysis of the association of depth of response and survival in patients with metastatic non-small-cell lung cancer treated with a targeted therapy or immunotherapy

Ann Oncol 2017; 28: 2707–2714 (doi: 10.1093/annonc/mdx414)

http://ift.tt/2HNZX5l

The patient's perspective on breast radiotherapy: Initial fears and expectations versus reality

BACKGROUND

Although the efficacy and toxicity of breast radiotherapy (RT) has been studied extensively, to the authors' knowledge little is known regarding the patient's perspective on the modern breast RT experience. To better inform future patients and providers, the authors explored patient perceptions of their RT experience.

METHODS

Consecutive patients who were free of disease recurrence and who had been treated between 2012 and 2016 were surveyed regarding their original fears, how short-term and long-term toxicities compared with initial expectations, and how pretreatment beliefs concerning RT compared with the actual experience.

RESULTS

A total of 502 patients were surveyed, with a response rate of 65% (327 patients). The median patient age and posttreatment follow-up was 59 years and 31 months, respectively. Approximately 83% of patients (269 patients) underwent breast conservation therapy. Although approximately 68% of patients (221 patients) endorsed that they initially had little to no knowledge regarding RT, approximately 47% (152 patients) reported that they had heard frightening stories. Approximately 2% of patients (6 patients) agreed that the negative stories they previously heard about RT were actually true. Approximately 92% of patients treated with breast conservation (247 patients) and 81% of patients who underwent mastectomy (47 patients) agreed with the statement "If future patients knew the real truth about RT, they would be less scared about treatment." Approximately 83% (272 patients) and 84% (274 patients), respectively, of all patients reported the overall severity of short-term and long-term side effects to be better than or as expected.

CONCLUSIONS

Breast RT is associated with misconceptions and fears. Patients' experiences with modern breast RT appear to be superior to expectations, and the majority of patients in the current study agreed that their initial negative impressions were unfounded. Cancer 2017. © 2017 American Cancer Society.



http://ift.tt/2sVZ4Ex

Survival of breast cancer patients in rural Ethiopia

Abstract

Purpose

To describe the histopathological characteristics and survival of female breast cancer (BC) patients in a rural setting with limited access to adjuvant treatment.

Methods

A prospective study of 107 histologically confirmed BC patients treated with surgery from 2010 to 2016 from rural parts of western Ethiopia. Referral pathology was performed, and active follow-up was conducted. Adjusted cox regression analysis (hazard ratio [HR]) was performed.

Results

The median age at diagnosis was 45 (16–83) years; 57% of the patients presented with cT3/4 tumors, 71% with clinically positive lymph nodes, 21% with HER2-overexpression (Dako3+) and 68% with grade 3 tumors. Estrogen and/or progesterone receptor expressions were present in 66% and triple-negative disease in 25%. The estimated 1- and 2-year overall survival probability rates were 78 and 53%, respectively. The 2-year survival for patients with clinically positive lymph nodes was 44% compared to 73% for patients with lymph node-negative disease (HR 2.44; 95% confidence interval [95% CI] 1.19–5.02). The corresponding 2-year survival for patients with cT4 tumors was 25% versus 68% for patients with cT1–2 tumors (cT1–3 vs. cT4 HR 3.86; 95% CI 1.82–13.63). The 2-year survival for patients with hormone receptor-negative disease was 40% compared to 59% for patients with hormone receptor-positive disease (HR 1.92; 95% CI 1.06–3.47).

Conclusion

The majority of breast cancer patients treated with surgery in rural parts of western Ethiopia are diagnosed at advanced stage and have hormone receptor-positive disease. Nearly half of the patients die within 2 years. These findings underscore the need for provision of adjuvant hormonal therapy and for the establishment of pathology service including hormone receptor testing.



http://ift.tt/2HO8WDJ

Glioblastoma-activated pericytes support tumor growth via immunosuppression

Abstract

Glioblastoma multiforme is the most common and aggressive primary brain tumor, with an extremely poor prognosis. The lack of detailed knowledge about the cellular and molecular mechanisms involved in glioblastoma development restricts the design of efficient therapies. A recent study using state-of-art technologies explores the role of pericytes in the glioblastoma microenvironment. Glioblastoma-activated pericytes develop an immunosuppressive phenotype, reducing T-cell activation through the induction of an anti-inflammatory response. Strikingly, pericytes support glioblastoma growth in vitro and in vivo. Here, we describe succinctly the results and implications of the findings reported in pericytes' and glioblastomas' biology. The emerging knowledge from this study will be essential for the treatment of brain tumors.

Thumbnail image of graphical abstract

Glioblastoma-activated pericytes develop an immunosuppressive phenotype, reducing T-cell activation through the induction of an anti-inflammatory response. Pericytes support glioblastoma growth in vitro and in vivo.



http://ift.tt/2oqroKO

Validating the pivotal role of the immune system in low-dose radiation-induced tumor inhibition in Lewis lung cancer-bearing mice

Abstract

Although low-dose radiation (LDR) possesses the two distinct functions of inducing hormesis and adaptive responses, which result in immune enhancement and tumor inhibition, its clinical applications have not yet been elucidated. The major obstacle that hinders the application of LDR in the clinical setting is that the mechanisms underlying induction of tumor inhibition are unclear, and the risks associated with LDR are still unknown. Thus, to overcome this obstacle and elucidate the mechanisms mediating the antitumor effects of LDR, in this study, we established an in vivo lung cancer model to investigate the participation of the immune system in LDR-induced tumor inhibition and validated the pivotal role of the immune system by impairing immunity with high-dose radiation (HDR) of 1 Gy. Additionally, the LDR-induced adaptive response of the immune system was also observed by sequential HDR treatment in this mouse model. We found that LDR-activated T cells and natural killer cells and increased the cytotoxicity of splenocytes and the infiltration of T cells in the tumor tissues. In contrast, when immune function was impaired by HDR pretreatment, LDR could not induce tumor inhibition. However, when LDR was administered before HDR, the immunity could be protected from impairment, and tumor growth could be inhibited to some extent, indicating the induction of the immune adaptive response by LDR. Therefore, we demonstrated that immune enhancement played a key role in LDR-induced tumor inhibition. These findings emphasized the importance of the immune response in tumor radiotherapy and may help promote the application of LDR as a novel approach in clinical practice.

Thumbnail image of graphical abstract

We demonstrate that immune enhancement plays a key role in low-dose radiation (LDR)-induced tumor inhibition. Our findings emphasize the importance of immune response in tumor radiotherapy and may help promote the application of LDR as a novel approach in clinical practice.



http://ift.tt/2ov5CEG

Establishment and validation of a two-step screening scheme for improved performance of serological screening of nasopharyngeal carcinoma

Abstract

Nasopharyngeal carcinoma (NPC), which is closely associated with Epstein–Barr virus (EBV), is one of the most prevalent cancers in southeast China. Most NPC patients are diagnosed at late stage due to inconspicuous symptoms at the early stage, and the prognosis of these patients is poor. The early diagnosis rate of NPC could be significantly increased by serological screening, but the positive predictive value (PPV) is relatively low. A simple two-step serological screening scheme was established to improve the PPV of the screening strategy and was validated by a prospective cohort. Serum antibodies specific for EBNA1, Zta, Thymidine Kinase (TK), EAD, EAR, and VCA were detected by enzyme-linked immunosorbent assay. The combination of EBNA1/IgA and VCA/IgA was used in the first step of screening, and anti-early antigens (EAs) were used in the second step of screening. EAD/IgA was the most prominent marker in the second step of screening, and other anti-EAs were complementary to EAD/IgA. As validated by a prospective cohort including 4200 participants, using the combination of EAD/IgA and TK/IgA in the second step decreased the number of high-risk participants from 128 to 27, and increased the PPV from 4.69% to 18.52%, with only one very early-stage case missed. The two-step screening scheme provides a standardized approach for NPC screening with an improved PPV and may be used in future field studies. With this two-step serological screening method, more people benefit from the screening program without increasing the need for fiberoptic endoscopy.

Thumbnail image of graphical abstract

A simple two-step screening scheme was established to improve the PPV of the screening, with the combination of EBNA1/IgA and VCA/IgA in the first step of screening and anti-EAs in the second step. The PPV could be increased from 4.69% in the first step of screening to 18.52% after the second step of screening. With this two-step serological screening, more people could be benefited from the screening program.



http://ift.tt/2CjUNyO

Prognostic Value of Secretoneurin in Patients With Severe Sepsis and Septic Shock: Data From the Albumin Italian Outcome Sepsis Study

Objectives: Secretoneurin directly influences cardiomyocyte calcium handling, and circulating secretoneurin levels seem to improve risk prediction in patients with myocardial dysfunction by integrating information on systemic stress, myocardial function, and renal function. Accordingly, in this study, we hypothesized that secretoneurin would improve risk prediction in patients with sepsis and especially in patients with septic shock as these patients are more hemodynamically unstable. Design: Multicenter, interventional randomized clinical trial. Setting: Multicenter, pragmatic, open-label, randomized, prospective clinical trial testing fluid administration with either 20% human albumin and crystalloids or crystalloid solutions alone in patients with severe sepsis or septic shock (The Albumin Italian Outcome Sepsis). Patients or Subjects: In total, 540 patients with septic shock and 418 patients with severe sepsis. Interventions: Either 20% human albumin and crystalloids or crystalloid solutions alone. Measurements and Main Results: We measured secretoneurin on days 1, 2, and 7 after randomization and compared the prognostic value of secretoneurin for ICU and 90-day mortality with established risk indices and cardiac biomarkers in septic shock and severe sepsis. High secretoneurin levels on day 1 were associated with age and serum concentrations of lactate, bilirubin, creatinine, and N-terminal pro-B-type natriuretic peptide. Adjusting for established risk factors and cardiovascular biomarkers, secretoneurin levels on day 1 were associated with ICU (odds ratio, 2.27 [95% CI, 1.05–4.93]; p = 0.04) and 90-day mortality (2.04 [1.02–4.10]; p = 0.04) in patients with septic shock, but not severe sepsis without shock. Secretoneurin levels on day 2 were also associated with ICU (3.11 [1.34–7.20]; p = 0.008) and 90-day mortality (2.69 [1.26–5.78]; p = 0.01) in multivariate regression analyses and improved reclassification in patients with septic shock, as assessed by the net reclassification index. Randomized albumin administration did not influence the associations between secretoneurin and outcomes. Conclusions: Secretoneurin provides early and potent prognostic information in septic patients with cardiovascular instability. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/29S62lw). A complete list of centers and investigators participating in the Albumin Italian Outcome Sepsis substudy has been published elsewhere: Masson S, Caironi P, Spanuth E, et al; ALBIOS Study Investigators: Presepsin (soluble CD14 subtype) and procalcitonin levels for mortality prediction in sepsis: Data from the Albumin Italian Outcome Sepsis trial. Crit Care 2014; 18:R6. The Albumin Italian Outcome Sepsis trial was funded by a grant from the Agenzia Italiana del Farmaco (AIFA) (grant FARM6JS3R5, 2006). This project was also funded by Akershus University Hospital, the Research Council of Norway, the University of Oslo, and the South-Eastern Norway Regional Health Authority. Supported, in part, by funding from the Italian Ministry of Health (Ricerca Finalizzata, grant number RF-2011-02348358). Roche Diagnostics (Rotkreuz, Switzerland) provided in kind reagents for measuring N-terminal pro B-type natriuretic peptide and high-sensitive cardiac troponin T. Dr. Røsjø received personal fees from Novartis and CardiNor AS. Dr. Røsjø disclosed that this project was funded by Akershus University Hospital, the Research Council of Norway, the University of Oslo, and the South-Eastern Norway Regional Health Authority. Roche Diagnostics (Rotkreuz, Switzerland) provided in kind reagents for measuring N-terminal pro B-type natriuretic peptide and high sensitive cardiac troponin T. Dr. Røsjø has financial interests in CardiNor AS, which holds the license to commercialize secretoneurin. Drs. Masson's and Caironi's institutions received funding from the AIFA (grant FARM6JS3R5, 2006) and the Italian Ministry of Health (Ricerca Finalizzata, grant number RF-2011-02348358). Dr. Caironi received funding from Bbraun (lecture honoraria), Grifols (lecture honoraria and grant: Albumin Awards Program Grifols Award), and Ortho Diagnostic (lecture honoraria). Dr. Stridsberg received personal fees from CardiNor AS. Drs. Røsjø, Stridsberg, and Omland are partners in a patent filed by the University of Oslo regarding the use of secretoneurin as a biomarker in patients with cardiovascular disease and patients with critical illness. Dr. Christensen disclosed that he is a partner in a patent filed by the University of Oslo regarding the use of secretoneurin as a biomarker in patients with cardiovascular disease and patients with critical illness and has financial interests in CardiNor AS, which holds the license to commercialize secretoneurin. Dr. Urbano received support for article research from the National Institutes of Health and disclosed work for hire. Dr. Gattinoni received funding from Grifols (jury member for Albumin Grifols Award) and expert testimony in legal trials. Dr. Pesenti's institution received funding from AIFA Official Italian agency for drug safety and studies, and he received funding from Xenios and Baxter. Dr. Omland's institution received funding from Akershus University Hospital, Research Council of Norway, University of Oslo, and the South-Eastern Norway Regional Health Authority, and he received funding from Roche Diagnostics, Abbott Diagnostics, Bayer, Novartis, and CardiNor. The remaining authors have disclosed that they do not have any potential conflicts of interest. Address requests for reprints to: Helge Røsjø, MD, PhD, Division of Medicine, Akershus University Hospital, Sykehusveien 25, 1478 Lørenskog, Norway. E-mail: helge.rosjo@medisin.uio.no Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

http://ift.tt/2oqAwib

Neuraxial Anesthesia During Cesarean Delivery for Placenta Previa With Suspected Morbidly Adherent Placenta: A Retrospective Analysis

BACKGROUND: General anesthesia (GA) is often selected for cesarean deliveries (CD) with placenta previa and suspected morbidly adherent placenta (MAP) due to increased risk of hemorrhage and hysterectomy. We reviewed maternal outcomes and risk factors for conversion to GA in a cohort of patients undergoing CD and hysterectomy under neuraxial anesthesia (NA). METHODS: We performed a single-center, retrospective cohort study of parturients undergoing nonemergent CD for placenta previa with suspected MAP from 1997 to 2015. Patients were classified according to whether they received GA, NA, or intraoperative conversion from NA to GA. The primary outcome measure was postoperative acuity, defined as the need for intensive care unit admission, arterial embolization, reoperation, or ongoing transfusion with ≥3 units packed red blood cells. We additionally identified variables positively associated with intraoperative conversion from NA to GA during hysterectomy. Confounding was controlled with logistic regression models. RESULTS: Of 129 patients undergoing nonemergent CD for placenta previa with suspected MAP, 122 (95%) received NA as the primary anesthetic. NA was selected in the majority of patients with a body mass index ≥40 kg/m2 (9 of 10, 90%), a history of ≥3 prior CDs (18 of 20, 90%), suspected placenta increta or percreta (29 of 35, 83%), and Mallampati classification ≥3 (19 of 21, 90%). Of 72 patients with NA at the time of delivery who required hysterectomy, 15 (21%) required conversion to GA intraoperatively. Converted patients had a higher rate of major packed red blood cell transfusion (60% vs 25%; P = .01), with similar rates of massive transfusion (9% vs 7%; P = 1.0). Converted patients also had a higher incidence of postoperative acuity (47% vs 4%; P

http://ift.tt/2sUV7A4

Point-of-Care Fibrinogen Testing in Pregnancy

Agreement between estimated fibrinogen concentration via thromboelastography and traditional assays is not established in the parturient. We therefore recruited 56 parturients and performed Clauss and functional fibrinogen level (FLEV) tests. Mean difference of measurements was 36.8 mg/dL (95% CI, 21.8–51.9) with a standard deviation of 52.8 mg/dL. Calculated limits of agreement were 140.2 mg/dL (95% CI, 166.3–114.6) and −66.6 mg/dL (95% CI, −40.8 to −92.5), within the maximum allowable difference of 165 mg/dL. We therefore conclude that while most measurements fell within the limits of agreement, more work is needed to clearly define the role of this test in the obstetric population. Accepted for publication December 29, 2017. Funding: None. The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/KegmMq). Summary Statement: In this study, the relationship between formal laboratory Clauss and thromboelastography-derived fibrinogen counts is examined. Reprints will not be available from the authors. Address correspondence to Daniel Katz, MD, Icahn School of Medicine at Mount Sinai, 1 Gustave L Levy Pl, Box 1010 KCC 8th Floor, New York, NY 10029. Address e-mail to Daniel.Katz@mountsinai.org. © 2018 International Anesthesia Research Society

http://ift.tt/2F2i5tU

Pupillary Dilation Reflex Measurement: Ideal Time—Pre- or Postsurgery?

No abstract available

http://ift.tt/2sTkZfM

Treatment of Chronic Pain Conditions: A Comprehensive Handbook

No abstract available

http://ift.tt/2Cj56mE

Analgesic Effects of Oxycodone Relative to Those of Sufentanil, in the Presence of Midazolam, During Endoscopic Injection Sclerotherapy for Patients With Cirrhosis and Esophageal Varices

BACKGROUND: We evaluated the efficacy and gastroenterologist/patient satisfaction of midazolam combined with oxycodone, relative to that of midazolam combined with sufentanil, for anesthesia during endoscopic injection sclerotherapy (EIS) in patients with cirrhosis and esophageal varices. METHODS: Patients with cirrhosis (20–69 years of age), body mass index, 18–25 kg/m2, American Society of Anesthesiology patient classification physical status I–II who underwent elective EIS were randomly assigned to 1 of 2 groups. In this prospective, double-blinded, randomized controlled trial, 1 group received midazolam and oxycodone (n = 64), and the other group received midazolam and sufentanil (n = 63). Primary and secondary outcome measures were compared between groups. The primary outcome measure was the incidence of hypoxia. Secondary outcome measures included perioperative limb movement, need for rescue analgesics, need for additional sedative propofol, specified adverse reactions (postoperative myoclonus, nausea, vomiting, dizziness, and drowsiness), gastroenterologist satisfaction, and patient satisfaction with postoperative analgesia. RESULTS: Patients in the midazolam–oxycodone group had 32% fewer episodes of hypoxia than did those in the midazolam–sufentanil group (95% confidence interval [CI], –45% to –18%; P

http://ift.tt/2sSICou

Perioperative Temperature Management

No abstract available

http://ift.tt/2CjuNU2

Inflammation Triggered by the Use of Blood Products

No abstract available

http://ift.tt/2sT8Mrl

In Response

No abstract available

http://ift.tt/2F1Tky6

Does A Low 6-Minute Walk Distance Predict Elevated Postoperative Troponin?

Our study of 100 major vascular and renal transplant patients evaluated the 6-minute walk test (6MWT) as an indicator of perioperative myocardial injury, using troponin as a marker. Using logistic regression and the area under the receiving operator characteristic curve, we compared the 6MWT to the Revised Cardiac Risk Index and metabolic equivalents. Only the 6MWT was associated with elevated postoperative troponins (95% CI, 0.98–0.99). However, the 6MWT area under the receiving operator characteristic curve (0.71 [95% CI, 0.57–0.85]) was not different from the Revised Cardiac Risk Index (P = .23) or metabolic equivalents (P = .14). The 6MWT may have a role in cardiac risk stratification in the perioperative setting. Accepted for publication January 16, 2018. Funding: None. The authors declare no conflicts of interest. Institutional review board contact information: 310-825-5344; webIRBHelp@research.ucla.edu. Reprints will not be available from the authors. Address correspondence to Dana L. Russell, MPH, Department of Anesthesiology, David Geffen School of Medicine, University of California Los Angeles, 757 Westwood Pl, Los Angeles, CA 90095. Address e-mail to danarussell@mednet.ucla.edu. © 2018 International Anesthesia Research Society

http://ift.tt/2sSpwPD

The Migration of Caudally Threaded Thoracic Epidural Catheters in Neonates and Infants

BACKGROUND: The migration of pediatric thoracic epidural catheters via a thoracic insertion site has been described. We assessed the migration of caudally threaded thoracic epidural catheters in neonates and infants at our institution. METHODS: The anesthesia records and diagnostic imaging studies of neonates and infants who had caudal epidural catheters placed during a 26-month period at our hospital were analyzed. Imaging studies were reviewed for changes in epidural catheter tip position. RESULTS: Eighty-five patients 1–325 days of age (median, 51 days; interquartile range, 39–78 days) and weights of 2.5–9.5 kg (median, 5 kg; interquartile range, 4.3–5.8 kg) met the study criteria. Fifty-four (64%) of the patients (95% CI, 52%–73%) experienced catheter migration of 1 or more vertebral levels (range, 3 levels caudad [outward] to 3 levels cephalad [inward]), and 23 (27%) of the patients (95% CI, 18%–38%) experienced catheter migration to the T4 level or higher. Migration of 2 or more vertebral levels occurred only in children who weighed

http://ift.tt/2Co6BzY

Beyond the “E” in OSCE

No abstract available

http://ift.tt/2sWbbS0

Correlation Coefficients: Appropriate Use and Interpretation

Correlation in the broadest sense is a measure of an association between variables. In correlated data, the change in the magnitude of 1 variable is associated with a change in the magnitude of another variable, either in the same (positive correlation) or in the opposite (negative correlation) direction. Most often, the term correlation is used in the context of a linear relationship between 2 continuous variables and expressed as Pearson product-moment correlation. The Pearson correlation coefficient is typically used for jointly normally distributed data (data that follow a bivariate normal distribution). For nonnormally distributed continuous data, for ordinal data, or for data with relevant outliers, a Spearman rank correlation can be used as a measure of a monotonic association. Both correlation coefficients are scaled such that they range from –1 to +1, where 0 indicates that there is no linear or monotonic association, and the relationship gets stronger and ultimately approaches a straight line (Pearson correlation) or a constantly increasing or decreasing curve (Spearman correlation) as the coefficient approaches an absolute value of 1. Hypothesis tests and confidence intervals can be used to address the statistical significance of the results and to estimate the strength of the relationship in the population from which the data were sampled. The aim of this tutorial is to guide researchers and clinicians in the appropriate use and interpretation of correlation coefficients. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Accepted for publication January 11, 2018. Funding: None. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Patrick Schober, MD, PhD, MMedStat, Department of Anesthesiology, VU University Medical Center, De Boelelaan 1117, 1081HV Amsterdam, the Netherlands. Address e-mail to p.schober@vumc.nl. © 2018 International Anesthesia Research Society

http://ift.tt/2F6NefQ

Treatment Patterns and Clinical Outcomes in Neonates Diagnosed With Respiratory Distress Syndrome in a Low-Income Country: A Report From Bangladesh

Respiratory distress syndrome remains a leading cause of neonatal mortality worldwide. This retrospective study describes practice patterns for respiratory distress syndrome in a resource-limited setting and seeks to identify both risk factors for mortality and beneficial treatment modalities. Health, demographic, and treatment data were collected. Potential associations were analyzed using univariable and multivariable logistic regression. Of 104 children included for analysis, 38 died. Although most children were initially treated with noninvasive respiratory support, 59 progressed to invasive ventilation. Requirement for invasive ventilation was associated with death. A clear trend toward improved survival in mechanically ventilated patients was seen with surfactant administration. Accepted for publication January 11, 2018. Funding: This study was supported in part by the National Institutes of Heath (NIH) Building Interdisciplinary Research Careers in Women's Health (BIRCWH) NIH K12HD043441 scholar funds to G.L. The project described was supported by NIH through grant number UL1TR001857. Support for data collection on-site in Bangladesh ($650 total) was provided via the crowd-funding website https://experiment.com/. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Richard M. Hubbard, MD, 710 Beaver St, Sewickley, PA 15143. Address e-mail to rhubbardmd@gmail.com. © 2018 International Anesthesia Research Society

http://ift.tt/2sTGMUy

Research Needs Assessment for Children With Obstructive Sleep Apnea Undergoing Diagnostic or Surgical Procedures

Recent concerns have been raised about the quality and safety of adenotonsillectomy, a common surgery performed to treat obstructive sleep apnea (OSA) in children. OSA is a risk factor for opioid-related perioperative respiratory complications including those associated with anoxic brain injury or death. Our objective was to identify controversial issues related to the care of children with OSA. A standardized Delphi consensus technique involving an interdisciplinary group of 24 pediatric OSA experts identified 3 key issues: "postoperative disposition, preoperative screening, and pain management." These topics are prime candidates for future systematic reviews and will guide Society of Anesthesia and Sleep Medicine–related research endeavors. Accepted for publication December 19, 2017. Funding: This study was supported solely by institutional and/or departmental sources. The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/KegmMq). Reprints will not be available from the authors. Address correspondence to Kimmo T. Murto, MD, FRCPC, Department of Anesthesiology and Pain Medicine, Children's Hospital of Eastern Ontario-Ottawa Children's Treatment Center, University of Ottawa, 401 Smyth Rd, Ottawa, ON K1H 8L1, Canada. Address e-mail to kmurto@cheo.on.ca. © 2018 International Anesthesia Research Society

http://ift.tt/2F4c13V

Opioid Omission Is Not Opioid Sparing. Response to “Surgery-Induced Opioid Dependence: Adding Fuel to the Fire?”

No abstract available

http://ift.tt/2CjBlSy

Development and Initial Evaluation of a Novel, Ultraportable, Virtual Reality Bronchoscopy Simulator: The Computer Airway Simulation System

BACKGROUND: Virtual reality (VR) simulation is an effective and safe method of teaching bronchoscopic skills. Few VR bronchoscopy simulators exist; all are expensive. The present study aimed to describe the design, development, and evaluation of a new, affordable, VR bronchoscopy simulator. METHODS: Anesthesiologists and engineers collaborated to design and develop the Computer Airway Simulation System (CASS), an iPad-based, high-fidelity, VR bronchoscopy simulator. We describe hardware and software development, as well as the technical and teaching features of the CASS. Twenty-two senior anesthesiologists evaluated various aspects of the simulator (using a 5-point Likert scale) to assess its face validity. RESULTS: Anesthesiologists performed a simulated bronchoscopy (mouth to carina) with a median (range) procedural time of 66 seconds (30–96). The simulator's ease of use was rated 4.3 ± 0.8 and the bronchoscope proxy's handling 4.0 ± 0.7. Criticisms included that excessive system reactivity created handling difficulties. Anatomical accuracy, 3-dimensional bronchial segmentation, and mucosal texture were judged to be very realistic. The simulator's usefulness for teaching and its educational value were highly rated (4.9 ± 0.3 and 4.8 ± 0.4, respectively). CONCLUSIONS: We describe the design, development, and initial evaluation of the CASS—a new, ultraportable, affordable, VR bronchoscopy simulator. The simulator's face validity was supported by excellent assessments from senior anesthesiologists with regard to anatomical realism, quality of graphics, and handling performance, even though some future refinements are required. All the practitioners agreed on the significant educational potential of the CASS. Accepted for publication December 29, 2017. Funding: Cardiocentro Ticino's Department of Cardiac Anesthesia and Intensive Care in Lugano, Switzerland, employs Gabriele Casso and Tiziano Cassina. This institution received financial support for the CASS research and development project from the Foundation for Cardiological Research and Education and the FLAVA Foundation (Fondation Latine des Voies Aériennes), both charitable (not-for-profit) organizations. Conflicts of Interest: See Disclosures at the end of the article. Reprints will not be available from the authors. Address correspondence to Gabriele Casso, MD, Department of Cardiac Anesthesia and Intensive Care, Cardiocentro Ticino, Lugano, Switzerland. Address e-mail to gabriele.casso@cardiocentro.org. © 2018 International Anesthesia Research Society

http://ift.tt/2sTGOf8

Baicalin Downregulates RLRs Signaling Pathway to Control Influenza A Virus Infection and Improve the Prognosis

The objective of this study is to investigate the effects of baicalin on controlling the pulmonary infection and improving the prognosis in influenza A virus (IAV) infection. PCR and western blot were used to measure the changes of some key factors in RLRs signaling pathway. MSD electrochemiluminescence was used to measure the expression of pulmonary inflammatory cytokines including IFN-γ, TNF-α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, and KC/GRO. Flow cytometry was used to detect the proportion of Th1, Th2, Th17, and Treg. The results showed that IAV infection led to low body weight and high viral load and high expression of RIG-I, IRF3, IRF7, and NF-κB mRNA, as well as RIG-I and NF-κB p65 protein. However, baicalin reduced the rate of body weight loss, inhibited virus replication, and downregulated the key factors of the RLRs signaling pathway. Besides, baicalin reduced the high expression inflammatory cytokines in lung and decreased the ratios of Th1/Th2 and Th17/Treg to arouse a brief but not overviolent inflammatory response. Therefore, baicalin activated a balanced host inflammatory response to limit immunopathologic injury, which was helpful to the improvement of clinical and survival outcomes.

http://ift.tt/2EQ5aMi

Baseline Predictors of Visual Acuity Outcome in Patients with Wet Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is one of the leading causes of severe vision loss in people over 60 years. Wet AMD (wAMD) causes more severe visual acuity (VA) loss compared with the dry form due to formation of choroidal neovascularization (CNV). Antivascular endothelial growth factor (anti-VEGF) agents such as ranibizumab and aflibercept are now the standard of care treatment for wAMD. Unfortunately, up to a quarter of anti-VEGF-treated wAMD patients might not fully benefit from intravitreal injections and CNV activity may not respond to the treatment and these patients are called anti-VEGF nonresponders. This article aims to discuss the baseline factors associated with VA outcome such as age, initial VA, lesion types, disease duration, optical coherence tomography (OCT) features, fundus autofluorescence findings, and the presence of particular genotype risk alleles in patients with wAMD. Recommendations are provided regarding when to consider discontinuation of therapy because of either success or futility. Understanding the predictive factors associated with VA outcome and treatment frequency response to anti-VEGF therapy may help retina specialists to manage patients' expectations and guide treatment decisions from the beginning of treatment on the basis of "personalized medicine."

http://ift.tt/2sUALa1

Familial PDGFRA mutation- syndrome: somatic and gastrointestinal phenotype

Germline activating platelet derived growth factor receptor alpha (PDGFRA) mutations have been described in four families. All the index patients have presented with multiple mesenchymal tumors of the gastrointestinal tract. We identified a fifth family with four first-degree relatives that harbor a PDGFRA exon 18 (D846V) germline mutation. The affected kindred have a unique phenotype including coarse facies and skin, broad hands and feet, and previously undescribed premature tooth loss. While the index patient presented with multiple small bowel inflammatory fibroid polyps (IFPs) and has a gastric gastrointestinal stromal tumor (GIST), no tumors have yet been identified in other family members.

http://ift.tt/2CiE4vH

Expression profiles of stemness genes in gastrointestinal stromal tumor

Gastrointestinal stromal tumor (GIST) is believed to originate from intestinal cells of Cajal or their stem-cell precursors, and expresses stemness-related markers, such as CD117, CD34, DOG1 and nestin. To further characterize phenotypic features of GISTs, we examined expression profiles of a panel of stemness genes in GISTs, by analyzing existing gene expression profiling datasets. Our results showed that mRNA levels of B-lymphoma moloney murine leukaemia virus insertion region-1 (BMI1), kruppel-like factor 4 (KLF4), sal-like protein 4 (SALL4) and telomerase reverse transcriptase (TERT) were significantly unregulated in GISTs.

http://ift.tt/2oxLhPg

Standardization of the Manufacturing Process of Bee Venom Pharmacopuncture Containing Melittin as the Active Ingredient

Background. Pharmacopuncture is a unique treatment in oriental medicine that combines chemical stimulation with conventional acupuncture. However, there are no standardized methods for preparing the herbal medicines used in pharmacopuncture, and it is not clear whether the active ingredients are safe and stable. Several studies have investigated nonstandardized preparation processes, but few investigations have addressed safety and preparation methods. Pharmacopuncture may provide an alternative treatment for incurable diseases. However, it must be as valid and safe as standardized medicine. In this way, the present project may contribute to the industrialization of medicine in Korea. It may also expand health insurance coverage by promoting evidence-based medical insurance benefits. Thus, the present study attempted to standardize and improve the raw materials, preparation, and efficacy of bee venom pharmacopuncture (BVP), which is a highly effective technique in oriental medicine. Method. To purify the crude bee venom, the extract was subjected to a stepped-gradient open column (ODS-A; 120 Å, 150 mesh). Using this method, the yield of melittin was significantly increased and the allergen proteins were effectively removed. The melittin content of the purified bee venom was determined using HPLC, and the product was then diluted to 0.1 mg/mL using injection water in preparation for BVP. Results. In the present study, we standardized the purification process to provide safe and stable BVP by increasing the main effective components and eliminating allergens. This study will be seminal in the industrialization and regulation of BVP. Conclusion. We developed an effective strategy for melittin purification and allergen removal from bee venom to create safe BVP.

http://ift.tt/2owk67l

Effects of 4-Week Intervention with Ulmus macrocarpa Hance Extract on Immune Function Biomarkers in Healthy Adults: A Randomized Controlled Trial

Ulmus macrocarpa extract has been shown to have immune-related effects in animals, but no studies have yet been performed in humans. This randomized, double-blind, placebo-controlled trial was conducted to determine the effect of short-term administration of Ulmus macrocarpa Hance extract (UME) on immune function biomarkers and its safety in human subjects. Fifty-eight subjects were randomly assigned to a UME group or a placebo group. Subjects in the UME group were given 500 mg per day of UME orally for 4 weeks. Mean fluorescence intensity (MFI) of tumor necrotic factor-α increased only in the UME group at 1 week . The MFI of interleukin-2 decreased less significantly in the UME group than in the placebo group at 1 week . However, unfortunately, at 4 weeks, no intergroup differences were detected in MFIs of cytokine. In conclusion, administration of UME for 1 week increased serum TNF-α and sustains IL-2 in human, which suggests that UME increases Th1-related immune function in the short term in healthy people. However, additional studies are needed to confirm the results of this first-stage study and further trials are required to decide on optimal dosage and duration of administration. This trial is registered with ClinicalTrials.gov Identifier: NCT02414412.

http://ift.tt/2CkiRBt

Profiling and Bioinformatic Analyses Indicate Differential circRNA and miRNA/isomiR Expression and Interactions

As a novel class of noncoding RNAs, circular RNAs (circRNAs) have been reported to play a role in various biological processes. Some circRNAs may serve as microRNA (miRNA) sponges, regulating transcription or splicing. Herein, we investigated the expression profiles and interactions of miRNAs/isomiRs and circRNAs in male patients with esophageal cancer. We found that some miRNA genes generated two deregulated miRNA products (miR-#-5p and miR-#-3p), and these products were consistently abnormally expressed. Some circRNAs were predicted to be miRNA sponges for specific miRNAs. Some of these typically showed opposing expression patterns in cancer tissues: one upregulated and the other downregulated. Although fewer miRNAs were predicted to interact with circRNAs, the number of predicted interactions would be substantially increased if detailed isomiRs were involved. High sequence similarity across multiple isomiRs suggested that they might interact with circRNAs, similar to the interaction of homologous miRNAs with circRNAs. At the isomiR level, due to the characteristics of the sequences and expression patterns involved, the cross-talk between different ncRNAs is complicated despite simplification of the isomiRs involved through clustering. We expect that our results may provide methods for further study of the cross-talk among ncRNAs and elucidate their biological roles in human diseases.

http://ift.tt/2CHfcJL

Use of health services in the last year of life and cause of death in people with intellectual disability: a retrospective matched cohort study

Objective

To describe the cause of death together with emergency department presentations and hospital admissions in the last year of life of people with intellectual disability.

Method

A retrospective matched cohort study using de-identified linked data of people aged 20 years or over, with and without intellectual disability who died during 2009 to 2013 in Western Australia. Emergency department presentations and hospital admissions in the last year of life of people with intellectual disability are described along with cause of death.

Results

Of the 63 508 deaths in Western Australia from 2009 to 2013, there were 591 (0.93%) decedents with a history of intellectual disability. Decedents with intellectual disability tended to be younger, lived in areas of more social disadvantage, did not have a partner and were Australian born compared with all other decedents. A matched comparison cohort of decedents without intellectual disability (n=29 713) was identified from the general population to improve covariate balance.

Decedents with intellectual disability attended emergency departments more frequently than the matched cohort (mean visits 3.2 vs 2.5) and on average were admitted to hospital less frequently (mean admissions 4.1 vs 6.1), but once admitted stayed longer (average length of stay 5.2 days vs 4.3 days). People with intellectual disability had increased odds of presentation, admission or death from conditions that have been defined as ambulatory care sensitive and are potentially preventable. These included vaccine-preventable respiratory disease, asthma, cellulitis and convulsions and epilepsy.

Conclusion

People with intellectual disability were more likely to experience potentially preventable conditions at the end of their lives. This indicates a need for further improvements in access, quality and coordination of healthcare to provide optimal health for this group.



http://ift.tt/2opD9ks

Propolin C Inhibited Migration and Invasion via Suppression of EGFR-Mediated Epithelial-to-Mesenchymal Transition in Human Lung Cancer Cells

Controlling lung cancer cell migration and invasion via epithelial-to-mesenchymal transition (EMT) through the regulation of epidermal growth factor receptor (EGFR) signaling pathway has been demonstrated. Searching biological active phytochemicals to repress EGFR-regulated EMT might prevent lung cancer progression. Propolis has been used as folk medicine in many countries and possesses anti-inflammatory, antioxidant, and anticancer activities. In this study, the antimigration and anti-invasion activities of propolin C, a c-prenylflavanone from Taiwanese propolis, were investigated on EGFR-regulated EMT signaling pathway. Cell migration and invasion activities were dose-dependently suppressed by noncytotoxic concentration of propolin C. Downregulations of vimentin and snail as well as upregulation of E-cadherin expressions were through the inhibition of EGFR-mediated phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) and extracellular signal-regulated kinase (ERK) signaling pathway in propolin C-treated cells. In addition, EGF-induced migration and invasion were suppressed by propolin C-treated A549 lung cancer cells. No significant differences in E-cadherin expression were observed in EGF-stimulated cells. Interestingly, EGF-induced expressions of vimentin, snail, and slug were suppressed through the inhibition of PI3K/Akt and ERK signaling pathway in propolin C-treated cells. Inhibition of cell migration and invasion by propolin C was through the inhibition of EGF/EGFR-mediated signaling pathway, followed by EMT suppression in lung cancer.

http://ift.tt/2CHP6WQ

Alternative test models for skin aging research

Abstract

Increasing ethical concerns regarding animal experimentation have led to the development of various alternative methods based on the 3Rs (Refinement, Reduction, and Replacement), first described by Russell and Burch in 1959. Cosmetic and skin aging research are particularly susceptible to concerns related to animal testing. In addition to animal welfare reasons, there are scientific and economic reasons to reduce and avoid animal experiments. Importantly, animal experiments may not reflect findings in humans mainly because of the differences of architectures and immune responses between animal skin and human skin. Here we review the shift from animal testing to the development and application of alternative non-animal based methods and the necessity and benefits of this shift. Some specific alternatives to animal models are discussed, including biochemical approaches, two-dimensional and three-dimensional cell cultures, and volunteer studies, as well as future directions, including genome-based research and the development of in silico computer simulations of skin models. Among the in vitro methods, three-dimensional reconstructed skin models are highly popular and useful alternatives to animal models however still have many limitations. With careful selection and skillful handling, these alternative methods will become indispensable for modern dermatology and skin aging research.

This article is protected by copyright. All rights reserved.



http://ift.tt/2BOFWew

The Relationship between Serum Zinc Level and Heart Failure: A Meta-Analysis

Zinc is essential for the maintenance of normal cellular structure and functions. Zinc dyshomeostasis can lead to many diseases, such as cardiovascular disease. However, there are conflicting reports on the relationship between serum zinc levels and heart failure (HF). The purpose of the present study is to explore the relationship between serum zinc levels and HF by using a meta-analysis approach. PubMed, Web of Science, and OVID databases were searched for reports on the association between serum zinc levels and HF until June 2016. 12 reports with 1453 subjects from 27 case-control studies were chosen for the meta-analysis. Overall, the pooled analysis indicated that patients with HF had lower zinc levels than the control subjects. Further subgroup analysis stratified by different geographic locations also showed that HF patients had lower zinc levels than the control subjects. In addition, subgroup analysis stratified by HF subgroups found that patients with idiopathic dilated cardiomyopathy (IDCM) had lower zinc levels than the control subjects, except for patients with ischemic cardiomyopathy (ICM). In conclusion, the results of the meta-analysis indicate that there is a significant association between low serum zinc levels and HF.

http://ift.tt/2F3c0xi

Effect of Upright and Slouched Sitting Postures on the Respiratory Muscle Strength in Healthy Young Males

Objective. The present study compared the effects of upright and slouched sitting postures on the respiratory muscle strength in healthy young males. Methods. A total of 35 adult male subjects aged 18–35 years participated in this study. Respiratory muscle strength was determined by measurement of sniff nasal inspiratory pressure (SNIP) using a MicroRPM device in the upright and slouched sitting positions. The subjects were asked to perform the pulmonary function test including peak expiratory flow (PEF), forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and FEV1/FVC ratio at baseline. Body composition was also determined. Results. There was a significant difference of SNIP score between upright sitting and slouched sitting positions (). The mean difference of SNIP score between upright sitting and slouched sitting positions was 8.7 cmH2O. Significant correlations were found between SNIP in upright sitting and FEV1% predicted values [R = .651], SNIP in slouched sitting and FEV1% predicted values [R = .579], and SNIP in upright sitting and SNIP in slouched sitting positions [R = .926] ( for all). There were no significant correlations between SNIP scores, demographic variables, and other baseline clinical data (). Conclusions. The slouched sitting position had a lower SNIP score compared to upright sitting position suggesting a reduced diaphragm tension and movement as a result of altered body posture.

http://ift.tt/2CHuKNL

Effects of Propranolol on Neurodevelopmental Outcomes in Patients with Infantile Hemangioma: A Case-Control Study

Background. The aim of this study was to examine whether oral propranolol has any effect on neurodevelopment outcomes in young children with problematic infantile hemangiomas (IHs). Methods. Thirty-six children with a diagnosis of problematic IH who were treated with oral propranolol were compared with 34 healthy children with no history of propranolol therapy. Patients received propranolol therapy for at least 3 months. Gesell developmental schedules (GDS) were used to evaluate neurodevelopment outcomes in the two groups. The scores of each GDS domain were compared between the two groups. Results. There were no significant differences in developmental quotient (DQ) values for any of the five domains between the patients and healthy controls . Multiple stepwise regression analyses showed that none of the domains in the control group were influenced by the children's gender or age . In addition, we found that gender, age at the initiation of therapy, age at the time of the neurodevelopment test, and treatment duration had no effect on any domain of the GDS in the patient group . Conclusion. Propranolol has no obvious effect on neurodevelopmental outcomes in children. Early treatment and treatment duration had no negative effect on central nervous system (CNS) development.

http://ift.tt/2EOWUfI

LncRNA RP11-552M11.4 promotes cells proliferation, migration and invasion by targeting BRCA2 in ovarian cancer

Summary

This study aimed to investigate the effect of long non-coding RNA (lncRNA) RP11-552M11.4 on cells proliferation, apoptosis, migration and invasion as well as its targeting genes in epithelial ovarian cancer (EOC) cells. LncRNA RP11-552M11.4 expression was detected in 67 tumor tissues and paired adjacent tissues obtained from EOC patients. lncRNA RP11-552M11.4 mimic/inhibitor plasmids were transferred into ovarian cancer cells (SKOV3, A-2780) and normal ovarian epithelial cells (IOSE80 cells). In addition, rescue experiment was performed by transferring BRCA2 inhibitor&lncRNA RP11-552M11.4 inhibitor plasmids into SKOV3 and A-2780 cells. qPCR, western blot, CKK-8, AV/PI, wound-healing and matrigel invasion assays were performed to detect RNA expression, protein expression, cells proliferation, apoptosis, migration and invasion respectively. LncRNA RP11-552M11.4 expression was elevated in tumor tissues compared with paired adjacent tissues and correlated with higher pathological grade, FIGO stage and worse overall survival in EOC patients. LncRNA RP11-552M11.4 promoted SKOV3 cells proliferation, migration and invasion while inhibited the apoptosis. Rescue experiment and luciferase reporter assay revealed that lncRNA RP11-552M11.4 regulated SKOV3 cells functions via binding BRCA2. Further experiments in A-2780 cells also validated that lncRNA RP11-552M11.4 induced A-2780 cells proliferation while repressed apoptosis by targeting BRCA2. In addition, upregulation of lncRNA RP11-552M11.4 increased IOSE80 cells proliferation, migration and invasion while decreased apoptosis. In conclusion, lncRNA RP11-552M11.4 correlates with worse prognosis, and promotes cells proliferation, migration, invasion and inhibits cells apoptosis by downregulating BRCA2 in EOC.

This article is protected by copyright. All rights reserved.



http://ift.tt/2CJ31Mn

Bortezomib plus dexamethasone versus thalidomide plus dexamethasone for relapsed or refractory multiple myeloma

Abstract

A randomized phase II selection design study (JCOG0904) was conducted to evaluate the more promising regimen between bortezomib (Bor) plus dexamethasone (Dex: BD) and thalidomide (Thal) plus Dex (TD) in Bor and Thal-naïve patients with relapsed or refractory multiple myeloma (RRMM). Patients ≥ 20 and < 80 years old with a documented diagnosis of symptomatic multiple myeloma (MM) with ≥ 1 prior therapies were randomized to receive BD (Bor 1.3 mg/m2) or TD (Thal 200 mg/day). In both arms, 8 cycles of induction (3-week cycle) were followed by maintenance phase (5-week cycle) until disease progression, unacceptable toxicity or patient refusal. The primary endpoint was 1-year progression-free survival (PFS). Forty-four patients were randomized and assigned to receive BD and TD (n = 22, each). At a median follow-up of 34.3 months, the 1-year PFS in the BD and TD arms were 45.5% (95% confidence interval (CI) 24.4%-64.3%) and 31.8% (95%CI 14.2%-51.1%), respectively, while the overall response rates were 77.3% and 40.9% respectively. The 3-year overall survival (OS) was 70.0% (95%CI 44.9%-85.4%) in the BD, and 48.8% (95%CI 25.1%-69.0%) in the TD arm. Among grade 3/4 adverse events, thrombocytopenia (54.5% vs 0%) and sensory peripheral neuropathy (22.7% vs 9.1%) were more frequent in BD when compared with the TD arm. BD had better outcomes than TD with regard to the 1-year PFS and 3-year OS. Thus, BD was prioritized over TD for further investigations in Bor and Thal-naïve RRMM patients. (UMIN000003135).

This article is protected by copyright. All rights reserved.



http://ift.tt/2ETjIec

The roles of protein kinase R in cancer: Potential as a therapeutic target

Summary

Double-stranded (ds) RNA-dependent protein kinase (PKR) is a ubiquitously expressed serine/threonine protein kinase. It was initially identified as an innate immune anti-viral protein induced by interferon (IFN) and activated by dsRNA. PKR is recognized as a key executor of the antiviral host defense. Moreover, it contributes to inflammation and immune regulation through several signaling pathways. In addition to IFN and dsRNA, PKR is activated by multiple stimuli and regulates various signaling pathways including the mitogen-activated protein kinase (MAPK) and nuclear factor kappa-light-chain-enhancer of activated B cells pathways. PKR was initially thought to be a tumor suppressor due to its ability to suppress cell growth and interact with major tumor suppressor genes. However, in several types of malignant diseases such as colon and breast cancers, its role remains controversial. In hepatocellular carcinoma, hepatitis C virus is the main cause of liver cancer, and PKR inhibits HCV replication, indicating its role as a tumor suppressor. However, PKR is overexpressed in cirrhotic patients, and acts as a tumor promoter through enhancement of cancer cell growth by mediating MAPK or signal transducer and activator of transcription pathways. Moreover, PKR is reportedly required for the activation of inflammasomes and influences metabolic disorders. In this review, we introduce the multifaceted roles of PKR such as antiviral function, tumor cell growth, regulation of inflammatory immune responses, and maintaining metabolic homeostasis; and discuss future perspectives on PKR biology including its potential as a therapeutic target for liver cancer.

This article is protected by copyright. All rights reserved.



http://ift.tt/2CGsdn0

Frequency of unsatisfactory cervical cytology smears in cancer screening of Japanese women: A systematic review and meta-analysis

Abstract

The Bethesda system (TBS) has been used for cervical cytological diagnosis in Japan since 2008. Evaluation of specimen adequacy is the most important aspect of quality assurance and for precise diagnosis in TBS. A systematic review and meta-analysis were performed to assess the unsatisfactory specimen rate in the primary cervical cancer screening setting in Japan.

Ovid MEDLINE and Ichushi-Web were searched from inception through May 2017. Prospective and retrospective studies that reported the proportion of unsatisfactory specimens in healthy asymptomatic Japanese women in a cervical cancer screening program were eligible for inclusion; 17 studies were included in the meta-analysis.

The random-effects model meta-analysis calculated summary estimates of the unsatisfactory rate of 0.60% (95% CI: 0.18 – 1.96%; I2 = 99%) for conventional cytology and 0.04% (95% CI: 0.00 – 0.35%; I2 = 99%) for liquid-based cytology (LBC). However, comparative results between conventional and liquid-based cytology, based on 4 direct and 9 comparative studies, showed no significant difference (summary odds ratio = 3.5×10-2 favoring LBC [95% CI: 6.9×10-4 – 1.7]; I2 = 98%). In the subgroup analyses and meta-regressions, use of non-cotton devices for conventional cytology and use of a particular platform for LBC were associated with lower unsatisfactory rates. Meta-regression also suggested chronological improvement in unsatisfactory rates for both tests.

In Japanese cervical cancer screening programs, conventional cytology remains prevalent. Future research needs to focus on evaluating the impact of screening programs using LBC by comparing the accuracy, performance, and cost-effectiveness with conventional cytology in the Japanese population.

This article is protected by copyright. All rights reserved.



http://ift.tt/2ER4yGc

Skip the guilt: Red wine could protect your oral health

If you're scared that your nightly glass of red wine will eventually cause your teeth to rot, that's a worry that you can dispel right now. A new study from Spain suggests that red wine compounds may actually do your oral health a world of good.

http://ift.tt/2HJsfhu

Testing for NRAS Mutations in Serous Borderline Ovarian Tumors and Low-Grade Serous Ovarian Carcinomas

The Idylla NRAS Mutation Test, performed on the Biocartis Idylla system, is an in vitro diagnostic tool for the qualitative assessment of 18 NRAS mutations in codons 12, 13, 59, 61, 117, and 146. Low-grade serous ovarian cancer (LGSC) represents less than 10% of all serous ovarian carcinomas. LGSCs are believed to arise from preexisting cystadenomas or serous borderline tumors (SBOTs) that eventually progress to an invasive carcinoma. The molecular analysis of cancer-causing mutations and the development of targeted biological therapies constitute a milestone in the diagnosis and therapy of ovarian malignancies. According to some authors, NRAS may be an important oncogene for the progression of SBOT to a frankly invasive disease. The primary aim of this study was to verify if a fully integrated, real-time PCR-based Idylla system can be used for the rapid determination of the NRAS mutation status in patients with serous borderline ovarian tumors and low-grade serous ovarian carcinomas. The study included tissue specimens from 12 patients with histopathologically verified ovarian masses, operated on at the Department of Obstetrics and Gynecology, Nicolaus Copernicus University, Collegium Medicum in Bydgoszcz (Poland), between January 2009 and June 2012. The mean age of the study patients was 52.5 years (range 27–80 years). NRAS mutation in codon 13 (G13D, p.Gly13Asp; nucleotide: c.38G>A) was found in one patient, a woman with low-grade serous ovarian carcinoma. To the best of our knowledge, our experiment was the first published study using the novel Idylla NRAS Mutation Test for the evaluation of ovarian tumors in a clinical setting. The Idylla platform is an interesting ancillary first-line rapid and fully automated instrument to detect NRAS mutations in SBOTs and LGSCs. However, the clinical usefulness of this method still needs to be verified in larger groups of cancer patients.

http://ift.tt/2CHWOQX

Immune Escape Mechanisms and Future Prospects for Immunotherapy in Neuroblastoma

Neuroblastoma (NB) is the most common extracranial solid tumor in childhood with 5-year survival rate of 40% in high-risk patients despite intensive therapies. Recently, adoptive cell therapy, particularly chimeric antigen receptor (CAR) T cell therapy, represents a revolutionary treatment for hematological malignancies. However, there are challenges for this therapeutic strategy with solid tumors, as a result of the immunosuppressive nature of the tumor microenvironment (TME). Cancer cells have evolved multiple mechanisms to escape immune recognition or to modulate immune cell function. Several subtypes of immune cells that infiltrate tumors can foster tumor development, harbor immunosuppressive activity, and decrease an efficacy of adoptive cell therapies. Therefore, an understanding of the dual role of the immune system under the influences of the TME has been crucial for the development of effective therapeutic strategies against solid cancers. This review aims to depict key immune players and cellular pathways involved in the dynamic interplay between the TME and the immune system and also to address challenges and prospective development of adoptive T cell transfer for neuroblastoma.

http://ift.tt/2CGcWCA

The Role of miRNA-132 against Apoptosis and Oxidative Stress in Heart Failure

Objective. To explore the effect of microRNA-132 of heart failure and provide theoretical guidance for clinical treatment of heart failure (HF). Methods. Peripheral blood was collected from HF patients. RT-qPCR was used to determine microRNA-132 expression. Mouse models of heart failure were established. Color Doppler ultrasound was utilized to measure the changes of cardiac function. HE and Masson staining were applied to observe pathological changes of the myocardium. After H9C2 cells were transfected with microRNA-132, MTT assay was employed to detect the stability of H9C2 cells. ELISA was used to measure the levels of oxidative stress factors. Western blot assay and RT-qPCR were utilized to determine the expression of Bax, Bcl-2, TGF-β1, and smad3. Results. MicroRNA-132 expression was downregulated in HF patients' blood. After establishing mouse models of HF, cardiac function obviously decreased. HE staining revealed the obvious edema and hypertrophy of cardiomyocytes. Masson staining demonstrated that cardiomyocytes were markedly fibrotic. After microRNA-132 transfection and H9C2 cell apoptosis induced by H2O2, antioxidant stress and antiapoptotic ability of the H9C2 cells obviously increased. TGF-β1 and smad3 expression remarkably diminished. Conclusion. Overexpression of microRNA-132 dramatically increased the antioxidant stress and antiapoptotic ability of H9C2 cells and decreased the expression of TGF-β1 and smad3.

http://ift.tt/2ETcbMs

Preparation and Evaluation of Combined Detection of Norovirus GI and GII: An Innovative Fluorescent Particles Test Strip

This study was designed to prepare and evaluate the sensitivity and specificity of a Norovirus GI and GII fluorescent particles combined detection test strip method. Using selected chromatographic materials and antibodies specific to Norovirus GI and GII, the Norovirus GI and GII fluorescent particles combined detection test strip (tested method) was prepared as a conventional double antibody sandwich. The samples assayed included cultured rotavirus and 465 specimens from patients with symptoms of gastrointestinal infection. Norovirus was detected using the tested method and a reference method (CerTest Norovirus GI-GII test card). The results indicated that the sensitivity of the tested method was 4 (for GI detection) or 8 times (for GII detection) greater than the reference method. Neither of the two methods cross-reacted with rotavirus and so on. For specimens, 29 were found to be negative by the reference method and positive by the tested method, and 8 were found to be negative by the tested method and positive by the reference method. Furthermore, a retesting of these samples by qPCR showed that 28 of the 29 were positive, and 3 of the 8 were positive. In summary, the Norovirus GI and GII fluorescent particles combined detection test strip was successfully prepared and had good detection performance.

http://ift.tt/2City7v