Targeting the Wnt/beta-catenin Pathway in Cancer: Update on Effectors and Inhibitors

Publication date: Available online 13 November 2017
Source:Cancer Treatment Reviews
Author(s): Nithya Krishnamurthy, Razelle Kurzrock
The Wnt/beta -catenin pathway is a family of proteins that is implicated in manyvital cellular functions like stem cell regeneration and organogenesis. Several intra-cellular signal transduction pathways are induced by Wnt, notably the Wnt/beta-catenin dependent pathway or canonical pathway and the non-canonical or beta-catenin-independent pathway, the latter includes the Wnt/Ca2+ and Planar Cell Polarity pathway (PCP). Wnt activation occurs at the intestinal crypt floor, and is critical to optimal maintenance of stem cells. Colorectal cancers show evidence of Wnt signaling pathway activation and this is associated with loss of function of the tumor regulator APC. Wnt activation has been observed in breast, lung, and hematopoietic malignancies and contributes to tumor recurrence. The Wnt pathway cross talks with the Notch and Sonic Hedgehog pathways, which has implications for therapeutic interventions in cancers. There are significant challenges in targeting the Wnt pathway, including finding agents that are efficacious without damaging the system of normal somatic stem cell function in cellular repair and tissue homeostasis. Here, we comprehensively review the Wnt pathway and its interactions with the Notch and Sonic Hedgehog pathways. We present the state of the field in effectors and inhibitors of Wnt signaling, including updates on clinical trials in various cancers with inhibitors of Wnt, Notch, and Sonic Hedgehog.

Graphical abstract

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Triple negative breast cancer: emerging therapeutic modalities and novel combination therapies

Publication date: Available online 13 November 2017
Source:Cancer Treatment Reviews
Author(s): Alice Lee, Mustafa B.A. Djamgoz
Triple negative breast cancer (TNBC) is a complex and aggressive subtype of breast cancer which lacks oestrogen receptors, progesterone receptors and HER2 amplification, thereby making it difficult to target therapeutically. In addition, TNBC has the highest rates of metastatic disease and the poorest overall survival of all breast cancer subtypes. Resultantly, development of targeted therapies for TNBC is urgently needed. Recent efforts aimed at molecular characterisation of TNBCs have revealed various emerging therapeutic targets including PARP1, receptor and non-receptor tyrosine kinases, immune-checkpoint proteins, the androgen receptor and epigenetic proteins. Key successes include that of the PARP inhibitor, olaparib, which prolonged progression-free survival in a trial of BRCA-mutated breast cancer and for which clinical approval (in this setting) appears imminent. Nevertheless, the heterogeneity of TNBC has limited the clinical benefits of many trialled therapies in 'unselected' patients. Further, drug resistance develops following use of many targeted monotherapies due to upregulation of compensatory signalling pathways. In this review, we evaluate the current status of investigational targeted treatments and present evidence for the role of novel biomarkers and combination therapies in increasing response rates and circumventing drug-induced resistance. Additionally, we discuss promising novel targets in metastatic TNBC identified through preclinical and/or epidemiological studies.



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An evaluation of the predictive validity of the URICA and ANSOCQ scales for weight gain in adults with AN in an outpatient eating disorders program: a prospective cohort study

Abstract

Background

The Transtheoretical Model (TTM) which focuses on stage of change has been the main conceptual model used in understanding the lack of motivation to change in patients with Anorexia Nervosa (AN). Whilst there is evidence to support the prognostic value of the TTM in AN, this evidence base sufferers from limitations including limited studies in adults and none in outpatient populations. The primary aim of this study was to clarify whether readiness to change, as measured by the University Rhode Island Change Assessment Scale (URICA) and the Anorexia Nervosa Stages of Change Questionnaire (ANSOCQ) could predict weight gain in adults with AN following treatment in an outpatient setting.

Methods

This was a prospective cohort analysis, which selectively used data from an existing clinical database at an outpatient eating disorders service. 119 patients met eligibility criteria and were included in this study. This included all adult patients who had a diagnosis of AN and were assessed, but not necessarily treated at the outpatient eating disorders program (Group 1). A subgroup of 63 patients (Group 2) was also analysed which only included patients who had received treatment at the program. Baseline measures included the URICA score, the ANSOCQ score, the Eating Disorders Examination Questionnaire (EDE-Q) and body mass index (BMI). BMI was also measured on discharge.

Results

The URICA scale had poor predictive validity for weight gain (r = 0.05, p = 0.725). The ANSOCQ had moderate predictive validity (Pearson's r = 0.57, p = 0.007), and accounted for 32.7% of variance in weight gain. The URICA and ANSOCQ were moderately correlated in both groups. The URICA was moderately predictive of symptom severity, measured by the EDE-Q in both groups. The ANSOCQ was moderately correlated with the EDE-Q scores in both Groups 1 and 2.

Conclusions

To the authors' knowledge this is the only study evaluating stage of change, in an adult outpatient population with AN. The findings of this study suggest that while both the URICA and ANSOCQ were associated with eating disorder symptom severity, only the ANSOCQ was able to predict weight gain in outpatients with AN suggesting its greater utility in this context.

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The removal of COD and NH 3 -N from atrazine production wastewater treatment using UV/O 3 : experimental investigation and kinetic modeling

Abstract

In this study, a UV/O₃ hybrid advanced oxidation system was used to remove chemical oxygen demand (COD), ammonia nitrogen (NH₃-N), and atrazine (ATZ) from ATZ production wastewater. The removal of COD and NH₃-N, under different UV and O₃ conditions, was found to follow pseudo-first-order kinetics with rate constants ranging from 0.0001–0.0048 and 0.0015–0.0056 min⁻¹, respectively. The removal efficiency of ATZ was over 95% after 180 min treatment, regardless the level of UV power. A kinetic model was further proposed to simulate the removal processes and to quantify the individual roles and contributions of photolysis, direct O₃ oxidation, and hydroxyl radical (OH·) induced oxidation. The experimental and kinetic modeling results agreed reasonably well with deviations of 12.2 and 13.1% for the removal of COD and NH₃-N, respectively. Photolysis contributed appreciably to the degradation of ATZ, while OH· played a dominant role for the removal of both COD and NH₃-N, especially in alkaline environments. This study provides insights into the treatment of ATZ containing wastewater using UV/O₃ and broadens the knowledge of kinetics of ozone-based advanced oxidation processes.

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Nut Consumption and Risk of Cardiovascular Disease

AbstractBackground

The associations between specific types of nuts, specifically peanuts and walnuts, and cardiovascular disease remain unclear.

Objectives

The authors sought to analyze the associations between the intake of total and specific types of nuts and cardiovascular disease, coronary heart disease, and stroke risk.

Methods

The authors included 76,364 women from the Nurses' Health Study (1980 to 2012), 92,946 women from the Nurses' Health Study II (1991 to 2013), and 41,526 men from the Health Professionals Follow-Up Study (1986 to 2012) who were free of cancer, heart disease, and stroke at baseline. Nut consumption was assessed using food frequency questionnaires at baseline and was updated every 4 years.

Results

During 5,063,439 person-years of follow-up, the authors documented 14,136 incident cardiovascular disease cases, including 8,390 coronary heart disease cases and 5,910 stroke cases. Total nut consumption was inversely associated with total cardiovascular disease and coronary heart disease after adjustment for cardiovascular risk factors. The pooled multivariable hazard ratios for cardiovascular disease and coronary heart disease among participants who consumed 1 serving of nuts (28 g) 5 or more times per week, compared with the reference category (never or almost never), were 0.86 (95% confidence interval: 0.79 to 0.93; p for trend = 0.0002) and 0.80 (95% confidence interval: 0.72 to 0.89; p for trend <0.001), respectively. Consumption of peanuts and tree nuts (2 or more times/week) and walnuts (1 or more times/week) was associated with a 13% to 19% lower risk of total cardiovascular disease and 15% to 23% lower risk of coronary heart disease.

Conclusions

In 3 large prospective cohort studies, higher consumption of total and specific types of nuts was inversely associated with total cardiovascular disease and coronary heart disease.

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JACC Instructions for Authors

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Eat Nuts, Live Longer

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Reply: The Need to Define Treatment Goals for Protein-Losing Enteropathy in Fontan Care and Research

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The Need to Define Treatment Goals for Protein-Losing Enteropathy in Fontan Care and Research

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Influence of Diabetes on CABG Patency: Targeting Functional Status After CABG in Patients With DM

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Sexual Activity as a Trigger for Sudden Cardiac Arrest

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Combination Cell Therapy for Ischemic Cardiomyopathy: Is the Whole Greater Than Sum of Its Parts?

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ACC/AATS/AHA/ASE/EACTS/HVS/SCA/SCAI/SCCT/SCMR/STS 2017 Appropriate Use Criteria for the Treatment of Patients With Severe Aortic Stenosis: A Report of the American College of Cardiology Appropriate Use Criteria Task Force, American Association for Thoracic Surgery, American Heart Association, American Society of Echocardiography, European Association for Cardio-Thoracic Surgery, Heart Valve Society, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventi

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Myofilament Calcium-Buffering Dependent Action Potential Triangulation in Human-Induced Pluripotent Stem Cell Model of Hypertrophic Cardiomyopathy

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Cardiovascular Complications of Cancer Therapy: Best Practices in Diagnosis, Prevention, and Management: Part 1

Abstract

Modern cancer therapy has successfully cured many cancers and converted a terminal illness into a chronic disease. Because cancer patients often have coexisting heart diseases, expert advice from cardiologists will improve clinical outcome. In addition, cancer therapy can also cause myocardial damage, induce endothelial dysfunction, and alter cardiac conduction. Thus, it is important for practicing cardiologists to be knowledgeable about the diagnosis, prevention, and management of the cardiovascular complications of cancer therapy. In this first part of a 2-part review, we will review cancer therapy–induced cardiomyopathy and ischemia. This review is based on a MEDLINE search of published data, published clinical guidelines, and best practices in major cancer centers. With the number of cancer survivors expanding quickly, the time has come for cardiologists to work closely with cancer specialists to prevent and treat cancer therapy–induced cardiovascular complications.

http://ift.tt/2zAg1Xu

Cardiovascular Complications of Cancer Therapy: Best Practices in Diagnosis, Prevention, and Management: Part 2

Abstract

In this second part of a 2-part review, we will review cancer or cancer therapy–associated systemic and pulmonary hypertension, QT prolongation, arrhythmias, pericardial disease, and radiation-induced cardiotoxicity. This review is based on a MEDLINE search of published data, published clinical guidelines, and best practices in major cancer centers. Newly developed targeted therapy can exert off-target effects causing hypertension, thromboembolism, QT prolongation, and atrial fibrillation. Radiation therapy often accelerates atherosclerosis. Furthermore, radiation can damage the heart valves, the conduction system, and pericardium, which may take years to manifest clinically. Management of pericardial disease in cancer patients also posed clinical challenges. This review highlights the unique opportunity of caring for cancer patients with heart problems caused by cancer or cancer therapy. It is an invitation to action for cardiologists to become familiar with this emerging subspecialty.

http://ift.tt/2zTTSnx

A Combination of Allogeneic Stem Cells Promotes Cardiac Regeneration

AbstractBackground

The combination of autologous mesenchymal stem cells (MSCs) and cardiac stem cells (CSCs) synergistically reduces scar size and improves cardiac function in ischemic cardiomyopathy. Whereas allogeneic (allo-)MSCs are immunoevasive, the capacity of CSCs to similarly elude the immune system remains controversial, potentially limiting the success of allogeneic cell combination therapy (ACCT).

Objectives

This study sought to test the hypothesis that ACCT synergistically promotes cardiac regeneration without provoking immunologic reactions.

Methods

Göttingen swine with experimental ischemic cardiomyopathy were randomized to receive transendocardial injections of allo-MSCs + allo-CSCs (ACCT: 200 million MSCs/1 million CSCs, n = 7), 200 million allo-MSCs (n = 8), 1 million allo-CSCs (n = 4), or placebo (Plasma-Lyte A, n = 6). Swine were assessed by cardiac magnetic resonance imaging and pressure volume catheterization. Immune response was tested by histologic analyses.

Results

Both ACCT and allo-MSCs reduced scar size by –11.1 ± 4.8% (p = 0.012) and –9.5 ± 4.8% (p = 0.047), respectively. Only ACCT, but not MSCs or CSCs, prevented ongoing negative remodeling by offsetting increases in chamber volumes. Importantly, ACCT exerted the greatest effect on systolic function, improving the end-systolic pressure-volume relation (+0.98 ± 0.41 mm Hg/ml; p = 0.016). The ACCT group had more phospho-histone H3+ (a marker of mitosis) cardiomyocytes (p = 0.04), and noncardiomyocytes (p = 0.0002) than did the placebo group in some regions of the heart. Inflammatory sites in ACCT and MSC-treated swine contained immunotolerant CD3⁺/CD25⁺/FoxP3⁺ regulatory T cells (p < 0.0001). Histologic analysis showed absent to low-grade inflammatory infiltrates without cardiomyocyte necrosis.

Conclusions

ACCT demonstrates synergistic effects to enhance cardiac regeneration and left ventricular functional recovery in a swine model of chronic ischemic cardiomyopathy without adverse immunologic reaction. Clinical translation to humans is warranted.

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Long-Term Outcomes of Acute Heart Failure: Where Are We Now?

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Change Is Not Always Good

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Type of Atrial Fibrillation and Outcomes in Patients With Heart Failure and Reduced Ejection Fraction

AbstractBackground

Atrial fibrillation (AF) is common in heart failure (HF), but the outcome by type of AF is largely unknown.

Objectives

This study investigated outcomes related to type of AF (paroxysmal, persistent or permanent, or new onset) in 2 recent large trials in patients with HF with reduced ejection fraction.

Methods

The study analyzed patients in the PARADIGM-HF (Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure) and ATMOSPHERE (Aliskiren Trial to Minimize Outcomes in Patients with Heart Failure) trials. Multivariable Cox regression models were used to estimate hazard ratios (HRs) for outcomes related to AF type.

Results

Of 15,415 patients, 5,481 (35.6%) had a history of AF at randomization, and of these, 1,645 (30.0%) had paroxysmal AF. Compared with patients without AF, patients with paroxysmal AF at randomization had a higher risk of the primary composite endpoint of cardiovascular death or HF hospitalization (HR: 1.20; 95% confidence interval [CI]: 1.09 to 1.32; p < 0.001), HF hospitalization (HR: 1.34; 95% CI: 1.19 to 1.51; p < 0.001), and stroke (HR: 1.34; 95% CI: 1.02 to 1.76; p = 0.037), whereas the corresponding risks in patients with persistent or permanent AF were not elevated. Neither type of AF was associated with higher mortality. New onset AF was associated with the greatest risk of adverse outcomes: primary endpoint (HR: 2.21; 95% CI: 1.80 to 2.71), HF hospitalization (HR: 2.11; 95% CI: 1.58 to 2.81), stroke (HR: 2.20; 95% CI: 1.25 to 3.88), and all-cause mortality (HR: 2.26; 95% CI: 1.86 to 2.74), all p values < 0.001, compared with patients without AF. Anticoagulants were used less often in patients with paroxysmal (53%) and new onset (16%) AF than in patients with persistent or permanent AF (71%).

Conclusions

Among HF patients with a history of AF, those with paroxysmal AF were at greater risk of HF hospitalization and stroke than were patients with persistent or permanent AF, underlining the importance of anticoagulant therapy. New onset AF was associated with increased risk of all outcomes. (Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure [PARADIGM-HF]; NCT01035255) (Aliskiren Trial to Minimize Outcomes in Patients with Heart Failure [ATMOSPHERE]; NCT00853658)

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Predicting Subclinical Atherosclerosis in Low-Risk Individuals: Ideal Cardiovascular Health Score and Fuster-BEWAT Score

AbstractBackground

The ideal cardiovascular health score (ICHS) is recommended for use in primary prevention. Simpler tools not requiring laboratory tests, such as the Fuster-BEWAT (blood pressure [B], exercise [E], weight [W], alimentation [A], and tobacco [T]) score (FBS), are also available.

Objectives

The purpose of this study was to compare the effectiveness of ICHS and FBS in predicting the presence and extent of subclinical atherosclerosis.

Methods

A total of 3,983 participants 40 to 54 years of age were enrolled in the PESA (Progression of Early Subclinical Atherosclerosis) cohort. Subclinical atherosclerosis was measured in right and left carotids, abdominal aorta, right and left iliofemoral arteries, and coronary arteries. Subjects were classified as having poor, intermediate, or ideal cardiovascular health based on the number of favorable ICHS or FBS.

Results

With poor ICHS and FBS as references, individuals with ideal ICHS and FBS showed lower adjusted odds of having atherosclerotic plaques (ICHS odds ratio [OR]: 0.41; 95% confidence interval [CI]: 0.31 to 0.55 vs. FBS OR: 0.49; 95% CI: 0.36 to 0.66), coronary artery calcium (CACS) ≥1 (CACS OR: 0.41; 95% CI: 0.28 to 0.60 vs. CACS OR: 0.53; 95% CI: 0.38 to 0.74), higher number of affected territories (OR: 0.32; 95% CI: 0.26 to 0.41 vs. OR: 0.39; 95% CI: 0.31 to 0.50), and higher CACS level (OR: 0.40; 95% CI: 0.28 to 0.58 vs. OR: 0.52; 95% CI: 0.38 to 0.72). Similar levels of significantly discriminating accuracy were found for ICHS and FBS with respect to the presence of plaques (C-statistic: 0.694; 95% CI: 0.678 to 0.711 vs. 0.692; 95% CI: 0.676 to 0.709, respectively) and for CACS ≥1 (C-statistic: 0.782; 95% CI: 0.765 to 0.800 vs. 0.780; 95% CI: 0.762 to 0.798, respectively).

Conclusions

Both scores predict the presence and extent of subclinical atherosclerosis with similar accuracy, highlighting the value of the FBS as a simpler and more affordable score for evaluating the risk of subclinical disease.

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Heart Failure With Preserved, Borderline, and Reduced Ejection Fraction: 5-Year Outcomes

AbstractBackground

Patients with heart failure (HF) have a poor prognosis and are categorized by ejection fraction (EF).

Objectives

This study sought to characterize differences in outcomes in patients hospitalized with heart failure with preserved ejection fraction (HFpEF) (EF ≥50%), heart failure with borderline ejection fraction (HFbEF) (EF 41% to 49%), and heart failure with reduced ejection fraction (HFrEF) (EF ≤40%).

Methods

Data from GWTG-HF (Get With The Guidelines–Heart Failure) were linked to Medicare data for longitudinal follow-up. Multivariable models were constructed to examine 5-year outcomes and to compare survival to median survival of the U.S. population.

Results

A total of 39,982 patients from 254 hospitals who were admitted for HF between 2005 and 2009 were included: 18,299 (46%) had HFpEF, 3,285 (8.2%) had HFbEF, and 18,398 (46%) had HFrEF. Overall, median survival was 2.1 years. In risk-adjusted survival analysis, all 3 groups had similar 5-year mortality (HFrEF 75.3% vs. HFpEF 75.7%; hazard ratio: 0.99 [95% confidence interval: 0.958 to 1.022]; HFbEF 75.7% vs. HFpEF 75.7%; hazard ratio: 0.99 [95% confidence interval: 0.947 to 1.046]). In risk-adjusted analyses, the composite of mortality and rehospitalization was similar for all subgroups. Cardiovascular and HF readmission rates were higher in those with HFrEF and HFbEF compared with those with HFpEF. When compared with the U.S. population, HF patients across all age and EF groups had markedly lower median survival.

Conclusions

Among patients hospitalized with HF, patients across the EF spectrum have a similarly poor 5-year survival with an elevated risk for cardiovascular and HF admission. These findings underscore the need to improve treatment of patients with HF.

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Cardiovascular Health, Simplified

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Expression of p27 Kip1 and p18 Ink4c in human multiple endocrine neoplasia type 1-related pancreatic neuroendocrine tumors

Abstract

Purpose

Pancreatic neuroendocrine tumors are a major manifestation of multiple endocrine neoplasia type 1 (MEN1). This tumor syndrome is caused by germline mutations in MEN1, encoding menin. Insight into pathogenesis of these tumors might lead to new biomarkers and therapeutic targets for these patients. Several lines of evidence point towards a role for p27^Kip1 and p18^Ink4c in MEN1-related tumor development in animal models for MEN1, but their contribution to human MEN1-related pancreatic neuroendocrine tumor development is not known.

Methods

In this study, we characterized protein expression of p27^Kip1 and p18^Ink4c in human MEN1-related PanNETs by immunohistochemistry. From the nationwide DutchMEN1 Study Group database including > 90% of the Dutch MEN1 population, MEN1-patients, who underwent pancreatic surgery, were selected. A tissue micro-array was constructed with available paraffin tissue blocks, and PanNETs from 61 MEN1 patients were eligible for analysis.

Results

Expression of p27^Kip1 was high in 57 (93%) PanNETs and 67% of the tumors showed low expression of p18^Ink4c (67.3%). No association was found between expression of either p27^Kip1 or p18^Ink4c and clinic-pathological characteristics.

Conclusions

These findings indicate that loss of p18^Ink4c, but not p27^Kip1, is a common event in the development of MEN1-related PanNETs. Restoration of p18^Ink4c function through CDK4/6 inhibitors could be a therapeutic option for MEN1-related PanNETs.

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Patterns of relapse as determined by 68 Ga-PSMA ligand PET/CT after radical prostatectomy

Abstract

Purpose

To evaluate the patterns of relapse and impact on the intended treatment when using ⁶⁸Ga-prostate-specific membrane antigen (PSMA) ligand positron emission tomography/computed tomography (PET/CT) imaging for restaging of disease in patients with biochemical relapse after radical prostatectomy (RP) before salvage radiotherapy (sRT).

Methods

In all, 39 patients with biochemical recurrence after RP who had no primary indication for adjuvant RT due to the absence of biologically unfavorable disease (e.g., extracapsular extension, seminal vesicle invasion, positive margins, or lymph node involvement) underwent a ⁶⁸Ga-PSMA ligand PET/CT for planning of sRT.

Results

PET/CT was positive in 84.6% (33/39) of patients. A total of 61 lesions were observed in these patients (on average 1.8 lesions per patient); 30.3% (10/33) of patients had locally recurrent disease in the prostatic bed. The clinical TNM stage (TNM: tumour-lymph nodes-metastasis-classification) was altered in 69.7% (23/33) of patients following PET, resulting in individualized treatment concepts. A prostate-specific antigen (PSA) >1.0 ng/mL was significantly associated with an increased risk of extrapelvic metastatic disease (p = 0.048). The PSA level at the time of PSMA ligand PET/CT correlated with the peak standardized uptake value (SUV_peak; p = 0.002). According to current clinical guidelines, the remaining 15.4% (6/39) of patients without evidence of disease on PET received sRT with a dose of 66.0 Gy.

Conclusion

Our results suggest that in patients with biochemical recurrence who did not receive early sRT, a ⁶⁸Ga-PSMA ligand PET/CT for restaging of disease allows for tailoring and individualizing treatment. Particularly in patients with PSA levels above 1.0 ng/mL, a ⁶⁸Ga-PSMA ligand PET/CT should be performed for therapy planning, since patients often have metastases not confined to the pelvis.

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Revisiting interhemispheric imbalance in chronic stroke: A tDCS study

Publication date: January 2018
Source:Clinical Neurophysiology, Volume 129, Issue 1
Author(s): Alana B. McCambridge, James W. Stinear, Winston D. Byblow
ObjectiveChronic stroke patients with moderate-severe motor impairment may have an increased reliance on contralesional vs ipsilesional motor areas to control the paretic arm. We hypothesised that increasing contralesional excitability with anodal transcranial direct current stimulation (a-tDCS) would benefit motor performance in patients with moderate-severe impairment.MethodsTen patients with motor impairment at the chronic stage after stroke received a-tDCS, cathodal (c-tDCS) and sham with the target electrode over contralesional motor cortex (M1). Motor performance was quantified from the circularity and size of planar movements made with the paretic arm. Contralateral and ipsilateral corticospinal excitability was inferred using transcranial magnetic stimulation. Corticospinal tract integrity and basal GABA concentration were assessed with magnetic resonance imaging and spectroscopy.ResultsAnodal tDCS increased contralesional corticomotor excitability evident from motor evoked potentials in both wrist extensors (both P<0.043). Cathodal tDCS did not affect corticomotor excitability (P>0.37). The effect of tDCS on motor performance with the paretic limb was negatively associated with ipsilesional GABA concentration after c-tDCS (P=0.001).ConclusionsFurther investigation of noninvasive brain stimulation protocols that facilitate contralesional M1 is warranted.SignificanceThe inter-hemispheric imbalance model of stroke recovery may not apply to patients with more severe impairment.



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Mucociliary transport, differential white blood cells, and cyto-genotoxicity in peripheral erythrocytes in fish from a polluted urban pond

Abstract

The present study evaluated the water quality of a polluted pond through the analysis of in vitro mucociliary transport, hematological parameters, and biomarkers of cyto-genotoxicity in the Nile tilapia (Oreochromis niloticus). Blood and mucus samples were collected from ten specimens from the polluted pond and from ten specimens from a control area. The fish were anesthetized with 3% benzocaine, mucus was collected directly from the gills, and blood was drawn from the caudal artery. Blood smears were stained using the May-Grünwald Giemsa process for the differential leukocyte counts and to determine the frequency of leukocytes, thrombocytes, erythroblasts, micronuclei, and nuclear abnormalities. The results revealed low transportability in vitro, a high percentage of monocytes and eosinophils, and increased frequency of leukocytes and nuclear abnormalities in fish from the polluted pond. However, the frequency of thrombocytes and erythroblasts and the percentage of lymphocytes and neutrophils were significantly lower. It is possible to conclude that changes in fish are due to poor water quality and that these non-destructive biomarkers can be used for the biomonitoring of aquatic environments vulnerable to contamination.

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Toxicities and risk assessment of heavy metals of the six most consumed fish from the Marmara Sea

Abstract

Bream, anchovy, horse mackerel, sea bass, sardine, and whiting that are commonly consumed by the Turkish community were collected from the Marmara Sea in September and March and were analyzed for trace elements and for fat content. The total concentrations of some metals in these fish were determined using ICP-MS in acid extracts obtained after microwave digestion. The seasonal fat contents of the fish samples were determined gravimetrically following a Soxhlet extraction method. Experimental results were evaluated statistically using t tests and principal component analyses. This enabled the comparison of the elements' contents in the fish samples in March and September and also led to an investigation into whether or not there is a relationship between the elements' contents and the fat amount. The results of this work showed that a significant temporal difference was observed. This difference was not related to the seasonal variation in fat concentrations.

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Health risk assessment of arsenic and heavy metals (Cd, Cu, Co, Pb, and Sn) through consumption of caviar of Acipenser persicus from Southern Caspian Sea

Abstract

In the current study contents of As, Cd, Cu, Co, Pb, and Sn were determined in the caviar of Persian sturgeon collected from Southern Caspian Sea sampling site. After acid digestion of caviar specimens, the concentrations of elements determined using ICP-OES. The results showed that the mean concentrations (mg kg⁻¹) of elements in caviar samples were 0.01 for As, 0.05 for Cd, 1.42 for Cu, 0.01 for Co, 0.01 for Pb, and 0.28 for Sn and for all the elements are significantly lower than the adverse level for the human consumption. Also, health risk index (HRI) values were within the safe limits (HRI < 1). Therefore, there is no potential health risk to adults and children via consumption of caviar. Due to the discharge of hazardous chemicals into the marine ecosystems especially the Caspian Sea, residue analysis of pollutants in the sea foods is recommended.

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Diterpenoid natural compound C4 (Crassin) exerts cytostatic effects on triple-negative breast cancer cells via a pathway involving reactive oxygen species

Abstract

Purpose

Triple-negative breast cancers (TNBC) lack expression of three common cell surface receptors, i.e., estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2). Accordingly, TNBCs are associated with fewer treatment options and a relatively poor prognosis. Having screened a National Cancer Institute natural compound library, the purpose of this study was to investigate the bioactivity of compound C4 (Crassin) in TNBC cells.

Methods

Cell viability assays were performed in two TNBC cell lines, MDA-MB-231 and 4T1, following C4 treatment in the presence or absence of the antioxidant N-acetyl-L-cysteine (NAC). Phosphorylation of Akt and ERK was assessed by Western blotting. Apoptosis, necrosis, autophagy, necroptosis, ferroptosis and cytostasis assays were performed to explain viability deficits resulting from C4 exposure.

Results

We found that the viability of the TNBC cells tested decreased in a concentration- and time-dependent fashion following C4 treatment. This decrease coincided with an unexpected increase in the expression of the cell survival effectors pAkt and pERK. In addition, we found that both the decreased cell viability and the increased pAkt/pERK levels could be rescued by the antioxidant NAC, suggesting a central role for reactive oxygen species (ROS) in the mechanism of action of C4. Necrosis, apoptosis, necroptosis and ferroptosis could be ruled out as cell death mechanisms. Instead, we found that C4 induced cytostasis downstream of ROS activation. Finally, we observed a synergistic effect between C4 and the chemotherapeutic drug doxorubicin in TNBC cells.

Conclusions

From our in vitro data we conclude that C4 exerts cytostatic effects on triple-negative breast cancer cells via a pathway involving reactive oxygen species. Its potential value in combination with cytotoxic therapies merits deeper investigation in pre-clinical models.

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Glycogen synthase kinase-3β mediated regulation of matrix metalloproteinase-9 and its involvement in oral squamous cell carcinoma progression and invasion

Abstract

Purpose

Oral squamous cell carcinoma (OSCC)-related deaths mainly result from invasion of the tumor cells into local cervical lymph nodes. It has been reported that progressive basement membrane loss promotes the metastatic and invasive capacities of OSCCs. Matrix metalloproteinase-9 (MMP-9) is known to play a central role in tumor progression and invasion. However, the role of MMP-9 in OSCC invasion has so far remained paradoxical and little is known about its regulation. Here, we aimed to assess MMP-9 expression regulation and its activation by glycogen synthase kinase-3β during human OSCC progression and invasion.

Methods

In the present study, 178 human OSCC samples, including 118 fresh samples (18 adjacent normal, 42 noninvasive and 58 invasive tumor samples) and 60 archival human tissue microarray (TMA) tongue cancer samples, were included. mRNA expression, protein expression, MMP-9/-2 activity, protein-protein interaction and Snail, c-Myc, β-catenin and TIMP1 expression were assessed using RT-PCR, immunohistochemistry, Western blotting, co-immunoprecipitation and gelatin zymography analyses, respectively. Wnt5a and LPA mediated MMP-9 regulation was assessed in OCSCC-derived SCC-9 cells exogenously expressing GSK3β (WT) or non phosphoryable GSK3β (S9A).

Results

We observed a progressive up-regulation/activation of MMP-9 at various stages of oral tumor progression/invasion. Positive correlations were observed between MMP-9 and c-Myc expression, MMP-9 and MMP-2 activity, MMP-9 and TIMP1 expression and MMP-9 activity and TIMP1-MMP-9 interaction. In contrast, a negative correlation between phosphorylated β-catenin and MMP-9 expression was observed. Conversely, we found that in oral tongue SCC MMP-9 expression was positively correlated with inactivation of GSK3 signaling. Finally, we found that Wnt5a and LPA mediated increased MMP-9 and decreased GSK3β activities in tongue SCC-derived SCC-9 cells. MMP-9 regulation by GSK3β was confirmed by using phosphoryable/regulatory GSK3β (WT construct) and not by non-phosphoryable GSK3β (S9A construct).

Conclusions

Collectively, our results show that MMP-9 overexpression and activation are important events occurring during OSCC progression/invasion and that this overexpression/activation is regulated by c-Myc, active MMP-2 and inactive GSK3β mediated pathways.

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Capacity of six shrub species to retain atmospheric particulates with different diameters

Abstract

Garden plants can absorb and retain atmospheric particles and are important for remediating environmental pollution. In this study, the dust retention characteristics of six typical shrub species were measured in the greenbelt of a road in the Chengyang District of Qingdao, China, and the maximum capacity for dust retention of each species was determined. The different diameters and areas occupied by particulate matter (PM) were analyzed on the leaf surfaces of the plants. Based on the results for the six shrub species, the rank order of average content of dust retention per unit leaf area was Euonymus japonicus > Pyracantha fortuneana > Ligustrum vicaryi > Amygdalus triloba > Ligustrum sinense > Forsythia suspensa, whereas the rank order of average content per unit volume was E. japonicus > A. triloba > P. fortuneana > L. vicaryi > L. sinense > F. suspensa. The maximum content of dust retention per unit leaf area was reached in approximately 24 days. Plants retained atmospheric PM primarily on the upper leaf surfaces. The primary portion of particles on the leaves was PM₁₀ (over 80%), and PM_2.5 was the principal component of PM₁₀. Leaf surface structure significantly affected the abilities of plants to retain PM, and the plants with a thick wax layer or large and dense stomata adsorbed more PM, such as E. japonicus. This study provides a scientific basis for the capacity of landscape plants to retain different diameter particulates.

http://ift.tt/2zBFDCJ

Effect of water constituents on the degradation of sulfaclozine in the three systems: UV/TiO 2 , UV/K 2 S 2 O 8 , and UV/TiO 2 /K 2 S 2 O 8

Abstract

Bicarbonate, phosphate, chloride ions, and humic substances are among the constituents most widely present in natural waters. These non-target constituents can greatly affect the efficiency of advanced oxidation processes used for water decontamination due to their capacity to interfere with the adsorption of the target compounds on the surface of TiO₂, absorb photons, scavenge hydroxyl radicals (·OH), and generate photochemical reactive intermediates. In this work, the effect of these constituents on the degradation of sulfaclozine (SCL) was monitored in three different AOPs systems: UV/TiO₂, UV/K₂S₂O₈, and UV/TiO₂/K₂S₂O₈. It was shown that bicarbonate (HCO₃⁻) and phosphate (HPO₄²⁻) ions enhanced the degradation of SCL in UV/TiO₂ and UV/TiO₂/K₂S₂O₈ systems whereas the addition of humic substances influenced these rates with a much smaller extent. On the other hand, the degradation rate of SCL in the UV/K₂S₂O₈ system was not affected by the presence of HCO₃⁻ and HPO₄²⁻ but was inhibited in the presence of humic substances. In addition, the different mechanisms that can take place in the presence of these constituents were discussed and the degradation rate enhancement in presence of HCO₃⁻ and HPO₄²⁻ was attributed to the formation of new reactive species such as carbonate (CO₃^·–) and hydroxyl (·OH) radicals activated by TiO₂ holes (h⁺). In the presence of chloride (Cl⁻) and nitrate (NO₃⁻) ions, an enhancement of SCL adsorption on the surface of TiO₂ was observed. Finally, a comparative study of the degradation of SCL in river water and ultrapure water was reported.

http://ift.tt/2hq1JxW

MicroRNAs and their role for T stage determination and lymph node metastasis in early colon carcinoma

Abstract

Worldwide, colon cancer is among the most common cancer entities. Understanding the molecular background is the key to enable accurate stage determination, which is crucial to assess optimal therapy options. The search for preoperative biomarkers is ongoing. In recent years, several studies have proposed a diagnostic and prognostic role for miRNAs in cancer. Aim of this study was to evaluate miRNA expression patterns correlating with tumor stage, especially lymph node metastasis, in primary colon carcinoma tissue. Screening was accomplished using GeneChip^® miRNA v3.0 arrays (Thermo Fisher Scientific, Waltham, MA, USA) and validated via TaqMan^® qPCR assays (Thermo Fisher Scientific, Waltham, MA, USA) to investigate miRNA expressions in 168 FFPE and 83 fresh frozen colon carcinoma samples. Regarding lymph node status, analyses displayed no significantly differential miRNA expression. Interestingly, divergent expression of miR-18a-5p, miR-20a-5p, miR-21-5p, miR-152-3p and miR-1973 was detected in stage pT1. Although miRNAs might not represent reliable biomarkers regarding lymph node metastasis status, they could support risk assessment in stage T1 tumors.

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Editorial board members

Publication date: 1 September 2017
Source:Advanced Drug Delivery Reviews, Volume 118





http://ift.tt/2jo9998

Dopamine-modified Mn-doped ZnS quantum dots fluorescence probe for the sensitive detection of tyrosinase in serum samples and living cells imaging

Publication date: March 2018
Source:Sensors and Actuators B: Chemical, Volume 256
Author(s): Fangmei Zhang, Longbin Xu, Qingnan Zhao, Ying Sun, Xinghua Wang, Pinyi Ma, Daqian Song
Tyrosinase (TYR) plays vital roles in melanin biosynthesis and function as an important biomarker for melanoma cancer; and thus has made rapid and sensitive detections for its activity to be on urgent demands. In this study, a facile aqueous fluorescence probe based on dopamine-functionalized-Mn-doped ZnS quantum dots (Dopa-Mn:ZnS QDs) was developed to detect TYR activity. When dopamine moiety in Dopa-Mn:ZnS QDs was oxidized to dopaquinone derivative by TYR, an intra-particle photo-induced electron transfer (PET) process between Dopa-Mn:ZnS QDs and dopaquinone moiety takes place, and as a result, the fluorescence is quenched. Quantitative evaluation of TYR activity was studied in terms of the relationship between fluorescence quenching efficiency and TYR activity. The probe could detect TYR in a broad linear range of up to 1620UL⁻¹ with a low detection limit of 1.82UL⁻¹. It was then applied to detect TYR in chicken serum samples, in which, TYR could be recovered by 88.3–100.7%. Finally, the probe demonstrated low cytotoxicity as evaluated by MTT assay and successfully applied to intracellular imaging of A549 cells. This study has indicated potential applications of Dopa-Mn:ZnS QDs probe in monitoring TYR-associated diseases, clinical diagnostics, and drug discovery.

Graphical abstract

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Mutual effect of Phragmites australis, Arundo donax and immobilization agents on arsenic and trace metals phytostabilization in polluted soils

Publication date: 15 March 2018
Source:Geoderma, Volume 314
Author(s): Paola Castaldi, Margherita Silvetti, Rebeca Manzano, Giuseppe Brundu, Pier Paolo Roggero, Giovanni Garau
This study assessed the suitability of Phragmites australis and Arundo donax for the aided phytostabilization of metal(loid)s in polluted soils treated with an iron-rich water treatment residue (Fe-WTR), a municipal solid waste compost (MSW-C) and their combination (Fe-WTR+MSW-C). The three soils under study (S1, S2, S3) showed very high total concentrations of As (from 371 to 22,661mg·kg⁻¹ d.w.) and variable amounts of co-occurring trace metals (TMs) (i.e. Pb, 74–2162; Zn, 57-1535 and Cu, 19–412mg·kg⁻¹ d.w.). Results showed that P. australis and A. donax biomass was significantly increased in all the amended soils and followed the order: MSW-C>Fe-WTR+MSW-C>Fe-WTR>Control. For both plant species grown in the amended soils, metal(loid)s concentration in below ground organs were higher than those in above ground tissues. In S1 soil (the most polluted and acidic; pH3.77), the highest As bioaccumulation factors (BAFs) were recorded for plants grown on untreated soil (approx. 45% higher with respect to those recorded for plants in treated soils), where the concentration of labile As was significantly higher with respect to amended soils. By contrast, in S2 and S3 soils, the most effective As bioaccumulator plants were grown on soils treated with compost, even if the addition of this amendment induced a decrease of the soil As extractability. Similar results were detected for TMs in S1 soil, where P. australis and A. donax grown on soil amended with compost showed the highest Pb, Zn and Cu BAFs, while variable results were detected in S2 soil. The lowest As translocation factors (TFs ≪1.0) were detected for plants grown on compost-amended soils (25 and 51, 34 and 50, 64 and 55% lower with respect to P. australis and A. donax control plants in S1, S2 and S3 soils respectively), while TMs translocation from roots to shoots was more variable and depending on soil, TMs, amendment and plant species.Overall, our results indicate the suitability of P. australis and A. donax, and of Fe-WTR and MSW-C, for the aided phytostabilization of soils contaminated with arsenic and trace metals.



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Sensitive detection of pyrraline with a molecularly imprinted sensor based on metal-organic frameworks and quantum dots

Publication date: March 2018
Source:Sensors and Actuators B: Chemical, Volume 256
Author(s): Huilin Liu, Tianhong Ni, Lin Mu, Dianwei Zhang, Jing Wang, Shuo Wang, Baoguo Sun
A novel opto-sensor was constructed by anchoring the molecularly imprinted polymers (MIPs) onto the surfaces of metal-organic frameworks (MOFs) and CdSe/ZnS quantum dots (QDs) via one-step reverse micro-emulsion polymerization. It was used for highly selective and sensitive detection of pyrraline (PRL) in milk powders. High selectivity was guaranteed by molecular imprinting, and sensitivity was improved by double signal amplification using the CdSe/ZnS QDs nanocrystals as fluorescent elements and MOFs as an imprinting matrix. The QDs were introduced into the molecularly imprinted sensor as a tentacle to sense bonding interactions between the MIPs and target molecules and to transduce them into fluorescent signals. The opto-sensor had a high fluorescence quantum yield because of the use of hydrophobic CdSe/ZnS QDs and the reverse micro-emulsion. Under optimized conditions, the fluorescence intensity of the opto-sensor was linear with increasing PRL concentration over the range 5×10⁻⁶–1×10⁻³molL⁻¹, with a detection limit of 3.9×10⁻⁶molL⁻¹. Recoveries of 90–110% were achieved in direct selective detection of PRL in milk powders.



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Use of a Non-ICU Specialty Ward For Immediate Post-operative Management of Head and Neck Free Flap

Conditions:   Head and Neck Cancer;   Head and Neck Squamous Cell Carcinoma;   Head and Neck Carcinoma;   Trauma
Intervention:   Other: Non-ICU Specialty ward
Sponsor:   Arnaud Bewley
Recruiting

http://ift.tt/2zEBs9l

Multiorgan Metabolic Imaging Response Assessment of Abemaciclib

Conditions:   Esophageal Adenocarcinoma;   Esophagus SCC;   Cholangiocarcinoma;   Urothelial/Bladder Cancer, Nos;   Endometrial Cancer
Intervention:   Drug: Abemaciclib
Sponsors:   Jules Bordet Institute;   Eli Lilly and Company
Not yet recruiting

http://ift.tt/2hqarfs

Rhumatisme psoriasique en France, du nourrisson à la personne âgée : données de deux études transversales multicentriques

Publication date: Available online 13 November 2017
Source:Annales de Dermatologie et de Vénéréologie
Author(s): A. Galezowski, F. Maccari, S. Hadj-Rabia, M.-L. Sigal, A. Phan, M. Lahfa, A.-C. Bursztejn, H. Barthélémy, F. Boralévi, Z. Reguiai, C. Chiavérini, E. Estève, E. Bourrat, M. Ruer-Mulard, A. Beauchet, E. Mahé
IntroductionLe rhumatisme psoriasique touche 20 à 30 % des patients atteints de psoriasis cutané. Peu de données épidémiologiques sont disponibles en France sur sa prévalence, ses associations avec l'atteinte dermatologique et ses comorbidités.ObjectifsÉvaluer les aspects épidémiologiques et associations cliniques et épidémiologiques du rhumatisme psoriasique chez les enfants et les adultes, en France.MéthodesDeux études transversales, multicentriques ont été menées en France chez les enfants (χ-Psocar, 23 centres de dermatologie pédiatrique membres du GR SFDP, 1 an) et les adultes (Resopsocar, 29 centres de dermatologie membres du GEM RESOPSO, 4 mois) pour étudier les comorbidités cardiovasculaires et métaboliques du psoriasis.RésultatsParmi les 313 enfants (garçons : 47,6 % ; âge moyen, 9,4 ans) et 1954 adultes (hommes : 56,0 % ; âge moyen : 48,5 ans) atteints de psoriasis, 4,2 % des enfants et 21,0 % des adultes souffraient de rhumatisme psoriasique. La prévalence augmentait avec l'âge : 2,2 % des enfants, 14,2 % des adolescents et plus de 20 % après 40 ans. Elle diminuait après 70 ans (19,4 %). Quel que soit l'âge, le sexe n'était pas associé au rhumatisme psoriasique. Chez les enfants, le rhumatisme était associé à l'atteinte unguéale (p=0,04) et à la sévérité de la maladie (p=0,0004). Chez les adultes il était associé au psoriasis en plaques (p=0,002), à la sévérité de la maladie (p<0,0001) et à l'obésité (p<0,0001). Le psoriasis en plaques localisé (cuir chevelu, psoriasis palmo-plantaire par exemple) était moins souvent associé au rhumatisme psoriasique (p<0,05).ConclusionsCes deux études transversales menées en France sur 2267 patients, principalement hospitaliers, donnent une idée de la prévalence du rhumatisme psoriasique tout au long de la vie. La prévalence augmente progressivement avec l'âge, sans différence de genre, avant de diminuer chez les personnes âgées. Nous confirmons l'association avec l'onychopathie psoriasique dès l'enfance et avec l'obésité chez les adultes.BackgroundPsoriatic arthritis affects 20–30% of patients with psoriasis. Few epidemiological data are available in France about its prevalence and its association with skin lesions and comorbidities.ObjectivesTo assess the epidemiological aspects and the risk factors for psoriatic arthritis in children and adults in France.MethodsTwo cross-sectional studies were conducted in France in children (χ-Psocar, 23 pediatric dermatology centers belonging to the SFDP, 1 year) and adults (Resopsocar, 29 dermatology centers belonging to GEM RESOPSO, 4 months) to study the link between psoriasis and cardiovascular and metabolic comorbidities.ResultsThree hundred and thirteen children (males: 47.6%; mean age: 9.4 yrs) and 1,954 adults (males: 56.0%; mean age: 48.5 yrs) with psoriasis were included, with 4.2% of the children and 21.0% of the adults presenting psoriatic arthritis. Prevalence increased with age: 2.2% of children, 14.2% of adolescents, and over 20% after 40 years. It decreased after the age of 70 years (19.4%). Regardless of age, arthritis was not associated with gender. In the children's group, rheumatism was associated with nail involvement (P=0.04) and disease severity (P=0.0004). Adult rheumatism was associated with generalized plaque psoriasis (P=0.002), disease severity (P<0.0001), and obesity (P<0.0001). Localized plaque psoriasis was less often associated with arthritis (P<0.05).ConclusionsThese two cross-sectional studies conducted in 2267 patients in France yielded information on the prevalence of joint involvement from infants to elderly subjects. It is the first study conducted in a single population to provide data for the whole population. Prevalence gradually increases with age, without gender difference, before decreasing in old age. We confirm the association of nail involvement in the first years of life, and of obesity in adults.



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Ecotracer: analyzing concentration of contaminants and radioisotopes in an aquatic spatial-dynamic food web model

Publication date: January 2018
Source:Journal of Environmental Radioactivity, Volume 181
Author(s): William J. Walters, Villy Christensen
Ecotracer is a tool in the Ecopath with Ecosim (EwE) software package used to simulate and analyze the transport of contaminants such as methylmercury or radiocesium through aquatic food webs. Ecotracer solves the contaminant dynamic equations simultaneously with the biomass dynamic equations in Ecosim/Ecospace. In this paper, we give a detailed description of the Ecotracer module and analyze the performance on two problems of differing complexity. Ecotracer was modified from previous versions to more accurately model contaminant excretion, and new numerical integration algorithms were implemented to increase accuracy and robustness. To test the mathematical robustness of the computational algorithm, Ecotracer was tested on a simple problem for which we know an analytical solution. These results demonstrated the effectiveness of the program numerics. A much more complex model, the release of the cesium radionuclide ¹³⁷Cs from the Fukushima Dai-ichi nuclear accident, was also modeled and analyzed. A comparison of the Ecotracer results to sampled ¹³⁷Cs measurements in the coastal ocean area around Fukushima show the promise of the tool but also highlight some important limitations.



http://ift.tt/2jnwbwE

Next-generation Sequencing-based genomic profiling: Fostering innovation in cancer care?

OBJECTIVES: With the development of next-generation sequencing (NGS) technologies, DNA sequencing has been increasingly utilized in clinical practice. Our goal was to investigate the impact of genomic evaluation on treatment decisions for heavily pretreated patients with metastatic cancer. METHODS: We analyzed metastatic cancer patients from a single institution whose cancers had progressed after all available standard-of-care therapies and whose tumors underwent next-generation sequencing analysis. We determined the percentage of patients who received any therapy directed by the test, and its efficacy. RESULTS: From July 2013 to December 2015, 185 consecutive patients were tested using a commercially available next-generation sequencing-based test, and 157 patients were eligible. Sixty-six patients (42.0%) were female, and 91 (58.0%) were male. The mean age at diagnosis was 52.2 years, and the mean number of pre-test lines of systemic treatment was 2.7. One hundred and seventy-seven patients (95.6%) had at least one identified gene alteration. Twenty-four patients (15.2%) underwent systemic treatment directed by the test result. Of these, one patient had a complete response, four (16.7%) had partial responses, two (8.3%) had stable disease, and 17 (70.8%) had disease progression as the best result. The median progression-free survival time with matched therapy was 1.6 months, and the median overall survival was 10 months. CONCLUSION: We identified a high prevalence of gene alterations using an next-generation sequencing test. Although some benefit was associated with the matched therapy, most of the patients had disease progression as the best response, indicating the limited biological potential and unclear clinical relevance of this practice.

http://ift.tt/2zzqHWi

Longitudinal study of lung function in pregnant women: Influence of parity and smoking

OBJECTIVES: To evaluate pulmonary function in the first and third trimesters of pregnancy and analyze the influence of parity and smoking on spirometry parameters. METHODS: This longitudinal prospective study included a cohort of 120 pregnant women. The inclusion criteria were as follows: singleton pregnancy, gestational age less than 13.86 weeks, and no preexisting maternal diseases. The exclusion criteria were as follows: change of address, abortion, and inadequate spirometry testing. ClinicalTrials.gov: NCT02807038. RESULTS: A decrease in values of forced vital capacity and forced expiratory volume were noted in the first second from the first to third trimester. In the first and third trimesters, multiparous women demonstrated lower absolute forced vital capacity and forced expiratory volume values in the first second compared with nulliparous women (p<0.0001 and p=0.001, respectively). Multiparous women demonstrated reduced forced expiratory flow in 25% to 75% of the maneuver compared with nulliparous women in the first (p=0.005) and third (p=0.031) trimesters. The absolute values of forced expiratory flow in 25% to 75%, forced expiratory volume in the first second and predicted peak expiratory flow values in the third trimester were higher in smokers compared with nonsmokers (p=0.042, p=0.039, p=0.024, and p=0.021, respectively). CONCLUSION: There was a significant reduction in forced vital capacity and forced expiratory volume values in the first second during pregnancy. Parity and smoking significantly influence spirometric variables.

http://ift.tt/2zUffF6

Identification of the difference in the pathogenesis in heart failure arising from different etiologies using a microarray dataset

OBJECTIVES: Clinically, patients with chronic heart failure arising from different etiologies receive the same treatment. However, the prognoses of these patients differ. The purpose of this study was to elucidate whether the pathogenesis of heart failure arising from different etiologies differs. METHODS: Heart failure-related dataset GSE1145 was obtained from the Gene Expression Omnibus database. Differentially expressed genes were identified using R. A protein-protein interaction network of the differentially expressed genes was constructed using Search Tool for the Retrieval of Interacting Genes. The modules in each network were analyzed by Molecular Complex Detection of Cytoscape. The Database for Annotation, Visualization and Integrated Discovery was used to obtain the functions of the modules. RESULTS: Samples contained in GSE1145 were myocardial tissues from patients with dilated cardiomyopathy, familial cardiomyopathy, hypertrophic cardiomyopathy, ischemic cardiomyopathy, and post-partum cardiomyopathy. The differentially expressed genes, modules, and functions of the modules associated with different etiologies varied. Abnormal formation of extracellular matrix was overlapping among five etiologies. The change in cytoskeleton organization was specifically detected in dilated cardiomyopathy. The activation of the Wnt receptor signaling pathway was limited to hypertrophic cardiomyopathy. The change in nucleosome and chromatin assembly was associated with only familial cardiomyopathy. Germ cell migration and disrupted cellular calcium ion homeostasis were solely detected in ischemic cardiomyopathy. The change in the metabolic process of glucose and triglyceride was detected in only post-partum cardiomyopathy. CONCLUSION: These results indicate that the pathogenesis of heart failure arising from different etiologies varies, which may provide molecular evidence supporting etiology-based treatment for heart failure patients.

http://ift.tt/2zxgqcV

Comparison of short-segment monoaxial and polyaxial pedicle screw fixation combined with intermediate screws in traumatic thoracolumbar fractures: a finite element study and clinical radiographic review

OBJECTIVES: No studies have compared monoaxial and polyaxial pedicle screws with regard to the von Mises stress of the instrumentation, intradiscal pressures of the adjacent segment and adjacent segment degeneration. METHODS: Short-segment monoaxial/polyaxial pedicle screw fixation techniques were compared using finite element methods, and the redistributed T11-L1 segment range of motion, largest maximal von Mises stress of the instrumentation, and intradiscal pressures of the adjacent segment under displacement loading were evaluated. Radiographic results of 230 patients with traumatic thoracolumbar fractures treated with these fixations were reviewed, and the sagittal Cobb's angle, vertebral body angle, anterior vertebral body height of the fractured vertebrae and adjacent segment degeneration were calculated and evaluated. RESULTS: The largest maximal values of the von Mises stress were 376.8 MPa for the pedicle screws in the short-segment monoaxial pedicle screw fixation model and 439.9 MPa for the rods in the intermediate monoaxial pedicle screw fixation model. The maximal intradiscal pressures of the upper adjacent segments were all greater than those of the lower adjacent segments. The maximal intradiscal pressures of the monoaxial pedicle screw fixation model were larger than those in the corresponding segments of the normal model. The radiographic results at the final follow-up evaluation showed that the mean loss of correction of the sagittal Cobb's angle, vertebral body angle and anterior vertebral body height were smallest in the intermediate monoaxial pedicle screw fixation group. Adjacent segment degeneration was less likely to be observed in the intermediate polyaxial pedicle screw fixation group but more likely to be observed in the intermediate monoaxial pedicle screw fixation group. CONCLUSION: Smaller von Mises stress in the pedicle screws and lower intradiscal pressure in the adjacent segment were observed in the polyaxial screw model than in the monoaxial pedicle screw fixation spine models. Fracture-level fixation could significantly correct kyphosis and reduce correction loss, and adjacent segment degeneration was less likely to be observed in the intermediate polyaxial pedicle screw fixation group.

http://ift.tt/2zUfaRO

Effect of prophylactic non-invasive mechanical ventilation on functional capacity after heart valve replacement: a clinical trial

OBJECTIVE: During cardiac surgery, several factors contribute to the development of postoperative pulmonary complications. Non-invasive ventilation is a promising therapeutic tool for improving the functionality of this type of patient. The aim of this study is to evaluate the functional capacity and length of stay of patients in a nosocomial intensive care unit who underwent prophylactic non-invasive ventilation after heart valve replacement. METHOD: The study was a controlled clinical trial, comprising 50 individuals of both sexes who were allocated by randomization into two groups with 25 patients in each group: the control group and experimental group. After surgery, the patients were transferred to the intensive care unit and then participated in standard physical therapy, which was provided to the experimental group after 3 applications of non-invasive ventilation within the first 26 hours after extubation. For non-invasive ventilation, the positive pressure was 10 cm H2O, with a duration of 1 hour. The evaluation was performed on the 7th postoperative day/discharge and included a 6-minute walk test. The intensive care unit and hospitalization times were monitored in both groups. Brazilian Registry of Clinical Trials (REBeC): RBR number 8bxdd3. RESULTS: Analysis of the 6-minute walk test showed that the control group walked an average distance of 264.34±76 meters and the experimental group walked an average distance of 334.07±71 meters (p=0.002). The intensive care unit and hospitalization times did not differ between the groups. CONCLUSION: Non-invasive ventilation as a therapeutic resource was effective toward improving functionality; however, non-invasive ventilation did not influence the intensive care unit or hospitalization times of the studied cardiac patients.

http://ift.tt/2zA1Gdf

Local and systemic effects of fibrin and cyanoacrylate adhesives on lung lesions in rabbits

OBJECTIVES: Tissue adhesives can be used to prevent pulmonary air leaks, which frequently occur after lung interventions. The objective of this study is to evaluate local and systemic effects of fibrin and cyanoacrylate tissue adhesives on lung lesions in rabbits. METHODS: Eighteen rabbits were submitted to videothoracoscopy + lung incision alone (control) or videothoracoscopy + lung incision + local application of fibrin or cyanoacrylate adhesive. Blood samples were collected and assessed for leukocyte, neutrophil and lymphocyte counts and interleukin-8 levels preoperatively and at 48 hours and 28 days post-operatively. After 28 days, the animals were euthanized for gross examination of the lung surface, and lung fragments were excised for histopathological analysis. RESULTS: Fibrin and cyanoacrylate produced similar adhesion scores of the lung to the parietal pleura. Microscopic analysis revealed uniform low-cellular tissue infiltration in the fibrin group and an intense tissue reaction characterized by dense inflammatory infiltration of granulocytes, giant cells and necrosis in the cyanoacrylate group. No changes were detected in the leukocyte, neutrophil or lymphocyte count at any time-point, while the interleukin-8 levels were increased in the fibrin and cyanoacrylate groups after 48 hours compared with the pre-operative control levels (p<0.01). CONCLUSION: Both adhesive agents promoted normal tissue healing, with a more pronounced local inflammatory reaction observed for cyanoacrylate. Among the serum markers of inflammation, only the interleukin-8 levels changed post-operatively, increasing after 48 hours and decreasing after 28 days to levels similar to those of the control group in both the fibrin and cyanoacrylate groups.

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Impact assessment of an automated drug-dispensing system in a tertiary hospital

OBJECTIVE: To evaluate the costs and patient safety of a pilot implementation of an automated dispensing cabinet in a critical care unit of a private tertiary hospital in São Paulo/Brazil. METHODS: This study considered pre- (January-August 2013) and post- (October 2013-October 2014) intervention periods. We considered the time and cost of personnel, number of adverse events, audit adjustments to patient bills, and urgent requests and returns of medications to the central pharmacy. Costs were evaluated based on a 5-year analytical horizon and are reported in Brazilian Reals (R$) and US dollars (USD). RESULTS: The observed decrease in the mean number of events reported with regard to the automated drug-dispensing system between pre- and post-implementation periods was not significant. Importantly, the numbers are small, which limits the power of the mean comparative analysis between the two periods. A reduction in work time was observed among the nurses and administrative assistants, whereas pharmacist assistants showed an increased work load that resulted in an overall 6.5 hours of work saved/day and a reduction of R$ 33,598 (USD 14,444) during the first year. The initial investment (R$ 206,065; USD 88,592) would have been paid off in 5 years considering only personnel savings. Other findings included significant reductions of audit adjustments to patient hospital bills and urgent requests and returns of medications to the central pharmacy. CONCLUSIONS: Evidence of the positive impact of this technology on personnel time and costs and on other outcomes of interest is important for decision making by health managers.

http://ift.tt/2zA1Dhz

Review of magnetic resonance-guided focused ultrasound in the treatment of uterine fibroids

Uterine leiomyoma is the most frequently occurring solid pelvic tumor in women during the reproductive period. Magnetic resonance-guided high-intensity focused ultrasound is a promising technique for decreasing menorrhagia and dysmenorrhea in symptomatic women. The aim of this study is to review the role of Magnetic resonance-guided high-intensity focused ultrasound in the treatment of uterine fibroids in symptomatic patients. We performed a review of the MEDLINE and Cochrane databases up to April 2016. The analysis and data collection were performed using the following keywords: Leiomyoma, High-Intensity Focused Ultrasound Ablation, Ultrasonography, Magnetic Resonance Imaging, Menorrhagia. Two reviewers independently performed a quality assessment; when there was a disagreement, a third reviewer was consulted. Nineteen studies of Magnetic resonance-guided high-intensity focused ultrasound-treated fibroid patients were selected. The data indicated that tumor size was reduced and that symptoms were improved after treatment. There were few adverse effects, and they were not severe. Some studies have reported that in some cases, additional sessions of Magnetic resonance-guided high-intensity focused ultrasound or other interventions, such as myomectomy, uterine artery embolization or even hysterectomy, were necessary. This review suggests that Magnetic resonance-guided high-intensity focused ultrasound is a safe and effective technique. However, additional evidence from future studies will be required before the technique can be recommended as an alternative treatment for fibroids.

http://ift.tt/2zTMfgJ

Plasmid-mediated mcr-1 in carbapenem-susceptible Escherichia coli ST156 causing a blood infection: an unnoticeable spread of colistin resistance in Brazil?

OBJECTIVE: We describe an IncX4 pHC891/16mcr plasmid carrying mcr-1 in a colistin-resistant and carbapenem-susceptible E. coli isolate (HC891/16), ST156, which caused a blood infection in a Brazilian patient with gallbladder adenocarcinoma. METHODS: Strain HC891/16 was subjected to whole genome sequencing using the MiSeq Platform (Illumina, Inc., USA). Assembly was performed using Mira and ABACAS. RESULTS: The isolates showed resistance only to ciprofloxacin, ampicillin and cefoxitin, and whole-genome sequencing revealed the presence of aac(6')Ib-cr and blaTEM1. CONCLUSION: Our findings warn of the possible silent dissemination of colistin resistance by carbapenem-susceptible mcr-1 producers, as colistin susceptibility is commonly tested only among carbapenem-resistant isolates.

http://ift.tt/2zzko4O

Reduction of venous pressure during the resection of liver metastases compromises enteric blood flow: IGFBP-1 as a novel biomarker of intestinal barrier injury

OBJECTIVES: Disruption of the intestinal barrier and bacterial translocation commonly occur when intestinal blood flow is compromised. The aim of this study was to determine whether liver resection induces intestinal damage. METHODS: We investigated intestinal fatty-acid binding protein and insulin-like growth factor binding protein levels in the plasma of patients who underwent liver resection. RESULTS: We show that liver resection is associated with significant intestinal barrier injury, even if the Pringle maneuver is not performed. CONCLUSION: We propose the use of insulin-like growth factor binding protein-1 as a novel biomarker of intestinal damage in such situations.

http://ift.tt/2zTuDlk

Molecular photoprotection of human keratinocytes in vitro by the naturally occurring mycosporine-like amino acid (MAA) palythine

Summary

Background

Solar ultraviolet radiation (UVR) induces molecular and genetic changes in the skin, which result in skin cancer, photoageing and photosensitivity disorders. The use of sunscreens is advocated to prevent such photodamage, however most formulations contain synthetic UVR filters that are non-biodegradable and can damage fragile marine ecosystems. Mycosporine-like amino acids (MAA) are natural UVR-absorbing compounds that have evolved in marine species for protection against chronic UVR exposure in shallow-water habitats.

Objectives

To determine if palythine, a photostable model MAA, could offer protection against a range of UVR-induced damage biomarkers that are important in skin cancer and photoageing.

Methods

HaCaT human keratinocytes were used to assess the photoprotective potential of palythine using a number of endpoints including cell viability, DNA damage (non-specific, cyclobutane pyrimidine dimers and oxidatively generated damage), gene expression changes (linked to inflammation, photoageing and oxidative stress) and oxidative stress. The anti-oxidant mechanism was investigated using chemical quenching and Nrf2 pathway activation assays.

Results

Palythine offered statistically significant protection (p<0.005) against all endpoints tested even at extremely low concentrations (0.3% w/v). Additionally, palythine was found to be a potent antioxidant, reducing oxidatively generated stress, even when added post exposure.

Conclusions

Palythine is an extremely effective multifunctional photoprotective molecule in vitro that has potential to be developed as a natural and biocompatible alternative to synthetic UVR filters.

This article is protected by copyright. All rights reserved.

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How to get rid of a nose piercing bump

Even with the best aftercare, a bump may form around a nose piercing. In this article, learn how to treat and prevent a nose piercing bump.

http://ift.tt/2iRdYDL

DPYD*2A and MTHFR C677T predict toxicity and efficacy, respectively, in patients on chemotherapy with 5-fluorouracil for colorectal cancer

Abstract

Background

Significant inter-individual variation in the sensitivity to 5-fluorouracil (5-FU) represents a major therapeutic hindrance either by impairing drug response or inducing adverse drug reactions (ADRs). This study aimed at exploring the cause behind this inter-individual alterations in consequences of 5-fluorouracil-based chemotherapy by investigating the effects of DPYD*2A and MTHFR C677T polymorphisms on toxicity and response of 5-FU in Bangladeshi colorectal cancer patients.

Methods

Colorectal cancer patients (n = 161) receiving 5-FU-based chemotherapy were prospectively enrolled. DPYD and MTHFR polymorphisms were assessed in peripheral leukocytes. Multivariate analyses were applied to evaluate which variables could predict chemotherapy-induced toxicity and efficacy.

Results

Multivariate analyses showed that DPYD*2A polymorphism was a predictive factor (P = 0.023) for grade 3 and grade 4 5-fluorouracil-related toxicities. Although MTHFR C677T polymorphism might act as forecasters for grade 3 or grade 4 neutropenia, diarrhea, and mucositis, this polymorphism was found to increase significantly (P = 0.006) the response of 5-FU.

Conclusion

DPYD*2A and MTHFR C677T polymorphisms could explain 5-FU toxicity or clinical outcome in Bangladeshi colorectal patients.

http://ift.tt/2hu8YIJ

Skeletally anchored mesialization of molars using digitized casts and two surface-matching approaches

Abstract

Purpose

To (1) quantify the three-dimensional treatment effect of a Mesialslider appliance using superimposed digital models, (2) to evaluate anchorage loss (measured by incisor displacement), and (3) to assess agreement between two different matching approaches, i.e., control point (CP)-based and iterative closest point (ICP) matching.

Methods

In a retrospective study, the effects of a skeletally anchored uni- and bilateral mesialization appliance (Mesialslider) as well as simultaneous mesialization and distalization appliance (Mesio-Distalslider) were evaluated in 48 subjects (aged 11–53 years). Pre- and posttreatment casts were digitized and superimposed with two different approaches, i.e., using ten manually selected control points located at the anterior palate and by means of an automated ICP-matching approach using a standardized palatal reference area. The treatment effects were evaluated using control points on the maxillary central incisors and maxillary molar teeth, and the methods were compared through the application of linear regression analyses and computation of alignment errors.

Results

Average upper molar mesialization was 6.3 ± 2.6 mm. Anchorage loss, designated as the mean amount of upper incisor displacement, was less than 0.5 mm in all dimensions investigated. Using the measurement method sufficient registration was possible using both approaches and corresponding tooth movements were significantly correlated (p < 0.01).

Conclusions

Accurate measurements of tooth displacement can be performed using both CP- and ICP-based matching approaches. Within the limits of performing a retrospective study, a premolar width of molar mesialization appeared possible without clinically relevant anchorage loss.

http://ift.tt/2zCjTXe

Endocrine Pathology Society Hubert Wolfe Award for 2017: Call for Nominations

http://ift.tt/2iRkgDx

Mapping the mechanical gradient of human dentin-enamel-junction at different intratooth locations

Publication date: Available online 12 November 2017
Source:Dental Materials
Author(s): Zhengzhi Wang, Kun Wang, Wanyin Xu, Xiaoyu Gong, Feiyu Zhang
ObjectivesThe local structures and mechanical properties within tooth dentin-enamel-junction (DEJ) regions have been focused for numerous studies. The reported results, however, remain inconsistent particularly on the functional width and gradient architecture of the DEJ. The current study aims at systematically determining the mechanical gradient of the DEJ at different intratooth locations such that a clearer understanding on the tooth properties and the potential correlations with the tooth function could be obtained.MethodsWe re-examined how mechanical properties such as elastic modulus and hardness transitioned from those of dentin to those of enamel using combined static and dynamic nanoindentation mapping techniques. A new mapping method and associated image processing procedures were developed to improve the measurement accuracy and resolution.ResultsA thin, sigmoidally-transitioned interphase layer of the DEJ was identified with an accurate functional width of 2–3μm. The DEJ width and gradient architecture were found intratooth location-dependent, with the DEJ at the occlusal sites being wider and transitioning smoother than that at the cervical sites. Such different widths and architectures of the interphase layer at sites subjected to different types and magnitudes of loadings during mastication could promote more efficient stress transferring between enamel and dentin without compromising the overall stiffness of the tooth.SignificanceThe presented study not only adds our understanding in the local mechanical properties within tooth DEJ regions, it could also further advance the development of DEJ-mimetic, functional gradient interphase for strong and ultra-durable jointing between dissimilar materials.

Graphical abstract

http://ift.tt/2zAPidg

Scholar : Australian Journal of Earth Sciences, Volume 64, Issue 7, October 2017 is now available online on Taylor & Francis Online

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The online platform for Taylor & Francis Online content Australian Journal of Earth Sciences, Volume 64, Issue 7, October 2017 is now available online on Taylor & Francis Online. This new issue contains the following articles: Review Article Denudation history of the Southeastern Highlands of Australia J. A. Webb Pages: 841-850 | DOI: 10.1080/08120099.2017.1384759 Original Articles Naturaliste Plateau: constraints on the timing and evolution of the Kerguelen Large Igneous Province and its role in Gondwana breakup N. G. Direen , B. E. Cohen , R. Maas , F. A. Frey, J. M. Whittaker , M. F. Coffin , S. Meffre , J. A. Halpin & A. J. Crawford Pages: 851-869 | DOI: 10.1080/08120099.2017.1367326 The structural evolution of the Northern Hastings Block and southern Nambucca Block, southern New England Orogen, eastern Australia J. Yan, P. G. Lennox & R. Offler Pages: 871-887 | DOI: 10.1080/08120099.2018.1382573 Apparent conflicting Roadian–Wordian (middle Permian) CA-IDTIMS and palynology ages from the Canning Basin, Western Australia A. J. Mory , J. L. Crowley, J. Backhouse, R. S. Nicoll, S. E. Bryan , M. López Martínez & D. J. Mantle Pages: 889-901 | DOI: 10.1080/08120099.2017.1365586 A workflow for exploration sampling in regolith-dominated terranes using portable X-ray fluorescence: comparison with laboratory data and a case study M. F. Gazley, L. C. Bonnett, L. A. Fisher, W. Salama & J. H. Price Pages: 903-917 | DOI: 10.1080/08120099.2017.1367721 The significance and timing of sheetflood vs braided channel deposition on lacustrine fan deltas, Junggar Basin, NW China B. Peng, Z. Jin, J. Wang, T. Chang, X. Zhu & B. Gul Pages: 919-930 | DOI: 10.1080/08120099.2017.1379436 Tectono-stratigraphic evolution and hydrocarbon exploration in the Eocene Southern Lufeng Depression, Pearl River Mouth Basin, South China Sea J. W. Ge, X. M. Zhu, X. T. Zhang, B. G. Jones, F. S. Yu, Z. C. Niu & M. Li Pages: 931-956 | DOI: 10.1080/08120099.2017.1370613 Diagenesis and hydrocarbon emplacement in the Upper Triassic Yanchang Formation tight sandstones in the southern Ordos Basin, China H. Chen, X. Zhu, C. Chen, W. Yin, Q. Zhang & R. Shi Pages: 957-980 | DOI: 10.1080/08120099.2017.1375983 Errata Erratum Pages: 981-982 | DOI: 10.1080/08120099.2017.1388737 Browse papers on image & data fusion, GIS, LiDAR & more in the International Journal of Image and Data Fusion's exclusive Editor's Choice collection. To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Scholar : These new articles for Alcheringa: An Australasian Journal of Palaeontology are available online

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The online platform for Taylor & Francis Online content New for Alcheringa: An Australasian Journal of Palaeontology and online now on Taylor & Francis Online: Original Articles Kukulkanus, a new genus of buxtoniin brachiopod from the Artinskian–Kungurian (Early Permian) of Mexico Miguel A. Torres-Martínez, Francisco Sour-Tovar & Ricardo Barragán Pages: 1-8 | DOI: 10.1080/03115518.2017.1395073 Hoping to have your article read by anyone, anywhere and at any time? Find out more about publishing open access with Ecosystem Health and Sustainability. To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Reproductive factors, nutritional status and serum 25(OH)D levels in women with breast cancer: A case control study

Publication date: Available online 11 November 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Nighat Y. Sofi, Monika Jain, Umesh Kapil, Vuthaluru Seenu, Lakshmy R., Chander P. Yadav, Ravindra M. Pandey, Neha Sareen
The study was conducted with an objective to investigate the association between reproductive factors, nutritional status and serum 25(OH)D levels among women diagnosed with breast cancer (BC). A total of 200 women with BC attending a tertiary healthcare institute of Delhi, India matched with 200 healthy women for age (±2years) and socio economic status were included in the study. Data was collected on socio-demographic profile, reproductive factors, physical activity and dietary intake (24hour dietary recall and food frequency questionnaire) using interviewer administered structured questionnaires and standard tools. Non fasting blood samples (5ml) were collected for the biochemical estimation of serum 25(OH)D and calcium levels by chemiluminescent immunoassay and colorimetric assay technique. Data was analyzed by univariable conditional logistic regression and significant variables with (p< 0.05), were analyzed in final model by conditional multivariable logistic regression analysis. The mean age of patients at diagnosis of BC was 45±10years. Results of multivariable conditional logistic regression analysis revealed significantly higher odds of BC for reproductive factors like age at marriage (more than 23 years), number of abortions, history or current use of oral contraceptive pills (OCP), with [OR (95% CI)] of [2.4 (1.2 to 4.9)], [4.0 (1.6 to 12.6)], [2.4 (1.2 to 5.0)]. Women with physically light activities and occasional consumption of eggs were found to have higher odds of BC [4.6 (1.6 to 13.0)] and [3.2 (1.6 to 6.3)]. Women with serum 25(OH)D levels less than 20ng/ml and calcium levels less than 10.5mg/dl had higher odds of having BC [2.4 (1.2 to 5.1)] and [3.7 (1.5 to 8.8)]. A protective effect of urban areas as place of residence and energy intake greater than 50% of Recommended Dietary Allowance (RDA) per day against BC was observed (p<0.05). The findings of the present study revealed a significant association of reproductive and dietary factors in addition to sedentary physical activity and low serum 25(OH)D levels in women diagnosed with BC.



http://ift.tt/2zSrB0F

Skeletally anchored mesialization of molars using digitized casts and two surface-matching approaches

Abstract

Purpose

To (1) quantify the three-dimensional treatment effect of a Mesialslider appliance using superimposed digital models, (2) to evaluate anchorage loss (measured by incisor displacement), and (3) to assess agreement between two different matching approaches, i.e., control point (CP)-based and iterative closest point (ICP) matching.

Methods

In a retrospective study, the effects of a skeletally anchored uni- and bilateral mesialization appliance (Mesialslider) as well as simultaneous mesialization and distalization appliance (Mesio-Distalslider) were evaluated in 48 subjects (aged 11–53 years). Pre- and posttreatment casts were digitized and superimposed with two different approaches, i.e., using ten manually selected control points located at the anterior palate and by means of an automated ICP-matching approach using a standardized palatal reference area. The treatment effects were evaluated using control points on the maxillary central incisors and maxillary molar teeth, and the methods were compared through the application of linear regression analyses and computation of alignment errors.

Results

Average upper molar mesialization was 6.3 ± 2.6 mm. Anchorage loss, designated as the mean amount of upper incisor displacement, was less than 0.5 mm in all dimensions investigated. Using the measurement method sufficient registration was possible using both approaches and corresponding tooth movements were significantly correlated (p < 0.01).

Conclusions

Accurate measurements of tooth displacement can be performed using both CP- and ICP-based matching approaches. Within the limits of performing a retrospective study, a premolar width of molar mesialization appeared possible without clinically relevant anchorage loss.

http://ift.tt/2zCjTXe

Liver immunotolerance and hepatocellular carcinoma: Patho-physiological mechanisms and therapeutic perspectives

Publication date: December 2017
Source:European Journal of Cancer, Volume 87
Author(s): Gaël S. Roth, Thomas Decaens
At the moment of the diagnosis of hepatocellular carcinoma (HCC), 70% of patients have only access to palliative treatments, with very few therapeutic options. Liver immunology is very specific, and liver immunotolerance is particularly developed because of the constant and massive influx of antigens. Deregulation of hepatic immunotolerance is implicated in chronic liver diseases development and particularly in liver carcinogenesis. For these reasons, HCC may be an excellent candidate for anticancer immunotherapies such as immune checkpoint inhibitors targeting CTLA-4 and PD-L1/PD-1. Nonetheless, because of the specific immune environment of the liver and the frequent association of HCC with hepatocellular insufficiency, the safety and the efficacy of these new treatments have to be properly studied in this situation. Thus, multiple phase II and III studies are in progress studying immune checkpoint inhibitor monotherapies, combination of different immunotherapies or local strategies such as transarterial chemoembolization combined with immune checkpoint inhibitors. Currently, only the final results of the tremelimumab phase II and the Nivolumab phase I/II study (CheckMate-040) are available. The latter is promising but need to be confirmed by the ongoing phase III studies to confirm the place of immunotherapy in the treatment of HCC. With many new molecular targets and therapeutic combination, immunotherapy represents a new hope in treating HCC patients although serious evaluation is still needed to confirm its interest.



http://ift.tt/2zTJfAY

Editorial Board

Publication date: 15 March 2018
Source:Biosensors and Bioelectronics, Volume 101





http://ift.tt/2yUZbmt

Metals in Diplodus sargus cadenati and Sparisoma cretense —a risk assessment for consumers

Abstract

The increases in urbanization, demography and industrial activity, along with growing human needs which exploit the resources of the planet, have exponentially exacerbated pollution. In particular, the discharge of heavy metals into the marine ecosystem is a problem of global magnitude, as this may damage the diversity of marine species and ecosystems because of their toxicity, long persistence and bioaccumulation. Consequently, it is necessary to carry out an assessment of the risk of human exposure from the consumption of marine species potentially exposed to this type of pollutants. In the present study, the levels of toxic heavy metals (Cd, Pb and Al) as well as trace and essential metals (B, Ba, Co, Cu, Cr, Fe, Li, Mn, Mo, Ni, Sr, V and Zn) and macronutrients (Ca, K, Mg, Na) have been quantified in two species of fish for human consumption. In order to do this, a total of 80 muscle samples and 80 liver samples, belonging to two species of osteichthyes (bony fish), Diplodus sargus cadenati and Sparisoma cretense, were analyzed. The specimens studied were captured on the north coast of Gran Canaria (Canary Islands) using recreational fishing techniques. As they caught from the shore, the data obtained respond to the need to assess the toxic levels in two representative species of artisanal and recreational fishing in the area. The risk assessment indicated that these two fish species are safe for the average consumer; however, if the livers are frequently consumed, there may be potential risks because they exceed the Admissible Daily Intakes for Pb and Cd.

http://ift.tt/2yvhNoX

Benchmarking the scientific research on wastewater-energy nexus by using bibliometric analysis

Abstract

With an exponential increase in urbanization and industrialization, water pollution is an inevitable consequence of relatively lagging wastewater treatment facilities. The conventional activated sludge process for wastewater treatment primarily emphasizes the removal of harmful substances to maintain increasingly stringent effluent discharged standards, which is considered an energy-intensive technique. Therefore, innovative and sustainable wastewater treatment should pay more attention to energy and resource recovery in dealing with fossil fuel depletion, global-scale energy security, and climate change. A bibliometric analysis was applied to trace wastewater-energy nexus-related research during the period 1991 to 2015, with respect to the Science Citation Index EXPANDED (SCI-EXPANDED) database. Journal of Hazardous Materials, ranking 1st in h-index (79), was the most productive journal (431, 4.5%) during the same time, followed by International Journal of Hydrogen Energy (422, 4.4%) and Water Research (393, 4.1%) journal, the latter owning a topmost journal impact factor. Though, China (2154, 22.5%) was the most productive country, while the USA with highest h-index (88) was the favorest collaborative country. The Chinese Academy of Sciences, China (241, 2.5%) produced the maximum publications. A novel method called "word cluster analysis" showed that the emerging sustainable processes and novel renewable energy application are applied in response to the desire for a net wastewater-energy nexus system. Based on different wastewater types, the emerging energy and sources recovery treatment processes of Anammox, anaerobic digestion, and microbial fuel cells gained extensive innovation. Evaluation indicators including sustainability, life cycle assessment, and environmental impact were appropriately used to dissert feasibility of the novel treatment methods in regard of renewable energy utilization, energy savings, and energy recovery. The transformation of the new concept of "broaden income source, economize on expenditures and exploit inner potential" should be generalized in order to achieve an environmentally sustainable development of wastewater-energy nexus system.

http://ift.tt/2ADWnHr