bluuebunny/crossref_metadata_2025 huggingface dataset:
Recent Advances in the Use of Metformin: Can Treating Diabetes Prevent Breast Cancer?
Authors: Hatoum Diana , McGowan Eileen M.
Published: March 2015

There is substantial epidemiological evidence pointing to an increased incidence of breast cancer and morbidity in obese, prediabetic, and diabetic patients.In vitrostudies strongly support metformin, a diabetic medication, in breast cancer therapy. Although metformin has been heralded as an exciting new breast cancer treatment, the principal consideration is whether metformin can be used as a generic treatment for all breast cancer types. Importantly, will metformin be useful as an inexpensive therapy for patients with comorbidity of diabetes and breast cancer? In general, meta-analyses of clinical trial data from retrospective studies in which metformin treatment has been used for patients with diabetes and breast cancer have a positive trend; nevertheless, the supporting clinical data outcomes remain inconclusive. The heterogeneity of breast cancer, confounded by comorbidity of disease in the elderly population, makes it difficult to determine the actual benefits of metformin therapy. Despite the questionable evidence available from observational clinical studies and meta-analyses, randomized phases I–III clinical trials are ongoing to test the efficacy of metformin for breast cancer. This special issue review will focus on recent research, highlightingin vitroresearch and retrospective observational clinical studies and current clinical trials on metformin action in breast cancer.
The Incidence of Hepatocellular Carcinoma after Balloon-Occluded Retrograde Transvenous Obliteration
Authors: Yokoyama Keiji , Irie Makoto , Anan Akira , Yokoyama Masanori , Tsuchiya Naoaki , Fukunaga Atsushi , Takata Kazuhide , Tanaka Takashi , Hirano Genryu , Morihara Daisuke , Takeyama Yasuaki , Shakado Satoshi , Sohda Tetsuro , Sakisaka Shotaro
Published: March 2015

Balloon-occluded retrograde transvenous obliteration (BRTO) is a highly effective therapy for gastric varices with liver cirrhosis. We have investigated the incidence of hepatocellular carcinoma (HCC) after BRTO. We enrolled 71 patients with viral hepatitis in which HCC had not appeared with liver imaging findings at the time of BRTO. The overall survival rate after BRTO was 86.8%, 76.1%, and 50.5% at 1, 3, and 5 years. The occurrence rate of HCC after BRTO was 20.9%, 41.1%, and 60.7% at 1, 3, and 5 years, especially showing a higher occurrence of HCC at one year. Meanwhile, the occurrence rate of HCC after treatment which excluded BRTO for esophagogastric varices in patients was 6.3%, 19.2%, and 42.5% at 1, 3, and 5 years. The log-rank test revealed that the occurrence rate of HCC after treatment was significantly higher in the BRTO group compared with that in the non-BRTO group (P=0.0447). The recurrence rate of HCC after BRTO was 35.8% and 80.0% at 1 and 3 years. The present study demonstrated a high incidence of HCC after BRTO in liver cirrhosis patients with viral hepatitis infection. We have suggested the potential for BRTO to accelerate hepatocarcinogenesis.
Endoscopic Endonasal Approach of Congenital Meningoencephalocele Surgery: First Reported Case in Lithuania
Authors: Balseris Svajūnas , Strazdas Giedrius , Ročka Saulius , Jakštas Tomas
Published: March 2015

Meningoencephalocele is a rare condition that usually occurs in children and is treated by neurosurgeons with occasional help from ENT doctors. The symptoms of meningoencephalocele might not develop until adulthood, but usually they are apparent immediately after birth. The case of small anterior basal transethmoidal meningoencephalocele in a 24-year-old patient who had headaches and runny nose since childhood is presented. Endonasal endoscopic approach for meningoencephalocele removal and skull base defect reconstruction was used. It was concluded that endoscopic endonasal approach is less invasive and provides an acceptable operative outcome with short recovery time and less postoperative complications in comparison with other external microsurgical approaches.
Diagnostic Value of MRI Proton Density Fat Fraction for Assessing Liver Steatosis in Chronic Viral C Hepatitis
Authors: Paparo Francesco , Cenderello Giovanni , Revelli Matteo , Bacigalupo Lorenzo , Rutigliani Mariangela , Zefiro Daniele , Cevasco Luca , Amico Maria , Bandelloni Roberto , Cassola Giovanni , Forni Gian Luca , Rollandi Gian Andrea
Published: March 2015

Objective.To assess the diagnostic performance of a T1-independent, T2*-corrected multiecho magnetic resonance imaging (MRI) technique for the quantification of hepatic steatosis in a cohort of patients affected by chronic viral C hepatitis, using liver biopsy as gold standard.Methods.Eighty-one untreated patients with chronic viral C hepatitis were prospectively enrolled. All included patients underwent MRI, transient elastography, and liver biopsy within a time interval <10 days.Results.Our cohort of 77 patients included 43/77 (55.8%) males and 34/77 (44.2%) females with a mean age of 51.31 ± 11.27 (18–81) years. The median MRI PDFF showed a strong correlation with the histological fat fraction (FF) (r=0.754, 95% CI 0.637 to 0.836,P<0.0001), and the correlation was influenced by neither the liver stiffness nor the T2*decay. The median MRI PDFF result was significantly lower in the F4 subgroup (P<0.05). The diagnostic accuracy of MRI PDFF evaluated by AUC-ROC analysis was 0.926 (95% CI 0.843 to 0.973) forS≥1and 0.929 (95% CI 0.847 to 0.975) forS=2.Conclusions.Our MRI technique of PDFF estimation allowed discriminating with a good diagnostic accuracy between different grades of hepatic steatosis.
Multifunctional DNA Nanomaterials for Biomedical Applications
Authors: Tam Dick Yan , Lo Pik Kwan
Published: March 2015

The rapidly emerging DNA nanotechnology began with pioneer Seeman’s hypothesis that DNA not only can carry genetic information but also can be used as molecular organizer to create well‐designed and controllable nanomaterials for applications in materials science, nanotechnology, and biology. DNA‐based self‐assembly represents a versatile system for nanoscale construction due to the well‐characterized conformation of DNA and its predictability in the formation of base pairs. The structural features of nucleic acids form the basis of constructing a wide variety of DNA nanoarchitectures with well‐defined shapes and sizes, in addition to controllable permeability and flexibility. More importantly, self‐assembled DNA nanostructures can be easily functionalized to construct artificial functional systems with nanometer scale precision for multipurposes. Apparently scientists envision artificial DNA‐based nanostructures as tool for drug loading and in vivo targeted delivery because of their abilities in selective encapsulation and stimuli‐triggered release of cargo. Herein, we summarize the strategies of creating multidimensional self‐assembled DNA nanoarchitectures and review studies investigating their stability, toxicity, delivery efficiency, loading, and control release of cargos in addition to their site‐specific targeting and delivery of drug or cargo molecules to cellular systems.
A Note on the Existence of a Smale Horseshoe in the Planar Circular Restricted Three-Body Problem
Authors: Cheng Xuhua , She Zhikun
Published: March 2015

It has been proved that, in the classical planar circular restricted three-body problem, the degenerate saddle point processes transverse homoclinic orbits. Since the standard Smale-Birkhoff theorem cannot be directly applied to indicate the chaotic dynamics of the Smale horseshoe type, we in this note alternatively apply the Conley-Moser conditions to analytically prove the existence of a Smale horseshoe in this classical restricted three-body problem.
Management of Cutaneous and Extracutaneous Side Effects of Smoothened Inhibitor Therapy for Advanced Basal Cell Carcinoma
Authors: Mohan Shalini V. , Chang Anne Lynn S.
Published: March 2015

Smoothened inhibitors represent the first class of targeted drugs approved for use in advanced and metastatic basal cell carcinoma. For many patients with limited treatment options, this drug class has led to significant clinical improvements, but is not without side effects. In this review, we outline the basic mechanism of smoothened inhibitors and the most commonly observed cutaneous and extracutaneous side effects. We also highlight possible mechanisms for these adverse events and current management strategies. Clin Cancer Res; 21(12); 2677–83. ©2015 AACR.
Chemokines Control Mobilization, Recruitment, and Fate of Monocytes in Atherosclerosis
Authors: Drechsler Maik , Duchene Johan , Soehnlein Oliver
Published: March 2015

Atherosclerosis is a chronic inflammatory disease of large arteries and, among others, characterized by continuous influx of monocytes into the subendothelial space, subsequent macrophage accumulation, and foam cell formation. Chemokines and their receptors tightly orchestrate monocyte trafficking and fate from birth to death. This brief review summarizes our current understanding of the interplay between monocytes and chemokines entertaining crucial processes in atherosclerosis development, progression, and regression.
Gap Junction Coupling Is Required for Tumor Cell Migration Through Lymphatic Endothelium
Authors: Karpinich Natalie O. , Caron Kathleen M.
Published: March 2015

Objective—

The lymphatic vasculature is a well-established conduit for metastasis, but the mechanisms by which tumor cells interact with lymphatic endothelial cells (LECs) to facilitate escape remain poorly understood. Elevated levels of the lymphangiogenic peptide adrenomedullin are found in many tumors, and we previously characterized that its expression is necessary for lymphatic vessel growth within both tumors and sentinel lymph nodes and for distant metastasis.

Approach and Results—

This study used a tumor cell-LEC coculture system to identify a series of adrenomedullin-induced events that facilitated transendothelial migration of the tumor cells through a lymphatic monolayer. High levels of adrenomedullin expression enhanced adhesion of tumor cells to LECs, and further analysis revealed that adrenomedullin promoted gap junction coupling between LECs as evidenced by spread of Lucifer yellow dye. Adrenomedullin also enhanced heterocellular gap junction coupling as demonstrated by Calcein dye transfer from tumor cells into LECs. This connexin-mediated gap junction intercellular communication was necessary for tumor cells to undergo transendothelial migration because pharmacological blockade of this heterocellular communication prevented the ability of tumor cells to transmigrate through the lymphatic monolayer. In addition, treatment of LECs with adrenomedullin caused nuclear translocation of β-catenin, a component of endothelial cell junctions, causing an increase in transcription of the downstream target gene
C-MYC
. Importantly, blockade of gap junction intercellular communication prevented β-catenin nuclear translocation.

Conclusions—

Our findings indicate that maintenance of cell–cell communication is necessary to facilitate a cascade of events that lead to tumor cell migration through the lymphatic endothelium.
Inspiratory Resistance Improves Postural Tachycardia
Authors: Gamboa Alfredo , Paranjape Sachin Y. , Black Bonnie K. , Arnold Amy C. , Figueroa Rocío , Okamoto Luis E. , Nwazue Victor C. , Diedrich Andre , Plummer W. Dale , Dupont William D. , Robertson David , Raj Satish R.
Published: March 2015

Background—

The objective of this study was to determine the effect of inspiratory resistance through an impedance threshold device (ITD) on orthostatic tolerance in patients with postural tachycardia syndrome. We hypothesized that the ITD would result in a greater negative intrathoracic pressure to enhance cardiac venous return, improve stroke volume, and reduce heart rate in these patients.

Methods and Results—

We compared the effect of a sham device (sham, no resistance) versus an ITD (increased inspiratory resistance) in 26 patients with postural tachycardia syndrome in a randomized, single-blind, crossover study. Hemodynamic assessments were performed at baseline while supine and during head-up tilt to 70° for 10 minutes. We did not find differences in baseline hemodynamic parameters between the ITD and the sham devices. After 10 minutes of head-up tilt, the heart rate was lower with the ITD versus sham device (102±4 versus 109±4 beat/min, respectively;
P
=0.003). The ITD also improved stroke volume compared with the sham device (35±2 versus 26±1 mL;
P
=0.006).

Conclusions—

These findings suggest that increasing negative intrathoracic pressure with ITD breathing improves heart rate control in patients with postural tachycardia syndrome during upright posture.

Clinical Trial Registration—

clinicaltrials.gov
; Unique Identifier: NCT00962728.
Efficacy and Safety of Vorapaxar as Approved for Clinical Use in the United States
Authors: Magnani Giulia , Bonaca Marc P. , Braunwald Eugene , Dalby Anthony J. , Fox Keith A. A. , Murphy Sabina A. , Nicolau José Carlos , Oude Ophuis Ton , Scirica Benjamin M. , Spinar Jindrich , Theroux Pierre , Morrow David A.
Published: March 2015

Background

Vorapaxar is a protease‐activated receptor‐1 antagonist approved by the U.S. Food and Drug Administration (FDA) for the reduction of thrombotic cardiovascular (CV) events in patients with a history of myocardial infarction (MI) and peripheral artery disease (PAD), without a previous stroke or transient ischemic attack (TIA).

Methods and Results

We examined the efficacy and safety of vorapaxar in the intended use population, considering 20 170 patients randomized in the multinational, double‐blinded, placebo‐controlled TRA 2°P‐TIMI 50 trial. Of these, 16 897 qualified with a history of MI in the prior 2 weeks to 1 year and 3273 with PAD. At baseline 97% of the patients were treated with aspirin, 71% with a thienopyridine, and 93% a statin. At 3 years, the endpoint of CV death, MI, or stroke was significantly reduced with vorapaxar compared with placebo (7.9% versus 9.5%, HR, 0.80; 95% CI 0.73 to 0.89;
P
<0.001). Vorapaxar also significantly reduced the composite of CV death, MI, stroke, and urgent coronary revascularization (10.1% versus 11.8%, HR, 0.83; 95% CI 0.76 to 0.90;
P
<0.001), as well as the rate of CV death or MI (
P
<0.001). The safety endpoint of GUSTO moderate or severe bleeding, was increased in the vorapaxar group (3.7 versus 2.4, HR, 1.55; 95% CI 1.30 to 1.86,
P
<0.001). Intracranial bleeding (ICH) was 0.6% versus 0.4%,
P
=0.10 with vorapaxar versus placebo, with fatal bleeding 0.2% versus 0.2%;
P
=0.70.

Conclusions

In patients with prior MI or PAD who have not had a previous stroke or TIA, vorapaxar added to standard therapy is effective for long‐term secondary prevention of thrombotic CV events, while increasing moderate or severe bleeding.

Clinical Trial Registration

URL: clinicaltrials.gov Unique Identifier: NCT00526474.
Three‐Dimensional Echocardiography and 2D‐3D Speckle‐Tracking Imaging in Chronic Pulmonary Hypertension: Diagnostic Accuracy in Detecting Hemodynamic Signs of Right Ventricular (RV) Failure
Authors: Vitarelli Antonio , Mangieri Enrico , Terzano Claudio , Gaudio Carlo , Salsano Felice , Rosato Edoardo , Capotosto Lidia , D'Orazio Simona , Azzano Alessia , Truscelli Giovanni , Cocco Nino , Ashurov Rasul
Published: March 2015

Background

Our aim was to compare three‐dimensional (3D) and 2D and 3D speckle‐tracking (2D‐
STE
, 3D‐
STE
) echocardiographic parameters with conventional right ventricular (
RV
) indexes in patients with chronic pulmonary hypertension (
PH
), and investigate whether these techniques could result in better correlation with hemodynamic variables indicative of heart failure.

Methods and Results

Seventy‐three adult patients (mean age, 53±13 years; 44% male) with chronic
PH
of different etiologies were studied by echocardiography and cardiac catheterization (25 precapillary
PH
from pulmonary arterial hypertension, 23 obstructive pulmonary heart disease, and 23 postcapillary
PH
from mitral regurgitation). Thirty healthy subjects (mean age, 54±15 years; 43% male) served as controls. Standard 2D measurements (
RV
–fractional area change–tricuspid annular plane systolic excursion) and mitral and tricuspid tissue Doppler annular velocities were obtained. RV 3D volumes and global and regional ejection fraction (3D‐
RVEF
) were determined.
RV
strains were calculated by 2D‐
STE
and 3D‐
STE
.
RV
3D global‐free‐wall longitudinal strain (3D
GFW
‐
RVLS
), 2D global‐free‐wall longitudinal strain (
GFW
‐
RVLS
), apical‐free‐wall longitudinal strain, basal‐free‐wall longitudinal strain, and 3D‐
RVEF
were lower in patients with precapillary
PH
(
P
<0.0001) and postcapillary
PH
(
P
<0.01) compared to controls. 3D
GFW
‐
RVLS
(hazard ratio 4.6, 95%
CI
2.79 to 8.38,
P
=0.004) and 3D‐
RVEF
(hazard ratio 5.3, 95%
CI
2.85 to 9.89,
P
=0.002) were independent predictors of mortality. Receiver operating characteristic curves showed that the thresholds offering an adequate compromise between sensitivity and specificity for detecting hemodynamic signs of
RV
failure were 39% for 3D‐
RVEF
(
AUC
0.89), −17% for 3D
GFW
‐
RVLS
(
AUC
0.88), −18% for
GFW
‐
RVLS
(
AUC
0.88), −16% for apical‐free‐wall longitudinal strain (
AUC
0.85), 16 mm for tricuspid annular plane systolic excursion (
AUC
0.67), and 38% for
RV
‐
FAC
(
AUC
0.62).

Conclusions

In chronic
PH
, 3D, 2D‐
STE
and 3D‐
STE
parameters indicate global and regional
RV
dysfunction that is associated with
RV
failure hemodynamics better than conventional echo indices.
Cerebral Cavernous Malformation-1 Protein Controls DLL4-Notch3 Signaling Between the Endothelium and Pericytes
Authors: Schulz Gerald B. , Wieland Elfriede , Wüstehube-Lausch Joycelyn , Boulday Gwénola , Moll Iris , Tournier-Lasserve Elisabeth , Fischer Andreas
Published: March 2015

Background and Purpose—

Cerebral cavernous malformation (CCM) is a neurovascular dysplasia characterized by conglomerates of enlarged endothelial channels in the central nervous system, which are almost devoid of pericytes or smooth muscle cells. This disease is caused by loss-of-function mutations in
CCM1
,
CCM2
, or
CCM3
genes in endothelial cells, making blood vessels highly susceptible to angiogenic stimuli.
CCM1
- and
CCM3
-silenced endothelial cells have a reduced expression of the Notch ligand Delta-like 4 (DLL4) resulting in impaired Notch signaling and irregular sprouting angiogenesis. This study aimed to address if DLL4, which is exclusively expressed on endothelial cells, may influence interactions of endothelial cells with pericytes, which express Notch3 as the predominant Notch receptor.

Methods—

Genetic manipulation of primary human endothelial cells and brain pericytes. Transgenic mouse models were also used.

Results—

Endothelial cell–specific ablation of
Ccm1
and
Ccm2
in different mouse models led to the formation of CCM-like lesions, which were poorly covered by periendothelial cells. CCM1 silencing in endothelial cells caused decreased Notch3 activity in cocultured pericytes. DLL4 proteins stimulated Notch3 receptors on human brain pericytes. Active Notch3 induced expression of
PDGFRB2, N-Cadherin
,
HBEGF
,
TGFB1, NG2
, and
S1P
genes. Notch3 signaling in pericytes enhanced the adhesion strength of pericytes to endothelial cells, limited their migratory and invasive behavior, and enhanced their antiangiogenic function. Pericytes silenced for Notch3 expression were more motile and could not efficiently repress angiogenesis.

Conclusions—

The data suggest that Notch signaling in pericytes is important to maintain the quiescent vascular phenotype. Deregulated Notch signaling may, therefore, contribute to the pathogenesis of CCM.
Attention Deficits After Aneurysmal Subarachnoid Hemorrhage Measured Using the Test of Variables of Attention
Authors: Wallmark Svante , Lundström Erik , Wikström Johan , Ronne-Engström Elisabeth
Published: March 2015

Background and Purpose—

The aim of this pilot study was to assess attention deficits in patients with aneurysmal subarachnoid hemorrhage using the test of variables of attention (TOVA). This is a computer-based continuous performance test providing objective measures of attention. We also compared the TOVA results with the attention and concentration domains of Montgomery Åsberg Depression Rating Scale and Montreal cognitive assessment, 2 examiner-administrated neuropsychological instruments.

Methods—

Nineteen patients with moderate to good recovery (Glasgow outcome scale, 4–5) were assessed using the TOVA, Montgomery Åsberg Depression Rating Scale, and Montreal cognitive assessment. The measurements were done when the patients visited the hospital for a routine magnetic resonance imaging control of the aneurysm.

Results—

TOVA performance was pathological in 58%. The dominating pattern was a worsening of performance in the second half of the test, commonly a failing to react to correct stimuli. We found no correlation between TOVA and the performance in concentration and attention domains of Montgomery Åsberg Depression Rating Scale and Montreal cognitive assessment.

Conclusions—

Attention deficits, measured by the TOVA, were common after subarachnoid hemorrhage. This should be further studied to improve outcome.
The Distributed Cognitive Economics of Reform: A Framework
Authors: Lieber André
Published: March 2015

We present an enriched cognitive approach to the political economy of reform based on the notion of distributed cognition. Our aim is to describe the origination causation of economic reforms highlighting the interactions between people, artefacts as well as internal and external representations. In particular, we ask how reformers are able to turn a cognitively ill-defined situation into a cognitively well-defined situation. The proposed framework, we tentatively call ‘the distributed cognitive economics of reform’, emphasizes three key messages: First, economic reforms are creative processes largely driven by self-organized innovation and acts of public entrepreneurship. Second, the cognitive distance between individuals both enables and constraints cooperation and, most importantly, learning. Third, reformers’ ability to communicate to a wide range of audiences is crucial in times of reform. In consequence, successful reformers often rely on policy metaphors as primary means to manage high levels of uncertainty, complexity and ambiguity. Presenting post-1978 Chinese economic reform as a case study, we argue that the notion of distributed cognition can improve our understanding of economic reform processes.

JEL: B41, B52, P41, Z18
Pain Medicine and Palliative Care as an Alternative to Euthanasia in End-of-Life Cancer Care
Authors: Erdek Michael
Published: March 2015

There exists support for euthanasia or physician-assisted suicide (PAS) in cases of terminal cancer. One of the premises for this approach is the goal of the alleviation of suffering. Do current means of pain control in the greater overall setting of palliative care serve as a desirable alternative? A contrast comparison may be drawn between the above approaches using both theological and medical sources to show that the enlightened use of both interventional and non-interventional pain medicine approaches in an integrated palliative care setting are a theologically grounded and medically feasible alternative to euthanasia or PAS in this population.

Lay summary

Patients suffering from terminal cancer often have pain. Some have advocated euthanasia or physician-assisted suicide as a potential way of alleviating this suffering. Further examination of this topic, however, shows this approach may be essentially utilitarian and fail to consider the inherent value of human life. There has been significant development in recent years in the fields of pain medicine and palliative care, which afford alternate means of addressing suffering in this patient population.
Functional signatures of oral dysbiosis during periodontitis progression revealed by microbial metatranscriptome analysis
Authors: Yost Susan , Duran-Pinedo Ana E , Teles Ricardo , Krishnan Keerthana , Frias-Lopez Jorge
Published: March 2015

Background

Periodontitis is a polymicrobial biofilm-induced inflammatory disease that affects 743 million people worldwide. The current model to explain periodontitis progression proposes that changes in the relative abundance of members of the oral microbiome lead to dysbiosis in the host-microbiome crosstalk and then to inflammation and bone loss. Using combined metagenome/metatranscriptome analysis of the subgingival microbiome in progressing and non-progressing sites, we have characterized the distinct molecular signatures of periodontitis progression.

Methods

Metatranscriptome analysis was conducted on samples from subgingival biofilms from progressing and stable sites from periodontitis patients. Community-wide expression profiles were obtained using Next Generation Sequencing (Illumina). Sequences were aligned using ‘bowtie2’ against a constructed oral microbiome database. Differential expression analysis was performed using the non-parametric algorithm implemented on the R package ‘NOISeqBio’. We summarized global functional activities of the oral microbial community by set enrichment analysis based on the Gene Ontology (GO) orthology.

Results

Gene ontology enrichment analysis showed an over-representation in the baseline of active sites of terms related to cell motility, lipid A and peptidoglycan biosynthesis, and transport of iron, potassium, and amino acids. Periodontal pathogens (Tannerella forsythia and Porphyromonas gingivalis) upregulated different TonB-dependent receptors, peptidases, proteases, aerotolerance genes, iron transport genes, hemolysins, and CRISPR-associated genes. Surprisingly, organisms that have not been usually associated with the disease (Streptococcus oralis, Streptococcus mutans, Streptococcus intermedius, Streptococcus mitis, Veillonella parvula, and Pseudomonas fluorenscens) were highly active transcribing putative virulence factors. We detected patterns of activities associated with progression of clinical traits. Among those we found that the profiles of expression of cobalamin biosynthesis, proteolysis, and potassium transport were associated with the evolution towards disease.

Conclusions

We identified metabolic changes in the microbial community associated with the initial stages of dysbiosis. Regardless of the overall composition of the community, certain metabolic signatures are consistent with disease progression. Our results suggest that the whole community, and not just a handful of oral pathogens, is responsible for an increase in virulence that leads to progression.

Trial registration

NCT01489839, 6 December 2011.
Adipose-derived stem cell-based treatment for acute liver failure
Authors: Chen Guangfeng , Jin Yinpeng , Shi Xiujuan , Qiu Yu , Zhang Yushan , Cheng Mingliang , Wang Xiaojin , Chen Chengwei , Wu Yinxia , Jiang Fuzhu , Li Li , Zhou Heng , Fu Qingchun , Liu Xiaoqing
Published: March 2015

Introduction

Acute liver failure (ALF) is a highly lethal disease, for which effective therapeutic methods are limited. Although allogeneic liver transplantation is a viable treatment method for ALF, there is a serious shortage of liver donors. Recent studies suggest that stem cell transplantation is a more promising alternative. Hence, we investigate whether human adipose-derived stem cells (ASCs) have the therapeutic potential for ALF in this study based on the studies of rat models.

Methods

Sprague Dawley rats were used to establish ALF models by D-galactosamine injection. These rats were randomly divided into a human ASC-treated group and a phosphate-buffered saline (PBS) control group. The human ASCs or PBS was transplanted through the spleen of rats. The indices of hepatic function and hepatic histology were dynamically detected, and the survival rates of rats were also counted. Double-fluorescence immunohistochemistry was employed to detect the ASC fate after transplantation. Moreover, both concentrated ASC conditional media and ASC lysates were transplanted through the femoral vain of rats to investigate the therapeutic potential for ALF.

Results

The ASC transplantation group showed improved viability in comparison with the sham control. Histological and biochemical analysis suggested that liver morphology and function were improved in terms of cell proliferation and apoptosis. Although a plethora of ASCs persist in the spleen, the improvement in liver function was obvious. However, ASCs did not differentiate into hepatocytes after engrafting to livers within 3 days. In addition, both concentrated serum-free ASC conditional media and ASC lysates, characterized by high levels of hepatocyte growth factor and vascular endothelial growth factor, demonstrated obvious improvement in terms of high survival rates of ALF rats.

Conclusion

Our data suggest that ASC transplantation has the potential for ALF treatment partly by the mechanism of secreting growth factors contributing to liver regeneration.
ARP2/3 complex is required for directional migration of neural stem cell-derived oligodendrocyte precursors in electric fields
Authors: Li Yongchao , Wang Pei-Shan , Lucas George , Li Rong , Yao Li
Published: March 2015

Introduction

The loss of oligodendrocytes in a lesion of the central nervous system causes demyelination and therefore impairs axon function and survival. Transplantation of neural stem cell-derived oligodendrocyte precursor cells (NSC-OPCs) results in increased oligodendrocyte formation and enhanced remyelination. The directional migration of grafted cells to the target can promote the establishment of functional reconnection and myelination in the process of neural regeneration. Endogenous electric fields (EFs) that were detected in the development of the central nervous system can regulate cell migration.

Methods

NSCs were isolated from the brains of ARPC2+/+ and ARPC2−/− mouse embryo and differentiated into OPCs. After differentiation, the cultured oligospheres were stimulated with EFs (50, 100, or 200 mV/mm). The migration of OPCs from oligospheres was recorded using time-lapse microscopy. The cell migration directedness and speed were analyzed and quantified.

Results

In this study, we found that NSC-OPCs migrated toward the cathode pole in EFs. The directedness and displacement of cathodal migration increased significantly when the EF strength increased from 50 to 200 mV/mm. However, the EF did not significantly change the cell migration speed. We also showed that the migration speed of ARPC2−/− OPCs, deficient in the actin-related proteins 2 and 3 (ARP2/3) complex, was significantly lower than that of wild type of OPCs. ARPC2−/− OPCs migrated randomly in EFs.

Conclusions

The migration direction of NSC-OPCs can be controlled by EFs. The function of the ARP complex is required for the cathodal migration of NSC-OPCs in EFs. EF-guided cell migration is an effective model to understanding the intracellular signaling pathway in the regulation of cell migration directness and motility.
A population-based analysis of outcomes for small cell carcinoma of the breast by tumor stage and the use of radiation therapy
Authors: Hare Felicia , Giri Smith , Patel Jashmin K , Hahn Andrew , Martin Michael G
Published: March 2015

Purpose

Primary small cell carcinomas of the breast (SCCB) are rare tumors with limited data on outcomes and treatment strategies. Using a population based approach, we aimed to study outcomes of SCCB and determine whether the use of radiation therapy is associated with better survival among patients with SCCB.

Methods

Using the Surveillance, Epidemiology and End Results (SEER) registry, we identified patients with SCCB between1973 and 2010. We examined the stage specific survival of these patients and compared it to the stage specific survival of small cell lung cancer (SCLC) from the SEER database over the same accrual period. We further analyzed the impact of radiation therapy on overall survival for SCCB patients using a univariate and multivariate approach.

Results

A total of 199 patients with primary SCCB with staging were identified during the study period. Eighty-four patients (42%) had localized disease, 77 (39%) had regional disease and 38 (19%) had distant disease. For comparison, 81,933 patients with SCLC were identified. Outcomes were superior for patients with SCCB with localized (150 vs. 16 months, p < 0.01) and regional disease (56 vs. 13 months, p < 0.01), but not distant disease (7 vs. 7 months, p = 0.43). Use of radiation therapy was not associated with a significant difference in OS for patients with either localized (202 vs. 147 months, p = 0.48) or regional (52 vs. 75 months, p = 0.650) disease.

Conclusions

SCCB has a more favorable prognosis by stage for localized and regional disease than SCLC. Adjuvant radiation is not associated with an improvement in survival for patients with localized or regional SCCB in this dataset.
HDAC9 Inhibits Osteoclastogenesis via Mutual Suppression of PPARγ/RANKL Signaling
Authors: Jin Zixue , Wei Wei , Huynh HoangDinh , Wan Yihong
Published: March 2015

Recent studies suggest that the class II histone deacetylase (HDAC)9 plays important roles in physiology such as metabolism and immunity. Here, we report that HDAC9 also controls bone turnover by suppressing osteoclast differentiation and bone resorption. HDAC9 expression is down-regulated during osteoclastogenesis. Ex vivo osteoclast differentiation is accelerated by HDAC9 deletion but diminished by HDAC9 overexpression. HDAC9 knockout mice exhibit elevated bone resorption and lower bone mass. Bone marrow transplantation reveal that the osteoclastogenic defects are intrinsic to the hematopoietic lineage, because the excessive bone resorption phenotype can be conferred in wild-type (WT) mice receiving HDAC9-null bone marrow, and rescued in HDAC9-null mice receiving WT bone marrow. Mechanistically, HDAC9 forms a negative regulatory loop with peroxisome proliferator-activated receptor gamma (PPARg) and receptor activator of nuclear factor kappa-B ligand (RANKL) signaling. On one hand, PPARγ and nuclear factor κB suppress HDAC9 expression, on the other hand, HDAC9 inhibits PPARγ activity in synergy with silencing mediator of retinoic acid and thyroid hormone receptors (SMRT)/NCoR corepressors. These findings identify HDAC9 as a novel, important and physiologically relevant modulator of bone remodeling and skeletal homeostasis.
Modeling and study of the mechanism of dilated cardiomyopathy using induced pluripotent stem cells derived from individuals with Duchenne muscular dystrophy
Authors: Lin Bo , Li Yang , Han Lu , Kaplan Aaron D. , Ao Ying , Kalra Spandan , Bett Glenna C. L. , Rasmusson Randall L. , Denning Chris , Yang Lei
Published: March 2015

Duchenne muscular dystrophy (DMD) is caused by mutations in the dystrophin gene (DMD), and is characterized by progressive weakness in skeletal and cardiac muscles. Currently, dilated cardiomyopathy due to cardiac muscle loss is one of the major causes of lethality in late-stage DMD patients. To study the molecular mechanisms underlying dilated cardiomyopathy in DMD heart, we generated cardiomyocytes (CMs) from DMD and healthy control induced pluripotent stem cells (iPSCs). DMD iPSC-derived CMs (iPSC-CMs) displayed dystrophin deficiency, as well as the elevated levels of resting Ca2+, mitochondrial damage and cell apoptosis. Additionally, we found an activated mitochondria-mediated signaling network underlying the enhanced apoptosis in DMD iPSC-CMs. Furthermore, when we treated DMD iPSC-CMs with the membrane sealant Poloxamer 188, it significantly decreased the resting cytosolic Ca2+ level, repressed caspase-3 (CASP3) activation and consequently suppressed apoptosis in DMD iPSC-CMs. Taken together, using DMD patient-derived iPSC-CMs, we established an in vitro model that manifests the major phenotypes of dilated cardiomyopathy in DMD patients, and uncovered a potential new disease mechanism. Our model could be used for the mechanistic study of human muscular dystrophy, as well as future preclinical testing of novel therapeutic compounds for dilated cardiomyopathy in DMD patients.
ECG of the month
Authors: Regan Clare , Regan Martin
Published: March 2015

Clare Regan and Martin Regan present an ECG for you to analyse
Demystifying the cardiac action potential for nurses
Authors: Eggett Christopher J
Published: March 2015

The cardiac action potential reflects change in the electrical activity of individual heart muscle cells. This change occurs as a consequence of sodium, potassium and calcium ions moving across the cell membrane through protein-based structures known as ion channels. Alteration to ion channel structure and function affects the cardiac action potential. Consequently, drugs that block ion channels or genetic mutations that result in abnormal ion-channel formation change the electrical activity of heart-muscle cells. This article explains the appearance of the cardiac action potential in ventricular muscle cells and the pacemaker cells of the sinoatrial node. It also discusses the effect of anti-arrhythmic drugs upon the action potential and introduces the concept of ion-channel abnormalities, or ‘channelopathies’, that result in life-threatening arrhythmias as a consequence of action potential disruption.
Taking on apprentices
Authors: Steel Sarah
Published: March 2015

Due to the high number of young people who choose to work in childcare when they leave school, apprenticeships can offer a good route into the sector for both potential employee and employer.
Too soon or just the right time
Authors: Watson Greg
Published: March 2015

Despite the controversy, the reception baseline does not need to be a burden on teachers or children, states Greg Watson; here, he outlines the development and feedback process behind the assessment.
Management of adult coeliac disease with a dietitian-led virtual clinic
Authors: Stuckey Claire
Published: March 2015

Review of adults with coeliac disease is variable throughout the UK in terms of frequency, expertise, and the specialty of the health professionals undertaking the review. In this article, the author describes a dietitian-led virtual review clinic as a method for monitoring adults with established coeliac disease. Clinical audit of the first 24 months of running this service has shown that 91.7% of invited patients attended blood monitoring and returned a completed questionnaire for dietitian review. Moreover, 80% of patients reported that they prefer to alternate virtual review with face-to-face review annually rather than always attend an annual appointment. A virtual (telephone and postal) review clinic has been shown to be an effective method of reviewing adults with coeliac disease.
Making a difference in mental health
Authors: Day Asha
Published: March 2015

Asha Day has always had a passion for supporting new parents with perinatal mental health. As an iHV Fellow, she has a notable opportunity to further her work in this area.
Candida and Breastfeeding
Authors: Duncan Deborah
Published: March 2015

Candida albicans is the most common occurring of the candida species found as a commensal on mucosal tissue of mother and child. As a pathogen it can cause a distressing fungal infection for both mother and baby, resulting in nipple and breast pain for the mother and feeding difficulties for the infant. Clinicians can often presume that these symptoms are due to C. albicans, which has resulted in an overuse of systemic antifungal therapy in many of these patients. It is therefore important to ensure that there is a clear diagnosis and that the problem can be treated appropriately.
What is your purpose at work?
Authors: Oshikanlu Ruth
Published: March 2015

In order to feel fulfilled and get the most out of your job, it is essential to understand the reason you do what you do. Ruth Oshikanlu explores the idea of finding the ‘big why’.
My side of town
Authors: Pollitt Amanda
Published: March 2015

When challenged to think about social determinants of health as part of her SCPHN course, Amanda Pollitt was inspired to write a poem about inequalities close to home.
Forest inventory attribute prediction using airborne laser scanning in low-productive forestry-drained boreal peatlands
Authors: Niemi Mikko , Vastaranta Mikko , Peuhkurinen Jussi , Holopainen Markus
Published: March 2015

Nearly 30% of Finlandâs land area is covered by peatlands. In Northern parts of the country there is a significant amount of low-productive drained peatlands (LPDPs) where the average annual stem volume growth is less than 1 m ha. The re-use of LPDPs has been considered thoroughly since Finnish forest legislation was updated and the forest regeneration prerequisite was removed from LPDPs in January 2014. Currently, forestry is one of the re-use alternatives, thus detailed forest resource information is required for allocating activities. However, current forest inventory practices have not been evaluated for sparse growing stocks (e.g., LPDPs). The purpose of our study was to evaluate the suitability of airborne laser scanning (ALS) for mapping forest inventory attributes in LPDPs. We used ALS data with a density of 0.8 pulses per m, 558 field-measured reference plots (500 from productive forests and 58 from LPDPs) and nearest neighbour (-NN) estimation. Our main aim was to study the sensitivity of predictions to the number of LPDP reference plots used in the -NN estimation. When the reference data consisted of 500 plots from productive forest stands, the root mean square errors (RMSEs) for the prediction accuracy of Loreyâs height, basal area and stem volume were 1.4 m, 2.7 m ha and 13.7 m ha in LPDPs, respectively. When 30 additional reference plots were allocated to LPDPs, the respective RMSEs were 1.1 m, 1.7 m ha and 10.0Â m ha. Additional reference plot allocation did not affect the predictions in productive forest stands.3â12kkk2â13â12â13â1
Análisis del modelo eléctrico del mecanismo de hurto de energía eléctrica más utilizado en el sector industrial de Bogotá
Authors: Garzón Rodríguez Yaqueline , Doncel Díaz César Andrés
Published: March 2015

Este trabajo se inscribe en la línea de Investigación de Compatibilidad Electromagnética y analiza el modelo eléctrico del mecanismo de hurto más implementado en medida semidirecta, con el fin de comprender el fenómeno físico que se encuentra y, a su vez, generar algunas recomendaciones respecto a las situaciones que pueden propiciar o permitir la implementación de este tipo de mecanismos utilizados en celdas de medida semidirecta en el sector industrial de la ciudad de Bogotá.El trabajo se divide en cuatro partes; en la primera sección se hace referencia al proceso que se realizó para la obtención del mecanismo de hurto de energía eléctrica más utilizado en la ciudad de Bogotá, su jerarquización y descripción. En la segunda sección se presenta la elaboración del circuito eléctrico equivalente, así como las pruebas teóricas y experimentales efectuadas como parte de la comprobación de su funcionamiento. En la tercera sección se hace la documentación de las anomalías encontradas en las celdas de medida semidirecta, ya que se han identificado como principal causa de implementación de mecanismo de hurto; por último, en la cuarta sección se presentan las recomendaciones de solución sugeridas a las anomalías encontradas en dichas celdas.Para establecer el modelo eléctrico se tomó como base el diagrama unifilar de medida semidirecta y se realiza circuito equivalente monofásico teniendo presente que el medidor y el transformador de corriente (TC) son los principales elementos en donde actúa este dispositivo. Acto seguido se efectúa el análisis mediante simulación del circuito, contemplando esta alteración mediante la herramienta Simulink en MATLAB, en la cual se identifica la anulación de la señal de corriente que se dirige al medidor a causa de la corriente inversa que proviene de la caja negra y, por ende, se verifica el bajo registro del consumo, como se evidencia en las curvas de potencia y energía en la carga.Posteriormente se hacen pruebas experimentales, para lo cual se construye un prototipo y se efectúa medición con dos equipos diferentes. Como resultado, se identifica que el mecanismo de caja negra se implementa mediante un transformador de núcleo partido, que se instala en la fase a la cual se le hace la anulación de la corriente mediante un acople inductivo.
Using the delaunay triangulation and voronoi diagrams for navigation in observable environments
Authors: Martínez Santa Fernando , Martínez Sarmiento Fredy Hernán , Jacinto Gómez Edwar
Published: March 2015

The navigation system of mobile robot should have the capability of environment cognition, action decision, motion control, and state monitoring. This paper proposes a prediction algorithm route based on Voronoi diagrams, applicable for mobile robots with range sensors operating in indoor and unknown environments. The proposed control law is a hybrid navigation strategy composed of Voronoi diagrams and Delaunay triangulation, which is used to avoid the routes that may eventually block the advance of the robot. An efficient implementation of the control law is presented. Simulation results validate the efficacy of the proposed modified control law.
Prototipo de sistema experto en diagnóstico médico basado en síntomas de los pacientes. Caso de estudio: esclerosis múltiple
Authors: Rivera Berrío Juan Guillermo , Tabares Ospina Héctor Aníbal
Published: March 2015

Se presenta en este artículo un modelo de sistema experto para el diagnóstico de la esclerosis múltiple. Esta labor no es una tarea trivial, debido a la subjetividad que puede presentarse en su evaluación. Este proceso se puede complementar usando un sistema de apoyo a la toma de decisiones. El sistema desarrollado se dividió en cuatro fases: toma de requisitos, diseño, implementación y puesta en marcha. Con el prototipo software se logró modelar el conocimiento específico del experto neurólogo, lo que permitió obtener un diagnóstico de la esclerosis múltiple.
Un vistazo al proyecto emprendetronika
Authors: Marlene Olea Doris , Garzón Pablo Emilio , Montaña Henry
Published: March 2015

Emprendetronika
Freedom in Hegel: Contra Pippin
Authors: Englander Alex
Published: March 2015

The Kantian concept of self-legislation plays a central role in Robert Pippin’s influential interpretation of Hegel’s theory of freedom. I isolate two competing notions of freedom present within Pippin’s own specification of the concept: freedom as reflective transparency and freedom as self-identification with one’s deeds. The former is compatible with Hegel’s own quasi-Spinozist conception of freedom and allows for historical conceptual change. It is also consistent with Pippin’s truly Hegelian contention that the justification of “modern ethical life” must assume the form of a historical, developmental account, and that a plurality of our moral and social attachments can be integral to our freedom. The ideal of self-identification. however, and Pippin’s development of it in terms of self-legislation and a theory of the normative social conditions of rational agency, involves a dichotomous conception of freedom that is incompatible with Hegel’s. Pippin’s ultimate privileging of self-legislation thus introduces a tension into his account and prevents him from achieving his distinctly Hegelian ambitions.
Energy Taxes and Oil Price Shocks
Authors: Cremer Helmuth , Gahvari Firouz , Ladoux Norbert
Published: March 2015

This paper examines if an energy price shock should be compensated by a reduction in energy taxes to mitigate its impact on consumer prices. It shows that the consumer price should not increase by as much as the producer price, implying a small reduction in the energy tax in dollars. The energy tax rate, on the other hand, decreases sharply. This decline is primarily due to an adjustment in the Pigouvian component: A constant marginal social damage being divided by a higher producer price. The redistributive component of the tax remains at about 10% of the social cost of energy.