Sonic hedgehog and Wnt/β-catenin pathways mediate curcumin inhibition of breast cancer stem cells

Cancer stem cells (CSCs) play an essential role in the progression of many tumors. Sonic hedgehog (Shh) and Wnt/β-catenin pathways are crucial in maintaining the stemness of CSCs. Curcumin has been shown to possess anticancer activity. However, the interventional effect of curcumin on breast CSCs has not been elucidated. In the present study, we investigated the role of Shh and Wnt/β-catenin pathway in curcumin inhibition of breast CSCs. We showed that the levels of breast CSCs markers were significantly elevated in SUM159 and MCF7 sphere-forming cells. We further illustrated that curcumin effectively decreased breast CSCs activity by inhibiting tumor sphere formation, decreasing breast CSCs markers (CD44, ALDH1A1, Nanog, and Oct4), as well as inhibiting proliferation and inducing apoptosis. Moreover, we showed that downregulation of Shh and Wnt/β-catenin activity resulted in breast CSCs inhibition; curcumin exerted an inhibitory effect on breast CSCs by suppressing both Shh and Wnt/β-catenin pathways. Taken together, these results indicated curcumin inhibition of breast CSCs by downregulation of Shh and Wnt/β-catenin pathways. Findings from this study could provide new insights into the potential therapeutic application of curcumin in breast CSCs elimination and cancer intervention. *Xiaoting Li and Xiaoqian Wang contributed equally to the writing of this article. Correspondence to Caiyun Zhong, MD, PhD, DABT, Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, 818 East Tianyuan Road, Jiangning, Nanjing 211166, China Tel: +86 25 86868450; fax: +86 25 86868499; e-mail: cyzhong@njmu.edu.cn Correspondence to Yu Zhao, MD, Department of Medical Imaging, The First School of Clinical Medicine, Nanjing Medical University, 818 East Tianyuan Road, Jiangning, Nanjing 211166, China Tel/fax: +86 25 86868155; e-mail: zhaoyu@njmu.edu.cn Received July 4, 2017 Accepted November 20, 2017 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2rsfUu2

Antitumor effects of histone deacetylase inhibitor suberoylanilide hydroxamic acid in epidermal growth factor receptor-mutant non-small-cell lung cancer lines in vitro and in vivo

Histone acetylation is one of the most abundant post-translational modifications in eukaryotic cells; aberrant histone acetylation is related to a range of cancer types because of the dysregulation of histone deacetylases (HDACs). Inhibition of HDACs leads to suppression of tumor growth in multiple cancers, whereas the inhibitory effects of HDAC inhibitors remain incompletely understood in epidermal growth factor receptor (EGFR)-mutant lung cancers. In this study, the antitumor effects of HDACs inhibitor suberoylanilide hydroxamic acid (SAHA, vorinostat) were examined in EGFR-mutant lung cancer cell lines. The results of the present work showed that SAHA markedly inhibited cell viability and proliferation, induced cell apoptosis by arresting the cell cycle in the G2/M phase, and significantly reduced tumor growth in a xenograft model. Further study confirmed that the suppression function of SAHA might be mediated by regulating the ERK-dependent and/or the AKT-dependent pathway; meanwhile, angiogenesis abrogation induced by SAHA exerted effects on tumor regression in vivo. Taken together, our results identify the antitumor effects of HDACs inhibitor SAHA as an alternative therapeutic application for the epigenetic treatment of EGFR-mutant non-small-cell lung cancer. * Ye Wei and Fangzheng Zhou contributed equally to the writing of this article. Correspondence to Dandan Yu, MD, Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China Tel/fax: +86 027 6565 9931; e-mail: yudan7088@hotmail.com or Correspondence to Gang Wu, PhD, Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China Tel/fax: +86 027 6565 9931; e-mail: xhzlwg@163.com Received August 29, 2017 Accepted January 3, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2FYB8Db

What Factors Guide the Selection of Medicinal Plants in a Local Pharmacopoeia? A Case Study in a Rural Community from a Historically Transformed Atlantic Forest Landscape

The criteria that local people use for selecting medicinal plants have been a recurrent topic in pharmacology and ethnobotany. Two of the current hypotheses regarding this phenomenon, ecological apparency and diversification, attempt to explain the inclusion of "apparent" and "non-apparent" and native and exotic taxa, respectively, in local pharmacopoeia. This study addresses the following questions: Do "apparent" and "non-apparent" medicinal plants have the same importance in local pharmacopoeia? Do "non-apparent" plants occupy more local categories of diseases than "apparent" plants? Do native and exotic medicinal plants have the same importance? Do exotic and native plants occupy different local categories of diseases? This study was conducted with householders of a community from Northeastern Brazil. Out of the 66 plant species cited, most were herbs (39 species), followed by trees and shrubs (27). Herbaceous species also occupied more local categories of diseases (51) than tree and shrub species (28). Furthermore, most of the species cited by the informants were exotic (42). Out of the 94 therapeutic applications cited in this research, 65 were treated with exotic species and 29 with native species, distributed among 13 body systems. These results support both the hypotheses of ecological apparency and diversification.

http://ift.tt/2EWYasM

Intratidal Analysis of Intraoperative Respiratory System Mechanics: Keep it Simple

No abstract available

http://ift.tt/2DughJr

MicroRNAs as Clinical Biomarkers and Therapeutic Tools in Perioperative Medicine

Over the past decade, evolutionarily conserved, noncoding small RNAs—so-called microRNAs (miRNAs)—have emerged as important regulators of virtually all cellular processes. miRNAs influence gene expression by binding to the 3′-untranslated region of protein-coding RNA, leading to its degradation and translational repression. In medicine, miRNAs have been revealed as novel, highly promising biomarkers and as attractive tools and targets for novel therapeutic approaches. miRNAs are currently entering the field of perioperative medicine, and they may open up new perspectives in anesthesia, critical care, and pain medicine. In this review, we provide an overview of the biology of miRNAs and their potential role in human disease. We highlight current paradigms of miRNA-mediated effects in perioperative medicine and provide a survey of miRNA biomarkers in the field known so far. Finally, we provide a perspective on miRNA-based therapeutic opportunities and perspectives.

http://ift.tt/2F18Wy1

A Tale of Two Solutions: High vs Low-Chloride Intravenous Fluids

No abstract available

http://ift.tt/2DQiOLv

Alkalinized Lidocaine Preloaded Endotracheal Tube Cuffs Reduce Emergence Cough After Brief Surgery: A Prospective Randomized Trial

BACKGROUND: Alkalinized lidocaine in the endotracheal tube (ETT) cuff decreases the incidence of cough and throat pain on emergence after surgery lasting more than 2 hours. However, alkalinized lidocaine needs 60–120 minutes to cross the ETT cuff membrane; therefore, its usefulness in shorter duration surgery is unknown. This prospective double-blind randomized controlled trial tested the hypothesis that alkalinized lidocaine would reduce the incidence of emergence cough after surgeries lasting 90 minutes before intubation with either 2 mL of 2% lidocaine and 8 mL of 8.4% bicarbonate (group AL) or 10 mL of normal saline (group S). Cuffs were emptied immediately before intubation. After intubation, either 2 mL of 2% lidocaine (AL) or 2 mL of saline (S) were injected into the cuff. Additional 8.4% bicarbonate (AL) or saline (S) was injected into the cuff until there was no air leak. Anesthesia was maintained using desflurane, rocuronium, and either fentanyl or sufentanil to maintain vital signs within 20% of baseline values. Opioids administered in prophylaxis of extubation cough were proscribed. A standardized "no touch" emergence technique was used. A blinded assessor noted any cough above 0.2 minimum alveolar concentration (MAC) of expired desflurane. At 0.2 MAC, once every 30 seconds, the patient was instructed to open his eyes and extubation occurred once a directed response was noted. RESULTS: A total of 213 patients were randomized and 100 patients in each group completed the experimental protocol. The incidence of extubation cough in group AL was 12%, significantly lower (1-sided P = .045) than the 22% incidence in group S. The 1-tailed risk ratio for cough in group AL was 0.55 (0–0.94, P = .045). Total amount of opioids administered (P = .194), ETT cuff preloading times (P = .259), and extubation times (P = .331) were not significantly different between groups. The average duration of surgery was 59 ± 28 minutes in group AL and 52 ± 29 minutes in group S (P = .057). CONCLUSIONS: Alkalinized lidocaine in the ETT cuff significantly decreased general anesthesia emergence cough after surgeries with an average duration of slightly

http://ift.tt/2F17QCf

“Mirror, Mirror on the Wall”: Learning From Reflections on Quality

No abstract available

http://ift.tt/2Dll4ti

The Syringe Driver: Continuous Subcutaneous Infusions in Palliative Care, 4th ed.

No abstract available

http://ift.tt/2F17NX5

A Novel Approach to Synthesize the Evidence on Analgesic Adjuvants for Postoperative Pain

No abstract available

http://ift.tt/2DR2bQc

Sugammadex and Oral Contraceptives: Is It Time for a Revision of the Anesthesia Informed Consent?

No abstract available

http://ift.tt/2F17KKT

Learning From Human Factors Can Make Anesthesia Even Safer

No abstract available

http://ift.tt/2DmhleT

Pediatric Anesthesiology Fellows’ Perception of Quality of Attending Supervision and Medical Errors

BACKGROUND: Appropriate supervision has been shown to reduce medical errors in anesthesiology residents and other trainees across various specialties. Nonetheless, supervision of pediatric anesthesiology fellows has yet to be evaluated. The main objective of this survey investigation was to evaluate supervision of pediatric anesthesiology fellows in the United States. We hypothesized that there was an indirect association between perceived quality of faculty supervision of pediatric anesthesiology fellow trainees and the frequency of medical errors reported. METHODS: A survey of pediatric fellows from 53 pediatric anesthesiology fellowship programs in the United States was performed. The primary outcome was the frequency of self-reported errors by fellows, and the primary independent variable was supervision scores. Questions also assessed barriers for effective faculty supervision. RESULTS: One hundred seventy-six pediatric anesthesiology fellows were invited to participate, and 104 (59%) responded to the survey. Nine of 103 (9%, 95% confidence interval [CI], 4%–16%) respondents reported performing procedures, on >1 occasion, for which they were not properly trained for. Thirteen of 101 (13%, 95% CI, 7%–21%) reported making >1 mistake with negative consequence to patients, and 23 of 104 (22%, 95% CI, 15%–31%) reported >1 medication error in the last year. There were no differences in median (interquartile range) supervision scores between fellows who reported >1 medication error compared to those reporting ≤1 errors (3.4 [3.0–3.7] vs 3.4 [3.1–3.7]; median difference, 0; 99% CI, −0.3 to 0.3; P = .96). Similarly, there were no differences in those who reported >1 mistake with negative patient consequences, 3.3 (3.0–3.7), compared with those who did not report mistakes with negative patient consequences (3.4 [3.3–3.7]; median difference, 0.1; 99% CI, −0.2 to 0.6; P = .35). CONCLUSIONS: We detected a high rate of self-reported medication errors in pediatric anesthesiology fellows in the United States. Interestingly, fellows' perception of quality of faculty supervision was not associated with the frequency of reported errors. The current results with a narrow CI suggest the need to evaluate other potential factors that can be associated with the high frequency of reported errors by pediatric fellows (eg, fatigue, burnout). The identification of factors that lead to medical errors by pediatric anesthesiology fellows should be a main research priority to improve both trainee education and best practices of pediatric anesthesia.

http://ift.tt/2F17HPd

Ischemic Preconditioning and the Role of Antifibrinolytic Drugs: Translation From Bench to Bedside

No abstract available

http://ift.tt/2DRYI3R

Brain Monitoring and the Depth of Anesthesia: Another Goldilocks Dilemma

No abstract available

http://ift.tt/2mTqzIH

Emergency General Surgery: Time for Anesthesiology and Surgery to Work Together to Drive Improvement in Outcomes

No abstract available

http://ift.tt/2Dl3Dcc

Developing Reflective Practice: A Guide for Medical Students, Doctors, and Teachers

No abstract available

http://ift.tt/2roGKTI

New Diabetes Medications Raise New Perioperative Concerns for the Anesthesiologist

No abstract available

http://ift.tt/2DQiIn7

Not All Calcium Formulations Are Alike

No abstract available

http://ift.tt/2rq59sf

“That’s Not What I Said”: Seeking Fidelity in Citations

No abstract available

http://ift.tt/2Dl3C88

From Foundation to Demolition: The Influence of Perioperative Tranexamic Acid

No abstract available

http://ift.tt/2DmXAUH

Disparities in Anesthesia Care

No abstract available

http://ift.tt/2DQiEDT

Informed Consent and Cognitive Dysfunction After Noncardiac Surgery in the Elderly

Cognitive dysfunction 3 months after noncardiac surgery in the elderly satisfies informed consent thresholds of foreseeability in 10%–15% of patients, and materiality with new deficits observed in memory and executive function in patients with normal test performance beforehand. At present, the only safety step to avoid cognitive dysfunction after surgery is to forego surgery, thereby precluding the benefits of surgery with removal of pain and inflammation, and resumption of normal nutrition, physical activity, and sleep. To assure that consent for surgery is properly informed, risks of both cognitive dysfunction and alternative management strategies must be discussed with patients by the surgery team before a procedure is scheduled.

http://ift.tt/2EWYnfy

The effect and safety of diacerein in patients with type 2 diabetes mellitus : a systematic review and meta-analysis.

Related Articles

The effect and safety of diacerein in patients with type 2 diabetes mellitus : a systematic review and meta-analysis.

Am J Clin Exp Immunol. 2017;6(6):97-106

Authors: Zhang Q, Zhou J, Wang Y, Chen D

Abstract
The Background: Diacerein has been proposed as a treatment option for management of type 2 diabetes due to its anti-inflammatory properties.
PURPOSE: The aim of this systematic review and meta-analysis of randomized controlled trials (RCTs) is to examine the effect and safety of diacerein in patients with type 2 diabetes.
DATA SOURCES AND STUDY SELECTION: We searched Pubmed, Embase, and Cochrane Library for RCTs published from database inception to September 2017.
DATA EXTRACTION AND DATA SYNTHESIS: Among 44 studies that were initially identified, four were eligible and were included in the following analysis. Diacerein significantly reduced fasting glycemia [weighted mean differences (WMD) -0.66, 95% confidence interval (95% CI) -1.16 to -0.16] and glycated hemoglobin A1c (HbA1c ) (WMD -0.85, 95% CI -1.44 to -0.26). And the patients with a diacerein supplementation duration of ≤12 weeks had a greater decrease of fasting glycemia and HbA1c than the supplementation duration of >12 weeks. Furthermore, compared with placebo, diacerein revealed a significant increase in the relative risk (RR) of gastrointestinal symptoms (RR=2.50, 95% CI: 1.10 to 5.65), especially in the study subgroup with supplementation duration of >12 weeks (RR=4.01, 95% CI: 2.32 to 6.95).
LIMITATIONS: The sample size was relatively small and the duration of included studies was short so that the treatment efficacy and safety for longer duration was unknown.
CONCLUSIONS: Although further studies are needed, our findings clearly provide support to the use of diacerein in the clinical management of subjects with type 2 diabetes.

PMID: 29348985 [PubMed]

http://ift.tt/2mY5ygb

An immunohistochemical analysis of folate receptor beta expression and distribution in giant cell arteritis - a pilot study.

Related Articles

An immunohistochemical analysis of folate receptor beta expression and distribution in giant cell arteritis - a pilot study.

Am J Clin Exp Immunol. 2017;6(6):107-114

Authors: Albano-Aluquin S, Malysz J, Aluquin VR, Ratnam M, Olsen N

Abstract
BACKGROUND: Giant cell arteritis (GCA) is a chronic vasculitis of large and medium vessels in which no targetable biomarkers exist to allow selective treatment, predict disease activity and monitor therapeutic responses. The accessibility of the temporal artery (TA) for biopsy allows morphologic studies to characterize macrophages and T cells in the microenvironment of the arterial wall. We evaluated the expression of folate receptor beta (FRB), a candidate diagnostic/therapeutic biomarker, compared its expression with key macrophage markers and correlated it with GCA severity.
METHODS: Formalin-fixed paraffin-embedded tissue sections were examined from 6 patients with GCA and 2 controls. Immunohistochemistry was performed using FRB, ETB, CD68 and CD3 antibodies to evaluate for activated macrophages and T cells, assess FRB distribution along the intima, media and adventitial layers and composition of inflammatory infiltrates. We compared the expression of FRB, ETB and CD68 in GCA versus negative controls and in severe (with visual loss) versus mild (without visual loss) disease.
RESULTS: In GCA, moderate to severe inflammation was accompanied by >90% destruction of the internal elastic lamina. Macrophages comprised 36.3 ± 4.1% while CD3+ lymphocytes accounted for 61.7 ± 4.1% of total leukocytes. FRB was selectively expressed in macrophages and localized to the adventitia. GCA patients had marginally increased median FRB (9.8 cells/hpf vs. 0; p=0.095), ETB (20.5 vs. 0; p=0.095) and CD68 (38.8 vs. 5; p=0.071) expression versus controls. ETB was found in endothelial cells, smooth muscle cells and macrophages in intima/media. FRB positively correlated with ETB (r=0.90; p-0.037) and CD68 levels (r=0.90; p=0.037). ETB expression positively correlated with CD68 (r=1.0; p<0.0001). There was no difference in FRB between severe and mild GCA.
CONCLUSION: FRB is a potential diagnostic and therapeutic biomarker with restricted expression in GCA macrophages. FRB+ macrophages localized to the adventitia and their expression correlated with ETB and CD68 macrophages, suggesting that they contribute to GCA pathogenesis.

PMID: 29348986 [PubMed]

http://ift.tt/2DrYgMr

Human immune system during sleep.

Related Articles

Human immune system during sleep.

Am J Clin Exp Immunol. 2017;6(6):92-96

Authors: Asif N, Iqbal R, Nazir CF

Abstract
A joint function of tissues, organs and cells for the protection of body develops immune system. The human immune response against various infections during sleep, its mechanism, neuroimmune interactions, immunoregulatory effect of sleep along with sleep deprivation and role of cytokines in sleep deprivation were addressed. It is revealed that human immune system and sleep both are associated and influenced by each other. Sleep deprivation makes a living body susceptible to many infectious agents. In the result, immune system of human body is altered by releasing immunomodulators in the response of infections as reported by various researchers. Basic reasons and mechanisms of most of the poor sleep networks and release of proinflammatory modulators are still uncertain. The current situation requires improved sleep habits to make immune system efficient for a healthy life.

PMID: 29348984 [PubMed]

http://ift.tt/2DqWN9a

Cardiopulmonary Aerobic Fitness Assessment During Maximal and Submaximal Exercise Testing in Pediatric Oncology Patients After Chemotherapy

Purpose: The cardiopulmonary exercise test (CPET) is a valuable tool to assess cardiopulmonary exercise capacity in pediatric oncology patients after chemotherapy. In addition, few studies on the utility of submaximal testing have been performed, which could be important as some patients are unable to complete a maximal effort test secondary to deconditioning by both disease and treatment. Materials and Methods: We performed a retrospective chart review of pediatric cancer patients exposed to chemotherapy from 1992 to 2013 who underwent CPET with cycle ergometry (n=27). The study patients were compared with age-matched, sex-matched, and size-matched normal controls. The submaximal measure recorded was the oxygen consumption (VO2)@respiratory exchange ratio (RER) 1.0 during a maximal effort test. Results: The chemotherapy group demonstrated significantly lower exercise time (9.2±3.6 vs. 11.4±3.8; P=0.008), total work capacity (4914.4±3290.3 vs. 7664.4±4289.5; P=0.004), systolic blood pressure at peak exercise (162.9±23.2 vs. 177.3±23.8; P=0.01), indexed peak VO2 (33.9±6.9 vs. 40.0±6.3; P=0.001), and indexed peak oxygen pulse (6.1±1.3 vs. 7.0±1.5; P=0.004)). For the submaximal outcome measured, 11/27 of the chemotherapy patients had VO2@RER 1.0 values

http://ift.tt/2EY6rwB

Dendrimer-based Uneven Nanopatterns to Locally Control Surface Adhesiveness: A Method to Direct Chondrogenic Differentiation

A method to obtain dendrimer-based uneven nanopatterns that permit the nanoscale control of local arginine-glycine-aspartic acid (RGD) surface density is described and applied for the study of cell adhesion and chondrogenic differentiation.

http://ift.tt/2DToHI4

Microinjection of CRISPR/Cas9 Protein into Channel Catfish, Ictalurus punctatus, Embryos for Gene Editing

A simple and efficient microinjection protocol for gene editing in channel catfish embryos using the CRISPR/Cas9 system is presented. In this protocol, guide RNAs and Cas9 protein were microinjected into the yolk of one-cell embryos. This protocol has been validated by knocking out two channel catfish immune-related genes.

http://ift.tt/2DU5hCS

Loss of KRAS control as consequence of downregulated microRNA-622 in hepatocellular carcinoma and its potential therapeutic implication

Hepatocellular carcinoma (HCC) represents a serious and urgent global health problem because of its increasing incidence and the limited therapeutic options.1 2 The standard treatment for patients with advanced HCC is the multikinase inhibitor sorafenib, which shows only modest survival improvement of approximately 2–3 months and remains associated with disease progression in a large number of patients.3 4 Therefore, to improve the survival of patients with advanced HCC, it is fundamental to understand the mechanisms of sorafenib resistance.

The antitumour efficacy of sorafenib is mainly based on the inhibition of the proliferative RAF/mitogen-activated protein kinase (MAPK) pathway, which is regulated by upstream RAS proteins.5 6 The majority of human HCCs shows an activation of this pathway, which is associated with shorter survival.6–9 In contrast to other human tumours, RAS activation in HCC occurs...

http://ift.tt/2DvPpJC

Plasma cell-free DNA methylation: a liquid biomarker of hepatic fibrosis

We recently reported dynamic epigenetic markers of fibrosis detectable in patients' plasma that may have utility in non-invasive diagnosis and staging of fibrosis in patients with chronic liver disease.1 Specifically, we uncovered DNA methylation markers at the human PPAR promoter detectable in circulating cell-free DNA (ccfDNA) that display differential methylation densities. Remarkably, PPAR hypermethylation correlated with progression to cirrhosis in alcoholic liver disease (ALD) and with specific stages of liver fibrosis in non-alcoholic fatty liver disease (NAFLD). Furthermore, ccfDNA signatures were traced back to the molecular pathology in fibrotic liver tissue, providing a biomarker of the underlying pathological process and defining hepatocytes as the source of hypermethylated DNA found in plasma.1

The original study posed several important outstanding questions: (1) Can ccfDNA methylation be used as a biomarker of fibrosis in liver diseases of other aetiologies? (2) Does the presence of hepatocellular carcinoma (HCC) alter the biomarker...

http://ift.tt/2mTDzhC

The Relative Importance of Clinical, Economic, Patient Values and Feasibility Criteria in Cancer Drug Reimbursement in Canada: A Revealed Preferences Analysis of Recommendations of the Pan-Canadian Oncology Drug Review 2011–2017

Abstract

Background

Most Canadian provinces and territories rely on the pan-Canadian Oncology Drug Review (pCODR) to provide recommendations regarding public reimbursement of cancer drugs. The pCODR review process considers four dimensions of value—clinical benefit, economic evaluation, patient-based values and adoption feasibility—but they do not define weights for individual decision criteria or an acceptable threshold for any of the criteria. Given this implicit review process, it is of interest to understand which factors appear to carry the most weight in pCODR recommendations using a revealed preferences approach.

Methods

Using publicly available decision summaries (n = 91) describing submissions and resulting recommendations 2011–2017, we extracted ten attributes that characterized each submission. Using logistic regression, we identified statistically significant attributes and estimated their relative impact in final recommendations.

Results

Clinical aspects appear to carry the greatest weight in the decision to reject or not reject, along with aspects of patient value (treatments with no alternatives were less likely to be rejected). Cost effectiveness does not appear to play a role in the initial decision to reject or not reject but is critical in full versus conditional approvals. There is evidence of a maximum acceptable threshold of around $Can140,000 per quality-adjusted life-year (QALY) gained.

Conclusion

A set of factors driving pCODR recommendations is identifiable, supporting the consistency of the review process. However, the implicit nature of the review process and the difficulty of extracting and interpreting some of the attribute levels used in the analysis suggests that the process may still lack full transparency.

http://ift.tt/2mXDg5X

Protective effect of Gnetum africanum methanol leaf extract on pancreatic islet cells in rats

Abstract

Laboratory rats have played a central role in studies of islet biology. Their islets have a well-defined structure with a central core of β-cells representing 60–80% of islet cells and a layer of other endocrine cells surrounding the core including α-cells, δ-cells, and pluripotent cells. Gnetum africanum is a leafy vegetable used in the management of diabetes by the people of Southern Nigeria. Despite its wide usage, its effect on alloxan-induced pancreatic cells is largely unknown. Its protective effect on pancreatic islets was studied using rats, in which diabetes was induced using alloxan (160 mg/kg). Diabetic rats were randomly divided into five groups (n = 10). Groups 1 and 2 received 10 ml/kg of distilled water and 2 mg/kg of glibenclamide respectively, while groups 3–5 received 200, 400, and 800 mg/kg of the extract. All treatments were performed daily for 21 days, after which they were sacrificed and the pancreas was taken for histopathology. Antioxidant activity of the extract was studied using in vitro (1,1-diphenyl-2-picrylhydrazine (DPPH)) and in vivo (superoxide dismutase (SOD)) models. The extract caused a dose-dependent reversal of islet destruction, especially at the dose of 800 mg/kg, produced an increase in antioxidant activity that was dependent on the concentration using DPPH assay, and significantly (p < 0.05) increased SOD levels compared to the control. These findings suggest that G. africanum protects against pancreatic islet destruction and validates its use in diabetes management.

http://ift.tt/2FXshBx

Detailed information about chemotherapy in breast control arm might affect cognitive sequelae compared with endocrine therapy patients

http://ift.tt/2Dys0H2

CC Nerd-The Case of the Relative Insufficiency

When it comes to the efficacy of glucocorticoid therapy for the treatment of septic shock, we have existed in a state of ambiguity, torn between the results of two contradictory RCTs. The first, the Annane et al trial published in JAMA in 2002, suggested a mortality benefit in favor of the corticosteroid group in the […]

EMCrit Project by Rory Spiegel.

http://ift.tt/2mUUK2d

Biomarker-Driven Therapy in Metastatic Gastric and Esophageal Cancer: Real-Life Clinical Experience

Abstract

Background

Precision treatment of cancer uses biomarker-driven therapy to individualize and optimize patient care.

Objective

To evaluate real-life clinical experience with biomarker-driven therapy in metastatic gastric and esophageal cancer in Israel.

Patients and Methods

This multicenter retrospective cohort study included patients with metastatic gastric or esophageal cancer who were treated in the participating institutions and underwent biomarker-driven therapy. Treatment was considered to have a benefit if the ratio between the longest progression-free survival (PFS) post biomarker-driven therapy and the last PFS before the biomarker-driven therapy was ≥1.3. The null hypothesis was that ≤15% of patients gain such benefit.

Results

The analysis included 46 patients (61% men; median age, 58 years; 57% with poorly-differentiated tumors). At least one actionable (i.e., predictive of response to a specific therapy) biomarker was identified for each patient. Immunohistochemistry was performed on all samples and identified 1–8 (median: 3) biomarkers per patient (most commonly: low TS, high TOPO1, high TOP2A). Twenty-eight patients received therapy after the biomarker analysis (1–4 lines). In the 1st line after biomarker analysis, five patients (18%) achieved a partial response and five (18%) stable disease; the median (range) PFS was 129 (12–1155) days. Twenty-four patients were evaluable for PFS ratio analysis; in seven (29.2%), the ratio was ≥1.3. In a one-sided exact binomial test vs. the null hypothesis, p = 0.019; therefore, the null hypothesis was rejected.

Conclusions

Our findings demonstrated that implementing biomarker-driven analysis is feasible and could provide clinical benefit for a considerable proportion (~30%) of patients with metastatic gastric or esophageal cancer.

http://ift.tt/2EZACTP

Concentration-dependent effect of bleaching agents on the immunolabeling of interleukin-6, interleukin-17, and CD5-positive cells in the dental pulp

Abstract

Aim

To evaluate lymphocyte-like cell activation (CD5-positive cells) and the expression of interleukin (IL)-6 and IL-17 in the pulp after dental bleaching with two concentrations of hydrogen peroxide (H₂O₂).

Methodology

The right and left maxillary molars from 40 rats were treated randomly with bleaching gel with 20% H₂O₂ (BLUE group, 1 application of 50 min), 35% H₂O₂ (MAXX group, 3 applications of 15 min), or placebo gel (Control). After 2 and 30 days, the rats were killed (n=10), and the jaws were processed for histological and immunohistochemistry analysis of the pulp tissue. The scores of inflammation and immunolabeling (IL-6/IL-17) were submitted to Mann-Whitney and Kruskal-Wallis followed Dunn tests, respectively; ANOVA tests were used for comparisons of number of CD5-positive cells and pulp chamber area values (P<0.05).

Results

At 2 days, 60% of specimens of the BLUE group were associated with moderate inflammation in pulp horns, and in the MAXX group with necrosis (P<0.05). At 30 days, the pulp was organized, and tertiary dentine was formed. The MAXX group had superior immunolabeling of IL-17 at 2 days differing significantly from other groups (P<0.05). At 2 days, 90% of the specimens of the BLUE group had moderate immunolabeling of IL-6, and 50% of the MAXX group had severe immunolabeling, both significantly different from the control (P<0.05). There was no significant difference between the groups at 30 days (P>0.05). CD5-positive cells were present at 2 and 30 days, particularly in the bleached groups (P<0.05), without significant difference between time periods (P>0.05).

Conclusions

IL-6 and IL-17 participated in inflammation in the pulp tissue of rats after dental bleaching, particularly at 2 days. The immunolabeling was greater with increasing H₂O₂ concentration. This process was accompanied by the prolonged activation of CD5-positive cells.

This article is protected by copyright. All rights reserved.

http://ift.tt/2DlW3OL

Single nucleotide polymorphisms in genes encoding penicillin-binding proteins in β-lactamase-negative ampicillin-resistant Haemophilus influenzae in Japan

β-Lactamase-negative ampicillin-resistant Haemophilus influenzae is a common opportunistic pathogen of hospital- and community-acquired infections, harboring multiple single nucleotide polymorphisms in the ftsI g...

http://ift.tt/2DTP14L

A retrospective analysis of 5-fluorouracil plus cisplatin as first-line chemotherapy in the recent treatment strategy for patients with metastatic or recurrent esophageal squamous cell carcinoma

Abstract

Background

Patients with metastatic or recurrent esophageal squamous cell carcinoma (ESCC) have a poor prognosis. For decades, the most widely used first-line chemotherapy regimen for these patients has been the combination of 5-fluorouracil + cisplatin (CF). However, prognostic factors of CF as first-line chemotherapy for ESCC have not been clarified.

Methods

A total of 187 patients with metastatic or recurrent esophageal ESCC treated with CF at the National Cancer Center Hospital between January 2001 and December 2012 were enrolled in the study. The CF regimen comprised cisplatin (80 mg/m²) administered on day 1 and 5-fluorouracil (800 mg/m²) administered continuously on days 1–5, every 4 weeks. Multivariate Cox regression analysis was used to determine the potential prognostic factors.

Results

The median age of the patients was 62 (range 34–84) years. Metastasis and recurrence occurred in 116 and 71 of these patients, respectively. The overall response rate was 37.2%, with median progression-free and overall survival times of 4.8 and 10.4 months, respectively. In the multivariate analysis, higher serum C-reactive protein level and lower serum albumin level at the time of CF treatment initiation and number of metastatic sites were identified as independent prognostic factors for survival.

Conclusions

The results of this study corroborate previous findings on the efficacy of CF and will aid physicians in clinical decision-making and individual patient risk stratification, as well as in the further development of chemotherapy regimens.

http://ift.tt/2BhxQaf

Teaching of Anatomical Sciences: A blended Learning Approach

Abstract

Blended learning is the integration of different learning approaches, new technologies and activities that combine traditional face-to-face teaching methods with authentic online methodologies. Although advances in educational technology have helped to expand the selection of different pedagogies, the teaching of anatomical sciences has been challenged by implementation difficulties and other limitations. These challenges are reported to include lack of time, costs, and lack of qualified teachers. Easy access to online information and advances in technology make it possible to resolve these limitations by adopting blended learning approaches. Blended learning strategies have been shown to improve students' academic performance, motivation, attitude and satisfaction, and to provide convenient and flexible learning. Implementation of blended learning strategies has also proved cost effective. This review provides a theoretical foundation for blended learning and proposes a validated framework for the design of blended learning activities in the teaching and learning of anatomical sciences. This article is protected by copyright. All rights reserved.

http://ift.tt/2mYFcvb

UBE2C promotes rectal carcinoma via miR-381

.


http://ift.tt/2EVAy7N

DNA hypermethylation as a predictor of extramural vascular invasion (EMVI) in rectal cancer

.


http://ift.tt/2Dy3iGz

Surveillance for cancer recurrence in long-term young breast cancer survivors randomly selected from a statewide cancer registry

Abstract

Purpose

This study examined clinical breast exam (CBE) and mammography surveillance in long-term young breast cancer survivors (YBCS) and identified barriers and facilitators to cancer surveillance practices.

Methods

Data collected with a self-administered survey from a statewide, randomly selected sample of YBCS diagnosed with invasive breast cancer or ductal carcinoma in situ younger than 45 years old, stratified by race (Black vs. White/Other). Multivariate logistic regression models identified predictors of annual CBEs and mammograms.

Results

Among 859 YBCS (n = 340 Black; n = 519 White/Other; mean age = 51.0 ± 5.9; diagnosed 11.0 ± 4.0 years ago), the majority (> 85%) reported an annual CBE and a mammogram. Black YBCS in the study were more likely to report lower rates of annual mammography and more barriers accessing care compared to White/Other YBCS. Having a routine source of care, confidence to use healthcare services, perceived expectations from family members and healthcare providers to engage in cancer surveillance, and motivation to comply with these expectations were significant predictors of having annual CBEs and annual mammograms. Cost-related lack of access to care was a significant barrier to annual mammograms.

Conclusions

Routine source of post-treatment care facilitated breast cancer surveillance above national average rates. Persistent disparities regarding access to mammography surveillance were identified for Black YBCS, primarily due to lack of access to routine source of care and high out-of-pocket costs.

Implications

Public health action targeting cancer surveillance in YBCS should ensure routine source of post-treatment care and address cost-related barriers. Clinical Trials Registration Number: NCT01612338.

http://ift.tt/2mVRlAO

Adjunctive Glucocorticoid Therapy in Patients with Septic Shock

New England Journal of Medicine, Ahead of Print.


http://ift.tt/2EVv10X

Exploring Sexuality, Gender Diversity, and Intersectionality with Sexual Minorities and Transgender or Gender Nonconforming Clients

http://ift.tt/2mWcxGr

Singleplex quantitative real-time PCR for the assessment of human mitochondrial DNA quantity and quality

Abstract

Mitochondrial DNA (mtDNA) can provide a means for forensic identity testing when genotyping of nuclear DNA (nuDNA) targets is not possible due to degradation or lack of template. For degraded samples, an indication of the quantity and quality of mtDNA is essential to allow selection of appropriately sized targets for hypervariable region (HVR) analysis, which may conserve sample and resources. Three human-specific mtDNA targets of increasing length (86, 190 and 452 base pairs) were amplified by singleplex quantitative real-time PCR (qPCR), capable of providing an index of mtDNA degradation from fragment length information. Quantification was achieved by preparation of a standard curve for each target, using a purified mtDNA standard containing all three targets of interest, which produced a linear, accurate and precise result from 1×10⁸ to 10 copies. These novel assays demonstrated excellent sensitivity, specificity and reproducibility in line with the minimum information for qPCR experiments (MIQE) guidelines. Further, a separate inhibition control reaction was included to guide sample clean-up and ensure the validity of degradation assays. This protocol assists the selection and analysis of appropriately sized targets to maximize the chance of obtaining an informative result in downstream assays like sequencing.

http://ift.tt/2mWnAAb

Effects of wrist tendon vibration and eye movements on manual aiming

Abstract

In the present study, we investigated whether visual information mediates a proprioceptive illusion effect induced by muscle tendon vibration in manual aiming. Visual information was gradually degraded from a situation in which the targets were present and participants (n = 20; 22.3 ± 2.7 years) were permitted to make saccadic eye movements to designated target positions, to a condition in which the targets were not visible and participants were required to perform cyclical aiming while fixating a point between the two target positions. Local tendon vibration applied to the right wrist extensor muscles induced an illusory reduction of 15% in hand movement amplitude. This effect was greater in the fixation than in the saccade condition. Both anticipatory control and proprioceptive feedback are proposed to contribute to the observed effects. The primary saccade amplitude was also reduced by almost 4% when muscle tendon vibration was locally applied to the wrist. These results confirm a tight link between eye movements and manual perception and action. Moreover, the impact of the proprioceptive illusion on the ocular system indicates that the interaction between systems is bidirectional.

http://ift.tt/2DRnpgw

Adjunctive Glucocorticoid Therapy in Patients with Septic Shock

New England Journal of Medicine, Ahead of Print.


http://ift.tt/2EVv10X

Understanding intratumor heterogeneity by combining genome analysis and mathematical modeling

Abstract

Cancer is composed of multiple cell populations with different genomes. Each of the populations is called a clone (or subclone) and this phenomenon is called intratumor heterogeneity (ITH). ITH is observed in various types of cancers and presumed to be a major cause leading to therapeutic resistance. If a tumor harbors a major clone sensitive to a specific anti-cancer treatment, the tumor shrinks within a given period after the treatment. However, in most cases, a minor clone resistant to the chemotherapy exists in the tumor and predominantly regrows in spite of the intensive therapy. It is supposed that ITH can be generated by clonal branching during cancer evolution.

This article is protected by copyright. All rights reserved.

http://ift.tt/2DxFh2i

Limb Salvage Versus Amputation in Conventional Appendicular Osteosarcoma: a Systematic Review

Abstract

The overall survivorship in patients with appendicular osteosarcoma has increased in the past few decades. However, controversies and questions about performing an amputation or a limb salvage procedure still remain. Using three peer-reviewed library databases, a systematic review of the literature was performed to evaluate all studies that have evaluated the outcomes of appendicular osteosarcoma, either with limb salvage or amputation. The mean 5-year overall survivorship was 62% for salvage and 58% for amputation (p > 0.05). At mean 6-year follow-up, the local recurrence rates were 8.2% for salvage and 3.0% for amputation (p > 0.05). Additionally, at mean 6-year follow-up, the rate for metastasis was 33% for salvage and 38% for amputation (p > 0.05). The revision rates were higher with salvage (31 vs. 28%), and there were more complications in the salvage groups (52 vs. 34%; p > 0.05). Despite the heterogeneity of studies available for review, we observed similar survival rates between the two procedures. Although there was no significant statistical difference between rates of recurrence and metastasis, the local recurrence rate and risk of complications were higher for limb salvage as compared to amputation. Cosmetic satisfaction is often higher with limb salvage, whereas long-term expense is higher with amputation. Overall, current literature supports limb salvage procedures when wide surgical margins can be achieved while still retaining a functional limb.

http://ift.tt/2rmNMbz

Correction to: Seroprevalence of orf infection based on IgM antibody detection in sheep and goats from selected small ruminant farms in Malaysia

Abstract

There were errors in the original version of this article. First is the affiliation and spelling of one of the authors, Ashwaq Ahmed Abdullah. And the other is in the affiliation 1. Corrected data are presented here.

http://ift.tt/2FWbqPB

Detection of Toxoplasma gondii in infected meat samples by a latex agglutination test using anti-P30 recombinant antibody

Abstract

Detection of Toxoplasma gondii in meat products, which is responsible for severe disease in humans and in animals, is a great challenge. Recombinant antibodies (rAbs) have been offered as valuable tools for different diagnostic and therapeutic goals. In this study, a latex agglutination assessment for identification of Toxoplasma gondii in contaminated meat products was developed. For this propose, recombinant anti-P30 single-chain Fv (scFv) antibody gene was cloned into pET26b vector to express this antibody in high level. This gene's expression in Escherichia coli lead to production of significant amount of antibody (16 mg/L). After purification, the anti-P30 scFv was connected to beads of latex and used for agglutination test. These beads could agglutinate whole Toxoplasma gondii and contaminated meat samples. Thus, this rapid test may be applied to find contaminated samples.

http://ift.tt/2rnBqAh

Cancers, Vol. 10, Pages 24: Contemporary Management of Localized Resectable Pancreatic Cancer

Cancers, Vol. 10, Pages 24: Contemporary Management of Localized Resectable Pancreatic Cancer

Cancers doi: 10.3390/cancers10010024

Authors: Anuhya Kommalapati Sri Tella Gaurav Goyal Wen Ma Amit Mahipal

Pancreatic cancer is the third most common cause of cancer deaths in the United States. Surgical resection with negative margins still constitutes the cornerstone of potentially curative therapy, but is possible only in 15–20% of patients at the time of initial diagnosis. Accumulating evidence suggests that the neoadjuvant approach may improve R0 resection rate in localized resectable and borderline resectable diseases, and potentially downstage locally advanced disease to achieve surgical resection, though the impact on survival is to be determined. Despite advancements in the last decade in developing effective combinational chemo-radio therapeutic options, preoperative treatment strategies, and better peri-operative care, pancreatic cancer continues to carry a dismal prognosis in the majority. Prodigious efforts are currently being made in optimizing the neoadjuvant therapy with a better toxicity profile, developing novel agents, imaging techniques, and identification of biomarkers for the disease. Advancement in our understanding of the tumor microenvironment and molecular pathology is urgently needed to facilitate the development of novel targeted and immunotherapies for this setting. In this review, we detail the current literature on contemporary management of resectable, borderline resectable and locally advanced pancreatic cancer with a focus on future directions in the field.

http://ift.tt/2Du8JpV

Cancers, Vol. 10, Pages 26: Colorectal Cancers: An Update on Their Molecular Pathology

Cancers, Vol. 10, Pages 26: Colorectal Cancers: An Update on Their Molecular Pathology

Cancers doi: 10.3390/cancers10010026

Authors: Kentaro Inamura

Colorectal cancers (CRCs) are the third leading cause of cancer-related mortality worldwide. Rather than being a single, uniform disease type, accumulating evidence suggests that CRCs comprise a group of molecularly heterogeneous diseases that are characterized by a range of genomic and epigenomic alterations. This heterogeneity slows the development of molecular-targeted therapy as a form of precision medicine. Recent data regarding comprehensive molecular characterizations and molecular pathological examinations of CRCs have increased our understanding of the genomic and epigenomic landscapes of CRCs, which has enabled CRCs to be reclassified into biologically and clinically meaningful subtypes. The increased knowledge of the molecular pathological epidemiology of CRCs has permitted their evolution from a vaguely understood, heterogeneous group of diseases with variable clinical courses to characteristic molecular subtypes, a development that will allow the implementation of personalized therapies and better management of patients with CRC. This review provides a perspective regarding recent developments in our knowledge of the molecular and epidemiological landscapes of CRCs, including results of comprehensive molecular characterizations obtained from high-throughput analyses and the latest developments regarding their molecular pathologies, immunological biomarkers, and associated gut microbiome. Advances in our understanding of potential personalized therapies for molecularly specific subtypes are also reviewed.

http://ift.tt/2DyyaXH

Is invasion a necessary step for metastases in breast cancer?

Abstract

Purpose

To review the empirical evidence to support the conventional (sequential) model of breast cancer progression, which is based on the paradigm that cancer passes through several stages, including an in situ stage prior to an invasive stage, and thereafter (in some cases) disseminates to the lymph nodes and distant organs.

Methods

We review the cancer literature of the last 50 years which relates to the prevention of invasive breast cancer (through radiotherapy or surgery) and reductions in the mortality for breast cancer.

Results

For both invasive cancers and DCIS, the literature indicates that prevention of in-breast invasive recurrences does not prevent death from breast cancer. Moreover, the presence of residual cancer cells in the breast after breast-conserving surgery does not compromise the cure rate.

Conclusion

We propose an alternate (parallel) model of breast cancer wherein there is a small pool of cancer stem cells which have metastatic potential from their inception and which disseminate synchronously through several routes—to the breast stroma, to the lymph nodes and to distant organs. Cancer cells which disseminate to the breast give rise to cells which make up the bulk of the tumour mass but these are not the source of the distant metastases.

http://ift.tt/2rk4s3w