bluuebunny/crossref_metadata_2025 huggingface dataset:
Adult Stem Cell as New Advanced Therapy for Experimental Neuropathic Pain Treatment
Authors: Franchi Silvia , Castelli Mara , Amodeo Giada , Niada Stefania , Ferrari Daniela , Vescovi Angelo , Brini Anna Teresa , Panerai Alberto Emilio , Sacerdote Paola
Published: August 2014

Neuropathic pain (NP) is a highly invalidating disease resulting as consequence of a lesion or disease affecting the somatosensory system. All the pharmacological treatments today in use give a long lasting pain relief only in a limited percentage of patients before pain reappears making NP an incurable disease. New approaches are therefore needed and research is testing stem cell usage. Several papers have been written on experimental neuropathic pain treatment using stem cells of different origin and species to treat experimental NP. The original idea was based on the capacity of stem cell to offer a totipotent cellular source for replacing injured neural cells and for delivering trophic factors to lesion site; soon the researchers agreed that the capacity of stem cells to contrast NP was not dependent upon their regenerative effect but was mostly linked to a bidirectional interaction between the stem cell and damaged microenvironment resident cells. In this paper we review the preclinical studies produced in the last years assessing the effects induced by several stem cells in different models of neuropathic pain. The overall positive results obtained on pain remission by using stem cells that are safe, of easy isolation, and which may allow an autologous transplant in patients may be encouraging for moving from bench to bedside, although there are several issues that still need to be solved.
ApoA-I/HDL Generation and Intracellular Cholesterol Transport through Cytosolic Lipid-Protein Particles in Astrocytes
Authors: Ito Jinichi , Michikawa Makoto
Published: August 2014

Exogenous apolipoprotein A-I (apoA-I) associates with ATP-binding cassette transporter A1 (ABCA1) on the cell surface of astrocytes like various peripheral cells and enhances the translocation of newly synthesized cholesterol from the endoplasmic reticulum/Golgi apparatus (ER/Golgi) to the cytosol. The cholesterol translocated to the cytosol is incorporated to cytosolic lipid-protein particles (CLPP) together with phospholipids and proteins such as sphingomyelin, phosphatidylcholine, caveolin-1, protein kinase Cα(PK-Cα), and cyclophilin A. The CLPP are high density lipoproteins- (HDL-)like cytosolic lipid-protein complex with densities of 1.09–1.16 g/mL and diameters of 17-18 nm. The association of exogenous apoA-I with cellular ABCA1 induces tyrosine phosphorylation, activation, and translocation to the CLPP of ABCA1-associated phospholipase Cγ(PL-Cγ) in rat astrocytes. Furthermore, PK-Cαis translocated and activated to/in the CLPP through the　production of diacylglyceride in the CLPP. ApoA-I enhances both the association of CLPP with microtubules and the phosphorylation ofα-tubulin as a component of microtubules. The CLPP are dissociated from microtubules afterα-tubulin in microtubules is phosphorylated by the CLPP-associated PK-Cα. The association and dissociation between CLPP and microtubules may participate in the intracellular transport of cholesterol to the plasma membrane.
The Tin Whistle: A Rare and Serious Cause of Penetrating Oropharyngeal Trauma in Children
Authors: Francis E. C. , Browne K. M. , Eadie P. A.
Published: August 2014

Impalement injuries of the oral cavity are common in children and the potential for serious complications including internal carotid artery thrombosis can be unnoticed. We present a patient who sustained a penetrating injury in which a “tin whistle” caused herniation of the parotid gland which was not detected on clinical examination. We discuss the challenging clinical examination, the role of investigations, and consequences of these injuries aiming at increasing awareness and optimizing patient management.
Evaluation of Root Canal Configuration of Mandibular First Molars in a Palestinian Population by Using Cone-Beam Computed Tomography: An Ex Vivo Study
Authors: Mukhaimer Raed Hakam
Published: August 2014

Aim. The purpose of this study was to investigate the number of canals and variations in root canal configuration in the mandibular permanent first molar teeth of a Palestinian population using cone-beam computed tomography (CBCT). Methods. A sample of 320 extracted double-rooted mandibular permanent first molars from Palestinian population was collected for this study and scanned with CBCT scanner. The following observations were made: number of root canals per root and canal configuration in each root based on Vertucci’s classification. Results. Of the 320 mandibular first molars analyzed, 174 (54.4%) had three canals, 132 teeth (41.3%) had four canals, and only four teeth had two canals. The most common canal configuration in the mesial roots was Vertucci type IV (53.8%) followed by type II (38.8%). In the distal roots, the most prevalent canal configuration was Vertucci type I (57.5%) followed by type II ( 22.5%) and type III (10.6%). Conclusion. Our results showed that the number of canals and canal configuration in Palestinian population were consistent with previously reported data. The present study also indicates that CBCT is helpful as a diagnostic tool for the investigation of root canal morphology.
The Role of Intrinsic Pathway in Apoptosis Activation and Progression in Peyronie’s Disease
Authors: Loreto Carla , La Rocca Giampiero , Anzalone Rita , Caltabiano Rosario , Vespasiani Giuseppe , Castorina Sergio , Ralph David J. , Cellek Selim , Musumeci Giuseppe , Giunta Salvatore , Djinovic Rados , Basic Dragoslav , Sansalone Salvatore
Published: August 2014

Peyronie’s disease (PD) is characterized with formation of fibrous plaques which result in penile deformity, pain, and erectile dysfunction. The aim of this study was to investigate the activation of the intrinsic apoptotic pathway in plaques from PD patients. Tunica albuginea from either PD or control patients was assessed for the expression of bax, bcl-2 and caspases 9 and 3 using immunohistochemistry and by measurement of apoptotic cells using TUNEL assay. Bax overexpression was observed in metaplastic bone tissue, in fibroblasts, and in myofibroblast of plaques from PD patients. Little or no bcl-2 immunostaining was detected in samples from either patients or controls. Caspase 3 immunostaining was very strong in fibrous tissue, in metaplasic bone osteocytes, and in primary ossification center osteoblasts. Moderate caspase 9 immunostaining was seen in fibrous cells plaques and in osteocytes and osteoblasts of primary ossification centers from PD patients. Control samples were negative for caspase 9 immunostaining. In PD patients the TUNEL immunoassay showed intense immunostaining of fibroblasts and myofibroblasts, the absence of apoptotic cells in metaplasic bone tissue and on the border between fibrous and metaplastic bone tissue. Apoptosis occurs in stabilized PD plaques and is partly induced by the intrinsic pathway.
Correlation between Abortion and Infertility among Nonsmoking Women with a History of Passive Smoking in Childhood and Adolescence
Authors: Amirkhani Jila , Yadollah-Damavandi Soheila , Mirlohi Seyed Mohammad-Javad , Nasiri Seyede Mahnaz , Parsa Yekta , Gharehbeglou Mohammad
Published: August 2014

The aim of this study is to evaluate the correlation of exposing to the cigarette smoke in childhood and adolescence with infertility and abortion in women. This case-control study evaluated 178 women who had been attended to at the Amir-al-Momenin Hospital in Tehran in 2012-2013. Seventy-eight women with chief complaint of abortion, infertility, and missed abortion and 100 healthy women were considered as case and control groups, respectively. The tool was a questionnaire with two parts. In the first part demographic information was gathered and in the second part the information regarding the history of passive smoking in childhood and adolescence period, abortion, and infertility was gathered. The mean age in case and control groups was 26.24 ± 3.1 and 27.3 ± 4.2 years, respectively. The mean body mass index (BMI) was 25.74 ± 1.38 Kg/m2. Abortion rates among passive smoker and nonpassive smoker patients were statistically significant (P=0.036). Based on findings of this study, the experience of being a passive smoker in childhood and adolescence in women will increase the risk of abortion and infertility in the future, which could be the reason to encourage the society to step back from smoking cigarettes.
The Wedelolactone Derivative Inhibits Estrogen Receptor-Mediated Breast, Endometrial, and Ovarian Cancer Cells Growth
Authors: Xu Defeng , Lin Tzu-Hua , Yeh Chiuan-Ren , Cheng Max A. , Chen Lu-Min , Chang Chawnshang , Yeh Shuyuan
Published: August 2014

Estrogen and estrogen receptor (ER)-mediated signaling pathways play important roles in the etiology and progression of human breast, endometrial, and ovarian cancers. Attenuating ER activities by natural products and their derivatives is a relatively practical strategy to control and reduce breast, endometrial, and ovarian cancer risk. Here, we found 3-butoxy-1,8,9-trihydroxy-6H-benzofuro[3,2-c]benzopyran-6-one (BTB), a new derivative of wedelolactone, could effectively inhibit the 17-estradiol (E2)-induced ER transactivation and suppress the growth of breast cancer as well as endometrial and ovarian cancer cells. Our results indicate that 2.5 μM BTB effectively suppresses ER-positive, but not ER-negative, breast, endometrial, and ovarian cancer cells. Furthermore, our data indicate that BTB can modulate ER transactivation and suppress the expression of E2-mediated ER target genes (Cyclin D1, E2F1, and TERT) in the ER-positive MCF-7, Ishikawa, and SKOV-3 cells. Importantly, this BTB mediated inhibition of ER activity is selective since BTB does not suppress the activities of other nuclear receptors, including glucocorticoid receptor and progesterone receptor, suggesting that BTB functions as a selective ER signaling inhibitor with the potential to treat breast, endometrial, and ovarian cancers.
In Vitro Mass Multiplication and Assessment of Genetic Stability of In Vitro Raised Artemisia absinthium L. Plants Using ISSR and SSAP Molecular Markers
Authors: Kour B. , Kour G. , Kaul S. , Dhar M. K.
Published: August 2014

The present investigations were made attempting to develop a rapid, reliable, and reproducible in vitro regeneration protocol for Artemisia absinthium L., a medicinal plant of Kashmir Himalayas. Out of several auxin-cytokinin combinations tested, Murashige and Skoog’s (MS) medium supplemented with 0.5 mgL−1 2,4-dichlorophenoxyacetic acid (2,4-D) and 0.5 mgL−1 kinetin (Kn) was found to be the best for the callus induction. On the other hand, 4.5 mgL−1 6-benzylaminopurine (BAP) and 0.5 mgL−1 1-α-naphthaleneacetic acid (NAA) in the medium resulted in maximum shoot induction from the callus. Similarly, BAP and NAA at a concentration of 1.5 mgL−1 and 0.5 mgL−1, respectively, proved to be the best for the multiple shoot induction from nodal explants. Numerous shoots were obtained from nodal explants after third subculture. In vitro rooting was maximum on medium containing indole-3-butyric acid (IBA) at 0.5 mgL−1. The genetic stability of the in vitro raised plants of Artemisia absinthium was assessed using the intersimple sequence repeat (ISSR) and sequence-specific amplification polymorphism (SSAP) molecular markers. Both markers were able to detect the somaclonal variations in the callus regenerated plants, while no variation was detected in the plants regenerated from the nodal explants. SSAP has been found to be more useful in detection of variability as compared to ISSR molecular marker. The results of present study concluded that the direct regeneration protocol will be useful for the production of true to type plants of this medicinally important plant. This will go a long way in reducing the pressure on the natural populations for the secondary metabolite production, especially for extraction of essential oils.
In Vitro Free Radical Scavenging Activity of a Wild Edible Mushroom, Sparassis crispa (Wulf.) Fr., from North Western Himalayas, India
Authors: Joshi Madhavi , Sagar Anand
Published: August 2014

Bioactive compounds and antioxidant activity of methanolic extract of Sparassis crispa collected from North Western Himalayan region of India were analyzed. Phenolic content 11.14±0.08 mg tannic acid equivalent per g of the extract and flavonoids 1.96±04 mg catechin equivalent per g of the extract were recorded to be the major antioxidant components in this wild edible mushroom. Significant antioxidant efficiency on inhibition of 2,2-diphenyl-1-picrylhydrazyl (DPPH) was observed when compared to standard antioxidant like L-ascorbic acid. IC50 value of the extract was 2.11 mg/mL. The findings suggest S. crispa as an easily accessible source of natural antioxidants.
Birth Weight Ratio as an Alternative to Birth Weight Percentile to Express Infant Weight in Research and Clinical Practice: A Nationwide Cohort Study
Authors: Voskamp Bart Jan , Kazemier Brenda M. , Schuit Ewoud , Mol Ben Willem J. , Buimer Maarten , Pajkrt Eva , Ganzevoort Wessel
Published: August 2014

Objective. To compare birth weight ratio and birth weight percentile to express infant weight when assessing pregnancy outcome.Study Design. We performed a national cohort study. Birth weight ratio was calculated as the observed birth weight divided by the median birth weight for gestational age. The discriminative ability of birth weight ratio and birth weight percentile to identify infants at risk of perinatal death (fetal death and neonatal death) or adverse pregnancy outcome (perinatal death + severe neonatal morbidity) was compared using the area under the curve. Outcomes were expressed stratified by gestational age at delivery separate for birth weight ratio and birth weight percentile.Results. We studied 1,299,244 pregnant women, with an overall perinatal death rate of 0.62%. Birth weight ratio and birth weight percentile have equivalent overall discriminative performance for perinatal death and adverse perinatal outcome. In late preterm infants (33+0–36+6weeks), birth weight ratio has better discriminative ability than birth weight percentile for perinatal death (0.68 versus 0.63,P  0.01) or adverse pregnancy outcome (0.67 versus 0.60,P<0.001).Conclusion. Birth weight ratio is a potentially valuable instrument to identify infants at risk of perinatal death and adverse pregnancy outcome and provides several advantages for use in research and clinical practice. Moreover, it allows comparison of groups with different average birth weights.
Pressure Dynamic Characteristics of Pressure Controlled Ventilation System of a Lung Simulator
Authors: Shi Yan , Ren Shuai , Cai Maolin , Xu Weiqing , Deng Qiyou
Published: August 2014

Mechanical ventilation is an important life support treatment of critically ill patients, and air pressure dynamics of human lung affect ventilation treatment effects. In this paper, in order to obtain the influences of seven key parameters of mechanical ventilation system on the pressure dynamics of human lung, firstly, mechanical ventilation system was considered as a pure pneumatic system, and then its mathematical model was set up. Furthermore, to verify the mathematical model, a prototype mechanical ventilation system of a lung simulator was proposed for experimental study. Last, simulation and experimental studies on the air flow dynamic of the mechanical ventilation system were done, and then the pressure dynamic characteristics of the mechanical system were obtained. The study can be referred to in the pulmonary diagnostics, treatment, and design of various medical devices or diagnostic systems.
Galvanic Displacement of Gallium Arsenide Surface: A Simple and Low-Cost Method to Deposit Metal Nanoparticles and Films
Authors: Pham Ngoc Duy , Park Seok Ju , Lee Jun Pil , Oh Ilwhan
Published: August 2014

Herein, we report galvanic displacement of metal nanoparticles and films onto single-crystalline GaAs (100) substrates, a simple and cost-effective method to fabricate highly controlled metal/semiconductor interface. A time-resolved surface analysis of Au/GaAs system was conducted and microscopic mechanism of galvanic displacement was elucidated in detail. Quantitative temporal XPS measurements of the Au/GaAs interface showed that, initially, fast Au growth was slowed down as the deposition process proceeded. This was attributed to growing oxide layer blocking hole conduction and causing quenching of the deposition process. Addition of various inorganic acids, which function as oxide etchants, was found to enhance deposition rates by effectively removing surface oxide, with HF the most effective. Various precious metals, such as Pt and Ag, could be deposited onto GaAs through galvanic displacement, which demonstrates the versatility of the method.
Surgical Treatment of a Rare Isolated Bilateral Agenesis of Anterior and Posterior Cruciate Ligaments
Authors: Cerulli G. , Amanti A. , Placella G.
Published: August 2014

The isolated bilateral agenesis of both cruciate ligaments is a rare congenital disorder. A 17-year-old male came to our attention due to an alteration in gait pattern, pain, and tendency to walk on the forefoot with his knee flexed. The patient did not recall previous injuries. Upon physical examination anterior and posterior chronic instability were observed. Radiographic examination of both knees showed hypoplasia of the tibial eminence, a hypoplastic lateral femoral condyle, and a narrow intercondylar notch. MRI brought to light a bilateral agenesis of both posterior cruciate ligaments. Arthroscopic evaluation confirmed bilateral isolated agenesis of both cruciate ligaments. We recommended a rehabilitation program to prepare the patient for the arthroscopic construction of both cruciate ligaments.
Fixed Point Theory and the Ulam Stability
Authors: Brzdęk Janusz , Cădariu Liviu , Ciepliński Krzysztof
Published: August 2014

The fixed point method has been applied for the first time, in proving the stability results for functional equations, by Baker (1991); he used a variant of Banach's fixed point theorem to obtain the stability of a functional equation in a single variable. However, most authors follow the approaches involving a theorem of Diaz and Margolis. The main aim of this survey is to present applications of different fixed point theorems to the theory of stability of functional equations, motivated by a problem raised by Ulam in 1940.
Effect of Hydration on Physicochemical Properties of End-Capped PLGA
Authors: D’Souza Susan , Dorati Rossella , DeLuca Patrick P.
Published: August 2014

The objective of this study was to assess the physicochemical effects of hydrating a hydrophobic end-capped poly(lactide-co-glycolide) (PLGA) polymer in the liquid and vapor state. PLGA RG503 polymer was incubated at 37°C in 0.5% polyvinyl alcohol (PVA) solution and at 90% RH. Samples were withdrawn at predetermined intervals and changes to polymer properties like glass transition temperature (Tg), moisture uptake, molecular weight change, and % acid number were determined using differential scanning calorimetry, Karl Fisher titrimetry, gel permeation chromatography, and acid base titrimetry, respectively. Study results showed that Tgwas depressed instantaneously upon hydration, indicating that bulk water acted as a plasticizer of hydrophobic end-capped PLGA. Tgvalues decreased to levels below the incubation temperature when hydrated in 0.5% PVA solution but not in 90% RH. The drop in Tgexhibited a linear relationship (R2>0.99) to the amount of water uptake by the polymer; higher moisture uptake was noted with liquid water. Removal of moisture from the polymer matrix resulted in recovery of Tg, only up to a period of 14 days. Presence of water in liquid or vapor form caused a reduction in molecular weight of the polymer and a corresponding increase in % acid number over the duration of the study.
A New Hyperbolic Area Formula of a Hyperbolic Triangle and Its Applications
Authors: Bao Hui , Chen Xingdi
Published: August 2014

We study some characterizations of hyperbolic geometry in the Poincaré disk. We first obtain the hyperbolic area and length formula of Euclidean disk and a circle represented by its Euclidean center and radius. Replacing interior angles with vertices coordinates, we also obtain a new hyperbolic area formula of a hyperbolic triangle. As its application, we give the hyperbolic area of a Lambert quadrilateral and some geometric characterizations of Lambert quadrilaterals and Saccheri quadrilaterals.
The Construction and Approximation of the Neural Network with Two Weights
Authors: Quan Zhiyong , Zhang Zhengqiu
Published: August 2014

The technique of approximate partition of unity, the way of Fourier series, and inequality technique are used to construct a neural network with two weights and with sigmoidal functions. Furthermore by using inequality technique, we prove that the neural network with two weights can more precisely approximate any nonlinear continuous function than BP neural network constructed in (Chen et al., 2012).
Role of Inflammatory Mediators in the Pathogenesis of Epilepsy
Authors: Shimada Tadayuki , Takemiya Takako , Sugiura Hiroko , Yamagata Kanato
Published: August 2014

Epilepsy is one of the most common chronic brain disorders worldwide, affecting 1% of people across different ages and backgrounds. Epilepsy is defined as the sporadic occurrence of spontaneous recurrent seizures. Accumulating preclinical and clinical evidence suggest that there is a positive feedback cycle between epileptogenesis and brain inflammation. Epileptic seizures increase key inflammatory mediators, which in turn cause secondary damage to the brain and increase the likelihood of recurrent seizures. Cytokines and prostaglandins are well-known inflammatory mediators in the brain, and their biosynthesis is enhanced following seizures. Such inflammatory mediators could be therapeutic targets for the development of new antiepileptic drugs. In this review, we discuss the roles of inflammatory mediators in epileptogenesis.
Peakon, Cuspon, Compacton, and Loop Solutions of a Three-Dimensional 3DKP(3, 2) Equation with Nonlinear Dispersion
Authors: Zhao Haixia , Qiao Lijing , Tang Shengqiang
Published: August 2014

We study peakon, cuspon, compacton, and loop solutions for the three-dimensional Kadomtsev-Petviashvili equation (3DKP(3,2)equation) with nonlinear dispersion. Based on the method of dynamical systems, the 3DKP(3,2)equation is shown to have the parametric representations of the solitary wave solutions such as peakon, cuspon, compacton, and loop solutions. As a result, the conditions under which peakon, cuspon, compacton, and loop solutions appear are also given.
Streptococcus intermediusBacteremia and Liver Abscess following a Routine Dental Cleaning
Authors: Livingston Lachara V. , Perez-Colon Elimarys
Published: August 2014

Streptococcus intermediusis a member of theStreptococcus anginosusgroup of bacteria. This group is part of the normal flora of the oropharynx, genitourinary, and gastrointestinal tracts; however, they have been known to cause a variety of purulent infections including meningitis, endocarditis, and abscesses, even in immunocompetent hosts. In particular,S. intermediushas been associated with the development of liver and brain abscesses. There have been several case reports ofS. intermediusliver abscesses with active periodontal infection. To our knowledge, however, there has not been a case following a routine dental procedure. In fact, the development of liver abscesses secondary to dental procedures is very rare in general, and there are only a few case reports in the literature describing this in relation to any pathogen. We present a rare case ofS. intermediusbacteremia and liver abscess following a dental cleaning. This case serves to further emphasize that even routine dental procedures can place a patient at risk of the development of bacteremia and liver abscesses. For this reason, the clinician must be sure to perform a detailed history and careful examination. Timely diagnosis of pyogenic liver abscesses is vital, as they are typically fatal if left untreated.
Bacterial Treatment and Metal Characterization of Biomedical Waste Ash
Authors: Heera Shelly , Kunal  , Rajor Anita
Published: August 2014

Biomedical waste ash generated due to the incineration of biomedical waste contains large amounts of heavy metals and polycyclic aromatic hydrocarbons (PAHs), which is disposed of in regular landfills, and results in unfavorable amounts of hazardous materials seeping into the ground and may pollute surface water and groundwater. Therefore, it is essential to remove the toxicity of ash before disposal into landfills or reutilization. Environmental characteristic analysis of BMW ash showed increased hardness (1320 mg/L) and chloride (8500 mg/L) content in leachate compared to World Health Organization (WHO) and Environment Protection Agency (EPA) guidelines for drinking water (hardness, 300 mg/L; chloride, 250 mg/L). The alkalinity and pH of the ash leachate were 400 mg/L and 8.35, respectively. In this paper, study was carried out to investigate the metal tolerance level of bacterial isolates isolated from soil. The isolate Bacillus sp. KGMDI can tolerate up to 75 mg/L of metal concentration (Mn, Mo, Cr, Fe, Cu, and Zn) in enriched growth medium. This shows that the isolated culture is capable of growing in presence of high concentration of heavy metals and acts as potential biological tool to reduce the negative impact of BMW ash on the environment during landfilling.
GBV-C Infection and Risk of NHL among U.S. Adults
Authors: Chang Cindy M. , Stapleton Jack T. , Klinzman Donna , McLinden James H. , Purdue Mark P. , Katki Hormuzd A. , Engels Eric A.
Published: August 2014

Some retrospective studies suggest an association between infection with GB virus-C (GBV-C) and non-Hodgkin lymphoma (NHL). We evaluated this association prospectively in a nested case–control study within the U.S. Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Cases (N = 658) and controls (N = 1,316) were individually matched by age, sex, race/ethnicity, timing of study entry, and sample selection. Prediagnostic PLCO serum samples were tested for GBV-C RNA (as a measure of active infection) and E2 antibody (active or resolved infection). Logistic regression was used to estimate odds ratios (OR) for the association between GBV-C and NHL overall and NHL subtypes. Twelve cases (1.8%) and seven controls (0.5%) were GBV-C RNA-positive. GBV-C RNA positivity was associated with NHL overall [OR, 3.43; 95% confidence interval (CI), 1.35–8.71] and, based on small numbers, diffuse large B-cell lymphoma (OR, 5.31; 95% CI, 1.54–18.36). The association with NHL persisted when the interval between testing and selection was greater than 4 years (OR, 6.00; 95% CI, 1.21–29.73). In contrast, E2 antibody positivity was not associated with NHL risk (OR, 1.08; 95% CI, 0.74–1.58). Our study demonstrates that GBV-C infection precedes development of NHL. GBV-C infection may play an etiologic role in a small proportion of NHL cases, perhaps by causing chronic immune stimulation or impaired immunosurveillance. Cancer Res; 74(19); 5553–60. ©2014 AACR.
Combined Inhibition of Wee1 and PARP1/2 for Radiosensitization in Pancreatic Cancer
Authors: Karnak David , Engelke Carl G. , Parsels Leslie A. , Kausar Tasneem , Wei Dongping , Robertson Jordan R. , Marsh Katherine B. , Davis Mary A. , Zhao Lili , Maybaum Jonathan , Lawrence Theodore S. , Morgan Meredith A.
Published: August 2014

Purpose: While the addition of radiation to chemotherapy improves survival in patients with locally advanced pancreatic cancer, more effective therapies are urgently needed. Thus, we investigated the radiosensitizing efficacy of the novel drug combination of Wee1 and PARP1/2 inhibitors (AZD1775 and olaparib, respectively) in pancreatic cancer.

Experimental Design: Radiosensitization of AsPC-1 or MiaPaCa-2 human pancreatic cancer cells was assessed by clonogenic survival and tumor growth assays. Mechanistically, the effects of AZD1775, olaparib, and radiation on cell cycle, DNA damage (γH2AX), and homologous recombination repair (HRR) were determined.

Results: Treatment of AsPC-1 and MiaPaCa-2 cells with either AZD1775 or olaparib caused modest radiosensitization, whereas treatment with the combination significantly increased radiosensitization. Radiosensitization by the combination of AZD1775 and olaparib was associated with G2 checkpoint abrogation and persistent DNA damage. In addition, AZD1775 inhibited HRR activity and prevented radiation-induced Rad51 focus formation. Finally, in vivo, in MiaPaCa-2–derived xenografts, olaparib did not radiosensitize, whereas AZD1775 produced moderate, yet significant, radiosensitization (P < 0.05). Importantly, the combination of AZD1775 and olaparib produced highly significant radiosensitization (P < 0.0001) evidenced by a 13-day delay in tumor volume doubling (vs. radiation alone) and complete eradication of 20% of tumors.

Conclusions: Taken together, these results demonstrate the efficacy of combined inhibition of Wee1 and PARP inhibitors for radiosensitizing pancreatic cancers and support the model that Wee1 inhibition sensitizes cells to PARP inhibitor–mediated radiosensitization through inhibition of HRR and abrogation of the G2 checkpoint, ultimately resulting in unrepaired, lethal DNA damage and radiosensitization. Clin Cancer Res; 20(19); 5085–96. ©2014 AACR.
Head-Mounted Display for a Personal Integrated Image Monitoring System: Ureteral Stent Placement
Authors: Yoshida Soichiro , Kihara Kazunori , Takeshita Hideki , Nakanishi Yasukazu , Kijima Toshiki , Ishioka Junichiro , Matsuoka Yoh , Numao Noboru , Saito Kazutaka , Fujii Yasuhisa
Published: August 2014

The personal head-mounted display (HMD) has emerged as a novel image monitoring system. We present here the application of a high-definition organic electroluminescent binocular HMD in ureteral stent placement. Our HMD system displayed multiple forms of information such as integrated, sharp, high-contrast images using a four-split screen or a picture-in-picture technique both seamlessly and synchronously. When both the operator and the assistant wore an HMD, they could continuously and simultaneously monitor the cystoscopic and fluoroscopic images in an ergonomically natural position. Furthermore, each participant was able to modulate the displayed images depending on the procedure. In all five cases, both the operator and the assistant successfully used this system with no unfavorable event. No participants experienced any HMD wear-related adverse effects. We therefore believe this HMD system might be potentially beneficial during ureteral stent placement procedures. Furthermore, it is compact, easily introduced and affordable.
Predicting Fetal Lung Maturity Using the Fetal Pulmonary Artery Doppler Wave Acceleration/Ejection Time Ratio
Authors: Schenone Mauro H. , Samson Jacques E. , Jenkins Laura , Suhag Anju , Mari Giancarlo
Published: August 2014

Objective: To determine whether the acceleration/ejection time ratio of the fetal main pulmonary artery Doppler waveform (PATET) can accurately predict the results of fetal lung maturity testing in amniotic fluid. Methods: We prospectively studied pregnant women attending our ultrasound unit for clinically indicated fetal lung maturity testing. An ultrasound examination that included measurement of the PATET was performed before the results of the amniocentesis were reported. The results of the PATET and the surfactant/albumin ratio were compared, and a receiver operating characteristic curve was used to determine the PATET cutoff with the optimal sensitivity and specificity for predicting surfactant/albumin ratio results. p < 0.05 was considered statistically significant. Results: Forty-three patients were included in this study. The receiver operating characteristic curve demonstrated that a PATET cutoff of 0.3149 provided a specificity of 93% (95% CI 77-98%), a sensitivity of 73% (95% CI 48-89%), a negative predictive value of 87% (95% CI 70-95%), and a positive predictive value of 85% (95% CI 58-96%) for predicting immature surfactant/albumin ratio results. Conclusion: The PATET may provide a noninvasive means of determining fetal lung maturity with acceptable levels of sensitivity, specificity, and predictive values.
Treatment of Complicated Spontaneous Twin Anemia-Polycythemia Sequence via Fetoscopic Laser Ablation of the Vascular Communications
Authors: Abdel-Sattar Mira , Platt Larry D. , DeVore Greggory , Porto Manuel , Benirschke Kurt , Chmait Ramen H.
Published: August 2014

Monochorionic diamniotic twins share a single placenta and have intertwin vascular communications that link the circulatory systems of the twins together. Twin anemia-polycythemia sequence (TAPS) is an atypical form of twin-twin transfusion syndrome (TTTS) caused by net transfer of blood from one fetus to the other and is characterized by large intertwin hemoglobin differences in the absence of oligohydramnios and polyhydramnios. This condition may develop spontaneously (sTAPS) or as a result of residual vascular communications after prior laser surgery. Because of the relatively low prevalence and lack of clinical awareness, the natural history of sTAPS is unclear and the antenatal treatment remains controversial. Case series of sTAPS have described expectant management with timed delivery, intrauterine blood transfusion, and fetoscopic laser treatment. Favorable outcomes have been described in cases of uncomplicated sTAPS that underwent conservative measures. However, we believe that there may be a subgroup of high-risk or complicated sTAPS patients that may benefit from definitive treatment afforded by fetoscopic laser therapy. We describe 3 complicated cases of sTAPS successfully treated with selective laser photocoagulation of communicating vessels. In 2 of the cases, placental pathology identified thrombosed fetal vessels of the polycythemic twin.
Expression and Clinical Significance of ATP-Binding Cassette Transporter 1 in Serum and Placental Tissue in Chinese Patients with Preeclampsia
Authors: Liu Lixing , Zhang Min , Li Lijun , Li Caifeng , Min Xianhui , Zheng Ming
Published: August 2014

Aim: To investigate the expression and clinical significance of ATP-binding cassette transporter 1 (ABCA1) in pregnant women with preeclampsia (PE). Methods: 52 pregnant women with PE who were admitted for delivery were enrolled in the study, while 30 normal pregnant inpatients were chosen as controls. Blood lipid and serum ABCA1 concentrations were assayed by enzymatic analysis and ELISA, respectively, and the expression of the ABCA1 gene and its encoded protein were detected and quantified by RT-PCR and Western blotting. Results: In the study group, blood lipid levels were significantly higher than those in the control group (p < 0.01), while the ABCA1 gene and its encoded protein expression in both serum and placental tissue were lower than that of controls. These differences were highly correlated with disease severity (p < 0.05). In PE patients, serum ABCA1 concentration was positively correlated with ABCA1 protein expression in placental tissue (r = 0.384, p < 0.01) and high-density lipoprotein level (r = 0.318, p < 0.05), but negatively correlated with low-density lipoprotein level (r = -0.279, p < 0.05). Conclusion: In PE women, expression of ABCA1 was decreased, suggesting that ABCA1 may play an important role in onset of PE by altering blood lipid metabolism.
Does a Single Session of High-Intensity Interval Training Provoke a Transient Elevated Risk of Falling in Seniors and Adults?
Authors: Donath Lars , Kurz Eduard , Roth Ralf , Hanssen Henner , Schmidt-Trucksäss Arno , Zahner Lukas , Faude Oliver
Published: August 2014

Background: Balance and strength training can reduce seniors' fall risk up to 50%. Available evidence suggests that acute bouts of neuromuscular and endurance exercise deteriorate postural control. High-intensity endurance training has been successfully applied in different populations. Thus, it seemed valuable to examine the acute effects of high-intensity interval training (HIIT) on neuromuscular performance in seniors and young adults. Objective: The acute impact of a HIIT session on balance performance and muscle activity after exercise cessation and during post-exercise recovery was examined in young and old adults. We intended to investigate whether a transient exercise-induced fall-risk may occur in both groups. Methods: 20 healthy seniors (age 70 (SD 4) years) and young adults (age 27 (SD 3) years) were examined on 3 days. After exhaustive ramp-like treadmill testing in order to determine maximal heart rate (HRmax) on the first day, either a 4 × 4 min HIIT at 90% of HRmax or a control condition (CON) was randomly performed on the second and third day, respectively. Balance performance (postural sway) was assessed during single limb stance with open eyes (SLEO) and double limb stance with closed eyes (DLEC). EMG was recorded for the soleus (SOL), anterior tibialis (TIB), gastrocnemius (GM) and peroneus longus (PL) muscles at the dominant leg. All measures were collected before, immediately as well as 10, 30 and 45 min after HIIT and CON, respectively. Results: Compared to CON, HIIT induced significant increases of postural sway immediately after exercise cessation during SLEO in both groups (adults: p < 0.001, Δ = +25% sway; seniors: p = 0.007, Δ = +15% sway). Increased sway during DLEC was only found for seniors immediately and 10 min after HIIT (post: p = 0.003, Δ = +14% sway, 10 min post: p = 0.004, Δ = +18% sway). Muscle activity was increased during SLEO for TIB until 10 min post in seniors (0.008 < p < 0.03) and immediately after HIIT in adults (p < 0.001). Conclusion: HIIT training may cause an acute ‘open-fall-window' with a transient impairment of balance performance for at least 10 min after exercise cessation in both groups. Occluded vision in seniors seems to prolong this period up to 30 min. Thus, the advantage of HIIT with regard to time efficiency seems debatable when considering transient HIIT-induced impairments of neuromuscular function.
The Nonaspanins TM9SF2 and TM9SF4 Regulate the Plasma Membrane Localization and Signalling Activity of the Peptidoglycan Recognition Protein PGRP-LC in Drosophila
Authors: Perrin Jackie , Mortier Magda , Jacomin Anne-Claire , Viargues Perrine , Thevenon Dominique , Fauvarque Marie-Odile
Published: August 2014

Transmembrane 9 (TM9) proteins, or nonaspanins, are a family of proteins conserved throughout evolution and characterized by 9 transmembrane domains. In Drosophila, TM9 superfamily protein member 4 (TM9SF4) and its closest paralogue, TM9SF2, contribute to phagocytosis of various types of particles, while TM9SF4 displays non-redundant requirement in Gram-negative bacteria engulfment. In addition, the two TM9 proteins control the actin cytoskeleton in larval haemocytes and in Drosophila S2 cells. Here, we show that TM9SF4 and TM9SF2 co-immunoprecipitate with the peptidoglycan recognition protein (PGRP)-LC, which triggers the Drosophila immune response to bacterial infection. Furthermore, both TM9 proteins co-localize with this receptor in intracellular vesicles and at the plasma membrane in Drosophila S2 cells in culture and in the fly fat body. Silencing TM9SF4 prevents plasma membrane localization of PGRP-LC, whereas silencing TM9SF2 does not, which may account for the non-redundant role of TM9SF4 in phagocytosis of Gram-negative bacteria. Finally, we provide a set of data suggesting that TM9 proteins can prevent inappropriate signalling from the unstimulated receptor.
Large Urethro-Vesico-Vaginal Fistula due to a Vaginal Foreign Body in a 22-Year-Old Woman: Case Report and Literature Review
Authors: D'Elia Carolina , Curti Pierpaolo , Cerruto Maria Angela , Monaco Carmelo , Artibani Walter
Published: August 2014

In the non-industrialized countries of Africa and Asia obstetric fistulas are more frequently caused by prolonged labour, whereas in countries with developed healthcare systems they are generally the result of complications of gynaecological surgery or, rarely, benign pathologies like inflammation or foreign bodies. A 22-year-old woman was brought to the gynaecology clinic because of foul-smelling vaginal discharge. On pelvic examination a ring-like foreign body was impacted between the anterior and posterior vaginal wall. MRI scan confirmed the presence of a cylindrical foreign body in the vagina and the patient revealed that she had ‘involuntarily' inserted a plastic bubble bath cap into the vagina. At surgery removal of the cap was difficult and at the end of the manoeuver evidence of a huge urethro-vesico-vaginal fistula occurred. The patient was discharged with bilateral ureteral stents and suprapubic catheter. After 3 months we performed an end-to-end anastomotic urethroplasty to repair the urethral avulsion and restored the bladder/trigonal and vaginal/cervical defects with 3 layers of sutures; 3 months later the patient had no complaints. Complex genital fistulas represent an extremely debilitating morbidity. In our case, a vaginal approach was successful, but the choice between an abdominal or vaginal approach depends on the surgeon's experience and training.
Comparison of Trends and Outcomes of Carotid Artery Stenting and Endarterectomy in the United States, 2001 to 2010
Authors: Kim Luke K , Yang David C. , Swaminathan Rajesh V. , Minutello Robert M. , Okin Peter M. , Lee Min Kyeong , Sun Xuming , Wong S. Chiu , McCormick Daniel J. , Bergman Geoffrey , Allareddy Veerasathpurush , Singh Harsimran , Feldman Dmitriy N.
Published: August 2014

Background—

Given the controversy regarding whether carotid endarterectomy (CEA) or carotid artery stenting (CAS) may be superior for stroke prevention, it is uncertain how recent clinical evidence, guidelines, and reimbursement policies have influenced the volume and outcomes after these procedures.

Methods and Results—

We conducted a serial, cross-sectional study with time trends of patients undergoing CAS (n=124 265) and CEA (n=1 260 647) between 2001 and 2010 from the Nationwide Inpatient Sample database. During the 10-year period, the frequency of CEA declined, whereas CAS use slowly increased. After multivariate propensity score–matched analysis, CAS was associated with an increased risk of death (odds ratio [OR], 1.69; 95% confidence interval [CI], 1.40–2.04), stroke (OR, 1.43; 95% CI, 1.23–1.66), and major adverse events including death, stroke, and myocardial infarction (OR, 1.25; 95% CI, 1.13–1.39). In asymptomatic patients, there was no significant difference in major adverse events (OR, 1.08; 95% CI, 0.92–1.20;
P
=0.16 [
P
<0.001 for interaction between procedure type and symptom status]) between CAS and CEA. Importantly, there was a significant improvement in CAS outcomes during the course of 10 years (reduction in death [OR, 0.51; 95% CI, 0.49–0.67;
P
for trend=0.03] and major adverse events [OR, 0.75; 95% CI, 0.66–0.84;
P
for trend=0.05] comparing years 2010 versus 2001).

Conclusions—

In US hospitals between 2001 and 2010, CAS was associated with worse in-hospital outcomes, partly attributable to selection and ascertainment bias. Asymptomatic patients undergoing CAS versus CEA had similar adjusted rates of major adverse events. CAS outcomes improved significantly during the course of the decade likely attributable to improvements in patient selection, operator skills, and technological advancements.
White Matter Perivascular Spaces Are Related to Cortical Superficial Siderosis in Cerebral Amyloid Angiopathy
Authors: Charidimou Andreas , Jäger Rolf H. , Peeters Andre , Vandermeeren Yves , Laloux Patrice , Baron Jean-Claude , Werring David J.
Published: August 2014

Background and Purpose—

We set out to investigate whether MRI-visible centrum semiovale perivascular spaces (CSO-PVS), a potential biomarker of impaired interstitial fluid drainage in sporadic cerebral amyloid angiopathy, is associated with cortical superficial siderosis (cSS), reflecting recurrent hemorrhage from severe leptomeningeal and superficial cortical vascular amyloid.

Methods—

Retrospective multicenter cohort study of possible/probable cerebral amyloid angiopathy according to the Boston criteria. PVS were rated in basal ganglia and CSO (CSO-PVS) on axial T2-weighted sequences, using a validated 4-point visual rating scale and were classified as high (score >2) or low degree (score ≤2) for prespecified analyses. Independent risk factors for high CSO-PVS degree were investigated in logistic regression.

Results—

The final cohort consisted of 138 cerebral amyloid angiopathy patients (mean age, 71.8 years; 95% confidence interval, 70.2–73.4 years; 52.2% men). High CSO-PVS degree was present in 61.2% of cases. The prevalence of any cSS, and disseminated cSS (involving >3 sulci), was higher in patients with high versus low CSO-PVS degree (for any cSS 45.9% versus 13.5%;
P
<0.00005; for disseminated cSS 31.8% versus 0%;
P
<0.00005). In multivariable logistic regression analysis, cSS presence (odds ratio, 4.78; 95% confidence interval, 1.64–13.87;
P
=0.004) was an independent predictors of high CSO-PVS degree. We found no associations between basal ganglia PVS and cSS.

Conclusions—

High degree of CSO-PVS is highly prevalent in sporadic cerebral amyloid angiopathy and is related to cSS. Our findings suggest that severe leptomeningeal and cortical vascular amyloid (causing cSS) is related to impaired interstitial fluid drainage from cerebral white matter, although determining the causal direction of this relationship requires prospective studies.
Coronary Artery Calcification, Intima-Media Thickness, and Ankle-Brachial Index Are Complementary Stroke Predictors
Authors: Gronewold Janine , Bauer Marcus , Lehmann Nils , Mahabadi Amir A. , Kälsch Hagen , Weimar Christian , Berger Klaus , Moebus Susanne , Jöckel Karl-Heinz , Erbel Raimund , Hermann Dirk M.
Published: August 2014

Background and Purpose—

Coronary artery calcification (CAC), a marker of coronary atherosclerosis, predicts stroke in addition to established risk factors. Whether CAC’s predictive value can be improved by peripheral atherosclerosis markers, namely carotid intima-media thickness (CIMT) and ankle-brachial index (ABI), was unknown.

Methods—

A total of 3289 participants of the population-based Heinz Nixdorf Recall study (45–75 years; 48.8% men) without previous stroke or coronary heart disease were evaluated for incident stroke for 9.0±1.9 years. CAC, CIMT, and ABI were examined as stroke predictors.

Results—

Eighty-four strokes occurred during follow-up. In multivariable Cox proportional hazard regressions, CAC (hazard ratio, 1.45 [95% confidence interval, 1.11–1.88] per SD increase in ln(CAC+1); SD, 2.40), CIMT (1.34 [1.08–1.66] per SD increase; SD, 0.127 mm), and ABI (1.55 [1.32–1.82] per SD decrease; SD, 0.148) were associated with stroke in addition to established risk factors. When combined with each other, ln(CAC+1)’s hazard ratio remained similar when CIMT (1.41 [1.09–1.83]) was inserted into the multivariable model, but slightly decreased when ABI (1.31 [1.01–1.72]) or CIMT and ABI (1.29 [0.99–1.68]) were included. Although CAC alone did not significantly elevate the area under the curve in Harrell’s c-statistics (by 0.009;
P
=0.379) in addition to established risk factors, the combination of CAC and ABI increased area under the curve (by 0.029;
P
=0.047), as did ABI (by 0.025;
P
=0.038) but not CIMT (by 0.002;
P
=0.795) alone. The combination of CAC and ABI also resulted in significant category-free net reclassification and integrated discrimination improvement.

Conclusions—

CAC, CIMT, and ABI provide complementary information about stroke risk. ABI, which is distinctive in a small subpopulation, had the highest and CIMT, which is distributed across a larger range of values, had the lowest predictive value.