bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-Term Endoscopic Follow-Up of Patients with Chronic Radiation Proctopathy after Brachytherapy for Prostate Cancer
Authors: Ohtani Masahiro , Suto Hiroyuki , Nosaka Takuto , Saito Yasushi , Ozaki Yoshihiko , Hayama Ryoko , Naito Tatsushi , Takahashi Kazuto , Ofuji Kazuya , Matsuda Hidetaka , Hiramatsu Katsushi , Nemoto Tomoyuki , Shioura Hiroki , Kimura Hirohiko , Aoki Yoshitaka , Yokoyama Osamu , Nakamoto Yasunari
Published: June 2016

Background. Chronic radiation proctopathy (CRP) is late toxicity and associated with morbidity. Aim. To investigate the predictors of prognosis in patients with CRP after brachytherapy (BT). Methods. One hundred four patients with prostate cancer were treated with BT or BT followed by external-beam radiotherapy (BT + EBRT). We retrospectively investigated the 5-year incidence of rectal bleeding and endoscopic findings of CRP using the Vienna Rectoscopy Score (VRS). Twenty patients with VRS ≥ 1 were divided into the improved VRS group without treatment, unchanged VRS group, and treated group. The parameters associated with alteration of VRS were analyzed. Results. The incidence of rectal bleeding was 24%. The risk of rectal bleeding was higher in patients treated with BT + EBRT compared to those treated with BT (p<0.0001). The incidence of superficial microulceration was higher in the improved VRS group than in the unchanged VRS group (p<0.05). The incidence of multiple confluent telangiectasia or superficial ulcers > 1 cm2 was higher in the treated group than in both the improved and unchanged VRS groups (p<0.05). Conclusions. Patients treated with BT + EBRT have a high risk of CRP. Endoscopic findings were useful for prognostic prediction of CRP.
Giant Primary Schwannoma of the Left Nasal Cavity and Ethmoid Sinus
Authors: Wong Eugene , Kong Justin , Oh Lawrence , Cox Daniel , Forer Martin
Published: June 2016

A unilateral tumour in the nasal cavity or paranasal sinuses is commonly caused by polyps, cysts, and mucoceles, as well as invasive tumours such as papillomas and squamous cell carcinomas. Schwannomas, in contrast, are rare lesions in this area (Minhas et al., 2013). We present a case of a 52-year-old female who presented with a 4-year progressive history of mucous hypersecretion, nasal obstruction, pain, and fullness. Imaging of the paranasal sinuses showed complete opacification of the entire left nasal cavity and sinuses by a tumour causing subsequent obstruction of the frontal and maxillary sinuses. The tumour was completely excised endoscopically. Histopathology was consistent with that of a schwannoma.
Soluble Urokinase-Type Plasminogen Activator Receptor Plasma Concentration May Predict Susceptibility to High Altitude Pulmonary Edema
Authors: Hilty Matthias Peter , Zügel Stefanie , Schoeb Michele , Auinger Katja , Dehnert Christoph , Maggiorini Marco
Published: June 2016

Introduction.Acute exposure to high altitude induces inflammation. However, the relationship between inflammation and high altitude related illness such as high altitude pulmonary edema (HAPE) and acute mountain sickness (AMS) is poorly understood. We tested if soluble urokinase-type plasminogen activator receptor (suPAR) plasma concentration, a prognostic factor for cardiovascular disease and marker for low grade activation of leukocytes, will predict susceptibility to HAPE and AMS.Methods.41 healthy mountaineers were examined at sea level (SL, 446 m) and 24 h after rapid ascent to 4559 m (HA). 24/41 subjects had a history of HAPE and were thus considered HAPE-susceptible (HAPE-s). Out of the latter, 10/24 HAPE-s subjects were randomly chosen to suppress the inflammatory cascade with dexamethasone 8 mg bid 24 h prior to ascent.Results.Acute hypoxic exposure led to an acute inflammatory reaction represented by an increase in suPAR (1.9±0.4at SL versus2.3±0.5at HA,p<0.01), CRP (0.7±0.5at SL versus3.6±4.6at HA,p<0.01), and IL-6 (0.8±0.4at SL versus3.3±4.9at HA,p<0.01) in all subjects except those receiving dexamethasone. The ascent associated decrease in PaO2correlated with the increase in IL-6 (r=0.46,p<0.001), but not suPAR (r=0.27,p=0.08); the increase in IL-6 was not correlated with suPAR (r=0.16,p=0.24). Baseline suPAR plasma concentration was higher in the HAPE-s group (2.0±0.4versus1.8±0.4,p=0.04); no difference was found for CRP and IL-6 and for subjects developing AMS.Conclusion.High altitude exposure leads to an increase in suPAR plasma concentration, with the missing correlation between suPAR and IL-6 suggesting a cytokine independent, leukocyte mediated mechanism of low grade inflammation. The correlation between IL-6 and PaO2suggests a direct effect of hypoxia, which is not the case for suPAR. However, suPAR plasma concentration measured before hypoxic exposure may predict HAPE susceptibility.
A Pilot Study of Parent Mentors for Early Childhood Obesity
Authors: Foster Byron A. , Aquino Christian A. , Gil Mario , Gelfond Jonathan A. L. , Hale Daniel E.
Published: June 2016

Objective.To assess the feasibility of a parent mentor model of intervention for early childhood obesity using positive deviance-based methods to inform the intervention.Methods.In this pilot, randomized clinical trial, parent-child dyads (age: 2–5) with children whose body mass index (BMI) was ≥95th percentile were randomized to parent mentor intervention or community health worker comparison. The child’s height and weight were measured at baseline, after the six-month intervention, and six months after the intervention. Feasibility outcomes were recruitment, participation, and retention. The primary clinical outcome was BMIz-score change.Results.Sixty participants were enrolled, and forty-eight completed the six-month intervention. At baseline, the BMIz-score in the parent mentor group was 2.63 (SD = 0.65) and in the community health worker group it was 2.61 (SD = 0.89). For change in BMIz-score over time, there was no difference by randomization group at the end of the intervention: −0.02 (95% CI: −0.26, 0.22). At the end of the intervention, the BMIz-score for the parent mentor group was 2.48 (SD = 0.58) and for the community health worker group it was 2.45 (SD = 0.91), both reduced from baseline,p<0.001.Conclusion.The model of a parent mentor clinical trial is feasible, and both randomized groups experienced small, sustained effects on adiposity in an obese, Hispanic population.
Protein Adsorption on Hybrids of Thermoresponsive Polymers and Single-Walled Carbon Nanotubes
Authors: Umemura Kazuo , Izumi Katsuki , Kumashiro Yoshikazu , Oura Shusuke , Okano Teruo
Published: June 2016

Poly(N-isopropylacrylamide) (PNIPAAm) is one of the most popular thermoresponsive polymers. Adsorption of RecA proteins onto hybrids of PNIPAAm and single-walled carbon nanotubes (SWNTs) was observed in the presence and absence of DNA molecules. Although RecA molecules were adsorbed efficiently onto the hybrid surfaces at 37°C, even in the absence of DNA molecules, the adsorption of RecA was inhibited at 4°C. These results suggest that the thermoresponsive functions of PNIPAAm were effective, even on the SWNT surfaces, which supports the possibility of developing nanobiodevices using PNIPAAm-SWNT hybrids. However, although RecA is a DNA binding protein, there was no significant difference in the adsorption of RecA onto PNIPAAm-SWNT surfaces with and without DNA molecules. This study provides fundamental information for potential biological applications of PNIPAAm-SWNT hybrids.
Development of a Medical Care Terminal for Efficient Monitoring of Bedridden Subjects
Authors: Pereira Filipe , Carvalho Vítor , Soares Filomena , Machado José , Bezerra Karolina , Silva Rui , Matos Demétrio
Published: June 2016

This work is developed in the context of Ambient Assisted Living (AAL) and has as main objective the development of a mechatronic system that allows the care of bedridden patients with ongoing medical care handled by a single person. The developed Medical Care Terminal (MCT) improves autonomy in home care, safety, comfort, and hygiene of bedridden patients. The MCT has six biomedical sensors and four environmental sensors. Data acquisition and processing is performed using Arduino and LabVIEW platforms, respectively. The proposed solution has, as main feature, its adaptability to the patient needs. One of the MCT functionalities is the remote access to the patient data through the web. The caregiver may request help from a specialist who sends back information in real time to perform first aid assistance. This device has a flexible configuration allowing a fast and cheap reconfiguration according the specific needs of the patient. The proposed mechatronic system intends to meet the needs of bedridden patients improving their quality of life, health, safety, and comfort, while enabling the remote monitoring of the patients.
The Regional Centralization of Electronic Fetal Heart Rate Monitoring and Its Impact on Neonatal Acidemia and the Cesarean Birth Rate
Authors: Michikata Kaori , Sameshima Hiroshi , Urabe Hirotoshi , Tokunaga Syuichi , Kodama Yuki , Ikenoue Tsuyomu
Published: June 2016

Objective. The improvement of the accuracy of fetal heart rate (FHR) pattern interpretation to improve perinatal outcomes remains an elusive challenge. We examined the impact of an FHR centralization system on the incidence of neonatal acidemia and cesarean births.Methods. We performed a regional, population-based, before-and-after study of 9,139 deliveries over a 3-year period. The chi-squared test was used for the statistical analysis.Results. The before-and-after study showed no difference in the rates of acidemia, cesarean births, or perinatal death in the whole population. A subgroup analysis using the 4 hospitals in which an FHR centralization system was continuously connected (compliant group) and 3 hospitals in which the FHR centralization system was connected on demand (noncompliant group) showed that the incidence acidemia was significantly decreased (from 0.47% to 0.11%) without a corresponding increase in the cesarean birth rate due to nonreassuring FHR patterns in the compliant group. Although there was no difference in the incidence of nonreassuring FHR patterns in the noncompliant group, the total cesarean birth rate was significantly higher than that in the compliant group.Conclusion. The continuous FHR centralization system, in which specialists help to interpret results and decide clinical actions, was beneficial in reducing the incidence of neonatal acidemia (pH < 7.1) without increasing the cesarean birth rate due to nonreassuring FHR patterns.
Partial Control of a Continuous Bioreactor: Application to an Anaerobic System for Heavy Metal Removal
Authors: Neria-González M. I. , López-Pérez P. A. , Aguilar-López R.
Published: June 2016

This work presents a control strategy for a continuous bioreactor for heavy metal removal. For this aim, regulation of the sulfate concentration, which is considered the measured and controlled state variable, allowed diminishing the cadmium concentration in the bioreactor, where the corresponding controller was designed via nonlinear bounded function. Furthermore, a nonlinear controllability analysis was done, which proved the closed-loop instability of the inner or uncontrolled dynamics of the bioreactor. A mathematical model, experimentally corroborated for cadmium removal, was employed as a benchmark for the proposed controller. Numerical experiments clearly illustrated the successful implementation of this methodology; therefore, cadmium removal amounted to more than 99%, when the initial cadmium concentration was up to 170 mg/L in continuous operating mode.
Effect of Traditional Chinese Medicine on Inflammatory Mediators in Pediatric Asthma
Authors: Du Hui , Wang Yonghong , Shi Yumin , Yu Jian , Sun Wen , Zhang Yiqun
Published: June 2016

Objective. To observe the effects of empirical prescriptions of traditional Chinese medicine (TCM) on inflammatory mediators in pediatric asthma and to explore the underlying molecular mechanism in the treatment of asthma.Methods. A total of 182 children with asthma were randomly placed into either the TCM group (n=97) or the salbutamol and montelukast (SM) group (n=85). Patients in the TCM group were treated with a series of empirical prescriptions of TCM, while those in the SM group received salbutamol and montelukast. Both groups received their respective treatment for 12 weeks. There were 35 patients in TCM group and 34 patients in SM group providing venous blood. Real-time PCR was used to determine the mRNA expression levels of interleukin- (IL-) 10, IL-17, matrix metalloproteinase-9 (MMP-9), and transforming growth factorβ1 (TGF-β1) in peripheral blood mononuclear cells before and after treatment. Enzyme-linked immunosorbent assay was used to measure the levels of IL-10, IL-17, MMP-9, and TGF-β1 in peripheral blood before and after treatment.Results. The mRNA expression of TGF-β1 in the SM group was downregulated (P=0.00) after treatment. No significant differences were found between the TCM group and the SM group after treatment (P>0.05). In the TCM group, the levels of IL-10, IL-17, and MMP-9 significantly decreased after treatment (P=0.01, 0.04, and 0.03, resp.). In the SM group, IL-17, MMP-9, and TGF-β1 levels significantly decreased after treatment (P=0.00, 0.03, and 0.00, resp.). There was no significant difference between the two groups regarding the levels of IL-10, IL-17, TGF-β1, and MMP-9 (P>0.05). The difference of the level of IL-17 was negatively correlated with the change of C-ACT score in TCM group and SM group.Conclusion. TCM has a regulatory effect on the balance of some inflammatory mediators in pediatric asthma.
Multiresponse Optimization of a Compliant Guiding Mechanism Using Hybrid Taguchi-Grey Based Fuzzy Logic Approach
Authors: Dao Thanh-Phong
Published: June 2016

Because of a lack of precisely miniaturized guiding mechanism, micro/nanoindentation devices are now difficult to integrate inside scanning electron microscope. A compliant guiding mechanism (CGM) with a compact size, serving as an accurate positioning platform, is hence proposed in this paper. The displacement and first natural frequency are the most important quality responses of CGM. The geometric parameters of CGM and applied force play a vital role in determining those responses. The experiment plan is firstly designed by Taguchi’sL27orthogonal array. A hybrid approach of Taguchi-grey based fuzzy logic is then developed to optimize two responses, simultaneously. The grey relational analysis based on the fuzzy logic is used to achieve a grey-fuzzy reasoning grade (GFRG) that combines all the quality characteristics. The GFRG, serving as a performance index, determines optimal parameter levels. Analysis of variance is conducted to assess the significant parameters affecting the responses. The confirmation results revealed that the 195 μm displacement of the CGM was many times greater than that of the previous mechanisms. It could be concluded that the quality responses of CGM can be significantly improved through the hybrid optimization approach. The proposed methodology has great applications for related compliant mechanisms and engineering sciences. Taking benefits of a compact structure into account, CGM has a great ability for micro/nanoindentation device inside scanning electron microscope.
Assessment of Corneal Epithelial Thickness in Asymmetric Keratoconic Eyes and Normal Eyes Using Fourier Domain Optical Coherence Tomography
Authors: Catalan S. , Cadarso L. , Esteves F. , Salgado-Borges J. , Lopez M. , Cadarso C.
Published: June 2016

Purpose. To compare the characteristics of asymmetric keratoconic eyes and normal eyes by Fourier domain optical coherence tomography (OCT) corneal mapping.Methods. Retrospective corneal and epithelial thickness OCT data for 74 patients were compared in three groups of eyes: keratoconic (n=22) and normal fellow eyes (n=22) in patients with asymmetric keratoconus and normal eyes (n=104) in healthy subjects. Areas under the curve (AUC) of receiver operator characteristic (ROC) curves for each variable were compared across groups to indicate their discrimination capacity.Results. Three variables were found to differ significantly between fellow eyes and normal eyes (allp<0.05): minimum corneal thickness, thinnest corneal point, and central corneal thickness. These variables combined showed a high discrimination power to differentiate fellow eyes from normal eyes indicated by an AUC of 0.840 (95% CI: 0.762–0.918).Conclusions. Our findings indicate that topographically normal fellow eyes in patients with very asymmetric keratoconus differ from the eyes of healthy individuals in terms of their corneal epithelial and pachymetry maps. This type of information could be useful for an early diagnosis of keratoconus in topographically normal eyes.
Diplopia, Convergent Strabismus, and Eye Abduction Palsy in a 12-Year-Old Boy with Autoimmune Thyroiditis
Authors: Marques Pedro , Jacinto Sandra , Pinto Maria do Carmo , Limbert Catarina , Lopes Lurdes
Published: June 2016

Pseudotumor cerebri (PTC) is defined by clinical criteria of increased intracranial pressure, elevated intracranial pressure with normal cerebrospinal fluid (CSF) composition, and exclusion of other causes such tumors, vascular abnormalities, or infections. The association of PTC with levothyroxine (LT4) has been reported. A 12-year-old boy has been followed up for autoimmune thyroiditis under LT4. Family history was irrelevant for endocrine or autoimmune diseases. A TSH level of 4.43 μUI/mL (0.39–3.10) motivated a LT4 adjustment from 75 to 88 μg/day. Five weeks later, he developed horizontal diplopia, convergent strabismus with left eye abduction palsy, and papilledema. Laboratorial evaluation revealed elevated free thyroxine level (1.05 ng/dL [0.65–1.01]) and low TSH, without other alterations. Lumbar puncture was performed and CSF opening pressure was 24 cm H2O with normal composition. Blood and CSF cultures were sterile. Brain MRI was normal. LT4 was temporarily discontinued and progressive improvement was observed, with a normal fundoscopy at day 10 and reversion of diplopia one month later. LT4 was restarted at lower dose and gradually titrated. The boy is currently asymptomatic. This case discloses the potential role of LT4 in inducing PTC. Despite its rarity and unclear association, PTC must be seen as a potential complication of LT4, after excluding all other intracranial hypertension causes.
The Influence of Humidity on Assessing Irritation Threshold of Ammonia
Authors: Monsé Christian , Sucker Kirsten , Hoffmeyer Frank , Jettkant Birger , Berresheim Hans , Bünger Jürgen , Brüning Thomas
Published: June 2016

A large number of occupational exposure limit values (OELs) are based on avoiding of sensory irritation of the eyes and the upper respiratory tract. In order to investigate the chemosensory effect range of a chemical, odor and sensory irritation thresholds (lateralization thresholds, LTs) can be assessed. Humidity affects olfactory function and thus influences odor thresholds; however, a similar effect has not been shown for sensory irritation thresholds. The purpose of the present study was to explore whether LTs for ammonia vapor vary depending on the water vapor content of the inspired stimulus. Eight healthy nonsmoking volunteers were simultaneously exposed to ammonia vapor through one nostril and clean air through the other and were asked to determine which nostril received the chemical. Within experimental runs, ascending ammonia concentrations (60–350 ppm) that were either dry or humidified were administered at fixed time intervals. Geometric mean LTs obtained at wet (181 ppm) or dry (172 ppm) conditions did not differ significantly (P= 0.19) and were within the range of those reported by previous studies. These results suggest that humidity is not a critical factor in determining sensory irritation thresholds for ammonia, and future studies will examine if these findings are transferable to sensory irritation thresholds for other chemicals.
Disparities in Survival with Bystander CPR following Cardiopulmonary Arrest Based on Neighborhood Characteristics
Authors: Rivera Nina Thakkar , Kumar Shari L. , Bhandari Rohit K. , Kumar Sunil D.
Published: June 2016

The American Heart Association reports the annual incidence of out-of-hospital cardiopulmonary arrests (OHCA) is greater than 300,000 with a survival rate of 9.5%. Bystander cardiopulmonary resuscitation (CPR) saves one life for every 30, with a 10% decrease in survival associated with every minute of delay in CPR initiation. Bystander CPR and training vary widely by region. We conducted a retrospective study of 320 persons who suffered OHCA in South Florida over 25 months. Increased survival, overall and with bystander CPR, was seen with increasing income (p=0.05), with a stronger disparity between low- and high-income neighborhoods (p=0.01andp=0.03, resp.). Survival with bystander CPR was statistically greater in white- versus black-predominant neighborhoods (p=0.04). Increased survival, overall and with bystander CPR, was seen with high- versus low-education neighborhoods (p=0.03). Neighborhoods with more high school age persons displayed the lowest survival. We discovered a significant disparity in OHCA survival within neighborhoods of low-income, black-predominance, and low-education. Reduced survival was seen in neighborhoods with larger populations of high school students. This group is a potential target for training, and instruction can conceivably change survival outcomes in these neighborhoods, closing the gap, thus improving survival for all.
Computationally Efficient Assessments of the Effects of Radiative Transfer, Turbulence Radiation Interactions, and Finite Rate Chemistry in the Mach 20 Reentry F Flight Vehicle
Authors: Krishnamoorthy Gautham , Clarke Lauren Elizabeth
Published: June 2016

Effects of finite rate chemistry, radiative heat transfer, and turbulence radiation interactions (TRI) are assessed in a fully coupled manner in simulations of the Mach 20 Reentry F flight vehicle. Add-on functions were employed to compute a Planck mean absorption coefficient and the temperature self-correlation term (for TRI effects) in the optically thin shock layer. Transition onset was induced by specifying a wall roughness height at the experimentally observed transition location. The chemistry was modeled employing eight elementary reactions and an equilibrium approach allowing species to relax towards their chemical equilibrium values over the process characteristic time scale. The wall heat fluxes in the turbulent region, density, and velocity profiles compared reasonably well against measurements as well as similar calculations reported previously. The density predictions were more sensitive to the choice of modeling options than the velocities. The radiative source term magnitude agreed closely with its measurements deduced from shock tube experiments. The TRI model predicted a 60% enhancement in emission due to temperature fluctuations in the turbulent boundary layer. While the variations in density and velocity predictions among the models diminished along the length of the body, the O and NO prediction variations extended well into the turbulent boundary layer.
A Fractographic Study of Bending/Torsion Fatigue Failure in Metallic Materials with Protective Surface Layers
Authors: Slámečka Karel , Šesták Petr , Vojtek Tomáš , Kianicová Marta , Horníková Jana , Šandera Pavel , Pokluda Jaroslav
Published: June 2016

Results are given of a fractographic study of biaxial in-phase bending/torsion fatigue fractures in specimens made of nitrided steel and nickel-based superalloy with protective coatings (diffusion coatings and plasma-sprayed thermal barrier coatings). Fracture surfaces were examined by optical and scanning electron microscopes while stereophotogrammetry and optical profilometry were employed to obtain 3D surface data of selected fracture surface regions. The studied materials exhibited a wide range of fracture mechanisms depending on the microstructure and applied mechanical loading.
Functional Smart Dispersed Liquid Crystals for Nano- and Biophotonic Applications: Nanoparticles-Assisted Optical Bioimaging
Authors: Kamanina N. V. , Likhomanova S. V. , Zubtcova Yu. A. , Kamanin A. A. , Pawlicka A.
Published: June 2016

Functional nematic liquid crystal structures doped with nano- and bioobjects have been investigated. The self-assembling features and the photorefractive parameters of the structured liquid crystals have been comparatively studied via microscopy and laser techniques. Fullerene, quantum dots, carbon nanotubes, DNA, and erythrocytes have been considered as the effective nano- and biosensitizers of the LC mesophase. The holographic recording technique based on four-wave mixing of the laser beams has been used to investigate the laser-induced change of the refractive index in the nano- and bioobjects-doped liquid crystal cells. The special accent has been given to novel nanostructured relief with vertically aligned carbon nanotubes at the interface: solid substrate-liquid crystal mesophase. It has been shown that this nanostructured relief influences the orienting ability of the liquid crystal molecules with good advantage. As a result, it provokes the orientation of the DNA. The modified functional liquid crystal materials have been proposed as the perspective systems for both the photonics and biology as well as the medical applications.
Torsion of the Appendix Testis in a Neonate
Authors: Krishnan Arvind , Rich Mark A. , Swana Hubert S.
Published: June 2016

Torsion of the appendix testis is a rare cause of scrotal swelling in the neonatal period. We present a case of torsion of the appendix testis in a one-day-old male. We discuss the physical examination and radiologic studies used to make the diagnosis. Nonoperative therapy was recommended and the patient has done well. Recognition of this condition in the neonatal period can prevent surgical intervention and its associated risks.
FRTL-5 Rat Thyroid Cells Release Thyroglobulin Sequestered in Exosomes: A Possible Novel Mechanism for Thyroglobulin Processing in the Thyroid
Authors: Vlasov Pavel , Doi Sonia Q. , Sellitti Donald F.
Published: June 2016

Exosomes are 30–100 nm, membrane-bound vesicles containing specific cellular proteins, mRNAs, and microRNAs that take part in intercellular communication between cells. A possible role for exosomes in thyroid function has not been fully explored. In the present study, FRTL-5 rat thyroid cells were grown to confluence and received medium containing either thyroid stimulating hormone (TSH), exogenous bovine thyroglobulin (bTg), or neither additive for 24 or 48 hours followed by collection of spent medium and ultracentrifugation to isolate small vesicles. Transmission electron microscopy and Western blotting for CD9 indicated the presence of exosomes. Western blotting of exosome extract using a monoclonal anti-Tg antibody revealed a Tg-positive band at ~330 kDa (the expected size of monomeric Tg) with a higher density in TSH-treated cells compared to that in untreated cells. These results are the first to show that normal thyroid cells in culture produce exosomes containing undegraded Tg.
Animal Model of Gestational Diabetes Mellitus with Pathophysiological Resemblance to the Human Condition Induced by Multiple Factors (Nutritional, Pharmacological, and Stress) in Rats
Authors: Abdul Aziz Siti Hajar , John Cini Mathew , Mohamed Yusof Nur Intan Saidaah , Nordin Massita , Ramasamy Rajesh , Adam Aishah , Mohd Fauzi Fazlin
Published: June 2016

This study attempts to develop an experimental gestational diabetes mellitus (GDM) animal model in female Sprague-Dawley rats. Rats were fed with high fat sucrose diet, impregnated, and induced with Streptozotocin and Nicotinamide on gestational day 0 (D0). Sleeping patterns of the rats were also manipulated to induce stress, a lifestyle factor that contributes to GDM. Rats were tested for glycemic parameters (glucose, C-peptide, and insulin), lipid profiles (total cholesterol, triglycerides, HDL, and LDL), genes affecting insulin signaling (IRS-2, AKT-1, and PCK-1), glucose transporters (GLUT-2 and GLUT-4), proinflammatory cytokines (IL-6, TNF-α), and antioxidants (SOD, CAT, and GPX) on D6 and D21. GDM rats showed possible insulin resistance as evidenced by high expression of proinflammatory cytokines, PCK-1 and CRP. Furthermore, low levels of IRS-2 and AKT-1 genes and downregulation of GLUT-4 from the initial to final phases indicate possible defect of insulin signaling. GDM rats also showed an impairment of antioxidant status and a hyperlipidemic state. Additionally, GDM rats exhibited significantly higher body weight and blood glucose and lower plasma insulin level and C-peptide than control. Based on the findings outlined, the current GDM animal model closely replicates the disease state in human and can serve as a reference for future investigations.
Caspase-11 Modulates Inflammation and AttenuatesToxoplasma gondiiPathogenesis
Authors: Coutermarsh-Ott Sheryl L. , Doran John T. , Campbell Caroline , Williams Tere M. , Lindsay David S. , Allen Irving C.
Published: June 2016

Toxoplasma gondiiis an obligate intracellular parasite that is the etiologic agent responsible for toxoplasmosis. Infection withT. gondiiresults in activation of nucleotide binding domain and leucine rich repeat containing receptors (NLRs). NLR activation leads to inflammasome formation, the activation of caspase-1, and the subsequent cleavage of IL-1βand IL-18. Recently, a noncanonical inflammasome has been characterized which functions through caspase-11 and appears to augment many biological functions previously considered to be dependent upon the canonical inflammasome. To better elucidate the function of this noncanonical inflammasome in toxoplasmosis, we utilizedAsc−/−andCasp11−/−mice and infected these animals withT. gondii. Our data indicates that caspase-11 modulates the innate immune response toT. gondiithrough a mechanism which is distinct from that currently described for the canonical inflammasome.Asc−/−mice demonstrated increased disease pathogenesis during the acute phase ofT. gondiiinfection, whereasCasp11−/−mice demonstrated significantly attenuated disease pathogenesis and reduced inflammation. This attenuated host response was associated with reduced local and systemic cytokine production, including diminished IL-1β. During the chronic phase of infection, caspase-11 deficiency resulted in increased neuroinflammation and tissue cyst burden in the brain. Together, our data suggest that caspase-11 functions to protect the host by enhancing inflammation during the early phase of infection in an effort to minimize disease pathogenesis during later stages of toxoplasmosis.
Eradication of Acute Myeloid Leukemia with FLT3 Ligand–Targeted miR-150 Nanoparticles
Authors: Jiang Xi , Bugno Jason , Hu Chao , Yang Yang , Herold Tobias , Qi Jun , Chen Ping , Gurbuxani Sandeep , Arnovitz Stephen , Strong Jennifer , Ferchen Kyle , Ulrich Bryan , Weng Hengyou , Wang Yungui , Huang Hao , Li Shenglai , Neilly Mary Beth , Larson Richard A. , Le Beau Michelle M. , Bohlander Stefan K. , Jin Jie , Li Zejuan , Bradner James E. , Hong Seungpyo , Chen Jianjun
Published: June 2016

Acute myeloid leukemia (AML) is a common and fatal form of hematopoietic malignancy. Overexpression and/or mutations of FLT3 have been shown to occur in the majority of cases of AML. Our analysis of a large-scale AML patient cohort (N = 562) indicates that FLT3 is particularly highly expressed in some subtypes of AML, such as AML with t(11q23)/MLL-rearrangements or FLT3-ITD. Such AML subtypes are known to be associated with unfavorable prognosis. To treat FLT3-overexpressing AML, we developed a novel targeted nanoparticle system: FLT3 ligand (FLT3L)-conjugated G7 poly(amidoamine) (PAMAM) nanosized dendriplex encapsulating miR-150, a pivotal tumor suppressor and negative regulator of FLT3. We show that the FLT3L-guided miR-150 nanoparticles selectively and efficiently target FLT3-overexpressing AML cells and significantly inhibit viability/growth and promote apoptosis of the AML cells. Our proof-of-concept animal model studies demonstrate that the FLT3L-guided miR-150 nanoparticles tend to concentrate in bone marrow, and significantly inhibit progression of FLT3-overexpressing AML in vivo, while exhibiting no obvious side effects on normal hematopoiesis. Collectively, we have developed a novel targeted therapeutic strategy, using FLT3L-guided miR-150–based nanoparticles, to treat FLT3-overexpressing AML with high efficacy and minimal side effects. Cancer Res; 76(15); 4470–80. ©2016 AACR.
RETRACTED: PHGDH Expression Is Required for Mitochondrial Redox Homeostasis, Breast Cancer Stem Cell Maintenance, and Lung Metastasis
Authors: Samanta Debangshu , Park Youngrok , Andrabi Shaida A. , Shelton Laura M. , Gilkes Daniele M. , Semenza Gregg L.
Published: June 2016

Intratumoral hypoxia stimulates enrichment of breast cancer stem cells (BCSC), which are critical for metastasis and patient mortality. Here we report a metabolic adaptation that is required for hypoxia-induced BCSC enrichment and metastasis. Hypoxia-inducible factors coordinately regulate expression of genes encoding phosphoglycerate dehydrogenase (PHGDH) and five downstream enzymes in the serine synthesis pathway and mitochondrial one-carbon (folate) cycle. RNAi-mediated silencing of PHGDH expression in both estrogen receptor–positive and negative breast cancer cells led to decreased NADPH levels, disturbed mitochondrial redox homeostasis, and increased apoptosis, which abrogated BCSC enrichment under hypoxic conditions. PHGDH-deficient cells exhibited increased oxidant levels and apoptosis, as well as loss of BCSC enrichment, in response to treatment with carboplatin or doxorubicin. PHGDH-deficient cells were relatively weakly tumorigenic and tumors that did form were deficient in BCSCs, abolishing metastatic capacity. Our findings highlight a role for PHGDH in the formation of secondary (recurrent or metastatic) tumors, with potential implications for therapeutic targeting of advanced cancers. Cancer Res; 76(15); 4430–42. ©2016 AACR.
Inhibition of SOAT1 Suppresses Glioblastoma Growth via Blocking SREBP-1–Mediated Lipogenesis
Authors: Geng Feng , Cheng Xiang , Wu Xiaoning , Yoo Ji Young , Cheng Chunming , Guo Jeffrey Yunhua , Mo Xiaokui , Ru Peng , Hurwitz Brian , Kim Sung-Hak , Otero Jose , Puduvalli Vinay , Lefai Etienne , Ma Jianjie , Nakano Ichiro , Horbinski Craig , Kaur Balveen , Chakravarti Arnab , Guo Deliang
Published: June 2016

Purpose: Elevated lipogenesis regulated by sterol regulatory element-binding protein-1 (SREBP-1), a transcription factor playing a central role in lipid metabolism, is a novel characteristic of glioblastoma (GBM). The aim of this study was to identify effective approaches to suppress GBM growth by inhibition of SREBP-1. As SREBP activation is negatively regulated by endoplasmic reticulum (ER) cholesterol, we sought to determine whether suppression of sterol O-acyltransferase (SOAT), a key enzyme converting ER cholesterol to cholesterol esters (CE) to store in lipid droplets (LDs), effectively suppressed SREBP-1 and blocked GBM growth.

Experimental Design: The presence of LDs in glioma patient tumor tissues was analyzed using immunofluorescence, immunohistochemistry, and electronic microscopy. Western blotting and real-time PCR were performed to analyze protein levels and gene expression of GBM cells, respectively. Intracranial GBM xenografts were used to determine the effects of genetically silencing SOAT1 and SREBP-1 on tumor growth.

Results: Our study unraveled that cholesterol esterification and LD formation are signature of GBM, and human patients with glioma possess elevated LDs that correlate with GBM progression and poor survival. We revealed that SOAT1 is highly expressed in GBM and functions as a key player in controlling the cholesterol esterification and storage in GBM. Targeting SOAT1 suppresses GBM growth and prolongs survival in xenograft models via inhibition of SREBP-1–regulated lipid synthesis.

Conclusions: Cholesterol esterification and storage in LDs are novel characteristics of GBM, and inhibiting SOAT1 to block cholesterol esterification is a promising therapeutic strategy to treat GBM by suppressing SREBP-1. Clin Cancer Res; 22(21); 5337–48. ©2016 AACR.
Beyond BMI: Conceptual Issues Related to Overweight and Obese Patients
Authors: Müller Manfred James , Braun Wiebke , Enderle Janna , Bosy-Westphal Anja
Published: June 2016

BMI is widely used as a measure of weight status and disease risks; it defines overweight and obesity based on statistical criteria. BMI is a score; neither is it biologically sound nor does it reflect a suitable phenotype worthwhile to study. Because of its limited value, BMI cannot provide profound insight into obesity biology and its co-morbidity. Alternative assessments of weight status include detailed phenotyping by body composition analysis (BCA). However, predicting disease risks, fat mass, and fat-free mass as assessed by validated techniques (i.e., densitometry, dual energy X ray absorptiometry, and bioelectrical impedance analysis) does not exceed the value of BMI. Going beyond BMI and descriptive BCA, the concept of functional body composition (FBC) integrates body components into regulatory systems. FBC refers to the masses of body components, organs, and tissues as well as to their inter-relationships within the context of endocrine, metabolic and immune functions. FBC can be used to define specific phenotypes of obesity, e.g. the sarcopenic-obese patient. Well-characterized obesity phenotypes are a precondition for targeted research (e.g., on the genomics of obesity) and patient-centered care (e.g., adequate treatment of individual obese phenotypes such as the sarcopenic-obese patient). FBC contributes to a future definition of overweight and obesity based on physiological criteria rather than on body weight alone.
Investigation for Paediatric Cushing's Syndrome Using Twenty-Four-Hour Urinary Free Cortisol Determination
Authors: Shapiro Lucy , Elahi Shezan , Riddoch Fiona , Perry Leslie A. , Martin Lee , Akker Scott A. , Monson John P. , Drake William M. , Grossman Ashley B. , Savage Martin O. , Storr Helen L.
Published: June 2016

Objective: Paediatric Cushing's syndrome (CS) remains a challenge to diagnose and exclude. We assessed the accuracy of 24-hour urinary free cortisol (UFC) determination in children referred for suspected CS. Design: We conducted a retrospective study of paediatric patients referred to our centre with suspected CS between 1982 and 2014. Patients: Of 66 subjects (mean age 12.9 years; range 4.4-16.9), there were 47 cases of CS (29 males), which included Cushing's disease (CD; 39 patients, 25 males), primary pigmented nodular adrenocortical disease (8 patients, 4 males) and 19 ‘controls' (6 males) in whom the diagnosis of CS was excluded. Measurements: The subjects had between one and five 24-hour UFC collections analysed by radioimmunoassay, chemiluminescent immunoassay or liquid chromatography-mass spectrometry. The data were normalised, corrected for body surface area (m2) and assessed using receiver operating characteristic analysis and an independent two-tailed t test. Results: The diagnostic accuracy of 24-hour UFC for CS was excellent (area under the curve 0.98, 95% CI 0.946-1.00, sensitivity 89%, specificity 100%). Conclusions: Twenty-four-hour UFC is a reliable and practical investigation with high diagnostic accuracy for paediatric CS. However, further investigations may be required if the UFC is normal but there is a high diagnostic suspicion of CS.
Hemoperitoneum Following Sexual Intercourse in a Woman with Deep Infiltrating Endometriosis
Authors: Buggio Laura , Aimi Giorgio , Vercellini Paolo
Published: June 2016

Endometriosis is an estrogen-dependent chronic inflammatory disease, defined by the presence of endometrial glands and stroma at ectopic sites. A rare and life-threatening complication associated with endometriosis is represented by spontaneous hemoperitoneum due to the rupture of utero-ovarian vessels. Most cases of spontaneous hemoperitoneum previously described involved pregnant women affected by endometriosis; here, we present a case of acute and massive hemoperitoneum in a nulliparous woman with deep infiltrating endometriosis. When acute abdominal pain with hemoperitoneum occurs in non-gravid reproductive age women, with no positive findings for liver or spleen lesions, a possible spontaneous rupture of utero-ovarian vessels related to the presence of deep infiltrating endometriosis should be included among the possible causes of the condition.
Effect of high or low protamine dosing on postoperative bleeding following heparin anticoagulation in cardiac surgery
Authors: Meesters Michael I. , Veerhoek Dennis , de Lange Fellery , de Vries Jacob-Willem , de Jong Jan R. , Romijn Johannes W. A. , Kelchtermans Hilde , Huskens Dana , van der Steeg Robin , Thomas Pepijn W. A. , Burtman David T. M. , van Barneveld Laurentius J. M. , Vonk Alexander B. A. , Boer Christa
Published: June 2016

While experimental data state that protamine exerts intrinsic anticoagulation effects, protamine is still frequently overdosed for heparin neutralisation during cardiac surgery with cardiopulmonary bypass (CPB). Since comparative studies are lacking, we assessed the influence of two protamine-to-heparin dosing ratios on perioperative haemostasis and bleeding, and hypothesised that protamine overdosing impairs the coagulation status following cardiac surgery. In this open-label, multicentre, single-blinded, randomised controlled trial, patients undergoing on-pump coronary artery bypass graft surgery were assigned to a low (0.8; n=49) or high (1.3; n=47) protamine-to-heparin dosing group. The primary outcome was 24-hour blood loss. Patient haemostasis was monitored using rotational thromboelastometry and a thrombin generation assay. The low protamine-to-heparin dosing ratio group received less protamine (329 ± 95 vs 539 ± 117 mg; p<0.001), while post-protamine activated clotting times were similar among groups. The high dosing group revealed increased intrinsic clotting times (236 ± 74 vs 196 ± 64 s; p=0.006) and the maximum post-protamine thrombin generation was less suppressed in the low dosing group (38 ± 40% vs 6 ± 9%; p=0.001). Postoperative blood loss was increased in the high dosing ratio group (615 ml; 95% CI 500–830 ml vs 470 ml; 95% CI 420–530 ml; p=0.021) when compared to the low dosing group, respectively. More patients in the high dosing group received fresh frozen plasma (11% vs 0%; p=0.02) and platelet concentrate (21% vs 6%; p=0.04) compared to the low dosing group. Our study confirms in vitro data that abundant protamine dosing is associated with increased postoperative blood loss and higher transfusion rates in cardiac surgery.
UBC9-Mediated Sumoylation Favorably Impacts Cardiac Function in Compromised Hearts
Authors: Gupta Manish K. , McLendon Patrick M. , Gulick James , James Jeanne , Khalili Kamel , Robbins Jeffrey
Published: June 2016

Rationale:

SUMOylation plays an important role in cardiac function and can be protective against cardiac stress. Recent studies show that SUMOylation is an integral part of the ubiquitin proteasome system, and expression of the small ubiquitin–like modifier (SUMO) E2 enzyme UBC9 improves cardiac protein quality control. However, the precise role of SUMOylation on other protein degradation pathways, particularly autophagy, remains undefined in the heart.

Objective:

To determine whether SUMOylation affects cardiac autophagy and whether this effect is protective in a mouse model of proteotoxic cardiac stress.

Methods and Results:

We modulated expression of UBC9, a SUMO E2 ligase, using gain- and loss-of-function in neonatal rat ventricular cardiomyocytes. UBC9 expression seemed to directly alter autophagic flux. To confirm this effect in vivo, we generated transgenic mice overexpressing UBC9 in cardiomyocytes. These mice have an increased level of SUMOylation at baseline and, in confirmation of the data obtained from neonatal rat ventricular cardiomyocytes, demonstrated increased autophagy, suggesting that increased UBC9-mediated SUMOylation is sufficient to upregulate cardiac autophagy. Finally, we tested the protective role of SUMOylation-mediated autophagy by expressing UBC9 in a model of cardiac proteotoxicity, induced by cardiomyocyte-specific expression of a mutant α-B-crystallin, mutant CryAB (CryAB
R120G
), which shows impaired autophagy. UBC9 overexpression reduced aggregate formation, decreased fibrosis, reduced hypertrophy, and improved cardiac function and survival.

Conclusions:

The data showed that increased UBC9-mediated SUMOylation is sufficient to induce relatively high levels of autophagy and may represent a novel strategy for increasing autophagic flux and ameliorating morbidity in proteotoxic cardiac disease.
Bonding beyond the pair in a monogamous bird: impact on social structure in adult rooks (Corvus frugilegus)
Authors: Boucherie Palmyre H. , Mariette Mylène M. , Bret Céline , Dufour Valérie
Published: June 2016

The formation of social bonds outside the mated pair is not frequently reported in monogamous birds, although it may be expected in some species like rooks, living in groups all year round. Here we explore the social structure of captive adult rooks over three breeding seasons. We recorded proximities and affiliations (i.e., allofeeding, allopreening, contact-sit) to classify relationships according to their strength. Three categories of relationships emerged: primary (i.e., pairs), secondary and weak relationships. Affiliations and sexual behaviours were not restricted to pairs, and secondary relationships were clearly recognizable. Mixed-sex secondary relationships were qualitatively equivalent to pairs (i.e., same behaviours in the same proportions), although they were quantitatively less intense. Same sex pairs occurred, and were qualitatively equivalent to mixed-sex pairs. Overall we found that rooks social structure is more than just an aggregation of pairs, which highlights the importance of considering extra-pair relationships in socially monogamous birds.
Domestic Dogs and Human Infants Look More at Happy and Angry Faces Than Sad Faces
Authors: Yong Min Hooi , Ruffman Ted
Published: June 2016

Dogs respond to human emotional expressions. However, it is unknown whether dogs can match emotional faces to voices in an intermodal matching task or whether they show preferences for looking at certain emotional facial expressions over others, similar to human infants. We presented 52 domestic dogs and 24 seven-month-old human infants with two different human emotional facial expressions of the same gender simultaneously, while listening to a human voice expressing an emotion that matched one of them. Consistent with most matching studies, neither dogs nor infants looked longer at the matching emotional stimuli, yet dogs and humans demonstrated an identical pattern of looking less at sad faces when paired with happy or angry faces (irrespective of the vocal stimulus), with no preference for happyversusangry faces. Discussion focuses on why dogs and infants might have an aversion to sad faces, or alternatively, heightened interest in angry and happy faces.