Integrin-Mediated Interactions Control Macrophage Polarization in 3D Hydrogels

Adverse immune reactions prevent clinical translation of numerous implantable devices and materials. Although inflammation is an essential part of tissue regeneration, chronic inflammation ultimately leads to implant failure. In particular, macrophage polarity steers the microenvironment toward inflammation or wound healing via the induction of M1 and M2 macrophages, respectively. Here, this paper demonstrates that macrophage polarity within biomaterials can be controlled through integrin-mediated interactions between human monocytic THP-1 cells and collagen-derived matrix. Surface marker, gene expression, biochemical, and cytokine profiling consistently indicate that THP-1 cells within a biomaterial lacking cell attachment motifs yield proinflammatory M1 macrophages, whereas biomaterials with attachment sites in the presence of interleukin-4 (IL-4) induce an anti-inflammatory M2-like phenotype and propagate the effect of IL-4 in induction of M2-like macrophages. Importantly, integrin α2β1 plays a pivotal role as its inhibition blocks the induction of M2 macrophages. The influence of the microenvironment of the biomaterial over macrophage polarity is further confirmed by its ability to modulate the effect of IL-4 and lipopolysaccharide, which are potent inducers of M2 or M1 phenotypes, respectively. Thus, this study represents a novel, versatile, and effective strategy to steer macrophage polarity through integrin-mediated 3D microenvironment for biomaterial-based programming.

Macrophage polarity steers the microenvironment toward inflammation or wound healing via the induction of M1 and M2 macrophages, respectively. However, active control over macrophage polarity has remained elusive. This study reveals that biomaterial-based integrin attachment can steer human monocytic cells differentiation into a specific macrophage lineage and thus has broad clinical implications.

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An Accessible Organotypic Microvessel Model Using iPSC-Derived Endothelium

While organotypic approaches promise increased relevance through the inclusion of increased complexity (e.g., 3D extracellular microenvironment, structure/function relationships, presence of multiple cell types), cell source is often overlooked. Induced pluripotent stem cell (iPSC)-derived cells are potentially more physiologically relevant than cell lines, while also being less variable than primary cells, and recent advances have made them commercially available at costs similar to cell lines. Here, the use of induced pluripotent stem cell-derived endothelium for the generation of a functional microvessel model is demonstrated. High precision structural and microenvironmental control afforded by the design approach synergizes with the advantages of iPSC to produce microvessels for modeling endothelial biology in vitro. iPSC microvessels show endothelial characteristics, exhibit barrier function, secrete angiogenic and inflammatory mediators, and respond to changes in the extracellular microenvironment by altering vessel phenotype. Importantly, when deployed in the investigation of neutrophils during innate immune recruitment, the presence of the iPSC endothelial vessel facilitates neutrophil extravasation and migration toward a chemotactic source. Relevant cell sources, such as iPSC, combine with organotypic models to open the way for improved and increasingly accessible in vitro tissue, disease, and patient-specific models.

Improved cell sources, such as induced pluripotent stem cells (iPSCs), are critical complements to the increased relevance organotypic in vitro models provide. Coupling a robust 3D lumen microfabrication approach with iPSC-derived endothelium, a functional in vitro endothelial vessel is presented that provides structure, regulates barrier function, secretes cytokines, and is capable of supporting innate immune modeling.

http://ift.tt/2hBsn9Z

Emerging Diagnostic and Therapeutic Strategies for Tauopathies

Abstract

Purpose of Review

Tauopathies represent a spectrum of incurable and progressive age-associated neurodegenerative diseases that currently are diagnosed definitively only at autopsy. Few clinical diagnoses, such as classic Richardson's syndrome of progressive supranuclear palsy, are specific for underlying tauopathy and no clinical syndrome is fully sensitive to reliably identify all forms of clinically manifest tauopathy. Thus, a major unmet need for the development and implementation of tau-targeted therapies is precise antemortem diagnosis. This article reviews new and emerging diagnostic therapies for tauopathies including novel imaging techniques and biomarkers and also reviews recent tau therapeutics.

Recent Findings

Building evidence from animal and cell models suggests that prion-like misfolding and propagation of pathogenic tau proteins between brain cells are central to the neurodegenerative process. These rapidly growing developments build rationale and motivation for the development of therapeutics targeting this mechanism through altering phosphorylation and other post-translational modifications of the tau protein, blocking aggregation and spread using small molecular compounds or immunotherapy and reducing or silencing expression of the MAPT tau gene.

Summary

New clinical criteria, CSF, MRI, and PET biomarkers will aid in identifying tauopathies earlier and more accurately which will aid in selection for new clinical trials which focus on a variety of agents including immunotherapy and gene silencing.

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Cancer survivorship and opioid prescribing rates: A population-based matched cohort study among individuals with and without a history of cancer

BACKGROUND

Little is known about opioid prescribing among individuals who have survived cancer. Our aim is to examine a predominantly socio-economically disadvantaged population for differences in opioid prescribing rates among cancer survivors compared with matched controls without a prior diagnosis of cancer.

METHODS

This was a retrospective population-wide matched cohort study. Starting in 2010, individuals residing in Ontario, Canada, who were 18 to 64 years of age and at least 5 years past their cancer diagnosis were matched to controls without a prior cancer diagnosis based on sex and calendar year of birth. Follow-up was terminated at any indication of cancer recurrence, second malignancy, or new cancer diagnosis. To examine the association between survivorship and the rate of opioid prescriptions, an Andersen-Gill recurrent event regression model was implemented, adjusting for numerous individual-level characteristics and also accounting for the matched design.

RESULTS

The rate of opioid prescribing was 1.22 times higher among survivors than among their corresponding matched controls (adjusted relative rate, 1.22; 95% CI, 1.11-1.34). Individuals from lower income quintiles who were younger, were from rural neighborhoods, and had more comorbidities had significantly higher prescribing rates. Sex was not associated with prescribing rates. This increased rate of opioid prescribing was also seen among survivors who were 10 or more years past their cancer diagnosis (compared with their controls).

CONCLUSION

This study demonstrates substantially higher opioid prescribing rates among cancer survivors, even long after attaining survivorship. This raises concerns about the diagnosis and management of chronic pain problems among survivors stemming from their cancer diagnosis or treatment. Cancer 2017. © 2017 American Cancer Society.

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Interactions between cannabidiol and commonly used antiepileptic drugs

Summary

Objective

To identify potential pharmacokinetic interactions between the pharmaceutical formulation of cannabidiol (CBD; Epidiolex) and the commonly used antiepileptic drugs (AEDs) through an open-label safety study. Serum levels were monitored to identify interactions between CBD and AEDs.

Methods

In 39 adults and 42 children, CBD dose was started at 5 mg/kg/day and increased every 2 weeks by 5 mg/kg/day up to a maximum of 50 mg/kg/day. Serum AED levels were obtained at baseline prior to CBD initiation and at most study visits. AED doses were adjusted if it was determined that a clinical symptom or laboratory result was related to a potential interaction. The Mixed Procedure was used to determine if there was a significant change in the serum level of each of the 19 AEDs with increasing CBD dose. AEDs with interactions seen in initial analysis were plotted for mean change in serum level over time. Subanalyses were performed to determine if the frequency of sedation in participants was related to the mean serum N-desmethylclobazam level, and if aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were different in participants taking concomitant valproate.

Results

Increases in topiramate, rufinamide, and N-desmethylclobazam and decrease in clobazam (all p < 0.01) serum levels were seen with increasing CBD dose. Increases in serum levels of zonisamide (p = 0.02) and eslicarbazepine (p = 0.04) with increasing CBD dose were seen in adults. Except for clobazam and desmethylclobazam, all noted mean level changes were within the accepted therapeutic range. Sedation was more frequent with higher N-desmethylclobazam levels in adults (p = 0.02), and AST/ALT levels were significantly higher in participants taking concomitant valproate (p < 0.01).

Significance

Significantly changed serum levels of clobazam, rufinamide, topiramate, zonisamide, and eslicarbazepine were seen. Abnormal liver function test results were noted in participants taking concomitant valproate. This study emphasizes the importance of monitoring serum AED levels and LFTs during treatment with CBD.

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Check your microbiota when taking the drug

Abstract

In this edition of Hepatology, Yip's article entitled "The Liver-Gut Microbiota Axis Modulates Hepatotoxicity of Tacrine in the Rat" [1] elegantly uncovers the impact of the intestinal microbiota in the inter-individual variation of tacrine-induced hepatotoxicity. This article is protected by copyright. All rights reserved.

http://ift.tt/2vwc43W

Metformin enhances doxorubicin sensitivity via inhibition of doxorubicin efflux in P-gp-overexpressing MCF-7 cells

Abstract

Resistance against chemotherapy is still a major problem in successful cancer treatment in the clinic. Therefore, identifying new compounds with lower side effects and higher efficacy is an important approach to overcome multidrug resistance (MDR). Here, we investigated the activity and possible mechanism of the antidiabetic drug, metformin, in human doxorubicin (DOX) resistant breast cancer (MCF-7/DOX) cells. The effect of metformin on the cytotoxicity of DOX was evaluated by MTT assay. The P-gp mRNA/protein expression levels following treatment with metformin was determined using real time polymerase chain reaction (RT-PCR) and western blot analysis, respectively. Intracellular rhodamine 123 accumulation assay was performed to evaluate the P-gp function. Cellular ATP content was determined using ATP assay kit. The effect of metformin on DOX-induced apoptosis was evaluated by annexin V/FITC assay. Exposure to metformin considerably enhanced the cytotoxicity of DOX. Metformin had no substantial effect on P-gp expression, while, the activity of P-gp and intracellular ATP content decreased with metformin treatment in a dose-dependent manner. Furthermore, metformin significantly increased the DOX-induced apoptosis. These results indicate that metformin could reverse MDR in breast cancer cells by reducing P-gp activity. Therefore, metformin can be suggested as a potent adjuvant in breast cancer chemotherapy.

This article is protected by copyright. All rights reserved.

The activity and possible anticancer mechanism of antidiabetic drug, metformin, in doxorubicin resistant MCF-7 (MCF-7/DOX) cells was investigated. Metformin sensitized MCF-7/DOX cells and increased apoptosis via inhibition of P-gp activity and ATP depletion, with no substantial effect on P-gp expression.

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Co-occurrence of Sturge–Weber syndrome and Klippel–Trenaunay–Weber syndrome phenotype: Consideration of the historical aspect

http://ift.tt/2vEc4P9

A survey of epilepsy knowledge, attitudes and practice in school-aged children in Bangkok, Thailand

Objectives

To estimate the level of knowledge about epilepsy, attitude towards PWE and practice in school-aged children in Bangkok, Thailand. Significant findings from this study will be employed to develop a relevant and effective tool to educate children.

Materials and Methods

This cross-sectional survey study was conducted in Bangkok, Thailand, from August 2014 to December 2015. Study population included school-aged children between 9 and 14 years (4th to 8th grade). A structured age-appropriate, Thai culture-adjusted and simple 20-item questionnaire was used for this survey. The questionnaire comprised three domains which were eight items for knowledge (K), seven items for attitudes (A), and five items for practice (P). Descriptive and analytic statistics including Pearson's correlation were used to find correlation among KAP domains and age with KAP scores.

Results

A total of 1040 students from 13 schools participated in our survey study. Mean age was 11.27 (SD 0.94). Some basic knowledge about epilepsy and practice of inserting objects into mouth of seizing persons account for a high magnitude of misunderstanding. Girls and older-aged children are associated with better positive attitudes towards epilepsy. It seems that educating children with knowledge of both epilepsy and first aid is necessary to improve positive attitudes among this age group.

Conclusions

Given the findings, our study suggests that a lack of knowledge in some aspects of KAP in children exists. Educational materials should contain basic knowledge about the simple pathogenesis of seizure, seizure types and seizure characteristics, and provide explanation as to why inserting objects into mouths of seizing persons is not recommended.

http://ift.tt/2wyyPRo

Don't Bet Against the Elderly

This is a challenging and not uncommon scenario. Although the patient (1) is older, according to the US Social Security Life Tables, he has a median life expectancy of >4 years (and given good health, this could be longer).

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The Red Journal's Outstanding Reviewer Awards for 2016

Peer review has been under intense scrutiny in recent years, its merits heatedly debated, its shortcomings perhaps unfairly magnified. Various alternatives have been bandied about and evaluated (1) and its demise continuously predicted—disruptive technologies to upend it and better systems to replace it.

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In Reply to Belderbos et al

To the Editor: We thank Belderbos et al for the astute comments regarding our recent article (1, 2). As we reiterated throughout the report, we concur that the results of our study should be considered hypothesis generating. We wholeheartedly agree that hippocampal avoidance should be used only in the context of clinical trials until we have more definitive data to support its safety and efficacy. In fact, the importance of the randomized studies and our desire to support these ongoing cooperative group efforts was our impetus to close our single-institution study and report the results for the patients enrolled to date.

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A Multi-institutional Prospective Observational Study of Stereotactic Radiosurgery for Patients With Multiple Brain Metastases (JLGK0901 Study Update): Irradiation-related Complications and Long-term Maintenance of Mini-Mental State Examination Scores

The JLGK0901 study showed the noninferiority of stereotactic radiosurgery (SRS) alone as initial treatment of 5 to 10 brain metastases (BMs) compared with 2 to 4 BMs in terms of overall survival and most secondary endpoints (Lancet Oncol 2014;15:387-95). However, observation periods were not long enough to allow confirmation of the long-term safety of SRS alone in patients with 5 to 10 BMs.

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In Regard to Redmond et al

To the Editor: With interest we read the article by Redmond et al (1) reporting on a prospective study of hippocampal-sparing prophylactic cranial irradiation (HS-PCI) in limited stage small cell lung cancer (SCLC). Within this trial, 20 patients with limited-stage SCLC showing a complete response to chemoradiation therapy and no brain metastases received HS-PCI up to 25 Gy in 10 fractions. At baseline and at 6 and 12 months, magnetic resonance imaging and a battery of neuropsychological tests were performed.

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In Reply to Morris and Tyldesley

To the Editor: We thank Drs Morris and Tyldesley for pointing out our error in reporting the results of the ASCENDE-RT trial (1, 2). When reading the abstract (3) we were mistaken in reading the "Results" section. Specifically, the results reporting begins with reference to biochemical failure scored via the Phoenix definition (4) and then proceeds to report specific percentages using a 0.2-ng/mL threshold definition. We made an error in assuming that the entire reporting of biochemical results was according to the definition mentioned in the initial sentences.

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The “Dirty Harry” Approach

Clinical decisions around this case (1) hinge on the intent of treatment. The reluctance to operate implies significant comorbidity or frailty, calling into question this individual's tolerance of radical therapy, and the inability to achieve a complete transurethral resection of bladder tumor predicts suboptimal outcomes with curative approaches (2). The prior pelvic radiation therapy raises the spectre of significant cumulative radiation toxicity. With these factors in mind, a therapeutic plan should heed Dirty Harry's advice: "A man's got to know his limitations."

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Less Is More

First I do not think this case (1) really represents a folie à trois (a shared delusional belief of three) but does have at least 3 "issues" that are problematic—which are that none of the 3 cancer specialists (in urology, radiation oncology, and medical oncology) judge that their therapies, alone or together, when administered in a potentially curative schema, can be safely given to this patient. Yes, I would advise palliative external beam radiation given with a likely well-tolerated technique and dose to significantly delay symptoms from his cancer.

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Erratum to Ringash J, Fisher R, Peters L, et al. Effect of p16 status on the quality-of-life experience during chemoradiation for locally advanced oropharyngeal cancer: a substudy of randomized trial trans-Tasman radiation oncology group (TROG) 02.02 (HeadSTART). Int J Radiat Oncol Biol Phys 2017;97:678-686.

The author list of this article should read Jolie Ringash, MD∗, Richard Fisher, PhD†, Lester Peters, MD†, Andy Trotti, MD‡, Brian O'Sullivan, MD∗, June Corry, MD†, Lizbeth Kenny, MD§, Sandra Nuyts, MD, PhD‖, Chris Wratten, MD¶, and Danny Rischin, MD†

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Meetings

September 11-13, 2017

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Issue Highlights

Daly and Palma

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In Regard to Ciezki et al

To the Editor: We read with interest a recent report from the Cleveland Clinic (1) detailing 5- and 10-year oncologic endpoints for National Comprehensive Cancer Network high-risk prostate cancer (HRCaP) based on a large consecutive cohort treated at that facility. Although the article has much to recommend it, we were disappointed to find a factually incorrect and potentially misleading comment in the Discussion (page 969, paragraph 2); we quote:Comparisons between the ASCENDE-RT trial and this series for bRFS are challenging because only two-thirds of the patients in ASCENDE-RT had HRCaP, whereas the remaining one third had intermediate-risk disease.

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The Folie à Trois

A 90-year-old man (World Health Organization performance status 1) presents with a T3N0M0 muscle-invasive bladder cancer on the right anterolateral bladder wall (Fig. 1). The diagnosis was obtained with needle biopsy rather than transurethral resection of the bladder, and gross disease was left behind. The surgeon is reluctant to take to theater, even for a repeat transurethral resection of the bladder. The patient had previously had prostate external beam radiation therapy to 72 Gy in 2001 with a 4-field block, based on a cystourethrogram and barium in rectum.

http://ift.tt/2vcC5mc

Prophylactic Cranial Irradiation for Small Cell Lung Cancer: New Insights

In this edition of Oncology Scan, we review recent literature that raises new questions on the topic of prophylactic cranial irradiation (PCI) for small cell lung cancer. Prophylactic cranial irradiation has been considered a standard component of treatment for both limited-stage (LS) and extensive-stage (ES) small cell lung cancer (SCLC) on the basis of high-level evidence demonstrating survival benefits. In 1999, a large meta-analysis pooled individual patient data from 987 LS-SCLC patients in complete remission treated on 7 trials conducted between 1977 and 1994 with a randomization between PCI and observation (1).

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A Rare Case of Cutaneous Plasmacytosis in a Korean Male

Cutaneous and systemic plasmacytosis are reactive disease processes that occur in middle-aged Japanese and Chinese men. Systemic plasmacytosis, defined by plasmacytic infiltration of two organ systems, might rarely progress to lymphoma. Cutaneous plasmacytosis, however, is chronic and benign and is characterized by the development of multiple plasma cell-rich infiltrates in the skin. We present a case of cutaneous plasmacytosis in a 46-year-old Korean male. The patient demonstrated classic features of the disease entity, including disseminated red-brown plaques, differentiated plasmacytoid infiltrates on biopsy, hypergammaglobulinemia, and the absence of systemic disease.

http://ift.tt/2vclLSi

Professors’ Behaviors and Attributes that Promote U.S. Women’s Success in Male-Dominated Academic Majors: Results from a Mixed Methods Study

Abstract

High rates of attrition of women from male-dominated academic majors may stem from both individual-level personal attributes (e.g., lower confidence in skills; Sax et al. 2015) and non-supportive environmental factors (e.g., chilly climate; Blickenstaff 2005; Hill et al. 2010). Grounded in social cognitive career theory (Lent et al. 1994), the present study utilized a mixed methods approach to identify faculty behaviors and attributes that support women in male-dominated majors and help to prevent attrition. In Study 1, data from eight focus groups involving 23 senior women in male-dominated majors at a mid-sized U.S. Midwestern university were coded to identify common themes exploring why certain professors' behaviors/attributes are useful to women in male-dominated majors. Results indicated that professors' behaviors led to learning experiences that helped women create personal connections within departments and provided them with department or career-related information as well as opportunities to gauge/demonstrate their skills to combat the idea that they fit the incompetent-woman stereotype. In Study 2, survey data (n = 65) examined professors' support, academic advising time, and percentage of female faculty within a department as buffers against the negative effects of sexism on women's academic achievement, physical health, and social belongingness. Sexist events in the department were associated with women's reduced sense of belonging, but academic advising time served as a buffer of this association. Overall, our results indicated that proximal environments are important and that professors' behaviors that support women without singling them out were most helpful.

http://ift.tt/2uxXtjS

Clinical Effects of Laser Acupuncture plus Chinese Cupping on the Pain and Plasma Cortisol Levels in Patients with Chronic Nonspecific Lower Back Pain: A Randomized Controlled Trial

Objectives. Chronic nonspecific lower back pain (LBP) is a common disease. Insufficient data is currently available to conclusively confirm the analgesic effects of laser acupuncture on LBP. This study evaluated the effectiveness of laser acupuncture plus Chinese cupping in LBP treatment. Methods. Patients with chronic nonspecific LBP were enrolled for a randomized controlled trial and assigned to the laser acupuncture group (laser acupuncture plus Chinese cupping) and control group (sham laser plus Chinese cupping). Laser acupuncture (808 nm; 40 mW; 20 Hz; 15 J/cm2) and Chinese cupping were applied on the Weizhong (BL40) and Ashi acupoints for 5 consecutive days. Plasma cortisol levels were assessed before and after the 5-day treatment session. The visual analog scale (VAS) scores were recorded at baseline and throughout the 5-day treatment session. Results. After the treatment session, the plasma cortisol levels and VAS scores decreased significantly in both groups. In the laser acupuncture group, the VAS scores decreased significantly on days 4 and 5, and an enhanced reduction in VAS scores was observed. Conclusion. Laser acupuncture plus Chinese cupping at the Weizhong (BL40) and Ashi acupoints effectively reduced pain and inflammation in chronic nonspecific LBP. This therapy could be a suitable option for LBP treatment in clinical settings.

http://ift.tt/2vb88EN

Clinical Applications of Immunotherapy Combination Methods and New Opportunities for the Future

In the last decade, we have gained a deeper understanding of innate immune system. The mechanism of the continuous guarding of progressive mutations happening in a single cell was discovered and the production and the recognition of tumor associated antigens by the T-cells and elimination of numerous tumors by immune-editing were further understood. The new discoveries on immune mechanisms and its relation with carcinogenesis have led to development of a new class of drugs called immunotherapeutics. T lymphocyte-associated antigen 4, programmed cell death protein 1, and programmed cell death protein ligand 1 are the classes drugs based on immunologic manipulation and are collectively known as the "checkpoint inhibitors." Checkpoint inhibitors have shown remarkable antitumor efficacy in a broad spectrum of malignancies; however, the strongest and most durable immune responses do not last long and the more durable responses only occur in a small subset of patients. One of the solutions which have been put forth to overcome these challenges is combination strategies. Among the dual use of methods, a backbone with either PD-1 or PD-L1 antagonist drugs alongside with certain cytotoxic chemotherapies, radiation, targeted drugs, and novel checkpoint stimulators is the most promising approach and will be on stage in forthcoming years.

http://ift.tt/2fkQjxF

Robustification of Naïve Bayes Classifier and Its Application for Microarray Gene Expression Data Analysis

The naïve Bayes classifier (NBC) is one of the most popular classifiers for class prediction or pattern recognition from microarray gene expression data (MGED). However, it is very much sensitive to outliers with the classical estimates of the location and scale parameters. It is one of the most important drawbacks for gene expression data analysis by the classical NBC. The gene expression dataset is often contaminated by outliers due to several steps involved in the data generating process from hybridization of DNA samples to image analysis. Therefore, in this paper, an attempt is made to robustify the Gaussian NBC by the minimum -divergence method. The role of minimum -divergence method in this article is to produce the robust estimators for the location and scale parameters based on the training dataset and outlier detection and modification in test dataset. The performance of the proposed method depends on the tuning parameter . It reduces to the traditional naïve Bayes classifier when . We investigated the performance of the proposed beta naïve Bayes classifier (-NBC) in a comparison with some popular existing classifiers (NBC, KNN, SVM, and AdaBoost) using both simulated and real gene expression datasets. We observed that the proposed method improved the performance over the others in presence of outliers. Otherwise, it keeps almost equal performance.

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Prevalence of Prostatitis-Like Symptoms and Outcomes of NIH-CPSI in Outpatients with Lifelong and Acquired PE: Based on a Large Cross-Sectional Study in China

Premature ejaculation (PE) is one of the most common sexual dysfunctions, which were associated with prostatitis-like symptoms (PLS). We intended to explore the prevalence of prostatitis-like symptoms and outcomes of National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) scores in outpatients with lifelong (LPE) and acquired premature ejaculation (APE). From December 2013 to December 2015, a total of 498 consecutive heterosexual men with PE and 322 male healthy subjects without PE were enrolled. Each of them completed a detailed questionnaire on demographics information, sexual and medical histories, and the NIH-CPSI. Assessment of NIH-CPSI and definition of PLS and PE were used to measure the PLS and NIH-CPSI scores and ejaculatory function for all subjects. Finally, a total of 820 subjects (including 498 men in PE group and 322 men in control group) were enrolled in our study. The mean ages were significantly different between PE and no PE groups. Men with PE reported worse PLS and higher NIH-CPSI scores (P

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Measuring Neuromuscular Junction Functionality

A functional assessment of the neuromuscular junction (NMJ) can provide essential information on the communication between muscle and nerve. Here we describe a protocol to comprehensively evaluate both the NMJ and muscle functionality using two different muscle-nerve preparations, i.e. soleus-sciatic and diaphragm-phrenic.

http://ift.tt/2fk5MOm

Efficacy of Topical Compound Danxiong Granules for Treatment of Dermatologic Toxicities Induced by Targeted Anticancer Therapy: A Randomized, Double-Blind, Placebo-Controlled Trial

Dermatologic toxicities resulting in dose reduction or discontinuation of treatment pose challenges for targeted anticancer therapies. We conducted this randomized, double-blind, placebo-controlled trial to investigate the efficacy of topical application of Compound Danxiong Granules (CDG) for treatment of dermatologic toxicities associated with targeted anticancer therapies. One hundred and ten patients with dermatologic toxicities induced by targeted anticancer therapies were randomly assigned to CDG or placebo group. Each crude herb (Rhizoma Chuanxiong, Paeonia suffruticosa Andr., Cortex Phellodendri, Geranium sibiricum L., and Flos Carthami) was prepared as an instant herbal powder. Application of the CDG via topical washes lasted 20 minutes, twice daily, for 10 days. The primary outcome was the total effective rate, defined as reduction in at least one grade of skin toxicity. The total effective rate was 77.61% (52/67) in the CDG group and 27.27% (9/33) in the placebo group (). Compared to the placebo treatment, CDG treatment achieved a higher total effective rate for hand-foot skin reaction (95.45% versus 27.27%), acneiform eruption (69.23% versus 30.78%), and paronychia (68.42% versus 22.22%). Topical application of CDG can effectively attenuate dermatologic toxicities induced by targeted anticancer therapies. The effect of CDG was more pronounced in hand-foot skin reaction.

http://ift.tt/2ufPPPI

Mite allergoids coupled to nonoxidized mannan from Saccharomyces cerevisae efficiently target canine dendritic cells for novel allergy immunotherapy in veterinary medicine.

Related Articles

Mite allergoids coupled to nonoxidized mannan from Saccharomyces cerevisae efficiently target canine dendritic cells for novel allergy immunotherapy in veterinary medicine.

Vet Immunol Immunopathol. 2017 Aug;190:65-72

Authors: Soria I, Alvarez J, Manzano AI, López-Relaño J, Cases B, Mas-Fontao A, Cañada FJ, Fernández-Caldas E, Casanovas M, Jiménez-Barbero J, Palomares O, Viñals-Flórez LM, Subiza JL

Abstract
We have recently reported that grass pollen allergoids conjugated with nonoxidized mannan of Saccharomyces cerevisae using glutaraldehyde results in a novel hypoallergenic mannan-allergen complex with improved properties for allergen vaccination. Using this approach, human dendritic cells show a better allergen uptake and cytokine profile production (higher IL-10/IL-4 ratio) for therapeutic purposes. Here we aim to address whether a similar approach can be extended to dogs using canine dendritic cells. Six healthy Spanish Greyhound dogs were used as blood donors to obtain canine dendritic cells (DC) derived from peripheral blood monocytes. Allergens from Dermatophagoides farinae mite were polymerized and conjugated with nonoxidized mannan. Nuclear magnetic resonance (NMR), gel electrophoresis (SDS-PAGE), immunoblotting and IgE-ELISA inhibition studies were conducted to evaluate the main characteristics of the allergoid obtained. Mannan-allergen conjugate and controls were assayed in vitro for canine DC uptake and production of IL-4 and IL-10. The results indicate that the conjugation of D. farinae allergens with nonoxidized mannan was feasible using glutaraldehyde. The resulting product was a polymerized structure showing a high molecular weight as detected by NMR and SDS-PAGE analysis. The mannan-allergen conjugate was hypoallergenic with a reduced reactivity with specific dog IgE. An increase in both allergen uptake and IL-10/IL-4 ratio was obtained when canine DCs were incubated with the mannan-allergen conjugate, as compared with the control allergen preparations (unmodified D. farinae allergens and oxidized mannan-allergen conjugate). We conclude that hypoallergenic D. farinae allergens coupled to nonoxidized mannan is a novel allergen preparation suitable for canine allergy immunotherapy targeting dendritic cells.

PMID: 28778325 [PubMed - in process]

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Interaction between Corneal and Internal Ocular Aberrations Induced by Orthokeratology and Its Influential Factors

Purpose. To investigate the interaction between corneal, internal, and total wavefront aberrations (WAs) and their influential factors during orthokeratology (OK) treatment in Chinese adolescents. Methods. Thirty teenagers ( eyes) were enrolled in the study; spherical equivalent refraction (SE), corneal curvature radius (CCR), central corneal thickness (CCT), WAs, and the difference in limbal transverse diameter and OK lens diameter (ΔLLD) were detected before and after one-month OK treatment. Every component of WAs was measured simultaneously by iTrace aberrometer. The influential factors of OK-induced WAs were analyzed. Results. SE and CCT decreased while CCR increased significantly (). Higher-order aberrations (HOAs), Spherical aberrations (SAs), and coma increased significantly (). Corneal horizontal coma (Z31-C) and corneal spherical aberrations (Z40-C) increased (). The HOAs, coma, SAs, Z31-C, Z31-T, Z40-C, and Z40-T were positively correlated with SE and CCR (). Z3−1-C showed negative correlations with (ΔLLD) and positive correlations with SE (). Conclusions. The increase in OK-induced HOAs is mainly attributed to Z31 and Z40 of cornea. Z3−1 in the internal component showed a compensative effect on the corneal vertical coma. The degree of myopic correction and increase in CCR may be the essential influential factors of the increase in Z31 and Z40. The appropriate size of the OK lens may be helpful to decrease OK-induced vertical coma.

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Comparison of Deep Tissue Massage and Therapeutic Massage for Lower Back Pain, Disease Activity, and Functional Capacity of Ankylosing Spondylitis Patients: A Randomized Clinical Pilot Study

Objectives. This study aims to compare the effectiveness of deep tissue massage (DTM) and therapeutic massage (TM) in the management of ankylosing spondylitis (AS) patients. Materials and Methods. This was a small, randomized clinical pilot study. Subjects were 27 men with diagnosed AS, randomly assigned to DTM group or TM group. Subjects in each group had 10 sessions of massage. Outcomes included the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Bath Ankylosing Spondylitis Functional Index (BASFI), Modified Schober Test, Finger to Floor Test, chest expansion, and pain intensity of lower back. Results. There are no statistical significant differences between groups, except for BASDAI and pain intensity of lower back. Conclusions. This study suggests that massage may have clinical benefits for treating ankylosing spondylitis patients. Additional scientific research in this area is warranted.

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Could a green tea extract help to treat tooth sensitivity?

Using a green tea compound, researchers develop a new material that protects patients with sensitive teeth and damaged dentin against cavities.

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Soluble CD14 as a Diagnostic and Prognostic Biomarker in Hematological Patients with Febrile Neutropenia

Objective. Elevated levels of a cell surface glycoprotein, soluble cluster of differentiation 14 (sCD14), have been observed in patients with sepsis. Only scarce data are available on sCD14 in hematological patients with chemotherapy-induced febrile neutropenia. The study aim was to investigate sCD14 as an early biomarker in febrile neutropenia after intensive chemotherapy to detect a rapidly deteriorating clinical course early enough to avoid serious infectious complications. Patients and Methods. This prospective study included 87 adult hematological patients at the start of febrile neutropenia after intensive chemotherapy for acute myeloid leukemia or after autologous stem cell transplantation. The study endpoints were septic shock, severe sepsis, and positive blood culture findings. sCD14 was analyzed from day 0 to day 2, and its prognostic capacity was compared to that of C-reactive protein and procalcitonin. Results. Plasma level of sCD14 predicted the development of septic shock on day 1 () and day 2 but not the development of severe sepsis or blood culture positivity in hematological patients with chemotherapy-induced febrile neutropenia. Conclusions. Soluble CD14 did not predict an overall complicated course at the early stages of febrile neutropenia. However, it was helpful in predicting the progression of the clinical course of neutropenic fever to septic shock.

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The Technology of Processed Electroencephalogram Monitoring Devices for Assessment of Depth of Anesthesia.

Commercial brain function monitors for depth of anesthesia have been available for more than 2 decades; there are currently more than 10 devices on the market. Advances in this field are evidenced by updated versions of existing monitors, development of new monitors, and increasing research unveiling the mechanisms of anesthesia on the brain. Electroencephalography signal processing forms an integral part of the technology supporting the brain function monitors for derivation of a depth-of-anesthesia index. This article aims to provide a better understanding of the technology and functionality behind these monitors. This review will highlight the general design principles of these devices and the crucial stages in electroencephalography signal processing and classification, with a focus on the key mathematical techniques used in algorithm development for final derivation of the index representing anesthetic state. We will briefly discuss the advantages and limitations of this technology in the clinical setting as a tool in our repertoire used for optimizing individualized patient care. Also included is a table describing 10 available commercial depth-of-anesthesia monitors. (C) 2017 International Anesthesia Research Society

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Atlas of Peripheral Regional Anesthesia Anatomy and Techniques, 3rd edition.

No abstract available

http://ift.tt/2vtAgUz

Perioperative Drill-Based Crisis Management.

No abstract available

http://ift.tt/2vaCCoy

Reduction in Operating Room Plasma Waste After Evidence-Based Quality Improvement Initiative.

Anesthesiologists request units of plasma in anticipation of transfusion. The amount of plasma transfused intraoperatively is less than that issued (requested, thawed, and sent). We presented institutional-specific data on plasma usage including anesthesiologist-specific ratios of plasma issued-to-transfused. In month-to-month comparisons from the year before the presentation (June-December 2015) to 7 months after (June-December 2016), plasma issued to the operating room was reduced from 434.9 +/- 81 to 327.3 +/- 65 units, a change of 107.6 units per month (95% confidence interval [CI], 22-193); plasma discarded by the blood bank was reduced from 109.7 +/- 48 units to 69.1 +/- 9 units, a change of 40.6 units per month (95% CI, 0.2-81); and plasma transfused went from 188.4 +/- 42 units to 160.7 +/- 52 units, a nonsignificant change of 27.7 units per month (95% CI, -27 to 83). (C) 2017 International Anesthesia Research Society

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An Appraisal of the Carlisle-Stouffer-Fisher Method for Assessing Study Data Integrity and Fraud.

Data fabrication and scientific misconduct have been recently uncovered in the anesthesia literature, partly via the work of John Carlisle. In a recent article in Anaesthesia, Carlisle analyzed 5087 randomized clinical trials from anesthesia and general medicine journals from 2000 to 2015. He concluded that in about 6% of studies, data comparing randomized groups on baseline variables, before the given intervention, were either too similar or dissimilar compared to that expected by usual sampling variability under the null hypothesis. Carlisle used the Stouffer-Fisher method of combining P values in Table 1 (the conventional table reporting baseline patient characteristics) for each study, then calculated trial P values and assessed whether they followed a uniform distribution across studies. Extreme P values targeted studies as likely to contain data fabrication or errors. In this Statistical Grand Rounds article, we explain Carlisle's methods, highlight perceived limitations of the proposed approach, and offer recommendations. Our main findings are (1) independence was assumed between variables in a study, which is often false and would lead to "false positive" findings; (2) an "unusual" result from a trial cannot easily be concluded to represent fraud; (3) utilized cutoff values for determining extreme P values were arbitrary; (4) trials were analyzed as if simple randomization was used, introducing bias; (5) not all P values can be accurately generated from summary statistics in a Table 1, sometimes giving incorrect conclusions; (6) small numbers of P values to assess outlier status within studies is not reliable; (7) utilized method to assess deviations from expected distributions may stack the deck; (8) P values across trials assumed to be independent; (9) P value variability not accounted for; and (10) more detailed methods needed to understand exactly what was done. It is not yet known to what extent these concerns affect the accuracy of Carlisle's results. We recommend that Carlisle's methods be improved before widespread use (applying them to every manuscript submitted for publication). Furthermore, lack of data integrity and fraud should ideally be assessed using multiple simultaneous statistical methods to yield more confident results. More sophisticated methods are needed for nonrandomized trials, randomized trial data reported beyond Table 1, and combating growing fraudster sophistication. We encourage all authors to more carefully scrutinize their own reporting. Finally, we believe that reporting of suspected data fraud and integrity issues should be done more discretely and directly by the involved journal to protect honest authors from the stigma of being associated with potential fraud. (C) 2017 International Anesthesia Research Society

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Mortality, Geriatric, and Nongeriatric Surgical Risk Factors Among the Eldest Old: A Prospective Observational Study.

BACKGROUND: Preoperative risk and postoperative outcomes among the elderly are the subject of extensive debate. However, the eldest old, that is, the fastest-growing and most vulnerable group, are insufficiently studied; even their mortality rate is unclear. This prospective observational study was performed with the aim of determining the mortality rate of this population and establishing which preoperative conditions were predictors of which postoperative outcomes. The study was undertaken between 2011 and 2015 in a major tertiary care university hospital. METHODS: All patients aged >=85 years undergoing any elective procedure during the study period were included. Patients were followed up for 30 days postoperatively. The preoperative conditions studied were demographic data, grade of surgical complexity (1-3), preoperative comorbidities, and some characteristically geriatric conditions (functional reserve, nutrition, cognitive status, polypharmacy, dependency, and frailty). The outcome measures were 30-day all-cause mortality (primary end point), morbidity, prolonged length of stay, and escalation of care in living conditions. RESULTS: Of 139 eligible patients, 127 completed follow-up. The 30-day mortality was 7.9%; 95% confidence interval (CI), 3.2-12.6. It had 3 predictors: malnutrition (odds ratio [OR], 15; 95% CI, 3-89), complexity 3 (OR, 9.1; CI, 2-52), and osteoporosis/osteoporotic fractures (OR, 14.7; CI, 2-126). Significant predictors for morbidity (40%) were ischemic heart disease (OR, 3.9; CI, 1-11) and complexity 3 (OR, 3.6; CI, 2-9), while a nonfrail phenotype (OR, 0.3; CI, 0.1-0.8) was found to be protective. Only 2 factors were found to be predictive of longer admissions, namely complexity 3 (OR, 4.4; CI, 2-10) and frailty (OR, 2.7; CI, 2-7). Finally, risk factors for escalation of care in living conditions were slow gait (a surrogate for frailty, OR, 2.5; CI, 1-6), complexity 3 (OR, 3.2; CI, 1-7), and hypertension (OR, 2.9; CI, 1-9). CONCLUSIONS: The eldest old is a distinct group with a considerable mortality rate and their own particular risk factors. Surgical complexity and certain geriatric variables (malnutrition and frailty), which are overlooked in American Society of Anesthesiologists and most other usual scores, are particularly relevant in this population. Inclusion of these factors along with appropriate comorbidities for risk stratification should guide better decision making for families and doctors alike and encourage preoperative optimization of patients. (C) 2017 International Anesthesia Research Society

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Perioperative Considerations for the Use of Sodium-Glucose Cotransporter-2 Inhibitors in Patients With Type 2 Diabetes.

No abstract available

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Phytotherapy and Nutritional Supplements on Breast Cancer

Breast cancer is the most frequent type of nonskin malignancy among women worldwide. In general, conventional cancer treatment options (i.e., surgery, radiotherapy, chemotherapy, biological therapy, and hormone therapy) are not completely effective. Recurrence and other pathologic situations are still an issue in breast cancer patients due to side effects, toxicity of drugs in normal cells, and aggressive behaviour of the tumours. From this point of view, breast cancer therapy and adjuvant methods represent a promising and challenging field for researchers. In the last few years, the use of some types of complementary medicines by women with a history of breast cancer has significantly increased such as phytotherapeutic products and nutritional supplements. Despite this, the use of such approaches in oncologic processes may be problematic and patient's health risks can arise such as interference with the efficacy of standard cancer treatment. The present review gives an overview of the most usual phytotherapeutic products and nutritional supplements with application in breast cancer patients as adjuvant approach. Regardless of the contradictory results of scientific evidence, we demonstrated the need to perform additional investigation, mainly well-designed clinical trials in order to establish correlations and allow for further validated outcomes concerning the efficacy, safety, and clinical evidence-based recommendation of these products.

http://ift.tt/2ww8V0H