Parents’ Influence on Infants’ Gender-Typed Toy Preferences

Abstract

Gender socialization influences children at early ages, shaping their developing identities. The toys provided by parents deliver some of the earliest gender-based messages by encouraging children to engage in activities associated with, for example, dolls and trucks. In the current study, we measured the influence of parental socialization by assessing 5- and 12 ½-month-old infants' exposure to dolls and trucks and by experimentally manipulating parents' encouragement to play with these toys. We found that infants displayed gender-typical toy preferences at 12 ½, but not 5 months, a pattern characteristic of previous studies. However, brief encouragement by a parent to play with toys from each category was ineffective in altering infants' preferences. Rather, the types of toys present in the home predicted preferences, suggesting that at-home exposure to toys may be influential in the development of toy preferences. These findings reveal that socialization processes may indeed play a role in the formation of early gender-typical toy preferences and highlight the importance of equal toy exposure during infancy to ensure optimal development.

http://ift.tt/2A1KTwr

Response to in vitro and physiologically-based pharmacokinetic assessment of the drug–drug interaction potential of canagliflozin

http://ift.tt/2hyZE32

Photodynamic therapy with 5-aminolevulinic acid suppresses IFN-γ-induced K17 expression in HaCaT cells via MAPK pathway

OBJECTIVE: Psoriasis is a chronic inflammatory skin disorder that greatly affects the patient's quality of life. Photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) has recently been applied for inflammatory dermatoses including psoriasis. However, the therapeutic effect of ALA-PDT is yet to be validated, and the underlying mechanisms remain unclear.

MATERIALS AND METHODS: In this study, a psoriatic model was established by treating HaCaT cells with 250 U/ml IFN-γ for 48 h. The effect of ALA-PDT treatment on HaCaT cell viability was assessed using MTT assay. The levels of p38, JNK, and ERK, as well as their phosphorylation status (P-p38, P-JNK, P-ERK), were assessed by immunoblotting.

RESULTS: Our data indicate that ALA-PDT can significantly inhibit the proliferation of IFN-g-treated HaCaT cells and the expression of keratin 17, both in a dose- and time-dependent manner. Furthermore, ALA-PDT can activate the MAPK pathway, and promote the expression of p38, JNK, and ERK. ALA-PDT showed pro-apoptotic effects by enhancing cell apoptosis and upregulating the apoptotic genes PARP and caspase 3.

CONCLUSIONS: Taken together, these findings indicate the possible pathways involved in ALA-PDT-mediated effects and highlight the potential of ALA-PDT in the development of novel therapeutic strategies.

L'articolo Photodynamic therapy with 5-aminolevulinic acid suppresses IFN-γ-induced K17 expression in HaCaT cells via MAPK pathway sembra essere il primo su European Review.

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Ischemic stroke and ST-elevation myocardial infarction revealing infective endocarditis

In this clinical scenario, we report the case of a patient who presented multiple embolic complications due to mitral infective endocarditis (IE). A 68-year-old woman had extended right hepatectomy for hilar cholangiocarcinoma. Unfortunately, she had multiple postoperative complications and had to be transferred to the Intensive Care Unit. During this stay, we have diagnosed an Enterococcus faecium IE after the occurrence of multiple embolic complications (myocardial infarction, ischemic stroke, digital emboli, splenic emboli, and renal emboli). The case is presented hereunder with illustrative imagings. While embolism is a known complication of IE, the presence of multiple emboli in various organs is rare.

L'articolo Ischemic stroke and ST-elevation myocardial infarction revealing infective endocarditis sembra essere il primo su European Review.

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Editorial – Non AIDS-defining malignancies: a new epidemic in HIV-infected population for the upcoming decades?

L'articolo Editorial – Non AIDS-defining malignancies: a new epidemic in HIV-infected population for the upcoming decades? sembra essere il primo su European Review.

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Genotype-based tacrolimus dosing guidelines: with or without CYP3A4*22?

Pharmacogenomics, Ahead of Print.


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An assessment of the impact of pharmacogenomics on health disparities: a systematic literature review

Pharmacogenomics, Ahead of Print.


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Impact of CYP2D6 and ADRB1 polymorphisms on heart rate of post-PCI patients treated with metoprolol

Pharmacogenomics, Ahead of Print.


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Triple-negative breast cancer and the potential for targeted therapy

Pharmacogenomics, Ahead of Print.


http://ift.tt/2gZOqnE

SLCO1B1 rs4149056 genetic polymorphism predicting methotrexate toxicity in Chinese patients with non-Hodgkin lymphoma

Pharmacogenomics, Ahead of Print.


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Pembrolizumab for treatment of advanced gastric and gastroesophageal junction adenocarcinoma

Future Oncology, Ahead of Print.


http://ift.tt/2h8H3xR

Prediction of Multiple-Trait and Multiple-Environment Genomic Data Using Recommender Systems

In genomic-enabled prediction, the task of improving the accuracy of the prediction of lines in environments is difficult because the available information is generally sparse and usually has low correlations between traits. In current genomic selection, while researchers have a large amount of information and appropriate statistical models to process it, there is still limited computing efficiency to do so. Although statistical models are usually mathematically elegant, they are also computationally inefficient, and they are impractical for many traits, lines, environments, and years because they need to sample from huge normal multivariate distributions. For these reasons, this study explores two recommender systems: a) item-based collaborative filtering (IBCF) and b) the matrix factorization algorithm (MF) in the context of multiple traits and multiple environments. The IBCF and matrix factorization methods were compared with two conventional methods on simulated and real data. Results of the simulated and real data sets show that the IBCF technique was slightly better in terms of prediction accuracy than the two conventional methods and the matrix factorization method when the correlation was moderately high. The IBCF technique is very attractive because it produces good predictions when there is high correlation between items (environment-trait combinations) and its implementation is computationally feasible, which can be useful for plant breeders who deal with very large data sets.

http://ift.tt/2A2WM55

Rectal cancer: so many surgical options. How do we choose?

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Laparoscopic and other colorectal trials: ethics of the learning curve

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Out-of-office hours intensive care admissions: implications for hospital governance

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Issue information - TOC

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Rural thoracotomy and asystolic arrests: a survivor

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Non-incisional traumatic lateral abdominal wall hernia

http://ift.tt/2A3dbqy

Medicine in small doses

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25, 50 & 75 years ago

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Outcome of three common bariatric procedures in the public sector

Background

In Australia, over 90% of bariatric surgery is performed in the private sector by paying patients with health insurance. The demand for government funded services is overwhelming and data are needed on the efficiency, safety and effectiveness of the current range of bariatric procedures in a public hospital setting. The aim of this study was to document medium term outcomes of gastric banding (laparoscopic adjustable gastric banding (LAGB)), gastric bypass (Roux-en-Y gastric bypass (RYGB)) and sleeve gastrectomy (SG) in a publicly funded programme.

Methods

Primary cases with minimum 18 months' follow up were included. Hospital usage, complications, weight loss and co-morbidity outcomes were compared.

Results

A total of 229 patients (125 LAGB, 42 RYGB, 62 SG) were included. Mean weight (body mass index) for LAGB, RYGB and SG was 130.6 (46.3), 137.2 (50.5) and 162.7 (55.2) kg (kg/m²), respectively (P < 0.001). Operative time and hospital stay were longest for RYGB and intensive care stay was longest for SG. Major complications occurred at 0.0%, 11.9% and 12.9% (P < 0.001) and major reoperations occurred over 5 years 11.2%, 21.4% and 6.5% (P = 0.064). Mean (standard deviation) excess weight loss was 29.9% (33.1), 75.7% (31.8) and 52.7% (19.7) with mean follow up of 3.6 years and 79.0% complete data.

Conclusions

In our public bariatric programme, LAGB patients perform relatively poorly. An increased focus on SG may be appropriate as weight loss is more reliable, major reoperation rates are low and follow up less important. Our experience should be useful for those considering how best to structure and fund a public bariatric programme.

http://ift.tt/1Mt5E9r

Data Science in Radiology: A Path Forward

Artificial intelligence (AI), especially deep learning, has the potential to fundamentally alter clinical radiology. AI algorithms, which excel in quantifying complex patterns in data, have shown remarkable progress in applications ranging from self-driving cars to speech recognition. The AI application within radiology, known as radiomics, can provide detailed quantifications of the radiographic characteristics of underlying tissues. This information can be used throughout the clinical care path to improve diagnosis and treatment planning, as well as assess treatment response. This tremendous potential for clinical translation has led to a vast increase in the number of research studies being conducted in the field, a number that is expected to rise sharply in the future. Many studies have reported robust and meaningful findings; however, a growing number also suffer from flawed experimental or analytical designs. Such errors could not only can result in invalid discoveries, but also may lead others to perpetuate similar flaws in their own work. This perspective article aims to increase awareness of the issue, identify potential reasons why this is happening, and provide a path forward.

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Diagnostic Performance of Contrast-Enhanced Ultrasound for Pancreatic Neoplasms: A Systematic Review and Meta-Analysis

Early diagnosis of pancreatic cancer is essential to optimize treatment strategies.

http://ift.tt/2zb2XFk

Aberrant expression of thyroid transcription factor-1 in schwannomas

Aberrant expression of thyroid transcription factor-1 (TTF-1) has been observed in tumors arising in locations other than thyroid gland, lung and ventral forebrain. However, TTF-1 expression in schwannomas has not yet been studied. Meanwhile, a few inconsistent changes in protein expression have been identified between schwannomas and other peripheral nerve sheath tumors. We evaluated TTF-1 expression in 161 schwannomas and 43 other peripheral nervous system lesions, including ganglioneuromas (n=8), malignant peripheral nerve sheath tumors (MPNSTs) (n=11), neurofibromas (n=24), and traumatic neuromas (n=9), using immunohistochemistry and verified it using quantitative real-time reverse transcription polymerase chain reaction (qPCR) to explore TTF-1 expression in peripheral nervous system lesions.

http://ift.tt/2AduWnS

Primary Mammary Analogue Secretory Carcinoma of the Lung: A Case Report

Mammary analogue secretory carcinoma (MASC) is a recently discovered salivary gland tumor described mostly in the major salivary glands and occasionally in the skin. We report a primary endobronchial tumor with histology, immunophenotype, and ETV6 rearrangement characteristic of MASC in a 62-year-old woman. The diagnosis was initially made on a transbronchial biopsy with FISH confirmation of ETV6 rearrangement. The patient underwent lobectomy demonstrating a large endobronchial mass. To our knowledge, this is the first report of MASC arising as a primary pulmonary tumor.

http://ift.tt/2xRXnGd

Pseudomyogenic Hemangioendothelioma of Skin, Bone and Soft tissue – A Clinicopathological, Immunohistochemical and Fluorescence in situ hybridization study

Pseudomyogenic hemangioendothelioma (PHE) is an uncommon neoplasm with propensity for local recurrence. The tumor mimics epithelioid hemangioendothelioma and epithelioid sarcoma, representing a possible diagnostic pitfall. We investigated the clinicopathological, immunohistochemical and fluorescence in situ hybridization features of PHEs. Eight cases of PHE were retrieved from our pathology archives. The clinical and outcome information was available in six patients. In six cases the tumors were located in the lower limb while the upper limb was involved in two cases.

http://ift.tt/2AduUMM

High TREM2 expression correlates with poor prognosis in gastric cancer

Triggering receptor expressed on myeloid cells 2 (TREM2) is a member of the immunoglobulin superfamily and associates with TYRO protein tyrosine kinase-binding protein at the cell membrane to form a receptor signaling complex. Gastric cancer (GC) is one of the most common human cancer in the word, we found that TREM2 expression in gastric cancer and adjacent tissues were significantly different. The goal of this study was to measure TREM2 protein and mRNA expression levels in GC tissues and evaluate their value as potential prognostic markers.

http://ift.tt/2A1wIr3

Unclassified Hemangioma-like Renal Cell Carcinoma: A Potential Diagnostic Pitfall

Recently, rare renal cell carcinomas (RCC) have been reported to closely mimic hemangioma; however, these have been largely recognizable as clear cell RCC. Conversely, true hemangiomas of the kidney are also increasingly recognized. We report a 62-year-old woman who underwent partial nephrectomy for a hemangioma-like RCC without appreciable clear cell morphology. Immunohistochemistry revealed luminal structures that stained positively for cytokeratin (CK), CK7, carbonic anhydrase IX, PAX8, and high molecular weight keratin (HMWK), admixed with a CD34, CD31, and ERG-positive complex network of vessels.

http://ift.tt/2hyTNe7

Clinical and biological significance of miR-193a-3p targeted KRAS in colorectal cancer pathogenesis

This study was to investigate the expression pattern, mechanisms and clinicopathological implications of miR-193a-3p in colorectal cancer. Fresh frozen tissues from 70 matched colorectal adenocarciomas and the adjacent non-neoplastic mucosae were prospectively collected. Two colorectal cancer cell lines (SW480 and SW48) and a non-neoplastic colon cell line (FHC) were also used. The expression levels of miR193a-3p in the cells and tissues were measured by quantitative real-time polymerase chain reaction.

http://ift.tt/2A1Ko5F

Results and evaluation of a first-in-human study of RG7342, a mGlu5 positive allosteric modulator, utilizing Bayesian adaptive methods

Summary

AIM

The objectives of this first-in-human study were to evaluate the safety and tolerability, pharmacokinetics and pharmacodynamics, and to determine the maximum tolerated dose (MTD) of single ascending oral doses of RG7342, a positive allosteric modulator (PAM) of the metabotropic glutamate receptor 5 (mGlu5) for the treatment of schizophrenia, in healthy male subjects.

METHODS

This was a single-centre, randomized, double-blind, adaptive study of 37 subjects receiving single ascending oral doses of RG7342 (ranging from 0.06-1.2 mg, n=27) or placebo (n=10). A modified continual reassessment method, with control for the probability of over-dosing based on the occurrence of dose-limiting events (DLEs), was applied to inform the subsequent dose decisions for RG7342.

RESULTS

DLEs consisted of dizziness, nausea and vomiting, and the incidence and severity of these adverse events increased in a concentration-dependent manner. RG7342 doses of 1.2 mg under fasted conditions, which reached a mean maximum plasma concentration (C_max) of 10.2 ng/mL, were not tolerated (four out of six subjects experienced DLEs). RG7342 showed dose-proportional pharmacokinetics with rapid absorption and a biphasic decline with a mean terminal half-life estimated to be >1000 hours.

CONCLUSIONS

Single oral doses of RG7342 were generally tolerated up to 0.6 mg under fasted and 0.9 mg under fed conditions in healthy subjects.

Bayesian adaptive methods describing the probability of DLEs were effectively applied to support dose-escalation. MTDs (fasted, fed) were associated with a C_max of 6.5 ng/mL.

The development of RG7342 was discontinued due to the potential challenges associated with a long half-life in context of the observed adverse events.

http://ift.tt/2xTaBCQ

Risk-adjusted colorectal cancer screening using the FIT and routine screening data: development of a risk prediction model

Risk-adjusted colorectal cancer screening using the FIT and routine screening data: development of a risk prediction model

Risk-adjusted colorectal cancer screening using the FIT and routine screening data: development of a risk prediction model, Published online: 02 November 2017; doi:10.1038/bjc.2017.375

http://ift.tt/2iWrycX

Inhibitor of DNA binding 2 is a novel therapeutic target for stemness of head and neck squamous cell carcinoma

Inhibitor of DNA binding 2 is a novel therapeutic target for stemness of head and neck squamous cell carcinoma

Inhibitor of DNA binding 2 is a novel therapeutic target for stemness of head and neck squamous cell carcinoma, Published online: 02 November 2017; doi:10.1038/bjc.2017.373

http://ift.tt/2iXFzXI

Cancer incidence in English children, adolescents and young people: past trends and projections to 2030

Cancer incidence in English children, adolescents and young people: past trends and projections to 2030

Cancer incidence in English children, adolescents and young people: past trends and projections to 2030, Published online: 02 November 2017; doi:10.1038/bjc.2017.341

http://ift.tt/2iZhK1x

Risk-adjusted colorectal cancer screening using the FIT and routine screening data: development of a risk prediction model

http://ift.tt/2lKbw6H

Inhibitor of DNA binding 2 is a novel therapeutic target for stemness of head and neck squamous cell carcinoma

http://ift.tt/2yrzGsy

Cancer incidence in English children, adolescents and young people: past trends and projections to 2030

http://ift.tt/2gZBAFK

Treatment of Acute Hepatitis C With Ledipasvir and Sofosbuvir in Patients with Hematological Malignancies Allows Early Re-start of Chemotherapy

http://ift.tt/2AdwTQX

Association Between Obesity and Discordance in Fibrosis Stage Determination by Magnetic Resonance vs Transient Elastography in Patients with Non-alcoholic Liver Disease

Magnetic resonance elastography (MRE) and transient elastography (TE) are noninvasive techniques used to detect liver fibrosis in NAFLD. MRE detects fibrosis more accurately than TE, but MRE is more expensive, and the concordance between MRE and TE have not been optimally assessed in obese patients. It is important to determine under which conditions TE and MRE produce the same readings, so that some patients can simply undergo TE evaluation to detect fibrosis. We aimed to assess the association between body-mass-index (BMI) and discordancy between MRE and TE findings, using liver biopsy as the reference, and validated our findings in a separate cohort.

http://ift.tt/2xQJaJF

Clinical and pharmacokinetic factors associated with adalimumab-induced mucosal healing in patients with Crohn’s disease

Concomitant azathioprine has marginal effects on endoscopic response in patients with Crohn's disease treated with adalimumab. Adalimumab trough level was associated with endoscopic response and mucosal healing in these patients.

http://ift.tt/2AdwNsz

Classifying Fecal Microbiota Transplantation Failure: An Observational Study Examining Timing and Characteristics of FMT Failures

http://ift.tt/2xQJ1WD

Diaphragmatic Breathing Reduces Belching and Proton Pump Inhibitor Refractory Gastroesophageal Reflux Symptoms

In patients with gastroesophageal reflux disease (GERD) and excessive belching, most belches are supragastric, and can induce reflux episodes and worsen GERD. Supragastric belching (SGB) might be reduced with diaphragmatic breathing exercises. We investigated whether diaphragmatic breathing therapy is effective in reducing belching and proton pump inhibitor (PPI) refractory gastroesophageal reflux symptoms.

http://ift.tt/2Ac4xGW

Trunk exercises improve gait symmetry in Parkinson disease: A blind phase II randomised-controlled trial.

Objective: Deficits in step-to-step symmetry and trunk muscle activations have been linked to falls in Parkinson's disease (PD). Given such symptoms are poorly managed with anti-parkinsonian medications, alternate therapies are needed. This blind phase II randomised-controlled trial sought to establish whether exercise can improve step-to-step symmetry in PD. Design: Twenty-four PD patients with a falls history completed baseline assessments of symptom severity, balance confidence, mobility and quality of life. Step-to-step symmetry was assessed by deriving harmonic ratios from three-dimensional accelerations collected for the head and trunk. Patients were randomly assigned to either 12-weeks of exercise and falls prevention education or falls prevention education only. Both groups repeated the baseline tests 12- and 24-weeks following the initial assessment. The Australian and New Zealand Clinical Trials Registry number is ACTRN12613001175763. Results: At 12-weeks, the Exercise group had statistically significant and clinically relevant improvements in anterior-posterior step-to-step trunk symmetry. In contrast, the Education group recorded statistically significant and clinically meaningful reductions in medial-lateral and vertical step-to-step trunk symmetry at 12-weeks. Conclusion: Given that step-to-step symmetry improved for the Exercise group and declined for the Education group post-intervention, active interventions appear more suited to increasing independence and quality of life for people with PD. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2A4kiPj

Intelligent assistant carer for active aging

We present the concept of an Intelligent Assistant Carer system for the elderly, designed to help with active aging and to facilitate the interactions with carers. The system is modular, allowing the users to ...

http://ift.tt/2zaqJkP

Benzoylphenyl thiocyanates are new, effective inhibitors of the mycobacterial resuscitation promoting factor B protein

Resuscitation promoting factors (Rpfs) are the proteins involved in the process of reactivation of the dormant cells of mycobacteria. Recently a new class of nitrophenylthiocyanates (NPTs), capable of inhibiti...

http://ift.tt/2ioYBSR

Biofilm and metallo beta-lactamase production among the strains of Pseudomonas aeruginosa and Acinetobacter spp. at a Tertiary Care Hospital in Kathmandu, Nepal

Pseudomonas aeruginosa and Acinetobacter spp. are found to be associated with biofilm and metallo-β-lactamase production and are the common causes of serious infections mainly in hospi...

http://ift.tt/2ioYzud

EMS scheduling software: Going strong since 2005

In March 2005, eCore was the fortunate recipient of an article write up in JEMS magazine and web site about our products. Prior to re branding to ePro Scheduler, the original product name was Net Scheduler Pro. Even back in 2005, the eCore team was offering top of the line EMS Scheduling Software to the industry JEMS serves. Where Scheduling Software has Been to Where We Are Now It is very exciting ...

http://ift.tt/2zrI4IH

The effects of lapatinib on CYP3A metabolism of midazolam in patients with advanced cancer

Abstract

Purpose

The potential inhibition of CYP3A4 by lapatinib was studied using midazolam as a probe substrate in patients with cancer.

Methods

This was a partially randomized, 4-period, 4-sequence, 4-treatment, cross-over study in 24 patients with advanced cancer. Single 1-mg IV and 3-mg oral doses of midazolam were given 2 days apart, in a partially random order, on study days 1, 3, 9, and 11. Lapatinib 1500-mg was administered orally once daily on study days 4 through 11. Midazolam plasma concentrations were measured up to 24-h post dosing, and lapatinib plasma concentrations measured prior to each midazolam dose.

Results

Lapatinib increased the geometric mean (95% CIs) midazolam AUC_(o−∞) by 45% (31–60%) after the oral dose and by 14% (0–29%) after the IV dose, and prolonged the midazolam elimination half-life by 48% (22–81%) after the oral dose and by 20% (2–40%) after the IV dose. Lapatinib decreased midazolam total clearance by 13% (1–23%), while total bioavailability was increased 23% (4–46%) without changes in apparent volume of distribution or hepatic bioavailability.

Conclusion

These data show that lapatinib caused weak inhibition of gastrointestinal CYP3A4 in vivo. This suggests that oral CYP3A4 drug substrates with a narrow therapeutic index may need dose reduction if lapatinib is to be co-prescribed.

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Transcranial Electrical Brain Stimulation in Alert Rodents

This protocol describes a surgical set-up for a permanent epicranial electrode socket and an implanted chest electrode in rodents. By placing a second electrode into the socket, different types of transcranial electrical brain stimulation can be delivered to the motor system in alert animals through the intact skull.

http://ift.tt/2z7LE7R

Effectiveness of training to promote routine enquiry for domestic violence by midwives and nurses: A pre-post evaluation study

Publication date: Available online 1 November 2017
Source:Women and Birth
Author(s): Kathleen M. Baird, Amornrat S. Saito, Jennifer Eustace, Debra K. Creedy
BackgroundAsking women about experiences of domestic violence in the perinatal period is accepted best practice. However, midwives and nurses may be reluctant to engage with, or effectively respond to disclosures of domestic violence due a lack of knowledge and skills.AimTo evaluate the impact of training on knowledge and preparedness of midwives and nurses to conduct routine enquiry about domestic violence with women during the perinatal period.MethodA pre-post intervention design was used. Midwives and nurses (n=154) attended a full day workshop. Of these, 149 completed pre-post workshop measures of knowledge and preparedness. Additional questions at post-training explored participants' perceptions of organisational barriers to routine enquiry, as well as anticipated impact of training on their practice. Training occurred between July 2015 and October 2016.FindingsUsing the Wilcoxon signed-rank test, all post intervention scores were significantly higher than pre intervention scores. Knowledge scores increased from a pre-training mean of 21.5–25.6 (Z=−9.56, p<0.001) and level of preparedness increased from 40.8 to 53.2 (Z=−10.12, p<0.001). Most participants (93%) reported improved preparedness to undertake routine enquiry after training. Only a quarter (24.9%) felt their workplace allowed adequate time to respond to disclosures of DV.ConclusionsBrief training can improve knowledge, preparedness, and confidence of midwives and nurses to conduct routine enquiry and support women during the perinatal period. Training can assist midwives and nurses to recognise signs of DV, ask women about what would be helpful to them, and address perceived organisational barriers to routine enquiry. Practice guidelines and clear referral pathways following DV disclosure need to be implemented to support gains made through training.



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Predictors of breastfeeding exclusivity and duration in a hospital without Baby Friendly Hospital Initiative accreditation: A prospective cohort study

Publication date: Available online 2 November 2017
Source:Women and Birth
Author(s): Michelle O'Connor, Jyai Allen, Jennifer Kelly, Yu Gao, Sue Kildea
AimThe aim of this study was to investigate the maternity care factors associated with exclusive breastfeeding duration at three months and six months postpartum in a setting without BFHI accrediation.MethodsA prospective cohort design. Participants from one tertiary maternity hospital were eligible if they intended to exclusively breastfeed, had birthed a live, term baby; were breastfeeding at recruitment; were rooming-in with their baby; were healthy and well; and understood English. Participants completed an infant feeding survey using 24-h recall questions at three time-points. Data were analysed using descriptive statistics, bivariate analysis and regression modelling.FindingsWe recruited 424 participants of whom 84% (n=355) responded to the survey at 3-months and 79% (n=335) at 6-months. Women who avoided exposure to intrapartum opioid analgesia (e.g. intramuscular, intraveous or epidural) were more likely to be exclusively breastfeeding at 3-months postpartum (adjusted odds ratio (aOR) 2.09, 95% confidence interval (CI) 1.15–3.80, probability value (p) 0.016). The only other modifiable predictor of exclusive breastfeeding at 3-months was non-exposure to artificial formula on the postnatal ward (aOR 2.44, 95% CI 1.43–4.18, p<0.001). At 6-months postpartum, the rate of exclusive breastfeeding had reduced to 5% (n=16) which rendered regression modelling untenable.DiscussionStrategies to decrease exposure to opioid analgesia in birth settings and the use of infant formula on the postnatal ward may improve exclusive breastfeeding at three months.ConclusionResults suggest that both intrapartum and postpartum maternity care practices can predict long-term breastfeeding success.



http://ift.tt/2iqkbGP

Renal clear cell carcinoma metastasis to the breast ten years after nephrectomy: a case report and literature review

Renal cell carcinoma most commonly metastasizes to the lungs, skeleton or liver. Metastatic renal cell carcinoma to the breast is very rare, especially for clear cell carcinoma, and few cases regarding this co...

http://ift.tt/2zs4edM

Complete mimicry: a case of alveolar rhabdomyosarcoma masquerading as acute leukemia

A small number of rhabdomyosarcoma (RMS) cases involve the bone marrow. A leukemic presentation of RMS has been reported in a few case series, although almost all cases of leukemic RMS are not completely mimic...

http://ift.tt/2zfhGRq

Assuming the Role of NCI Director: Working to Accelerate Progress

Norman Sharpless, M.D., discusses his appointment as the director of the National Cancer Institute and his plans for continuing NCI's long tradition of research excellence and commitment to improving people's lives.

http://ift.tt/2ypbWp4

In Vivo Detection and Analysis of Rb Protein SUMOylation in Human Cells

Small ubiquitin-related modifier (SUMO) family proteins are conjugated to the lysine residues of target proteins to regulate various cellular processes. This paper describes a protocol for the detection of retinoblastoma (Rb) protein SUMOylation under endogenous and exogenous conditions in human cells.

http://ift.tt/2lI2xD9

Accurate Evaluation of Tumour Necrosis in the Preoperative Period: A New Challenge: In Reply

http://ift.tt/2z8JVBC

Refining Tumor Resection Techniques for Managing Inferior Pole Breast Malignancies

http://ift.tt/2h6pZsm

Prediction of high airway pressure using a non-linear autoregressive model of pulmonary mechanics

For mechanically ventilated patients with acute respiratory distress syndrome (ARDS), suboptimal PEEP levels can cause ventilator induced lung injury (VILI). In particular, high PEEP and high peak inspiratory ...

http://ift.tt/2h6Hw3G

Comment on: Need for Differentiating Diabetes-Specific Mortality from Total Mortality when Comparing Metformin with Insulin Regarding Cancer Survival

http://ift.tt/2z6tshv

Empirical study of seven data mining algorithms on different characteristics of datasets for biomedical classification applications

Various kinds of data mining algorithms are continuously raised with the development of related disciplines. The applicable scopes and their performances of these algorithms are different. Hence, finding a sui...

http://ift.tt/2z7rEVl

Linear and exponential TAIL-PCR: a method for efficient and quick amplification of flanking sequences adjacent to Tn5 transposon insertion sites

Current genome walking methods are very time consuming, and many produce non-specific amplification products. To amplify the flanking sequences that are adjacent to Tn5 transposon insertion sites in Serratia marc...

http://ift.tt/2zdyp7D

Metagenomic analysis reveals potential interactions in an artificial coculture

Disentangling the interactions between cyanobacteria and associated bacterial community is important for understanding the mechanisms that mediate the formation of cyanobacterial blooms in freshwater ecosystem...

http://ift.tt/2zdycBn

Antimicrobial action of methanolic seed extracts of Syzygium cumini Linn. on Bacillus subtilis

Phytochemicals of Syzygium cumini are used for the treatment of various diseases as a traditional medicine but the mechanism behind their action is not well reported. Antimicrobial activity of methanolic seed ext...

http://ift.tt/2zqkfRy

Taxonomic identification of the thermotolerant and fast-growing fungus Lichtheimia ramosa H71D and biochemical characterization of the thermophilic xylanase LrXynA

The zygomycete fungus Lichtheimia ramosa H71D, isolated from sugarcane bagasse compost, was identified by applying phylogenetic analysis based on the DNA sequence of the Internal Transcribed Spacer (ITS), and sub...

http://ift.tt/2zrgnzZ

Non-invasively predicting differentiation of pancreatic cancer through comparative serum metabonomic profiling

Abstract

Background

The differentiation of pancreatic ductal adenocarcinoma (PDAC) could be associated with prognosis and may influence the choices of clinical management. No applicable methods could reliably predict the tumor differentiation preoperatively. Thus, the aim of this study was to compare the metabonomic profiling of pancreatic ductal adenocarcinoma with different differentiations and assess the feasibility of predicting tumor differentiations through metabonomic strategy based on nuclear magnetic resonance spectroscopy.

Methods

By implanting pancreatic cancer cell strains Panc-1, Bxpc-3 and SW1990 in nude mice in situ, we successfully established the orthotopic xenograft models of PDAC with different differentiations. The metabonomic profiling of serum from different PDAC was achieved and analyzed by using ¹H nuclear magnetic resonance (NMR) spectroscopy combined with the multivariate statistical analysis. Then, the differential metabolites acquired were used for enrichment analysis of metabolic pathways to get a deep insight.

Results

An obvious metabonomic difference was demonstrated between all groups and the pattern recognition models were established successfully. The higher concentrations of amino acids, glycolytic and glutaminolytic participators in SW1990 and choline-contain metabolites in Panc-1 relative to other PDAC cells were demonstrated, which may be served as potential indicators for tumor differentiation. The metabolic pathways and differential metabolites identified in current study may be associated with specific pathways such as serine-glycine-one-carbon and glutaminolytic pathways, which can regulate tumorous proliferation and epigenetic regulation.

Conclusion

The NMR-based metabonomic strategy may be served as a non-invasive detection method for predicting tumor differentiation preoperatively.

http://ift.tt/2h6CQuE

Therapy response testing of breast cancer in a 3D high-throughput perfused microfluidic platform

Abstract

Background

Breast cancer is the most common invasive cancer among women. Currently, there are only a few models used for therapy selection, and they are often poor predictors of therapeutic response or take months to set up and assay. In this report, we introduce a microfluidic OrganoPlate® platform for extracellular matrix (ECM) embedded tumor culture under perfusion as an initial study designed to investigate the feasibility of adapting this technology for therapy selection.

Methods

The triple negative breast cancer cell lines MDA-MB-453, MDA-MB-231 and HCC1937 were selected based on their different BRCA1 and P53 status, and were seeded in the platform. We evaluate seeding densities, ECM composition (Matrigel®, BME2rgf, collagen I) and biomechanical (perfusion vs static) conditions. We then exposed the cells to a series of anti-cancer drugs (paclitaxel, olaparib, cisplatin) and compared their responses to those in 2D cultures. Finally, we generated cisplatin dose responses in 3D cultures of breast cancer cells derived from 2 PDX models.

Results

The microfluidic platform allows the simultaneous culture of 96 perfused micro tissues, using limited amounts of material, enabling drug screening of patient-derived material. 3D cell culture viability is improved by constant perfusion of the medium. Furthermore, the drug response of these triple negative breast cancer cells was attenuated by culture in 3D and differed from that observed in 2D substrates.

Conclusions

We have investigated the use of a high-throughput organ-on-a-chip platform to select therapies. Our results have raised the possibility to use this technology in personalized medicine to support selection of appropriate drugs and to predict response to therapy in a real time fashion.

http://ift.tt/2z8N5W8

Effects of combination therapy using antithrombin and thrombomodulin for sepsis-associated disseminated intravascular coagulation

No single anticoagulant has been proven effective for sepsis-associated disseminated intravascular coagulation (DIC). Thus, the concomitant use of antithrombin concentrate and recombinant thrombomodulin has be...

http://ift.tt/2z7qPcB

Incidence of airway complications in patients using endotracheal tubes with continuous aspiration of subglottic secretions

Continuous aspiration of subglottic secretions is effective in preventing ventilator-associated pneumonia, but it involves a risk of mucosal damage. The main objective of our study was to determine the inciden...

http://ift.tt/2zr8sTj

Acute toxicity of image-guided hypofractionated proton therapy for localized prostate cancer

Abstract

Background

Hypofractionated proton therapy (HFPT) is expected to become an effective treatment approach for localized prostate cancer (PCa). The purpose of this study was to evaluate differences in acute toxicity among patients with localized PCa treated with either conventional fractionated proton therapy (CFPT) or HFPT.

Methods

A total of 526 eligible patients treated with proton therapy between February 2013 and May 2016 in three phase II trials were analyzed. We prescribed 74 gray relative biological effectiveness equivalents [Gy (RBE)]/37 fractions for low-risk patients and 78 Gy (RBE)/39 fractions for intermediate- and high-risk patients in the CFPT group (n = 254) and 60 Gy (RBE)/20 fractions for low-risk and 63 Gy (RBE)/21 fractions for intermediate- and high-risk patients in the HFPT group (n = 272). Patients were evaluated for acute toxicity with the Common Terminology Criteria for Adverse Events, version 4.0, and urinary quality-of-life change using the International Prostate Symptom Score (IPSS).

Results

No grade ≥3 acute toxicity was observed in either group. Among acute genitourinary toxicities, grade 2 rates were 15% (n = 38) in CFPT and 5.9% (n = 16) in HFPT (P ≤ 0.001). The median baseline IPSSs of the CFPT and HFPT groups were 7 (0–29) and 6 (0–31), respectively (P = 0.70). One-month post-treatment scores were 9 (0–32) and 11 (0–32), respectively (P = 0.036), and 6-month post-treatment scores were 7 (0–30) and 7 (0–33), respectively (P = 0.88). There were no significant differences in acute gastrointestinal toxicity between the two groups.

Conclusion

Our results demonstrated the safety of HFPT for localized PCa patients in terms of acute toxicity.

http://ift.tt/2z7oONB

Mucosa-associated invariant T cells link intestinal immunity with antibacterial immune defects in alcoholic liver disease

Background/aims

Intestinal permeability with systemic distribution of bacterial products are central in the immunopathogenesis of alcoholic liver disease (ALD), yet links with intestinal immunity remain elusive. Mucosa-associated invariant T cells (MAIT) are found in liver, blood and intestinal mucosa and are a key component of antibacterial host defences. Their role in ALD is unknown.

Methods/design

We analysed frequency, phenotype, transcriptional regulation and function of blood MAIT cells in severe alcoholic hepatitis (SAH), alcohol-related cirrhosis (ARC) and healthy controls (HC). We also examined direct impact of ethanol, bacterial products from faecal extracts and antigenic hyperstimulation on MAIT cell functionality. Presence of MAIT cells in colon and liver was assessed by quantitative PCR and immunohistochemistry/gene expression respectively.

Results

In ARC and SAH, blood MAIT cells were dramatically depleted, hyperactivated and displayed defective antibacterial cytokine/cytotoxic responses. These correlated with suppression of lineage-specific transcription factors and hyperexpression of homing receptors in the liver with intrahepatic preservation of MAIT cells in ALD. These alterations were stronger in SAH, where surrogate markers of bacterial infection and microbial translocation were higher than ARC. Ethanol exposure in vitro, in vivo alcohol withdrawal and treatment with Escherichia coli had no effect on MAIT cell frequencies, whereas exposure to faecal bacteria/antigens induced functional impairments comparable with blood MAIT cells from ALD and significant MAIT cell depletion, which was not observed in other T cell compartments.

Conclusions

In ALD, the antibacterial potency of MAIT cells is compromised as a consequence of contact with microbial products and microbiota, suggesting that the 'leaky' gut observed in ALD drives MAIT cell dysfunction and susceptibility to infection in these patients.

http://ift.tt/2h8zFCH

Chicago paramedic has responded to calls in every single city ambulance

By EMS1 Staff CHICAGO — A paramedic accomplished a personal goal by handling emergencies in each of the city's ambulances. FOX32 reported that Terry Sullivan spent decades responding to at least one call in every one of the ambulances in Chicago, and Wednesday he responded to a call in ambulance number 75. To achieve this goal that he made for himself 20 years ago, Sullivan traded shifts ...

http://ift.tt/2zaq7M5

A Method for Growing Bio-memristors from Slime Mold

This paper introduces an improved method for growing bio-memristors out of the plasmodium of Physarum polycephalum. Such a method has proven to decrease growth time, increase component lifespan, standardize electrical observations, and create a protected environment that can be integrated into conventional circuitry.

http://ift.tt/2iY4Lgz

An unusual cause of small bowel obstruction due to an ingested mango seed: a case report

Intestinal obstruction can occur due to multiple aetiologies. Intestinal obstruction due to phytobezoar have been reported. However, intestinal obstruction due to a mango seed has not been reported. Therefore,...

http://ift.tt/2gX1QAz

Pattern of neurological diseases in adult outpatient neurology clinics in tertiary care hospital

The burden of neurological diseases in developing countries is rising although little is known about the epidemiology and clinical pattern of neurological disorders. The objective of this study was to understa...

http://ift.tt/2inFoB9

Method and key points for isolation of human amniotic epithelial cells with high yield, viability and purity

Human amniotic epithelial cells (hAECs) which are isolated from the amniotic membrane have stem cell-like properties and immunomodulatory effects. Several protocols have been proposed for isolation of hAECs, n...

http://ift.tt/2gX1E4j

Subunit composition of respiratory chain complex 1 and its responses to oxygen in mitochondria from human donor livers

Donor liver function in transplantation is defined by mitochondrial function and the ability of mitochondria to recover from the sequence of warm and/or cold ischemia. Mitochondrial resilience maybe related to...

http://ift.tt/2ip6AiV

Antifungal susceptibility and phenotypic virulence markers of Candida species isolated from Nepal

Candida species are part of the commensal microflora in many anatomical sites of the human body; however, breach in the integrity of the body part and impaired immunity of the host can...

http://ift.tt/2gVt8Y5

Understanding Mitochondrial Polymorphisms in Cancer

Alterations in mitochondrial DNA (mtDNA) were once thought to be predominantly innocuous to cell growth. Recent evidence suggests that mtDNA undergo naturally occurring alterations, including mutations and polymorphisms, which profoundly affect the cells in which they appear and contribute to a variety of diseases, including cardiovascular disease, diabetes, and cancer. Furthermore, interplay between mtDNA and nuclear DNA has been found in cancer cells, necessitating consideration of these complex interactions for future studies of cancer mutations and polymorphisms. In this issue of Cancer Research, Vivian and colleagues utilize a unique mouse model, called Mitochondrial Nuclear eXchange mice, that contain the nuclear DNA from one inbred mouse strain, and the mtDNA from a different inbred mouse strain to examine the genome-wide nuclear DNA methylation and gene expression patterns of brain tissue. Results demonstrated there were alterations in nuclear DNA expression and DNA methylation driven by mtDNA. These alterations may impact disease pathogenesis. In light of these results, in this review, we highlight alterations in mtDNA, with a specific focus on polymorphisms associated with cancer susceptibility and/or prognosis, mtDNA as cancer biomarkers, and considerations for investigating the role of mtDNA in cancer progression for future studies. Cancer Res; 77(22); 1–9. ©2017 AACR.

http://ift.tt/2ypsDk9

Recent Advances of Cell-Cycle Inhibitor Therapies for Pediatric Cancer

This review describes the pivotal roles of cell-cycle and checkpoint regulators and discusses development of specific cell-cycle inhibitors for therapeutic use for pediatric cancer. The mechanism of action as well as the safety and tolerability of drugs in pediatric patients, including compounds that target CDK4/CDK6 (palbociclib, ribociclib, and abemaciclib), aurora kinases (AT9283 and MLN8237), Wee1 kinase (MK-1775), KSP (ispinesib), and tubulin (taxanes, vinca alkaloids), are presented. The design of mechanism-based combinations that exploit the cross-talk of signals activated by cell-cycle arrest, as well as pediatric-focused drug development, are critical for the advancement of drugs for rare childhood diseases. Cancer Res; 1–10. ©2017 AACR.

http://ift.tt/2lJBA1S

Uncoupling the Oncogenic Engine

Inhibition of oncogenic signaling and correction of aberrant metabolic processes may be key paradigms to eliminate cancer cells. The high incidence of activating RAS mutations and hyperactivated ERK1/2 signaling observed in many human tumors and the lack of effective targeted therapies to elicit long-term inhibition of the RAS-ERK1/2 signaling pathway add to the importance of discovering novel strategies to treat malignancies characterized by elevated RAS-ERK1/2 signaling. In this review, we describe connections between oncogenic signaling and cancer cell metabolism and how these links may be exploited for novel modern molecular medicine approaches. Cancer Res; 77(22); 1–5. ©2017 AACR.

http://ift.tt/2yoTcpQ

Adaptive evolution of the GDH2 allosteric domain promotes gliomagenesis by resolving IDH1R132H induced metabolic liabilities

Hot-spot mutations in the isocitrate dehydrogenase 1 (IDH1) gene occur in a number of human cancers and confer a neomorphic enzyme activity that catalyzes the conversion of α-ketoglutarate (αKG) to the oncometabolite D-(2)-hydroxyglutarate (D2HG). In malignant gliomas, IDH1R132H expression induces widespread metabolic reprogramming, possibly requiring compensatory mechanisms to sustain the normal biosynthetic requirements of actively proliferating tumor cells. We used genetically engineered mouse models of glioma and quantitative metabolomics to investigate IDH1R132H-dependent metabolic reprogramming and its potential to induce biosynthetic liabilities that can be exploited for glioma therapy. In gliomagenic neural progenitor cells, IDH1R132H expression increased the abundance of dipeptide metabolites, depleted key tricarboxylic acid (TCA) cycle metabolites, and slowed progression of murine gliomas. Notably, expression of glutamate dehydrogenase GDH2, a hominoid-specific enzyme with relatively restricted expression to the brain, was critically involved in compensating for IDH1R132H-induced metabolic alterations and promoting IDH1R132H glioma growth. Indeed, we found that recently evolved amino acid substitutions in the GDH2 allosteric domain conferred its non-redundant, glioma-promoting properties in the presence of IDH1 mutation. Our results indicate that among the unique roles for GDH2 in the human forebrain is its ability to limit IDH1R132H-mediated metabolic liabilities, thus promoting glioma growth in this context. Results from this study raise the possibility that GDH2-specific inhibition may be a viable therapeutic strategy for gliomas with IDH mutations.

http://ift.tt/2lIO5ut

Deletion of neuropilin 1 from microglia or bone marrow-derived macrophages slows glioma progression

Glioma-associated microglia and macrophages (GAM) which infiltrate high-grade gilomas represent constitute a major cellular component of these lesions. GAM behavior is influenced by tumor-derived cytokines that suppress initial anti-tumorigenic properties, causing them to support tumor growth and to convert and suppress adaptive immune responses to the tumor. Mice which lack the transmembrane receptor neuropilin-1 (Nrp1) which modulates GAM immune polarization exhibit a decrease in glioma volumes and neoangiogenesis and an increase in anti-tumorigenic GAM infiltrate. Here we show that replacing the peripheral macrophage populations of wild type mice with Nrp1-depleted bone marrow-derived macrophages (BMDM) confers resistance to the development of glioma. This resistance occurred in a similar fashion seen in mice in which all macrophages lacked Nrp1 expression. Tumors had decreased volumes, decreased vascularity, increased CTL infiltrate, and Nrp1-depleted BMDM adopted a more anti-tumorigenic phenotype relative to wild type GAM within the tumors. Mice with Nrp1-deficient microglia and wild type peripheral macrophages showed resistance to glioma development and had higher microglial infiltrate than mice with wild type GAM. Our findings show how manipulating Nrp1 in either peripheral macrophages or microglia reprograms their phenotype and relieve their pathogenic roles in tumor neovascularization and immunosuppression.

http://ift.tt/2yoW8T9

Rethinking ovarian cancer genomics: where genome-wide association studies stand?

Pharmacogenomics, Ahead of Print.


http://ift.tt/2z9hvI1

Distinctiveness of the Roma population within CYP2B6 worldwide variation

Pharmacogenomics, Ahead of Print.


http://ift.tt/2h6LXLJ

Pharmacogenetics of glatiramer acetate therapy for multiple sclerosis: the impact of genome-wide association studies identified disease risk loci

Pharmacogenomics, Ahead of Print.


http://ift.tt/2z9h4NT

Iatrogenic Vessel Dissection in Endovascular Treatment of Acute Ischemic Stroke

Abstract

Purpose

Knowledge about the localization and outcome of iatrogenic dissection (ID) during endovascular treatment of acute ischemic stroke (AIS) is limited. We aimed to determine the frequency, clinical aspects and morphology of ID in endovascular AIS treatment and to identify predictors of this complication.

Methods

Digital subtraction angiography (DSA) of ID carried out during endovascular treatment between January 2000 and March 2012 have been re-evaluated. The ID localization and morphology were analyzed and related to the interventional techniques. Baseline clinical and radiological findings, treatment modality and outcome were compared with patients without ID.

Results

Out of 866 patients 18 (2%) suffered an ID (44% female, median age 64 years). Localization was extracranial in 15 (83%, 14 internal carotid artery and 1 vertebral artery) and intracranial in 3 (17%; 1 vertebrobasilar dissection and 2 in the anterior circulation). Of the IDs 5 (28%) resulted in a high-degree, 3 (17%) in a moderate, 5 (28%) in a mild and 5 (28%) in no stenosis and 8 IDs were stented in the acute phase. At 3 months 7 (42%) patients had a favorable outcome (modified Rankin score mRS ≤ 2) and 6 (33%) patients had died. Patients with ID had a different stroke etiology (p = 0.041), were more likely to be smokers (44% versus 19%, p = 0.015) and were more likely to be treated with mechanical thrombectomy (100% versus 60%, p < 0.001). Although two ID patients had relevant complications, the outcome did not differ between the groups.

Conclusion

The occurrence of ID is a rare complication of endovascular AIS treatment associated with smoking and mechanical thrombectomy.

http://ift.tt/2h6q1jK

Positive surgical margin following radical nephrectomy is an independent predictor of local recurrence and disease-specific survival

Abstract

Background

Positive surgical margins (PSM) are recognized as an adverse prognostic sign and are often associated with higher rates of local and systemic disease recurrence. The data regarding the oncological outcome for PSM following radical nephrectomy (RN) is limited. We examined the predictive factors for PSM and its influence on survival and site of recurrence in patients treated with RN for renal cell carcinoma (RCC).

Methods

Clinical, pathologic and follow-up data on 714 patients undergoing RN for kidney cancer were analyzed. Secondary analysis included 44 patients with metastatic RCC upon diagnosis who underwent cytoreductive nephrectomy (CRN). Univariate and multivariable logistic regression models were fit to determine clinicopathologic features associated with PSM. A Cox proportional-hazards regression model was used to test the independent effects of clinical and pathologic variables on survival.

Results

PSM was documented in 17 cases (2.4%). PSM were associated with tumour size, advanced pathologic stage (pT3 vs. ≤ pT2) and presence of necrosis. On multivariate analysis, cancer-specific survival (CSS) was associated with tumour stage, size, presence of necrosis and PSM. PSM was also associated with local recurrence but not distant metastasis or overall survival (OS). CSS and OS were comparable between the PSM and metastatic RCC groups, but significantly lower than the negative margin group.

Conclusions

The prevalence of PSM following RN is rare. Pathological data, including advanced stage (> pT2), tumour necrosis and tumour size, are associated with the presence of PSM. PSM is associated with tumour recurrence and CSS. Patients with PSM are a potential group for adjuvant therapy or for more careful and thorough follow-up following surgery.

http://ift.tt/2hy3DN6

Stable red blood cell concentrations seen in astronauts on long space missions

Video summarises research in BMC Hematology, read the original article here: http://ift.tt/2ffb2jc

https://www.youtube.com/watch?v=1UMfQnAmbOM

The Results of Stricter Inclusion Criteria in an Immunomagnetic Detection Study of Micrometastatic Cells in Bone Marrow of Uveal Melanoma Patients - Relevance for Dormancy

Abstract

Approximately 50% of uveal melanoma patients develop metastases. We want to evaluate the effect of stricter criteria on our data from our previous study correlating survival and bone marrow (BM) micrometastasis results using our immunomagnetic separation (IMS) method. Mononuclear cell fractions (MNC) isolated from BM were examined for tumour cells and the patients were classified as BM positive (BM+) or BM negative (BM-). The study originally included 328 consecutive patients with uveal melanoma from 1997 to 2006. The cohort was limited to 217 patients when we introduced cyto- or histopathological verification of melanoma cells in the patient as a main new criterion for inclusion. Tumour cells were found in BM-samples in 38.7% (95% CI, 32–45) at enrolment. Until the latest work-up 43.8% (95% CI, 38–50) of patients had developed melanoma metastases. After a minimum follow-up time of 8.5 years, 60.4% (95% CI, 54–66) of patients had died. The causes were: melanoma metastases 69.5%, another type of cancer 5.4% and non-cancerous causes 19.5%. Overall median survival was shorter for the BM- patients (11.3 years) (95% CI, 10–12) compared to the BM+ (16.5 years) (95% CI, 12–14), p = 0.04, log rank test. All-cause mortality and specific melanoma mortality estimated after 12 year follow-up showed a highly significant difference comparing BM- and BM+, p = 0.010 and p = 0,017, respectively. IMS yields a high fraction of BM+ samples due to micrometastasis at diagnosis and these cells appear to have a positive prognostic impact strengthening our previous report. The late recurrences support the concept of tumour dormancy.

http://ift.tt/2zfkSwi

Gut region influences the diversity and interactions of bacterial communities in pikas ( Ochotona curzoniae and Ochotona daurica )

Abstract

The mammalian microbial communities in the gastrointestinal tract (GIT) play important roles in host nutrition and health. However, we still lack an understanding of how these communities are organized across GIT in natural environments. Here, using 16S rRNA gene sequencing, we analyzed the bacterial community diversity, network interactions and ecosystem stability across five gut regions (mouth, stomach, small intestine, caecum and colon) emanating from two common pika species in China, including Plateau pikas (Ochotona curzoniae) inhabiting high-altitude regions, as well as Daurian pikas (O. daurica) occupying low-altitude areas. The relative abundances of dominant Bacteroidetes and Firmicutes exhibited an increasing trend from mouth to colon. Caecum and colon harbored higher bacterial diversity compared with other anatomical regions. Gut region significantly influenced the structure of bacterial communities in the GIT. Network analysis indicated that topological features showed marked variations among gut regions. Interestingly, the ecosystem stability of bacterial communities increased gradually from mouth to colon. Our results suggest that gut region influences the diversity, structure, and network interactions of bacterial communities in pikas. For hindgut-fermenting herbivorous mammals, relatively higher bacterial diversity and ecosystem stability in the caecum may provide a favorable condition for the fermentation of indigestible plant polysaccharides.

http://ift.tt/2z8A4fq

Solving the puzzle of yeast survival in ephemeral nectar systems: exponential growth is not enough

Abstract

Flower nectar is a sugar-rich ephemeral habitat for microorganisms. Nectar-borne yeasts are part of the microbial community and can affect pollination by changing nectar chemistry, attractiveness to pollinators or flower temperature if yeast population densities are high. Pollinators act as dispersal agents in this system, however, pollination events lead potentially to shrinking nectar yeast populations.We here examine how sufficiently high cell densities of nectar yeast can develop in a flower. In laboratory experiments, we determined the remaining fraction of nectar yeast cells after nectar removal, and used honeybees to determine the number of transmitted yeast cells from one flower to the next. The results of these experiments directly fed into a simulation model providing an insight into movement and colonization ecology of nectar yeasts.We found that cell densities only reached an ecologically relevant size for an intermediate pollination probability. Too few pollination events reduce yeast inoculation rate and too many reduce yeast population size strongly. In addition, nectar yeasts need a trait combination of at least an intermediate growth rate and an intermediate remaining fraction to compensate for highly frequent decimations.Our results can be used to predict nectar yeast dispersal, growth and consequently their ecological effects.

http://ift.tt/2h7iCRd

Cost-effectiveness analysis of sensitive relapsed small-cell lung cancer based on JCOG0605 trial

Abstract

Purpose

Since combined strategy with cisplatin, etoposide, and irinotecan has shown the superiority to topotecan alone as second-line chemotherapy in patients with sensitive relapsed small-cell lung cancer, this study aimed to compare these two treatments based on JCOG0605 trail from Chinese cost-effectiveness perspective.

Methods

Basic medical information was derived from a multicenter, open-label, randomized phase III trial (JCOG0605). A Markov model including three health states: progression-free state, progressive disease (PD), and death, was developed to simulate the process of sensitive relapsed small-cell lung cancer. Cost was calculated from the perspective of Chinese society. Sensitivity analyses were applied to explore the impact of essential variables.

Results

Treatment with combination chemotherapy was estimated to increase costs by $6947.32 compared with topotecan alone, with a gain of 0.26 quality-adjusted life years (QALYs). Thus, the incremental cost-effective ratio was $26720.46/QALY for combination treatment versus monotherapy, which was beyond the threshold of 3 × the per capita GDP of China, $24423.00. The costs of PD state were the most influential factors to the model.

Conclusion

The combination chemotherapy with cisplatin, etoposide, and irinotecan was not a cost-effectiveness choice for patients with sensitive relapsed SCLC in China from the cost-effectiveness perspective.

http://ift.tt/2iqcK23

Selection and monitoring of patients with metastatic castration-resistant prostate cancer for treatment with radium-223

Abstract

Despite the improvement provided by androgenic suppression in the treatment of prostate cancer, most of tumors develop resistance to castration. However, new therapies have demonstrated an increase in patient survival such as radium-223 (Ra-223), an alpha emitter and calcium mimetic with the capability of targeting osteoblastic metastatic lesions. According to results of the ALSYMPCA phase III trial, Ra-223 has demonstrated its activity by improving symptoms and survival of patients with metastatic castration-resistant prostate cancer (mCRPC), symptomatic bone metastases, and no known visceral metastatic disease, without interfering with subsequent treatments. This review examines the key evidence to establish the best patient selection criteria to use Ra-223, how to assess the response to treatment, treatment-related toxicity, and follow-up, but also current research regarding imaging techniques and biomarkers to assess the efficacy of Ra-223. Finally, we briefly describe the clinical trials that are currently ongoing with Ra-223.

http://ift.tt/2gYaGho

SEOM clinical guideline in nasopharynx cancer (2017)

Abstract

Nasopharyngeal carcinoma (NPC) is distinct from other cancers of the head and neck in biology, epidemiology, histology, natural history, and response to treatment. Radiation therapy is an essential component of curative-intent of non-disseminated disease and the association of chemotherapy improves the rates of survival. In the case of metastatic disease stages, treatment requires platinum/gemcitabine-based chemotherapy and patients may achieve a long survival time.

http://ift.tt/2ioxo2S

Circular RNAs: emerging cancer biomarkers and targets

Abstract

CircRNAs are a class of RNA molecules that structurally form closed loops. CircRNAs are abundant in eukaryotic transcripts and show certain levels of tissue and cell specificity. CircRNAs have been suggested to regulate gene expression at transcriptional, post-transcriptional, and translational levels. An increasing number of studies have shown that circRNAs play important roles in the development and progression of diseases including cancer. In particular, circRNAs have shown great potential in cancer diagnosis, prognosis, and therapy. In this review, we provide an overview of the biogenesis and characteristics of circRNAs, succinctly describe their functions, and comprehensively discuss about the recent advances in the roles of circRNAs in cancer with an emphasis on their clinical values.

http://ift.tt/2ypgonQ

Calycosin inhibits the in vitro and in vivo growth of breast cancer cells through WDR7-7-GPR30 Signaling

Abstract

Background

Clinically, breast cancer is generally classified into estrogen receptor-positive (ER+) or estrogen receptor-negative (ER−) subtypes. The phytoestrogen calycosin has been shown to inhibit the proliferation of ER+ cells, which may be mediated by a feedback loop that involves miR-375, RAS dexamethasone-induced 1 (RASD1), and ERα. However, how calycosin acts on ER− breast cancer cells remains unclear.

Results

Here, we show that calycosin inhibited the proliferation of both ER− (MDA-MB-468 and SKBR3) and ER+ breast cancer cells (MCF-7 and T47D) and that these inhibitory effects were associated with the up-regulation of the long non-coding RNA (lncRNA) WDR7-7. For the first time, we demonstrate that the expression of WDR7-7 is reduced in breast cancer cell lines and that the overexpression of WDR7-7 inhibits growth through a mechanism that involves G-protein coupled estrogen receptor 30 (GPR30). Meanwhile, we show that calycosin stimulated the WDR7-7-GPR30 signaling pathway in MCF-7, T47D, MDA-MB-468, and SKBR3 breast cancer cells. In contrast, in MCF10A and GPR30-deficient MDA-MB-231 cells, due to a lack of WDR7-7-GPR30 for activation, calycosin failed to inhibit cell growth. Additionally, in all four GPR30-positive breast cancer lines, calycosin decreased the phosphorylation levels of SRC, EGFR, ERK1/2 and Akt, but the inhibition of WDR7-7 blocked these changes and increased proliferation. In mice bearing MCF-7 or SKBR3 xenografts, tumor growth was inhibited by calycosin, and changes in expression the levels of WDR7-7 and GPR30 in tumor tissues were similar to those in cultured MCF-7 and SKBR3 cells.

Conclusions

These results suggest the possibility that calycosin inhibited the proliferation of breast cancer cells, at least partially, through WDR7-7-GPR30 signaling, which may explain why calycosin can exert inhibitory effects on ER− breast cancer.

http://ift.tt/2lInSMT

Temporal and spatial dose distribution of radiation pneumonitis after concurrent radiochemotherapy in stage III non-small cell cancer patients

Abstract

Background and purpose

Radiation pneumonitis (RP) is the most common subacute side effect after concurrent chemoradiotherapy (CRT) for locally advanced non-small cell lung cancer. Several clinical and dose-volume (DV) parameters are associated with a distinct risk of symptomatic RP. The aim of this study was to assess the spatial dose distribution of the RP volume from first occurence to maximum volume expansion of RP.

Material and methods

Between 2007 and 2015, 732 patients with lung cancer were treated in an institution. Thirty-three patients met the following inclusion criteria: an RP grade II after CRT and a radiation dose ≥60 Gy and no prior medical history of cardiopulmonary comorbidities. The images of the first chest computed tomography (CT) confirming the diagnosis of RP and the CT images showing the maximum expansion of RP were merged with the treatment plan. The RP volume was delineated within the treatment plan, and a DV analysis was performed to evaluate the lung dose volume areas in which the RP manifested over time and whether dose volume changes within the RP volume occurred.

Results

A change from clinical diagnosis to maximum expansion of RP was observed as the RP at clinical appearance mainly manifested in the lower dose areas of the lung, whereas the RP volume at maximum expansion manifested in the higher dose areas, resulting in a significant shift of the assessed relative mean dose volume proportions within the RP volume. The mean relative dose volume proportion 0- ≤ 20 Gy decreased from 30.2% (range, 0–100) to 21.9% (range, 0–100; p = 0.04) at the expense of the dose volume > 40 Gy which increased from 39.2% (range, 0–100) to 49.8% (range, 0–100; p = 0.02), whereas the dose relative volume proportion > 20- ≤ 40 Gy showed no relevant change and slightly decreased from 30.6% (range, 0–85.7) to 28.3%, (range, 0–85.7; p = 0.34).

Conclusion

We observed a considerable increase in the relative dose proportions within the RP volume from diagnosis to maximum volume extent from low dose zones below 20 Gy to zones above 40 Gy. Although the clinical impact on RP remains unknown, a reduction of healthy healthy lung tissue receiving >40 Gy (V40) might be an additional parameter for irradiation planning in lung cancer patients.

http://ift.tt/2yp5E92

Corrigendum to “Effect of Taichi Softball on Function-Related Outcomes in Older Adults: A Randomized Control Trial”

http://ift.tt/2zdAikI

At Last: Gene Editing in Human Embryos to Understand Human Development

Our understanding of early human development is typically based on inference from animal models, which may not fully recapitulate human embryonic features. As proof of concept, Fogarty et al. (2017) used CRISPR/Cas9 to genetically ablate the OCT4 gene in human preimplantation embryos and found key differences from its function in model systems.

http://ift.tt/2z95Bv4

Neural Circuits Serve as Periscopes for NSCs

Neural stem cells (NSCs) within the hippocampal niche integrate local cues, such as activity of inhibitory interneurons, into their homeostatic fate choices. Now in Cell Stem Cell, Bao et al. (2017) describe how these local interneurons relay signals from distal brain regions to govern NSC quiescence and activation.

http://ift.tt/2iSYxyx

Hematopoietic Stem Cell Gene Therapy: Progress and Lessons Learned

Morgan et al. discuss the progress, successes, and remaining challenges toward the development of hematopoietic stem cell gene therapies and highlight lessons learned and how they can inform the development of future clinical stem cell therapies.

http://ift.tt/2z8vM57

Targeting Glioma Stem Cell-Derived Pericytes Disrupts the Blood-Tumor Barrier and Improves Chemotherapeutic Efficacy

The blood-brain barrier (BBB) blocks entry of harmful materials into normal brains, but the blood-tumor barrier (BTB) prevents anti-cancer drugs from penetrating GBM tumors. Targeting GSC-derived neoplastic pericytes selectively disrupted the BTB, but not BBB, and potently enhanced drug delivery to effectively improve GBM treatment.

http://ift.tt/2z8vGdL

Location, Location, Location: Spatio-Temporal Cues That Define the Cell of Origin in Melanoma

It is unclear whether melanoma initiates from mature melanocytes or stem cell precursors. In this issue of Cell Stem Cell, Moon et al. (2017) and Köhler et al. (2017) use in vivo lineage tracing to demonstrate that these two possibilities may occur downstream of the same pro-tumorigenic lesions, depending on environmental factors or the anatomical location.

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EMPhasis on Mutant Microglia: Dysregulation of Brain Sentinels Induces Neurodegeneration

Reactive microglia are often implicated in the pathology of neurodegenerative disease. In a recent study in Nature, Mass et al. (2017) demonstrate that targeted mutation of Braf in early erythro-myeloid precursors (EMPs) causes histiocytosis-associated late onset neurodegeneration driven by activated microglia.

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An endosiRNA-Based Repression Mechanism Counteracts Transposon Activation during Global DNA Demethylation in Embryonic Stem Cells

In this issue of Cell Stem Cell, Berrens et al. report the control of transposable elements by endosiRNAs during global DNA demethylation induced in mouse embryonic stem cells. The study uncovered an "immediate" repression of transposons accomplished by endosiRNAs followed by their "chronic/long-term" silencing by repressive histone modifications.

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Long-Range GABAergic Inputs Regulate Neural Stem Cell Quiescence and Control Adult Hippocampal Neurogenesis

Bao et al. demonstrate that long-range GABAergic projections from the medial septum control adult hippocampal neurogenesis through depolarizing GABA signaling onto local PV interneurons. Functionally, these long-range inputs are required for maintaining NSC quiescence and ablating them depletes the NSC pool and impairs neurogenesis.

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Incorporating 18 FDG-PET-defined pelvic active bone marrow in the automatic treatment planning process of anal cancer patients undergoing chemo-radiation

Abstract

Background

To investigate whether the incorporation of ¹⁸FDG-PET into the automatic treatment planning process may be able to decrease the dose to active bone marrow (BM) for locally advanced anal cancer patients undergoing concurrent chemo-radiation (CHT-RT).

Methods

Ten patients with locally advanced anal cancer were selected. Bone marrow within the pelvis was outlined as the whole outer contour of pelvic bones or employing ¹⁸FDG-PET to identify active BM within osseous structures. Four treatment planning solutions were employed with different automatic optimization approaches toward bone marrow. Plan A used iliac crests for optimization as per RTOG 05–29 trial; plan B accounted for all pelvic BM as outlined by the outer surface of external osseous structures; plan C took into account both active and inactive BM as defined using ¹⁸FDG-PET; plan D accounted only for the active BM subregions outlined with ¹⁸FDG-PET. Dose received by active bone marrow within the pelvic (^ACTPBM) and in different subregions such as lumbar-sacral (^ACTLSBM), iliac (^ACTIBM) and lower pelvis (^ACTLPBM) bone marrow was analyzed.

Results

A significant difference was found for ^ACTPBM in terms of D_mean (p = 0.014) V₂₀ (p = 0.015), V₂₅ (p = 0.030), V₃₀ (p = 0.020), V₃₅ (p = 0.010) between Plan A and other plans. With respect to specific subsites, a significant difference was found for ^ACTLSBM in terms of V₃₀ (p = 0.020)), V₃₅ (p = 0.010), V₄₀ (p = 0.050) between Plan A and other solutions. No significant difference was found with respect to the investigated parameters between Plan B,C and D. No significant dosimetric differences were found for ^ACTLSPBM and ^ACTIBM and inactive BM subregions within the pelvis between any plan solution.

Conclusions

Accounting for pelvic BM as a whole compared to iliac crests is able to decrease the dose to active bone marrow during the planning process of anal cancer patients treated with intensity-modulated radiotherapy. The same degree of reduction may be achieved optimizing on bone marrow either defined using the outer bone contour or through ¹⁸FDG-PET imaging. The subset of patients with a benefit in terms of dose reduction to active BM through the inclusion of ¹⁸FDG-PET in the planning process needs further investigation.

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YWHAE is a novel interaction partner of Helicobacter pylori CagA

Abstract

CagA, an important virulence factor of Helicobacter pylori, targets and interacts with a series of host proteins to activate signaling factors involved in many functions, such as development, cytoskeleton rearrangement, and inflammatory molecule release. Despite extensive efforts, the relationship between CagA and gastric cancer is far from completely understood. Here, the GAL4 yeast two-hybrid system was used to screen cellular proteins for binding to CagA, and five cellular proteins, including tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, epsilon (YWHAE), were identified. The CagA-YWHAE interaction was further verified not only in vitro by a glutathione S-transferase pull-down assay but also in vivo by immunolocalization and co-immunoprecipitation assays. In SGC7901 and AGS cells, overexpression of the YWHAE protein promoted the activation of NF-κB by CagA; conversely, knockdown of the YWHAE protein inhibited the activation of NF-κB by CagA. These results indicate that CagA enhances the YWHAE-mediated transactivation of NF-κB, providing a new clue to the molecular mechanisms of H. pylori-associated tumorigenesis mediated by CagA.

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Rac GTPase activating protein 1 promotes the oncogenic progression of epithelial ovarian cancer

Abstract

Rac GTPase activating protein 1 (RacGAP1) can regulate cytokinesis and cell differentiation. The oncogenic role of RacGAP1 has been partially studied in gastric cancer, colorectal cancer, and breast cancer. In this study, we endeavor to evaluate its expression and functions in epithelial ovarian cancer (EOC). We retrospectively collected the clinicopathological information of 117 patients who underwent curative surgery for EOC. The expression of RacGAP1 protein in primary tumor tissues was evaluated by immunohistochemistry, which was significantly associated with tumor pathological grade, tumor stage, and lymph node metastasis. Patients with lower RacGAP1 level had a longer survival time and lower recurrence risk. Multivariate results identified the independent prognostic role of RacGAP1 for both recurrence and survival in EOC patients. Cellular studies showed that RacGAP1 can positively regulate the activation of RhoA and Erk proteins. In addition, wound healing assay and Transwell assay found that RacGAP1 can up-regulate the migration and invasion process of EOC cells, respectively. In all, our results not only confirmed the prognostic role of RacGAP1 for recurrence and survival in EOC patients, but also highlighted its possible potency for drug development.

This article is protected by copyright. All rights reserved.

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Downregulation of CD24 suppresses bone metastasis of lung cancer

Summary

Suppression of bone metastasis can improve patient quality of life. Current drugs for bone metastasis have been shown to prolong progression-free survival but not overall survival; therefore, other potential therapeutic targets for bone metastasis should be investigated. Cell-surface antigens, such as CD24, have been recently shown to be involved in the metastasis of various cancers. However, whether CD24 plays a role in bone metastasis of lung cancer remains unknown. To observe metastasis of lung cancer cells by imaging technology, we introduced a near-infrared fluorescent protein, iRFP720, into a bone-seeking subclone established from lung cancer cells, HARA-B4 cells. The anchorage-independent growth of these cells was then evaluated by colony formation assays. We also compared cancer cell tropism to bone tissue with HARA-B4 cells in the presence or absence of CD24 by cell adhesion assays. To clarify the role of CD24 in bone metastasis, we intracardially injected CD24-knockdown HARA-B4 cells into mice and monitored metastasis via detection of iRFP720 using an in vivo imaging system. CD24-knockdown HARA-B4 cells in vitro showed reduced anchorage-independent growth and cancer cell tropism to bone. Bone metastasis was diminished in mice inoculated with CD24-knockdown HARA-B4 cells, which was rescued by add-back of CD24 in cells. Our findings indicate that iRFP720 is effective for in vivo imaging analysis of bone metastasis and that downregulation of CD24 suppresses bone metastasis of lung cancer cells. These findings collectively indicate that CD24 may be considered as a promising new therapeutic candidate for the prevention of bone metastasis of lung cancer.

This article is protected by copyright. All rights reserved.

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Clinical features of hematological disorders with increased large granular lymphocytes (LGLs): a retrospective study

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Optimal extent of completion lymphadenectomy for patients with melanoma and a positive sentinel node in the groin

Background

The optimal extent of groin completion lymph node dissection (CLND) (inguinal or ilioinguinal dissection) in patients with melanoma is controversial. The aim of this study was to evaluate whether the extent of groin CLND after a positive sentinel node biopsy (SNB) is associated with improved outcome.

Methods

Data from all sentinel node-positive patients who underwent groin CLND at four tertiary melanoma referral centres were retrieved retrospectively. Baseline patient and tumour characteristics were collected for descriptive statistics, survival analyses and Cox proportional hazards regression analyses.

Results

In total, 255 patients were included, of whom 137 (53·7 per cent) underwent inguinal dissection and 118 (46·3 per cent) ilioinguinal dissection. The overall CLND positivity rate was 18·8 per cent; the inguinal positivity rate was 15·5 per cent and the pelvic positivity rate was 9·3 per cent. The pattern of recurrence, and 5-year melanoma-specific survival, disease-free survival and distant-metastasis free survival rates were similar for both dissection types, even for patients with a positive CLND result. Cox regression analysis showed that type of CLND was not associated with disease-free or melanoma-specific survival.

Conclusion

There was no significant difference in recurrence pattern and survival rates between patients undergoing inguinal or ilioinguinal dissection after a positive SNB, even after stratification for a positive CLND result. An inguinal dissection is a safe first approach as CLND in patients with a positive SNB.

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Prevalence of HPV infection in hypopharyngeal and laryngeal squamous cell carcinoma at Thailand's largest tertiary referral center

Abstract

Background

Following the well-established relationship between human papillomavirus (HPV) and cervical carcinoma, the carcinogenicity of this virus has also been confirmed in subsets of head and neck carcinoma (HNCA), but mainly in the oropharynx. Other subsites of HNCA with less known association to HPV have never been studied in Thailand. Accordingly, the aim of this study was to investigate the prevalence of HPV DNA in hypopharyngeal and laryngeal squamous cell carcinoma in Thai population.

Methods

This cross-sectional study included hypopharyngeal and laryngeal squamous cell carcinoma patients diagnosed and treated at the Department of Otorhinolaryngology, Siriraj Hospital during the September 2011–December 2013 study period. Presence of HPV genome was confirmed by polymerase chain reaction from pathologically-confirmed fresh specimens. Demographic data and risk factors of HPV infection were evaluated.

Results

Eighty patients were included, and 95% of those were male. Only one patient was noted with positive HPV-62 serotype. Most patients consumed tobacco and/or alcohol. Five patients had no risk factors for cancer development. Risk of HPV infection was evaluated by self-reporting questionnaire. The mean age of sexual debut was 20.17 years. Forty-eight patients had multiple sexual partners. Sixteen and seven patients had history of sexually transmitted disease infection and habitual oral sex contact, respectively.

Conclusion

There was no oncogenic HPV DNA detected within pathologic specimens of laryngeal and hypopharyngeal cancers in this study. Compared to rates reported from developed countries, the prevalence of HPV-related HNCA in Thailand is very low.

http://ift.tt/2A8IHEa

Flexible Electrodes: Roll-to-Roll Production of Transparent Silver-Nanofiber-Network Electrodes for Flexible Electrochromic Smart Windows (Adv. Mater. 41/2017)

Flexible and transparent electrodes have attracted increasing attention as important applications for various fields. However, the mass production of large-area electrodes has always been a challenge. In article number 1703238, Ming Lei, Hui Wu, and co-workers develop a roll-to-roll process to assemble a flexible, extra-large and transparent Ag nanofiber (AgNF) network electrode for large-area electrochromic equipment.

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Conjugated Polymers: Exploring the Charge Transport in Conjugated Polymers (Adv. Mater. 41/2017)

Organic field-effect transistors are widely used to explore charge transport in conjugated polymers by measuring their current–voltage characteristics. In article number 1702729, Yong Xu, Yen-Fu Lin, Yong-Young Noh, and co-workers propose that planar polymer transistors are a more reliable platform to explore intrinsic charge transport than conventional polymer transistors, thanks to the lower extrinsic influences like Schottky barrier, access transport, and concurrent ambipolar conduction.

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Calcium Oxide: Multishelled CaO Microspheres Stabilized by Atomic Layer Deposition of Al2O3 for Enhanced CO2 Capture Performance (Adv. Mater. 41/2017)

Multishelled CaO microspheres coated with an atomic-layer-deposition-grown Al₂O₃ layer yield high-capacity CO₂ sorbents with improved cyclic stability, as demonstrated by Christoph R. Müller and co-workers in article number 1702896. The central void formed by the removal of the carbonaceous template accommodates the large volumetric changes of the material during cyclic operation, whereas the porous shells composed of Al₂O₃-coated CaO nanoparticles reduce diffusive transport limitations through the growing product layer of CaCO₃ and improve the thermal stability of the sorbent.

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Imaging the Molecular Motions of Autonomous Repair in a Self-Healing Polymer

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Selective Solar Absorbers: Scalable, “Dip-and-Dry” Fabrication of a Wide-Angle Plasmonic Selective Absorber for High-Efficiency Solar–Thermal Energy Conversion (Adv. Mater. 41/2017)

A simple, inexpensive, ecofriendly and scalable technique for fabricating highly efficient selective solar absorbers (SSAs) is reported by Nanfang Yu, Yuan Yang, and co-workers in article number 1702156. The technique yields SSAs with excellent wide-angle solar absorptance (≈96% at 0° and ≈79% at 70°), which is higher than, and low thermal emittance (<10%), which is on par with, those of existing designs.

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Contents: (Adv. Mater. 41/2017)

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Masthead: (Adv. Mater. 41/2017)

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Photoconductivity: Tailoring Semiconductor Lateral Multijunctions for Giant Photoconductivity Enhancement (Adv. Mater. 41/2017)

The successful synthesis of a two-dimensional monolayer lateral heterostructure with multijunctions WS₂/WS_2(1−x) Se_2x/WS₂ is presented in article number 1703680 by Keji Lai, Chih-Kang Shih, and co-workers. Using light-assisted microwave impedance microscopy, the multijunctions demonstrate functionality, which enhances local photoconductivity by two orders of magnitude over pure WS₂.

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Comparison of sentinel lymph node biopsy guided by indocyanine green, blue dye, and their combination in breast cancer patients: a prospective cohort study

Abstract

Background

Recent studies show that near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) has the potential to improve the performance of sentinel lymph node (SLN) mapping. The current cohort study was designed to assess the value of the combination of ICG and methylene blue (MB) dye in patients undergoing SLN biopsy.

Methods

A prospective self-controlled trial was designed to detect the difference in the detection efficacies of ICG, MB, and combined ICG and MB (ICG + MB) navigation methods. Between 2010 and 2013, 198 consecutive early breast cancer patients eligible for sentinel lymph node biopsy were enrolled and 200 biopsy procedures were performed by injection of both ICG and MB. SLNs were searched and removed under the guidance of fluorescence and/or blue dye. The mapping characteristics, the detection rate of SLNs and positive SLNs, and the number of SLNs of ICG, MB, and ICG + MB were compared. Injection safety of ICG and MB was evaluated.

Results

Fluorescence imaging of lymphatic flow, which is helpful to locate the incision site, could be seen in 184 of 200 procedures. The nodal detection rate of ICG, MB, and ICG + MB samples was 97, 89, and 99.5% (χ ² = 26.2, p < 0.001), respectively, with the combination method yielding a superior identification result. The addition of ICG to the MB method resulted in the identification of more lymph nodes (median 3 versus 2) and more positive axillas (22.7% involved axillas were discovered by fluorescence only) than either method alone. No acute or chronic allergic reaction was observed in this study. However, 23 patients (23/82) who received breast-conserving therapy reported temporary skin staining, and 5 patients had permanent tattooing. Palpable subcutaneous nodules at the injection sites were reported in nine patients. There were no reports of skin necrosis.

Conclusions

The lymphatic navigation by ICG fluorescence detects SLNs at a high detection rate and improves the mapping performance when added to the MB method. The novel ICG + MB dual tracing modality, without involvement of radioactive isotopes, exhibits great potential as an alternative to traditional standard mapping methods.

Trial registration

ACTRN12612000109808. Retrospectively registered on 23 January 2012.

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A Case of Ignatzschineria indica Bacteremia following Maggot Colonization

Ignatzschineria indica is a Gram-negative bacterium that is commonly associated with the larvae of flesh flies. I. indica is difficult to isolate in routine laboratory procedures but has been associated with neglected wounds infested with maggots, fever, elevated white blood count and C-reactive protein, and polymicrobial culture results. Other specific hematological/immunological changes are not known. We present a case of I. indica bacteremia and polymicrobial osteomyelitis resulting from infected decubitus ulcers. The patient improved after treatment with cefepime followed by levofloxacin.

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Biallelic mutations in FLNB cause a skeletal dysplasia with 46,XY gonadal dysgenesis by activating β-catenin

Filamin B (FLNB) functions as a switch that can affect chrondrocyte development and endochondral bone formation through a series of signaling molecules and transcription factors that also affect Sertoli cell development. Here, we report a subject with a novel skeletal dysplasia and co-existing 46,XY gonadal dysgenesis and biallelic mutations in FLNB.

Whole exome sequencing was performed to identify mutations. Quantitative qPCR and flow variant assays were performed to quantify RNA, proteins and phosphorylated proteins. The TOPFLASH reporter was performed to quantify β-catenin activity.

Mutations were identified in the FLNB gene (FLNB:p.F964L, FLNB:p.A1577V). These mutations increased binding of FLNB protein to the MAP3K1 and RAC1 signal transduction complex and activated β-catenin and had different effects on phosphorylation of MAP kinase pathway intermediates and SOX9 expression.

Direct activation of β-catenin through the FLNB-MAP3K1-RAC1 complex by FLNB mutations is a novel mechanism for causing 46,XY gonadal dysgenesis. The mechanism of action varies from those reported previously for loss-of-function mutations in SOX9 and gain-of-function mutations in MAP3K1.

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Usefulness of Endoscopic Managements in Patients with Ceftriaxone-Induced Pseudolithiasis Causing Biliary Obstruction

Ceftriaxone (CTRX) is known to cause reversible biliary stones/sludge, which is called biliary pseudolithiasis. We report two rare cases of biliary obstruction by pseudolithiasis shortly after completing CTRX treatment. Stones and sludge, which had not been detected before CTRX administration, appeared in the gallbladder and common bile duct and led to biliary obstruction and acute cholangitis. The obstructions were successfully treated with endoscopic retrograde biliary drainage and endoscopic sphincterotomy. CTRX-induced biliary pseudolithiasis has been reported mainly in children and adolescents but is also seen in adults with similar incidence rate. Although CTRX-induced biliary pseudolithiasis is usually asymptomatic and disappears spontaneously after discontinuing the drug, some patients develop biliary obstruction. Endoscopic managements should be considered in such cases.

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Medicinal Plants from North and Central America and the Caribbean Considered Toxic for Humans: The Other Side of the Coin

The consumption of medicinal plants has notably increased over the past two decades. People consider herbal products as safe because of their natural origin, without taking into consideration whether these plants contain a toxic principle. This represents a serious health problem. A bibliographic search was carried out using published scientific material on native plants from Mexico, Central America, and the Caribbean, which describe the ethnobotanical and toxicological information of medicinal plants empirically considered to be toxic. A total of 216 medicinal plants belonging to 77 families have been reported as toxic. Of these plants, 76 had been studied, and 140 plants lacked studies regarding their toxicological effects. The toxicity of 16 plants species has been reported in clinical cases, particularly in children. From these plants, deaths have been reported with the consumption of Chenopodium ambrosioides, Argemone mexicana, and Thevetia peruviana. In most of the cases, the principle of the plant responsible for the toxicity is unknown. There is limited information about the toxicity of medicinal plants used in Mexico, Central America, and the Caribbean. More toxicological studies are necessary to contribute information about the safe use of the medicinal plants cited in this review.

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Antcin-H Isolated from Antrodia cinnamomea Inhibits Renal Cancer Cell Invasion Partly through Inactivation of FAK-ERK-C/EBP-β/c-Fos-MMP-7 Pathways

Antcin-H, a natural triterpene, is purified from a famous anticancer medicinal mushroom, Antrodia cinnamomea, in Taiwan. This study showed that antcin-H inhibited the growth of human renal carcinoma 786-0 cells; the IC50 value (for 48 h) was 170 M. Besides, the migration and invasion of 786-0 cells were suppressed by antcin-H under noncytotoxic concentrations (

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Shenfu Injection Adjunct with Platinum-Based Chemotherapy for the Treatment of Advanced Non-Small-Cell Lung Cancer: A Meta-Analysis and Systematic Review

Platinum-based chemotherapy is one of the standard treatments for non-small-cell lung cancer (NSCLC), while its high toxicity and limited clinical effects raise big concerns. Shenfu injection (SFI) has been commonly used as an adjutant chemotherapy drug for NSCLC in China. We ascertained the beneficial and adverse effects of SFI in combination with platinum-based chemotherapy for advanced NSCLC by using meta-analysis methods. The randomized controlled trials (RCTs) involving advanced NSCLC treatment with SFI plus platinum-based chemotherapy versus chemotherapy alone were searched on 6 medical databases up to February 2017. Cochrane handbook 5.1.0 was applied to assess the quality of included trials and RevMan 5.3 software was employed for data analysis. 23 RCTs including 1574 patients met our inclusion criteria. We evaluated the following outcome measures: objective tumor response (ORR), disease control rate (DCR), Karnofsky performance score (KPS), adverse effects, and indicators of cellular immune function. The meta-analysis indicated that SFI plus platinum-based chemotherapy may benefit the patients with NSCLC on attenuated synergies of chemotherapy. These findings need to be confirmed by further rigorously designed high-quality and large-scale RCTs.

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Prognostic Prediction of Oral Squamous Cell Carcinoma by E-Cadherin and N-Cadherin Expression in Overall Cells in Tumor Nests or Tumor Cells at the Invasive Front

Abstract

Epithelial-mesenchymal transition (EMT) is a significant process in the invasion and metastasis of cancers including oral squamous cell carcinoma (OSCC), and the cadherin switch has been identified as one of the hallmarks of EMT. The aim of the present study was to evaluate the significance of the cadherin switch in the prognosis of OSCC and generate a model for prognostic predictions. Seventy-six biopsy and/or initial surgical specimens from OSCC patients were immunohistochemically analyzed for the expression of E-cadherin and N-cadherin in either overall OSCC cells in tumor nests or in OSCC cells at the invasive front. Among 76 OSCC cases, overall OSCC cells in tumor nests were negative for the expression of E-cadherin in 10 cases and positive for that of N-cadherin in 53 cases. Among 10 cases negative for the expression of E-cadherin, 4 cases were positive for that of N-cadherin. In OSCC cells at the invasive front, the expression of E-cadherin was negative in 62 cases, while that of N-cadherin was positive in 39 cases. Among 62 cases negative for the expression of E-cadherin, 33 cases were positive for that of N-cadherin. A logistic regression analysis showed that a model using the evaluation of N-cadherin expression in overall OSCC cells in tumor nests with a cut-off point of 70 years old was the best fit model. These results suggest that N-cadherin has significant value in prognostic predictions for OSCC patients.

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The Relationship between Physical Activity and Screen Time with the Risk of Hypertension in Children and Adolescents with Intellectual Disability

Introduction. Children and adolescents with intellectual disability (ID) have significantly lower levels of physical activity compared to their peers without ID. Association between the level of physical activity and screen time with hypertension (HPT) in children and adolescents with ID has not been reported yet. Aim. To assess the relationship between the level of physical activity and screen time with the prevalence of HPT in students with ID. Material and Methods. The study group consisted of 568 children with ID aged 7 to 18. The control group matched for age and gender consisted of 568 students without ID. Blood pressure (BP), body mass and height, level of physical activity, and screen time were assessed. Results. The level of physical activity in the study group was significantly lower than in the control group (score 1.99 versus 3.02, resp., in Physical Activity Questionnaire). The risk of HPT in the students with ID with low levels of physical activity was more than 4 times higher (OR = 4.40) and more than 2 times higher when screen time was ≥2 h/day. Conclusion. Low level of physical activity and long screen time were associated with significantly higher HPT risk among children and adolescents with ID.

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Legume Consumption and All-Cause and Cardiovascular Disease Mortality

Background. Legume consumption is suggested to have protective effects against cardiovascular disease (CVD) mortality in the general population, but the results have been equivocal. We conducted a meta-analysis of prospective cohort studies to assess the association between legume consumption and risk of CVD mortality and all-cause mortality. Methods and Results. Medline (via Ovid) and EMBASE (via Ovid) databases were searched through April 2017 to identify eligible studies. The two authors independently extracted the data and the adjusted relative risks (RRs) and 95% confidence intervals (CIs) were pooled by using a random-effects model. A total of 6 studies were identified, including the sizes of participants ranging from 23,601 to 59,485 with a sum of 21,8997. Comparing the highest category with the lowest, the pooled RR (95% CI) was 0.96 (0.86–1.06) for CVD mortality and 0.93 (0.87–0.99) for all-cause mortality. Conclusions. Results from the current study show that high legume intakes are associated with lower risk of all-cause mortality. In consideration of the small number of studies, the evidence for assessing relationship between legumes intake and risk of all-cause mortality remains inclusive and warrants further study in the future. Further, consuming legumes does not increase the risk of CVD mortality.

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A review on irisin, a new protagonist that mediates muscle–adipose–bone–neuron connectivity

Physical activity improves the quality of life and decreases the risk of several diseases (i.e. stroke, hypertension, myocardial infarction, obesity, and malignancies). Skeletal muscles are considered as an endocrine organ that produces myokines characterized by a paracrine or endocrine activity. Irisin is a circulating hormone-like myokine and is secreted as a product of fibronectin type III domain-containing protein 5 from skeletal muscle in response to exercise. This molecule regulates the energy metabolism and acts in adipose tissue, bones, and nervous system. As both animal and clinical studies confirmed the action of irisin in muscle and adipocytes, this protein is considered as adipomyokine. In adipose tissue, irisin stimulates the process of browning of beige precursor fat cells, which are present in white fat cells, and promotes energy expenditure. It affects bone metabolism by increasing osteoblast differentiation and reducing osteoclast maturation. In the nervous system, irisin influences hippocampal neurogenesis and neural differentiation of embryonic stem cells in mice and is considered as a messenger between exercise and brain function. However, the existence of this protein and its role in humans is a matter of debate. This study presents irisin as a new champion of the molecule, which could be considered as the messenger in the muscle-fat-bone-brain axis.

L'articolo A review on irisin, a new protagonist that mediates muscle–adipose–bone–neuron connectivity sembra essere il primo su European Review.

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Editorial – Non AIDS-defining malignancies: a new epidemic in HIV-infected population for the upcoming decades?

L'articolo Editorial – Non AIDS-defining malignancies: a new epidemic in HIV-infected population for the upcoming decades? sembra essere il primo su European Review.

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The role of prasugrel in the management of acute coronary syndromes: a systematic review

OBJECTIVE: Dual antiplatelet therapy (DAPT) is the treatment of choice in the medical management of patients with acute coronary syndrome (ACS). The combination of aspirin and a P2Y12 inhibitor in patients who receive a coronary stent reduces the rate of stent thrombosis and the rates of major adverse cardiovascular events. However, patients with acute coronary syndrome remain at risk of recurrent cardiovascular events despite the advance of medical therapy. The limitations of clopidogrel with variable antiplatelet effects and delayed onset of action are well established and lead to the development of newer P2Y12 inhibitors. Prasugrel is a selective adenosine diphosphate (ADP) receptor antagonist indicated for use in patients with ACS. Prasugrel provides greater inhibition of platelet aggregation than clopidogrel and has a rapid onset of action. We have conducted a systematic review to retrieve current evidence regarding the role of prasugrel in the management of ACS. Evidence comparing prasugrel, clopidogrel, and ticagrelor remain scant.

MATERIALS AND METHODS: A complete literature survey was performed using PubMed database search to gather available information regarding management of acute coronary syndromes and prasugrel. An explorative comparison of the safety and efficacy of prasugrel, clopidogrel, and ticagrelor was also conducted.

RESULTS: Prasugrel and ticagrelor are more efficacious than clopidogrel in reducing the occurrence of non-fatal myocardial infarction, stroke, or cardiovascular (CV) death but they have also an increased risk of major bleeding in comparison to clopidogrel.

CONCLUSIONS: Prasugrel and ticagrelor are today the recommended first-line agents in patients with ACS. The estimation of which drug is superior over the other cannot be reliably established from the current trials.

L'articolo The role of prasugrel in the management of acute coronary syndromes: a systematic review sembra essere il primo su European Review.

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Effectiveness of a novel boswellic acids delivery form (Casperome®) in the management of grade II ankle sprains due to sport trauma – a registry study

OBJECTIVE: In this study, we evaluated a novel delivery form of boswellic acids (Casperome®) in the management of signs and symptoms associated with ankle sprain grade II due to sport trauma.

PATIENTS AND METHODS: In this supplement registry study, 72 otherwise healthy subjects with grade II ankle sprain induced by sport activities were advised to either follow a standard management (SM, 37 subjects) for the condition or the SM with the additional daily intake of 1 tablet containing 250 mg Casperome® (35 subjects). Subjects were allowed to use rescue medications (ketoprofen tablets, 25 mg/tablet), and their intake was measured at the end of the management period of 7 days. Each individual was subjected to several non-invasive examinations (self-reported pain at rest and under moderate exercise, range of active and passive movement, presence of local hematomas by ultrasonography) at the following time periods: at inclusion, to evaluate the basal conditions of the subject before the beginning of the study, at day 3 and at the end of the week to evaluate the response differences between the two groups. Additionally, a blood sample from the Casperome® treated subjects (34 out of 35 subjects) was taken at day 7 and analyzed for the systemic concentration of boswellic acids.

RESULTS: The 72 individuals recruited in this study spontaneously decided which management to follow, either SM (n=37) or SM+Casperome® (n=35). Supplementation with Casperome® 250 mg/day showed beneficial effects in the reduction of signs and symptoms of ankle sprains evaluated at day 3 and day 7, and was shown to induce measurable plasma level of boswellic acids. Moreover, the supplementary use of Casperome® was well-tolerated and devoid of side effects.

CONCLUSIONS: Our pilot registry study showed the effectiveness of Casperome® supplementation in improving recovery after ankle sprain of mild severity (grade II), suggesting a potentially beneficial role in relieving the trauma associated with sport activities and in decreasing the use of rescue drugs.

L'articolo Effectiveness of a novel boswellic acids delivery form (Casperome®) in the management of grade II ankle sprains due to sport trauma – a registry study sembra essere il primo su European Review.

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