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Τετάρτη 14 Σεπτεμβρίου 2016

Practice Patterns in Distinguishing Between Background Pain and Breakthrough Pain During Patient Education: a Korean Physician Survey

Abstract

This study sought to explore the association between physician practice patterns and patient education, with a focus on breakthrough cancer pain (BTcP). A nationwide online survey was conducted by 92 Korean physicians. Thirteen questions on Korean physician's assessment, prescription, patient education practices, and knowledge regarding BTcP were administered. Based on their responses, physicians were divided using two methods: (1) by their patient education practices, where the "education group" always explained the distinction between background pain and BTcP and the "less education group" which explained it less frequently; and (2) by their definition of BTcP, as occurring "after control of background pain" or "regardless of background pain." We compared practice patterns using Fisher's exact test or Student's t test and performed multiple logistic regression analysis. The "education group" (65 physicians, 70.7 %) was more likely than the "less education group" to assess BTcP meticulously (odds ratio [OR] 17.13, 95 % confidence interval [CI] 4.98–58.94), prepare rescue medications in advance (OR 3.67, 95 % CI 1.36–9.90), and give explicit instructions regarding medications (OR 36.68, 95 % CI 5.63–239.15). Physicians who defined BTcP as occurring "after control of background pain" were more likely to explain how to take rescue medication (P < 0.05) than physicians who defined BTcP as occurring "regardless of background pain." Korean physicians' BTcP practice patterns may be affected by whether they consistently educate patients on the distinction between background pain and BTcP, regardless of their knowledge of the definition of BTcP.



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Podoplanin, ezrin, and Rho-A proteins may have joint participation in tumor invasion of lip cancer

Abstract

Introduction

Podoplanin and ezrin connection through Rho-A phosphorylation have been suggested as part of the activation pathway, in the process of tumor invasion and cell movement in oral squamous cell carcinomas.

Objective

The aim of this study was to evaluate the correlation among podoplanin, ezrin, and Rho-A immunoexpressions in 91 squamous cells carcinomas of the lower lip and their influence in patient's prognosis.

Material and methods

The immunoexpressions of podoplanin, ezrin, and Rho-A were evaluated through a semi-quantitative score method, based on the capture of 10 microscopic fields at the front of tumor invasion. The association and correlation of these proteins with the clinicopathological features were verified by Fischer's exact test and Spearman's test. The prognostic values were analyzed by Kaplan-Meier method and log-rank test.

Results

A statistically significant association between strong cytoplasmic podoplanin expression and alcohol (p = 0.024), loco-regional recurrences (p = 0.028), and lymph node metastasis (pN+) (p = 0.010) was found. The membranous (p = 0.000 and r = 0.384) and cytoplasmic (p = 0.000 and r = 0.344) podoplanin expression was statistically correlated with ezrin expression. Also, membranous podoplanin was significantly correlated with Rho-A expression (p = 0.006 and r = 0.282). The expressions of podoplanin, ezrin, and Rho-A were not significant prognostic factors for patients with squamous cell carcinomas of the lower lip.

Conclusions

Therefore, our results confirm a correlation among podoplanin, ezrin, and Rho-A expressions in squamous cell carcinoma of the lip suggesting a cooperative participation of these proteins in cell movement and invasion.

Clinical relevance

Furthermore, strong cytoplasmic podoplanin expression could be helpful to identify patients with squamous cell carcinoma of the lip and lower risk of loco-regional recurrences.



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The Interplay of Implicit Causality, Structural Heuristics, and Anaphor Type in Ambiguous Pronoun Resolution

Abstract

Two visual-world eye-tracking experiments investigating pronoun resolution in Finnish examined the time course of implicit causality information relative to both grammatical role and order-of-mention information. Experiment 1 showed an effect of implicit causality that appeared at the same time as the first-mention preference. Furthermore, when we counterbalanced the semantic roles of the verbs, we found no effect of grammatical role, suggesting the standard observed subject preference has a large semantic component. Experiment 2 showed that both the personal pronoun hän and the demonstrative tämä preferred the antecedent consistent with the implicit causality bias; tämä was not interpreted as referring to the semantically non-prominent entity. In contrast, structural prominence affected hän and tämä differently: we found a first-mention preference for hän, but a second-mention preference for tämä. The results suggest that semantic implicit causality information has an immediate effect on pronoun resolution and its use is not delayed relative to order-of-mention information. Furthermore, they show that order-of-mention differentially affects different types of anaphoric expressions, but semantic information has the same effect.



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Shift work practices and opportunities for intervention

There is increasing evidence that shift work, an occupational exposure affecting about one-fourth of the working population, increases the risk of major chronic disease outcomes, such as cardiovascular disease and cancer.1–4 Currently, there is an open discussion on whether shift work should be included in national lists of occupational hazards for compensation purposes. Denmark was the first (and to date only) country to consider breast cancer an occupational disease in shift workers, and to compensate women with over 20 years of night work who developed breast cancer. Chronic disease risk reduction and prevention in shift workers is an emerging field, which points to the need for more intervention studies. Whether and how companies or governments translate existing evidence into real-world policy or preventive actions currently remains largely unknown.

The study by Hall et al5 is a unique effort and first step to...



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Management strategy for treatment of vasospasm following transsphenoidal excision of craniopharyngioma

Abstract

We describe two cases of clinical and radiographic vasospasm after transsphenoidal resection of a craniopharyngioma. We review the literature on the association of vasospasm and craniopharyngioma and examine management options. Given the lack of evidence for the optimal management of these patients, treatment in concordance with protocols for vasospasm due to subarachnoid haemorrhage is recommended.



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Transcranial Doppler in the evaluation of infants treated with retrograde ventriculosinus shunt

Abstract

Introduction

Hydrocephalus is a prevalent condition among infants. Retrograde ventriculosinus shunt (RVSS) proposes a feasible option to treat hydrocephalus according to the principles presented by El-Shafei. In this essay, we analyze nuances and application of transcranial Doppler (TCD) in patients submitted to RVSS.

Methods

We consecutively enrolled patients diagnosed with hydrocephalus after surgical repair of myelomeningocele from January 2010 to January 2012, users of Hospital das Clinicas, University of Sao Paulo. They were treated with RVSS. Patients enrolled to the study were consecutively evaluated in an outpatient basis with TCD in preoperative, immediate postoperative period, and late postoperative period (1 year).

Results

Except for patient 3, there was an increase in mean flow velocity, decreased pulsatility index, and decreased resistance index in all vessels analyzed.

Discussion

In our sample, transcranial Doppler could be used as a diagnostic and follow-up tool to evaluate hemodynamics and hydrodynamics in the preoperative and postoperative phases of RVSS. It was technically feasible in all patients, had close relation with other clinical and image parameters, and was sensitive to identify system malfunction.



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Pathogenesis of cerebral palsy through the prism of immune regulation of nervous tissue homeostasis : literature review

Abstract

Background

The cerebral palsy is highly actual issue of pediatrics, causing significant neurological disability. Though the great progress in the neuroscience has been recently achieved, the pathogenesis of cerebral palsy is still poorly understood.

Methods

In this work, we reviewed available experimental and clinical data concerning the role of immune cells in pathogenesis of cerebral palsy. Maintaining of homeostasis in nervous tissue and its transformation in case of periventricular leukomalacia were analyzed.

Results

The reviewed data demonstrate involvement of immune regulatory cells in the formation of nervous tissue imbalance and chronicity of inborn brain damage. The supported opinion, that periventricular leukomalacia is not a static phenomenon, but developing process, encourages our optimism about the possibility of its correction.

Conclusions

The further studies of changes of the nervous and immune systems in cerebral palsy are needed to create fundamentally new directions of the specific therapy and individual schemes of rehabilitation.



http://ift.tt/2cYd3OA

Predicting ventriculoperitoneal shunt infection in children with hydrocephalus using artificial neural network

Abstract

Objectives

The relationships between shunt infection and predictive factors have not been previously investigated using Artificial Neural Network (ANN) model. The aim of this study was to develop an ANN model to predict shunt infection in a group of children with shunted hydrocephalus.

Materials and methods

Among more than 800 ventriculoperitoneal shunt procedures which had been performed between April 2000 and April 2011, 68 patients with shunt infection and 80 controls that fulfilled a set of meticulous inclusion/exclusion criteria were consecutively enrolled. Univariate analysis was performed for a long list of risk factors, and those with p value < 0.2 were used to create ANN and logistic regression (LR) models.

Results

Five variables including birth weight, age at the first shunting, shunt revision, prematurity, and myelomeningocele were significantly associated with shunt infection via univariate analysis, and two other variables (intraventricular hemorrhage and coincided infections) had a p value of less than 0.2. Using these seven input variables, ANN and LR models predicted shunt infection with an accuracy of 83.1 % (AUC; 91.98 %, 95 % CI) and 55.7 % (AUC; 76.5, 95 % CI), respectively. The contribution of the factors in the predictive performance of ANN in descending order was history of shunt revision, low birth weight (under 2000 g), history of prematurity, the age at the first shunt procedure, history of intraventricular hemorrhage, history of myelomeningocele, and coinfection.

Conclusion

The findings show that artificial neural networks can predict shunt infection with a high level of accuracy in children with shunted hydrocephalus. Also, the contribution of different risk factors in the prediction of shunt infection can be determined using the trained network.



http://ift.tt/2cwXdw6

Dorsal midbrain syndrome in two cases with two different presentations



http://ift.tt/2cYdBUG

Transcranial Doppler in the evaluation of infants treated with retrograde ventriculosinus shunt

Abstract

Introduction

Hydrocephalus is a prevalent condition among infants. Retrograde ventriculosinus shunt (RVSS) proposes a feasible option to treat hydrocephalus according to the principles presented by El-Shafei. In this essay, we analyze nuances and application of transcranial Doppler (TCD) in patients submitted to RVSS.

Methods

We consecutively enrolled patients diagnosed with hydrocephalus after surgical repair of myelomeningocele from January 2010 to January 2012, users of Hospital das Clinicas, University of Sao Paulo. They were treated with RVSS. Patients enrolled to the study were consecutively evaluated in an outpatient basis with TCD in preoperative, immediate postoperative period, and late postoperative period (1 year).

Results

Except for patient 3, there was an increase in mean flow velocity, decreased pulsatility index, and decreased resistance index in all vessels analyzed.

Discussion

In our sample, transcranial Doppler could be used as a diagnostic and follow-up tool to evaluate hemodynamics and hydrodynamics in the preoperative and postoperative phases of RVSS. It was technically feasible in all patients, had close relation with other clinical and image parameters, and was sensitive to identify system malfunction.



http://ift.tt/2cwYxPO

Pathogenesis of cerebral palsy through the prism of immune regulation of nervous tissue homeostasis : literature review

Abstract

Background

The cerebral palsy is highly actual issue of pediatrics, causing significant neurological disability. Though the great progress in the neuroscience has been recently achieved, the pathogenesis of cerebral palsy is still poorly understood.

Methods

In this work, we reviewed available experimental and clinical data concerning the role of immune cells in pathogenesis of cerebral palsy. Maintaining of homeostasis in nervous tissue and its transformation in case of periventricular leukomalacia were analyzed.

Results

The reviewed data demonstrate involvement of immune regulatory cells in the formation of nervous tissue imbalance and chronicity of inborn brain damage. The supported opinion, that periventricular leukomalacia is not a static phenomenon, but developing process, encourages our optimism about the possibility of its correction.

Conclusions

The further studies of changes of the nervous and immune systems in cerebral palsy are needed to create fundamentally new directions of the specific therapy and individual schemes of rehabilitation.



http://ift.tt/2cYd3OA

Predicting ventriculoperitoneal shunt infection in children with hydrocephalus using artificial neural network

Abstract

Objectives

The relationships between shunt infection and predictive factors have not been previously investigated using Artificial Neural Network (ANN) model. The aim of this study was to develop an ANN model to predict shunt infection in a group of children with shunted hydrocephalus.

Materials and methods

Among more than 800 ventriculoperitoneal shunt procedures which had been performed between April 2000 and April 2011, 68 patients with shunt infection and 80 controls that fulfilled a set of meticulous inclusion/exclusion criteria were consecutively enrolled. Univariate analysis was performed for a long list of risk factors, and those with p value < 0.2 were used to create ANN and logistic regression (LR) models.

Results

Five variables including birth weight, age at the first shunting, shunt revision, prematurity, and myelomeningocele were significantly associated with shunt infection via univariate analysis, and two other variables (intraventricular hemorrhage and coincided infections) had a p value of less than 0.2. Using these seven input variables, ANN and LR models predicted shunt infection with an accuracy of 83.1 % (AUC; 91.98 %, 95 % CI) and 55.7 % (AUC; 76.5, 95 % CI), respectively. The contribution of the factors in the predictive performance of ANN in descending order was history of shunt revision, low birth weight (under 2000 g), history of prematurity, the age at the first shunt procedure, history of intraventricular hemorrhage, history of myelomeningocele, and coinfection.

Conclusion

The findings show that artificial neural networks can predict shunt infection with a high level of accuracy in children with shunted hydrocephalus. Also, the contribution of different risk factors in the prediction of shunt infection can be determined using the trained network.



http://ift.tt/2cwXdw6

Dorsal midbrain syndrome in two cases with two different presentations



http://ift.tt/2cYdBUG

Integrated Acoustic Separation, Enrichment, and Microchip Polymerase Chain Reaction Detection of Bacteria from Blood for Rapid Sepsis Diagnostics

TOC Graphic

Analytical Chemistry
DOI: 10.1021/acs.analchem.6b00323
ancham?d=yIl2AUoC8zA


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Understanding the Impact of Methionine Oxidation on the Biological Functions of IgG1 Antibodies Using Hydrogen/Deuterium Exchange Mass Spectrometry

TOC Graphic

Analytical Chemistry
DOI: 10.1021/acs.analchem.6b01958
ancham?d=yIl2AUoC8zA


http://ift.tt/2cwSzhM

Covalent and Oriented Surface Immobilization of Antibody Using Photoactivatable Antibody Fc-Binding Protein Expressed in Escherichia coli

TOC Graphic

Analytical Chemistry
DOI: 10.1021/acs.analchem.6b02071
ancham?d=yIl2AUoC8zA


http://ift.tt/2cY8gg9

CNN Spotlights Mercy Virtual

Files: 
Media Contact: 
Show EMS Sitewide: 
Yes!
Widgets: 
Widget - Text - CNN spotlights Mercy Virtual
Widget - Image - Dr. Helton behind the scene CNN
Widget - Section Divider - Mercy Virtual in the News
Widget - Text - Mercy Virtual in the News ICYMI
Widget - Flickr - Mercy Virtual Flickr feed


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CNN Spotlights Mercy Virtual's

Files: 
Media Contact: 

 

 

Show EMS Sitewide: 
Yes!
Widgets: 
Widget - Text - Agility in Action
Widget - Image - Dr. Helton behind the scene CNN
Widget - Section Divider - Mercy Virtual in the News
Widget - Text - Mercy Virtual in the News ICYMI
Widget - Flickr - Mercy Virtual Flickr feed


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Myricitrin Protects against Doxorubicin-Induced Cardiotoxicity by Counteracting Oxidative Stress and Inhibiting Mitochondrial Apoptosis via ERK/P53 Pathway

Doxorubicin (Dox) is one of the most effective and widely used anthracycline antineoplastic antibiotics. Unfortunately, the use of Dox is limited by its cumulative and dose-dependent cardiac toxicity. Myricitrin, a natural flavonoid which is isolated from the ground bark of Myrica rubra, has recently been found to have a strong antioxidative effect. This study aimed to evaluate the possible protective effect of myricitrin against Dox-induced cardiotoxicity and the underlying mechanisms. An in vivo investigation in SD rats demonstrated that myricitrin significantly reduced the Dox-induced myocardial damage, as indicated by the decreases in the cardiac index, amelioration of heart pathological injuries, and decreases in the serum cardiac enzyme levels. In addition, in vitro studies showed that myricitrin effectively reduced the Dox-induced cell toxicity. Further study showed that myricitrin exerted its function by counteracting oxidative stress and increasing the activities of antioxidant enzymes. Moreover, myricitrin suppressed the myocardial apoptosis induced by Dox, as indicated by decreases in the activation of caspase-3 and the numbers of TUNEL-positive cells, maintenance of the mitochondrial membrane potential, and increase in the Bcl-2/Bax ratio. Further mechanism study revealed that myricitrin-induced suppression of myocardial apoptosis relied on the ERK/p53-mediated mitochondrial apoptosis pathway.

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In memory of Daniel H. Teitelbaum



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The Effects of Dexamethasone and L -NAME on Acute Lung Injury in Rats with Lung Contusion

Abstract

The therapeutic efficiency of an anti-inflammatory agent, dexamethasone (DXM), and a nitric oxide synthase (NOS) inhibitor, Nitro-L-arginine methyl ester (L-NAME), in lung tissue injury after lung contusion was investigated. Serum levels of tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), YKL-40, an inflammatory peptide, inducible NOS (iNOS), and Clara cell protein 16 (CC-16) were evaluated. Immunohistochemical analyses were also performed, and the lung tissue was examined histopathologically. The study consisted of eight groups of Sprague-Dawley rats (n = 10 in each group), weighing 250–300 g: (1) control, (2) contusion, (3) control + DXM, (4) contusion + DXM, (5) control + L-NAME (6) contusion + L-NAME, (7) control + DXM + L-NAME, and (8) contusion + DXM + L-NAME. A previously developed lung contusion model was used, in addition to the control group. The rats were administered DXM and L-NAME intraperitoneally (i.p.) at doses of 15 and 60 mg/kg/day, respectively. DXM and L-NAME administration decreased the iNOS level in the contusion groups. DXM increased the levels of YKL-40 and IL-10 in both the control and contusion groups, with higher levels in the contusion groups. L-NAME increased the serum level of IL-10 in the lung contusion groups. DXM increased the synthesis of CC-16 in the control and contusion groups. The combined use of a high-dose steroid and NOS inhibitor resulted in the death of the rats. Steroids can increase the level of cytokines, such as YKL-40 and IL-10, and the synthesis of CC-16 and prevent pneumonia, ALI/ARDS, and sepsis in lung contusion.



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Anti-inflammatory and Anti-oxidative Effects of Dexpanthenol on Lipopolysaccharide Induced Acute Lung Injury in Mice

Abstract

The aim of this study is to investigate the effects of dexpanthenol in a model of acute lung injury (ALI) induced by lipopolysaccharides (LPS). Lung injury was induced by exposure to atomized LPS. Mice were randomly divided into four groups: control group; Dxp (500 mg/kg) group; LPS group; LPS + Dxp (500 mg/kg) group. The effects of dexpanthenol on LPS-induced neutrophil recruitment, cytokine levels, total protein concentration, myeloperoxidase (MPO), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) contents were examined. Additionally, lung tissue was examined by histology to investigate the changes in pathology in the presence and absence of dexpanthenol. In LPS-challenged mice, dexpanthenol significantly improved lung edema. Dexpanthenol also markedly inhibited the LPS-induced neutrophiles influx, protein leakage, and release of TNF-α and IL-6 in bronchoalveolar lavage fluid (BALF). Furthermore, dexpanthenol attenuated MPO activity and MDA contents and increased SOD and GSH activity in the LPS-challenged lung tissue. These data suggest that dexpanthenol protects mice from LPS-induced acute lung injury by its anti-inflammatory and anti-oxidative activities.



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MicroRNA-142-3p Inhibits Chondrocyte Apoptosis and Inflammation in Osteoarthritis by Targeting HMGB1

Abstract

Osteoarthritis (OA) is a degenerative joint disease characterized by articular cartilage degradation and joint inflammation in which microRNAs are significantly involved. Previous studies have reported that miR-142-3p is a novel mediator of inflammatory signaling pathways, but whether miR-142-3p regulates OA remains unknown. In this study, we aimed to investigate the potential role of miR-142-3p in OA and the underlying molecular mechanism. We showed that miR-142-3p was significantly reduced in the articular cartilage tissues from experimental OA mice. The expression of miR-142-3p was also decreased in chondrocytes treated with lipopolysaccharide (LPS) in vitro. Moreover, the overexpression of miR-142-3p significantly inhibited cell apoptosis, nuclear factor (NF)-kB, and the production of proinflammatory cytokines, including interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-α induced by LPS. Interestingly, bioinformatics analysis demonstrated that high mobility group box 1 (HMGB1), an important inflammatory mediator of OA, was predicted as a target of miR-142-3p, which was validated by dual-luciferase reporter assay. The high expression of HMGB1 in chondrocytes induced by LPS was significantly inhibited by miR-142-3p overexpression. Furthermore, the restoration of HMGB1 markedly abrogated the effect of miR-142-3p. In OA mice, the overexpression of miR-142-3p by lentivirus-mediated gene transfer significantly inhibited HMGB1 expression, NF-kB signaling, and proinflammatory cytokines. Moreover, the overexpression of miR-142-3p significantly alleviated OA progression in OA mice in vivo. Taken together, our study suggests that miR-142-3p inhibits chondrocyte apoptosis and inflammation in OA by inhibiting the HMGB1-mediated NF-kB signaling pathway. The overexpression of miR-142-3p impedes the OA progression in mice in vivo indicating that miR-142-3p is a potential molecular target for OA treatment.



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Heterologous Expression of PA8FAD9 and Functional Characterization of a Δ9-Fatty Acid Desaturase from a Cold-Tolerant Pseudomonas sp. A8

Abstract

Fatty acid desaturase enzymes are capable of inserting double bonds between carbon atoms of saturated fatty acyl-chains to produce unsaturated fatty acids. A gene coding for a putative Δ9-fatty acid desaturase-like protein was isolated from a cold-tolerant Pseudomonas sp. A8, cloned and heterologously expressed in Escherichia coli. The gene named as PA8FAD9 has an open reading frame of 1185 bp and codes for 394 amino acids with a predicted molecular weight of 45 kDa. The enzyme showed high Δ9-fatty acid desaturase-like protein activity and increased overall levels of cellular unsaturated fatty acids in the recombinant E. coli cells upon expression at different temperatures. The results showed that the ratio of palmitoleic to palmitic acid in the recombinant E. coli cells increased by more than twice the amount observed in the control cells at 20 °C using 0.4 mM IPTG. GCMS analysis confirmed the ability of this enzyme to convert exogenous stearic acid to oleic acid incorporated into the recombinant E. coli membrane phospholipids. It may be concluded that the PA8FAD9 gene from Pseudomonas sp. A8 codes for a putative Δ9-fatty acid desaturase protein actively expressed in E. coli under the influence of temperature and an inducer.



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Glucose-6-Phosphate Dehydrogenase Deficiency and Sickle Cell Trait among Prospective Blood Donors: A Cross-Sectional Study in Berekum, Ghana

Background. Blood transfusion is a therapeutic procedure usually undertaken in patients with severe anaemia. In Ghana, severe anaemia is mostly due to malaria caused by severe Plasmodium falciparum infection, road traffic accidents, and haemoglobinopathy-induced acute haemolysis. Method. This cross-sectional study evaluated coinheritance of sickle cell haemoglobin variant and G6PD enzymopathy among individuals that donated blood at the Holy Trinity Hospital, Berekum, in the Brong-Ahafo Region, Ghana. Demographic data and other pertinent information were captured using questionnaire. Sickle cell haemoglobin variants were determined using cellulose acetate electrophoresis (pH 8.6). Qualitative G6PD status and quantitative G6PD enzyme activity were determined using methaemoglobin reduction and Trinity Biotech G6PD test kit, respectively. Results. Prevalence of sickle cell trait (SCT) and G6PD enzymopathy coinheritance was 7%. In addition, 19.5% of the donors had 10%–60% of normal G6PD enzyme activity suggesting that these donor units are prone to stressor-induced acute haemolysis when given to recipients. Mild G6PD activity (, OR: 2.410 (CI: 1.049–5.534)), commercial (, OR: 5.609 (CI: 1.309–24.035)), and voluntary (, OR: 2.404 (CI: 1.071–5.397)) donors were significantly associated with SCT. Conclusion. Screening for red cell pathologies must be incorporated into existing protocols for populations with high incidence of haemoglobinopathies to protect high-risk recipients.

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High–low reflectivity enhancement based retinal vessel projection for SD-OCT images

Purpose:

The retinal vessel visualization from spectral-domain optical coherence tomography (SD-OCT) images is important for ocular disease diagnosis and multimodal retinal image processing. The purpose is to display the retinal vessel in a single projection image from 3D SD-OCT images by using the light absorption and shadow characteristics of the retinal vessel.

Methods:

The authors present a novel retinal vessel projection method for SD-OCT images, which utilizes the light absorption and shadow characteristics of the retinal vessel, called high–low reflectivity enhancement (HLRE) method. The reflectivity of the retinal vessel increases between the internal limiting membrane and inner nuclear layer-outer plexiform layer (INL-OPL) layers because of the light absorption, and the reflectivity below the retinal vessel decreases because of the influence of the retinal vessel shadow. A retinal vessel mask image generated based on the reflectivity characteristics of the retinal vessel is used to enhance the subvolume projection image restricted between the INL-OPL and Bruch's membrane layers.

Results:

Experimental results with 22 SD-OCT cubes from 12 patients and 10 normal persons demonstrate that the authors' method is more effective in displaying the retinal vessel than the summed-voxel projection and other five region restriction based projection methods. The average of the mean difference between the retinal vessel and background regions based on their HLRE method is 0.1921.

Conclusions:

The proposed HLRE method was more effective for the visualization of the retinal vessels than the state-of-art methods because it provides higher contrast and distinction.



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A general algorithm for calculation of recombination losses in ionization chambers exposed to ion beams

Purpose:

Dosimetry with ionization chambers in clinical ion beams for radiation therapy requires correction for recombination effects. However, common radiation protocols discriminate between initial and general recombination and provide no universal correction method for the presence of both recombination types in ion beams of charged particles heavier than protons. The advent of multiple field optimization in ion beams, allowing for complex patterns of dose delivery in both temporal and spatial domains, results in new challenges for recombination correction where the resulting recombination depends on the plan delivered. Here, the authors present the open source code IonTracks version 1.0, where the combined initial and general recombination effects in principle can be predicted for any ion beam with arbitrary particle-energy spectrum and temporal structure.

Methods:

IonTracks uses track structure theory to distribute the charge carriers in ion tracks. The charge carrier movements are governed by a pair of coupled differential equations, based on fundamental physical properties as charge carrier drift, diffusion, and recombination, which are solved numerically while the initial and general charge carrier recombination is computed. A space charge screening of the electric field is taken into account and the algorithm furthermore allows an inclusion of a free-electron component.

Results:

The algorithm is numerically stable and in accordance with experimentally validated theories for initial recombination in heavy ion tracks and general recombination in a proton beam.

Conclusions:

Given IonTracks' ability to handle arbitrary inputs, IonTracks can in principle be applied to any complex particle field in the spatial and temporal domain. IonTracks is validated against the Jaffé's and Boag's theory of recombination in pulsed beams of multiple ion species. IonTracks is able to calculate the correction factor for initial and general recombination losses in parallel-plate ionization chambers. Even if only few experimental data on recombination effects in ionization chambers are available today, the universal concept of IonTracks is not limited to the ions investigated here. Future experimental investigations of recombination in pulsed and possibly also continuous ion beams may be conducted with IonTracks, which ultimately may lead to a more precise prediction of recombination factors in complex radiation fields.



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Reconstruction of multiple-pinhole micro-SPECT data using origin ensembles

Purpose:

The authors are currently developing a dual-resolution multiple-pinhole microSPECT imaging system based on three large NaI(Tl) gamma cameras. Two multiple-pinhole tungsten collimator tubes will be used sequentially for whole-body "scout" imaging of a mouse, followed by high-resolution (hi-res) imaging of an organ of interest, such as the heart or brain. Ideally, the whole-body image will be reconstructed in real time such that data need only be acquired until the area of interest can be visualized well-enough to determine positioning for the hi-res scan. The authors investigated the utility of the origin ensemble (OE) algorithm for online and offline reconstructions of the scout data. This algorithm operates directly in image space, and can provide estimates of image uncertainty, along with reconstructed images. Techniques for accelerating the OE reconstruction were also introduced and evaluated.

Methods:

System matrices were calculated for our 39-pinhole scout collimator design. SPECT projections were simulated for a range of count levels using the MOBY digital mouse phantom. Simulated data were used for a comparison of OE and maximum-likelihood expectation maximization (MLEM) reconstructions. The OE algorithm convergence was evaluated by calculating the total-image entropy and by measuring the counts in a volume-of-interest (VOI) containing the heart. Total-image entropy was also calculated for simulated MOBY data reconstructed using OE with various levels of parallelization.

Results:

For VOI measurements in the heart, liver, bladder, and soft-tissue, MLEM and OE reconstructed images agreed within 6%. Image entropy converged after ∼2000 iterations of OE, while the counts in the heart converged earlier at ∼200 iterations of OE. An accelerated version of OE completed 1000 iterations in image entropy performance, whereas the same dataset required ∼79 min to complete 1000 iterations of conventional OE. A combination of the two methods showed decreased reconstruction time and no loss of performance when compared to conventional OE alone.

Conclusions:

OE-reconstructed images were found to be quantitatively and qualitatively similar to MLEM, yet OE also provided estimates of image uncertainty. Some acceleration of the reconstruction can be gained through the use of parallel computing. The OE algorithm is useful for reconstructing multiple-pinhole SPECT data and can be easily modified for real-time reconstruction.



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Simultaneous 4D-CBCT reconstruction with sliding motion constraint

Purpose:

Current approaches using deformable vector field (DVF) for motion-compensated 4D-cone beam CT (CBCT) reconstruction typically utilize an isotropically smoothed DVF between different respiration phases. Such isotropically smoothed DVF does not work well if sliding motion exists between neighboring organs. This study investigated an anisotropic motion modeling scheme by extracting organ boundary local motions (e.g., sliding) and incorporated them into 4D-CBCT reconstruction to optimize the motion modeling and reconstruction methods.

Methods:

Initially, a modified simultaneous algebraic reconstruction technique (mSART) was applied to reconstruct high quality reference phase CBCT using all phase projections. The initial DVFs were precalculated and subsequently updated to achieve the optimized solution. During the DVF update, sliding motion estimation was performed by matching the measured projections to the forward projection of the deformed reference phase CBCT. In this process, each moving organ boundary was first segmented. The normal vectors of the boundary DVF were then extracted and incorporated for further DVF optimization. The regularization term in the objective function adaptively regularizes the DVF by (1) isotopically smoothing the DVF within each organ; (2) smoothing the DVF at boundary along the normal direction; and (3) leaving the tangent direction of boundary DVF unsmoothed (i.e., allowing for sliding motion). A nonlinear conjugate gradient optimizer was used. The algorithm was validated on a digital cubic tube phantom with sliding motion, nonuniform rotational B-spline based cardiac-torso (NCAT) phantom, and two anonymized patient data. The relative reconstruction error (RE), the motion trajectory's root mean square error (RMSE) together with its maximum error (MaxE), and the Dice coefficient of the lung boundary were calculated to evaluate the algorithm performance.

Results:

For the cubic tube and NCAT phantom tests, the REs are 10.2% and 7.4% with sliding motion compensation, compared to 13.4% and 8.9% without sliding modeling. The motion trajectory's RMSE and MaxE for NCAT phantom tests are 0.5 and 0.8 mm with sliding motion constraint compared to 3.5 and 7.3 mm without sliding motion modeling. The Dice coefficients for both NCAT phantom and the patients show a consistent trend that sliding motion constraint achieves better similarity for segmented lung boundary compared with the ground truth or patient reference.

Conclusions:

A sliding motion-compensated 4D-CBCT reconstruction and the motion modeling scheme was developed. Both phantom and patient study demonstrated the improved accuracy and motion modeling accuracy in reconstructed 4D-CBCT.



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Understanding paper degradation: identification of products of cellulosic paper decomposition at the wet-dry “tideline” interface using GC-MS

Abstract

Cellulose paper degradation products forming in the "tideline" area at the wet-dry interface of pure cellulose paper were analyzed using gas chromatography-electron ionization-mass spectrometry (GC-EI-MS) and high-resolution electrospray ionization-mass spectrometry (ESI-MS, LTQ Orbitrap) techniques. Different extraction protocols were employed in order to solubilize the products of oxidative cellulose decomposition, i.e., a direct solvent extraction or a more laborious chromophore release and identification (CRI) technique aiming to reveal products responsible for paper discoloration in the tideline area. Several groups of low molecular weight compounds were identified, suggesting a complex pathway of cellulose decomposition in the tidelines formed at the cellulose-water-oxygen interface. Our findings, namely the appearance of a wide range of linear saturated carboxylic acids (from formic to nonanoic), support the oxidative autocatalytic mechanism of decomposition. In addition, the identification of several furanic compounds (which can be, in part, responsible for paper discoloration) plus anhydro carbohydrate derivatives sheds more light on the pathways of cellulose decomposition. Most notably, the mechanisms of tideline formation in the presence of molecular oxygen appear surprisingly similar to pathways of pyrolytic cellulose degradation. More complex chromophore compounds were not detected in this study, thereby revealing a difference between this short-term tideline experiment and longer-term cellulose aging.



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Quencher-free fluorescence strategy for detection of DNA methyltransferase activity based on exonuclease III-assisted signal amplification

Abstract

This work demonstrates a novel method for DNA methyltransferase (MTase) activity detection with a quencher-free molecular beacon (MB) probe based on exonuclease (Exo) III-assisted signal amplification. In the presence of Dam MTase and DpnI endonuclease, the elaborately designed hairpin substrate (MB1) was cleaved into two parts (part A and part B). Exo III can then digest part A and release a single-stranded target of the 2-aminopurine-labeled MB (MB2). Subsequently, the MB2 can hybridize with its target to form a double-stranded structure with a protruding 3'-terminus and then trigger the digestion of MB2 by Exo III. During the digestion of MB2, the 2-aminopurine is separated from the DNA strands and released free in solution, inducing an increase of the fluorescent signal. Owing to the presence of a recessed 3'-terminus in the formed double-stranded DNA, Exo III-assisted recyclable cleavage of MB2 was achieved. Therefore, an amplified fluorescence signal was observed. Under the optimized conditions, Dam MTase can be detected in the range of 0.2–40 units/mL with a limit of detection of 0.2 units/mL and good selectivity. Furthermore, the present assay can be used for screening potential DNA MTase inhibitors.

Graphical Abstract

A quencher-free fluorescence assay for sensitive detection of DNA methyltransferase activity based on exonuclease III-assisted signal amplification is reported


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Use of administrative records to assess pneumococcal conjugate vaccine impact on pediatric meningitis and pneumonia hospitalizations in Rwanda

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Publication date: Available online 14 September 2016
Source:Vaccine
Author(s): Maurice Gatera, Jeannine Uwimana, Emmanuel Manzi, Fidele Ngabo, Friday Nwaigwe, Bradford D. Gessner, Jennifer C. Moïsi
BackgroundOngoing surveillance is critical to assessing pneumococcal conjugate vaccine (PCV) impact over time. However, robust prospective studies are difficult to implement in resource-poor settings. We evaluated retrospective use of routinely collected data to estimate PCV impact in Rwanda.MethodsWe collected data from admission registers at five district hospitals on children age <5yearsadmitted for suspected meningitis and pneumonia during 2002–2012. We obtained clinical and laboratory data on meningitis from sentinel surveillance at the national reference hospital in Kigali. We developed multivariable logistic regression models to estimate PCV effectiveness (VE) against severe pneumonia and probable bacterial meningitis and Poisson models to estimate absolute rate reductions. Haemophilus influenzae type b vaccine was introduced in January 2002, PCV7 in April 2009 and PCV13 in August 2011.ResultsAt the district hospitals, the severe pneumonia and suspected meningitis hospitalization rates decreased by 70/100,000 and 11/100,000 children for 2012 compared to baseline, respectively. VE against severe pneumonia calculated from logistic regression was 54% (95% CI 42–63%).In Kigali, from 2002 to 2012, annual suspected meningitis cases decreased from 170 pre-PCV7 to 40 post-PCV13 and confirmed pneumococcal meningitis cases from 7 to 0. VE against probable bacterial meningitis was 42% (95% CI −4% to 68%).ConclusionIn a resource-poor African setting, analysis of district hospital admission logbooks and routine sentinel surveillance data produced results consistent with more sophisticated impact studies conducted elsewhere. Our findings support applying this methodology in other settings and confirm the benefits of PCV in Rwanda.



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Vaccination with a ΔnorD ΔznuA Brucella abortus mutant confers potent protection against virulent challenge

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Publication date: Available online 14 September 2016
Source:Vaccine
Author(s): Xinghong Yang, Beata Clapp, Theresa Thornburg, Carol Hoffman, David W. Pascual
There remains a need for an improved livestock vaccine for brucellosis since conventional vaccines are only ∼70% efficacious, making some vaccinated animals susceptible to Brucella infections. To address this void, a vaccine capable of evoking protective immunity, while still being sufficiently attenuated to produce minimal disease, is sought. In this pursuit, the ΔnorD ΔznuA B. abortus-lacZ (termed as znBAZ) was developed to be devoid of functional norD and znuA B. abortus genes, and to contain the lacZ as a marker gene. The results show that znBAZ is highly attenuated in mouse and human macrophages, and completely cleared from mouse spleens within eight weeks post-vaccination. Producing less splenic inflammation, znBAZ is significantly more protective than the conventional RB51 vaccine by more than four orders of magnitude. Vaccination with znBAZ elicits elevated numbers of IFN-γ+, TNF-α+, and polyfunctional IFN-γ+ TNF-α+ CD4+ and CD8+ T cells in contrast to RB51-vaccinated mice, which show reduced numbers of proinflammatory cytokine-producing T cells. These results demonstrate that znBAZ is a highly efficacious vaccine candidate capable of eliciting diverse T cell subsets that confer protection against parenteral challenge with virulent, wild-type B. abortus.



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MicroRNA reduction of neuronal West Nile virus replication attenuates and affords a protective immune response in mice

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Publication date: Available online 13 September 2016
Source:Vaccine
Author(s): Terza Brostoff, Patricia A. Pesavento, Christopher M. Barker, Joan L. Kenney, Elizabeth A. Dietrich, Nisha K. Duggal, Angela M. Bosco-Lauth, Aaron C. Brault
West Nile virus (WNV) is an important agent of human encephalitis that has quickly become endemic across much of the United States since its identification in North America in 1999. While the majority (∼75%) of infections are subclinical, neurologic disease can occur in a subset of cases, with outcomes including permanent neurologic damage and death. Currently, there are no WNV vaccines approved for use in humans. This study introduces a novel vaccine platform for WNV to reduce viral replication in the central nervous system while maintaining peripheral replication to elicit strong neutralizing antibody titers. Vaccine candidates were engineered to incorporate microRNA (miRNA) target sequences for a cognate miRNA expressed only in neurons, allowing the host miRNAs to target viral transcription through endogenous RNA silencing. To maintain stability, these targets were incorporated in multiple locations within the 3′-untranslated region, flanking sequences essential for viral replication without affecting the viral open reading frame. All candidates replicated comparably to wild type WNV in vitro within cells that did not express the cognate miRNA. Insertional control viruses were also capable of neuroinvasion and neurovirulence in vivo in CD-1 mice. Vaccine viruses were safe at all doses tested and did not demonstrate mutations associated with a reversion to virulence when serially passaged in mice. All vaccine constructs were protective from lethal challenge in mice, producing 93–100% protection at the highest dose tested. Overall, this is a safe and effective attenuation strategy with broad potential application for vaccine development.



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Swallowing Rehabilitation in Patients With Head and Neck Cancer Receiving Radiotherapy

Condition:   Cancer of Head and Neck
Interventions:   Other: Early rehabilitation;   Other: Late rehabilitation
Sponsors:   Parc de Salut Mar;   Asociación Española contra el Cáncer
Recruiting - verified September 2016

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MED-C Registry: Advanced Malignancy or Myelodysplasia, Tested by Standard Sequencing and Treated by Physician Choice

Conditions:   Neoplasms;   Lung Neoplasms;   Colon Neoplasms;   Breast Neoplasms;   Pancreatic Neoplasms;   Prostate Neoplasms;   Kidney Neoplasms;   Liver Neoplasms;   Rectal Neoplasms;   Hematologic Neoplasms;   Multiple Myeloma;   Myelodysplastic Syndromes;   Ovarian Neoplasms;   Bladder Neoplasms;   Testicular Neoplasms;   Endometrial Neoplasms;   Brain Neoplasms;   Biliary Tract Neoplasms;   Head and Neck Neoplasms;   Uterine Cervical Neoplasms;   Skin Neoplasms;   Melanoma;   Gastric Neoplasms;   Anal Neoplasms;   Sarcoma
Intervention:   Other: Provider determined
Sponsor:   Molecular Evidence Development Consortium Inc.
Not yet recruiting - verified September 2016

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The Economic Burden of Otitis Media in Korea, 2012: A Nationally Representative Cross-Sectional Study

Background. Otitis media (OM) is a common communicable disease that is associated with a substantial economic burden. However, no Korean studies have evaluated OM-related trends after the introduction of the pneumococcal conjugate vaccines. Purpose. This study aimed to estimate the prevalence and economic burden of OM in Korea using nationally representative data. Methods. The burden of OM was estimated nationally representative data such as national health insurance claims data from 2012, based on the prevalence approach and the societal perspective. Results. In 2012, 1,788,303 patients visited medical institutions for treatment of OM, and the prevalence and burden of OM were 3.5% and 497.35 million US dollars, respectively. Patients who were 0–9 years old accounted for 59.7% of the cases and 55.2% of the total cost. Among adults, the total and perpatient costs were highest among 50–59-year-old adults. Direct medical costs and outpatient costs accounted for large proportions of the total cost (86.3% and 88.3%, resp.). Conclusion. The economic burden of OM decreased after the introduction of the pneumococcal conjugate vaccines. However, OM is still associated with a relatively large burden, especially among adults, and interventions are needed to reduce the burden of OM in this population.

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Comment on “Effect of Health Education on Willingness to Undergo HIV Screening among Antenatal Attendees in a Teaching Hospital in North Central Nigeria”



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Symptoms and Functional Limitations in the First Year Following a Myocardial Infarction: A Qualitative Study

Abstract

Background and Objectives

This qualitative interview study was designed to highlight the symptoms and functional limitations experienced by patients in the year following a myocardial infarction (MI). This information can support the use or development of patient-reported outcome (PRO) instruments in the post-MI population.

Methods

Individual face-to-face interviews were conducted with 38 participants who had experienced an MI (with or without ST segment elevation) within the past month to <6 months (n = 17), or 6 months to ≤12 months (n = 21). Using content and thematic analysis, patient reports of symptoms and functional limitations were coded and then grouped into categories. The specific content and frequency of the symptom and functional limitation reports were summarized.

Results

Nearly half of all symptom expressions were related to fatigue. Within this fatigue category, patients reported experiencing general tiredness, as well as a loss of physical energy, mental energy, and/or motivation. Chest pain and discomfort, sleep disruption, and shortness of breath were also frequently reported. Additionally, patients reported emotional effects, including worry and depression, as well as a negative impact on relationships and social activities.

Conclusions

Patients reported a wide variety of symptoms and functional limitations after an MI. Fatigue was the most commonly reported symptom and included several specific dimensions related to tiredness. Consideration of these concepts associated with the patient's experience following an MI may yield novel endpoints for use in clinical trials and better therapies.



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siRNA-Mediated Silencing of HMGA2 Induces Apoptosis and Cell Cycle Arrest in Human Colorectal Carcinoma

Abstract

Purpose

Overexpression of HMGA2, known as small non-histone chromosomal protein, is associated with progression of various tumors, including colorectal cancers. The aim of this study was to investigate the effect of a specific HMGA2 siRNA on apoptosis and cell cycle of HCT-116 (colorectal carcinoma) cells.

Methods

The cells were transfected with siRNAs using a transfection reagent. The cytotoxic effects of HMGA2 siRNA on colorectal carcinoma cells were determined using MTT assay. Relative HMGA2 mRNA and protein levels were measured by QRT-PCR and western blotting, respectively. Apoptosis was measured by a TUNEL test based on labeling of DNA strand breaks. We also evaluated caspase-3, caspase-8, and caspase-9 expression by QRTPCR to determine which pathway is involved in apoptosis. Cell cycle was assessed by FACS and cell cycle analysis using PI DNA staining.

Results

HMGA2 siRNA significantly reduced both mRNA and protein expression levels 48 h after transfection and dose-dependent manner in colorectal carcinoma cells. We also showed that the silencing of HMGA2 led to the induction of apoptosis through intrinsic pathway and cell cycle arrest in G2/M phases of interphase in HCT-116 cells in vitro.

Conclusions

These results propose that HMGA2 might play an important role in the progression of colorectal carcinoma and might be a potential therapeutic target for trigger apoptosis and cell cycle arrest in colorectal carcinoma.



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To Your Health: NLM update: Cancer risk warnings questioned


Listen to the NLM Director's Comments

Listen to the To Your Health: NLM update on Cancer risk warnings questioned. The transcript is also available.

The value of some consumer suggestions about a range of cancer risks from the International Agency for Research on Cancer have become increasingly questioned by scientific experts, suggests an interesting news article recently published in Science...



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Reoperations after primary breast conserving surgery in women with invasive breast cancer in Catalonia, Spain: a retrospective study

Abstract

Background

Although complete tumor resection is accepted as the best means to reduce recurrence, reoperations after lumpectomy are a common problem in breast cancer. The aim of this study was to assess the reoperation rates after primary breast conserving surgery in invasive breast cancer cases diagnosed in Catalonia, Spain, between 2005 and 2011 and to identify variations based on patient and tumour characteristics.

Methods

Women with invasive incident breast cancer identified from the Patient's Hospital Discharge Database [174.0–174.9 codes of the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) as the primary diagnosis] and receiving primary breast conserving surgery were included in the study and were followed up to 3 and 12 months by collecting information about repeat breast cancer surgery.

Results

Reoperation rates after primary breast conserving surgery decreased from 13.0 % in 2005 to 11.7 % in 2011 at 3 months and from 14.2 % in 2005 to 12.9 % in 2011 at 12 months' follow-up. While breast conservation reoperations saw a slight, non-significant increase in the same period (from 5.7 to 7.3 % at 3 months, and from 6.0 to 7.5 % at 12 months), there was a significant decrease in radical reoperation (from 7.3 to 4.4 % at 3 months and from 8.2 to 5.4 % at 12 months). Overall, additional breast surgeries decreased among younger women.

Conclusions

Despite the rise of breast conserving surgery, reoperation rates following initial lumpectomy in Catalonia decreased by 10 % at 3 and 12 months' follow-up, remaining low and almost unchanged. Ultimately, there was also a significant decrease in mastectomies.



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Early postoperative complications after middle lobe-preserving surgery for secondary lung cancer

Abstract

Purpose

Preservation of the middle lobe during lung surgery is traditionally avoided, because its presence in the hemithoracic cavity is considered a cause of complications. We report a series of lung cancer patients who underwent a secondary pulmonary resection with the preservation of the middle lobe to explore the complications and feasibility of these procedures.

Methods

We reviewed the clinical courses of six patients who underwent surgery for metachronous lung cancers. Five patients underwent right upper lobectomy, including one sleeve lobectomy, after having undergone prior right lower lobectomy. The remaining patient underwent a right lower lobectomy after having undergone a prior right upper lobectomy.

Results

There were no treatment-related deaths. One patient was readmitted for surgery to treat delayed air leakage progressing to pyothorax. One patient was treated for persistent air leakage. Two patients required intermittent drainage of pulmonary effusion, because of middle lobe atelectasis. The postoperative forced vital capacity and forced expiratory volume in 1 s were greater than the values predicted post-pneumonectomy in four evaluable patients.

Conclusions

While postoperative complications after middle lobe-preserving surgery are manageable, their high incidence should be considered when performing this surgery.



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A case of small intestinal endometrioid adenocarcinoma

Abstract

Endometriosis generally occurs in the ovary. Intestinal endometriosis is rare. About 1 % of all endometriosis cases become malignant. Malignant transformation of small intestinal endometriosis is very rare. A 55-year-old woman who underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy and omentectomy for endometriosis 7 years ago presented to her primary care doctor with melena. A tumor was detected in the right lower abdomen by ultrasonography. The doctor referred her to our hospital. Computed tomography demonstrated a lobulated tumor ventral to the right common iliac vessels. Magnetic resonance imaging demonstrated that the tumor had heterogeneous intensity on T2-weighted images. Several small cysts with high intensity were observed caudal to the tumor on T2-weighted images. We performed partial small intestinal resection for the lesion. The tumor was diagnosed as endometrioid adenocarcinoma of the small intestine. She has been relapse-free for 5 years after surgery. Only three cases of malignant transformation of small intestinal endometriosis have been reported previously. It is very rare for long-term survival to be obtained with surgery alone, as in our case. This case report highlights the imaging findings for malignant transformation of intestinal endometriosis.



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Computational analyses of the effect of novel amino acid clusters of human transglutaminase 2 on its structure and function

Abstract

Transglutaminase 2 (TGM2) is a unique protein of a nine member family with several enzymatic and non-enzymatic activities and interacting partners. Its physiological and pathological roles, however, are not fully understood. Comparative genomic and computational analysis reported here have revealed phylogenetic changes of TGM2 resulting in novel amino acid clusters in humans and other primates, which may impact secondary structure and increase protein stability. These clusters are located in intrinsically disordered regions and via short linear motifs influence interactions with TGM2 partners directly, or through post-translation modification (phosphorylation and N-glycosylation sites). Our data shed new light on the structural background and evolution of TGM2 multi-functionality and points to so far unrevealed biological roles of the enzyme.



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Cephenemyiosis, an emergent myiasis in roe deer ( Capreolus capreolus ) from northwestern Spain

Abstract

Cephenemyia stimulator larvae cause a specific myiasis in roe deer, which is widely distributed in Europe. In Spain, this parasite was detected by the first time in 2005, coinciding with a high mortality of this ruminant especially in northwest of the country. The aim of this study was to analyse the results obtained by necropsy and ELISA to elucidate when the first infestation by C. stimulator in roe deer from northwestern Spain occurred, as well as to determine the influence of some intrinsic factors on the prevalence and intensity of infestation. During 1994–2000, none seropositive roe deer was observed by ELISA. However, from 2007 to 2014, 38 % of animals were seropositive. The results of the necropsy pointed that prevalence and intensity of infestation had increased over the years. There was a positive and significant correlation between the number of animals harbouring C. stimulator larvae and seroprevalence values. This significant correlation was also observed between the seroprevalence and mean intensity of infestation. Adult roe deer showed higher prevalence and intensity of infestation than younger reaching statistical significance. It is also detected that the prevalence of infestation was significantly higher in males than in females although the mean number of larvae found in females were higher than in males. The combined use of direct and indirect techniques demonstrated a high prevalence of C. stimulator infestation in roe deer in the northwest of Spain, which certainly highlights the importance of this myiasis during the last years.



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Cryptosporidium spp. and Enterocytozoon bieneusi in introduced raccoons ( Procyon lotor )—first evidence from Poland and Germany

Abstract

The raccoon (Procyon lotor) carnivore native to North America is a fast spreading, invasive species in the Europe now. At the moment, the highest population occupies areas near the German-Polish border. The data on the occurrence of Cryptosporidium spp. and microsporidia in raccoons is limited to North America's territory and is totally lacking in the case of their introduction to Europe. Therefore, the objective of this study was to investigate the occurrence of microparasites, i.e., Cryptosporidium spp. and microsporidia in the introduced raccoons obtained from localities in Poland and Germany. A PCR-based approach that permitted genetic characterization via sequence analysis was applied to raccoon fecal samples (n = 49), collected during 2012–2014. All fecal samples were simultaneously tested with the use of genetic markers, and DNA of microsporidia and Cryptosporidium spp. was detected among the examined raccoons. The results of our research confirmed the presence of Cryptosporidium skunk genotype and Enterocytozoon bieneusi NCF2 genotype. The results suggest a possible role of raccoons in the contamination of the environment, including urban areas, with pathogens of zoonotic significance as well as their role in the transmission and introduction of new genotypes of microparasites in the areas where P. lotor has not been observed yet. To our knowledge, there has been no literature data on the above genotypes detected previously in humans or animals from the examined study sites so far.



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Scolicidal and apoptotic activities of albendazole sulfoxide and albendazole sulfoxide-loaded PLGA-PEG as a novel nanopolymeric particle against Echinococcus granulosus protoscoleces

Abstract

Treatment failures of human cystic echinococcosis (CE) with albendazole (ABZ) have attributed to its low solubility and poor drug absorption rate, resulting in low drug level in plasma. The scolicidal effects of ABZ-loaded liposome nanoparticles have recently evaluated; however, these particles have several challenges due to their low encapsulated load. This investigation was designed to evaluate and compare in vitro apoptotic activities of ABZ sulfoxide (ABZs) and ABZs-loaded poly(lactic-co-glycolic acid) (PLGA)-PEG against protoscoleces (PSCs). ABZs-loaded PLGA-PEG was prepared by a double-emulsion method (W1/O/W2). Various concentrations of ABZs and ABZs-loaded PLGA-PEG (50, 100, 150, and 200 μg/ml) were experimentally tested against PSC of CE at different exposure times (5, 10, 20, 30, and 60 min). ABZs-loaded PLGA-PEG at concentrations of 150 and 200 μg/ml was able to act at a 100 % scolicidal rate in all exposure times (5 to 60 min), while ABZs at a concentration of 200 μg/ml demonstrated 94, 100, and 100 % mortality rates following 20, 30, and 60 min of exposure times, respectively. The messenger RNA (mRNA) expression of caspase-3 was assessed by semi-quantitative RT-PCR after 15 h of exposure. Caspase-3 mRNA expression was higher in both PSC treated with ABZs and PSC treated with ABZs-loaded PLGA-PEG than that in control groups (P < 0.05). No significant difference was observed between the apoptotic intensity of PSC treated with ABZs and that of PSC treated with ABZs-loaded PLGA-PEG (P > 0.05). DNA fragmentation assay and ultrastructural changes revealed that ABZs and ABZs-loaded PLGA-PEG induced the apoptosis of PSC by activation of caspase-3. The higher permeability and scolicidal rate of ABZs-loaded PLGA-PEG can be addressed as an effectual alternative strategy to improve the treatment of human CE.



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Ultrastructural, ssrDNA sequencing of Myxobolus prochilodus and Myxobolus porofilus and details of the interaction with the host Prochilodus lineatus

Abstract

Myxobolus prochilodus and Myxobolus porofilus are parasites of Prochilodus lineatus, an economically important South American fish found in La Plata and Paraiba do Sul river basins. This study focusing on parasite-host interaction provides an ultrastructural and phylogenetic analysis, the latter based on ssrDNA sequencing of these parasites respectively infecting the gill filaments and fins of P. lineatus taken from the Mogi Guaçu River, São Paulo, Brazil. A total of 13 adult specimens were examined in this study. The prevalence of infection was 7.69 % for M. prochilodus and 15.38 % for M. porofilus. Phylogenetic analysis showed M. prochilodus and M. porofilus clustered in a subclade composed of parasites of the Prochilodontidae family. In M. prochilodus infecting gill filaments, where cellular degeneration in the epithelium was observed, the plasmodia were surrounded by a capsule composed of layers of fibrocyte-like cells, with cellular projections joined to the projections of other fibrocyte-like cells by desmosomes, and more externally typical fibroblast layers. Some granular leukocytes were seen interspersed among these layers. In M. porofilus infecting the fins, the capsule of connective tissue was represented only by loosely arranged collagen fibers, and no granular leucocytes were observed. Finally, several unusual vacuoles with filamentous content and some characteristics usually described as degenerative alterations, as myelin figure, were noted in plasmodia and pansporoblasts of both myxosporean species. The possible influence of inflammatory response and xenobiotics was considered to be the explanation for the alterations observed in Myxobolus species and its host.



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Insights on the host associations and geographic distribution of Hymenolepis folkertsi (Cestoda: Hymenolepididae) among rodents across temperate latitudes of North America

Abstract

Synoptic data and an understanding of helminth parasite diversity among diverse rodent assemblages across temperate latitudes of North America remain remarkably incomplete. Renewed attention to comprehensive survey and inventory to establish the structure of biodiverse faunas is essential in providing indicators and proxies for identifying the outcomes of accelerating change linked to climate warming and anthropogenic forcing. Subsequent to the description of Hymenolepis folkertsi in the oldfield mouse, Peromyscus polionotus, additional specimens of hymenolepidids were collected or discovered in archived museum repositories from multiple species of deer mice (Peromyscus maniculatus, Peromyscus leucopus), the golden mouse (Ochrotomys nuttalli), chipmunks (Tamias striatus, Tamias amoenus), the 13-lined ground squirrel (Ictidomys tridecemlineatus), and tree squirrels (Sciurus carolinensis, Sciurus niger) from disjunct localities in the USA spanning southern Georgia, Virginia, Pennsylvania, Connecticut, the Upper Peninsula of Michigan, Wisconsin, and central Idaho. Specimens were largely consistent morphologically with the original description of H. folkertsi. Initial DNA sequence data, from a portion of the mitochondrial NADH dehydrogenase subunit 1, demonstrated intraspecific variation among three apparently geographically isolated populations attributed to H. folkertsi (uncorrected genetic distances of 2.7 % (Idaho and Michigan), 2.4 % (Virginia + Pennsylvania and Michigan), and 1.89 % (VA + PA and ID). Geography rather than host association explains the distribution and occurrence of H. folkertsi, and host colonization among deer mice, chipmunks, and other sciurids within regional sites is indicated. Genetic divergence revealed across localities for H. folkertsi suggests historically isolated populations, consistent with extended evolutionary and biogeographic trajectories among hymenolepidids and species of Peromyscus and Tamias in North America. Field inventory, that revealed these parasite populations, substantially alters our understanding of the distribution of diversity and provides insights about the nature of the complex relationships that serve to determine cestode faunas in rodents.



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