bluuebunny/crossref_metadata_2025 huggingface dataset:
NOTCH1 and NOTCH2 regulate epithelial cell proliferation in mouse and human gastric corpus
Authors: Demitrack Elise S. , Gifford Gail B. , Keeley Theresa M. , Horita Nobukatsu , Todisco Andrea , Turgeon D. Kim , Siebel Christian W. , Samuelson Linda C.
Published: December 2016

The Notch signaling pathway is known to regulate stem cells and epithelial cell homeostasis in gastrointestinal tissues; however, Notch function in the corpus region of the stomach is poorly understood. In this study we examined the consequences of Notch inhibition and activation on cellular proliferation and differentiation and defined the specific Notch receptors functioning in the mouse and human corpus. Notch pathway activity was observed in the mouse corpus epithelium, and gene expression analysis revealed NOTCH1 and NOTCH2 to be the predominant Notch receptors in both mouse and human. Global Notch inhibition for 5 days reduced progenitor cell proliferation in the mouse corpus, as well as in organoids derived from mouse and human corpus tissue. Proliferation effects were mediated through both NOTCH1 and NOTCH2 receptors, as demonstrated by targeting each receptor alone or in combination with Notch receptor inhibitory antibodies. Analysis of differentiation by marker expression showed no change to the major cell lineages; however, there was a modest increase in the number of transitional cells coexpressing markers of mucous neck and chief cells. In contrast to reduced proliferation after pathway inhibition, Notch activation in the adult stomach resulted in increased proliferation coupled with reduced differentiation. These findings suggest that NOTCH1 and NOTCH2 signaling promotes progenitor cell proliferation in the mouse and human gastric corpus, which is consistent with previously defined roles for Notch in promoting stem and progenitor cell proliferation in the intestine and antral stomach.

NEW & NOTEWORTHY Here we demonstrate that the Notch signaling pathway is essential for proliferation of stem cells in the mouse and human gastric corpus. We identify NOTCH1 and NOTCH2 as the predominant Notch receptors expressed in both mouse and human corpus and show that both receptors are required for corpus stem cell proliferation. We show that chronic Notch activation in corpus stem cells induces hyperproliferation and tissue hypertrophy, suggesting that Notch may drive gastric tumorigenesis.
Impact of TGF-β inhibition during acute exercise on Achilles tendon extracellular matrix
Authors: Potter Ross M. , Huynh Richard T. , Volper Brent D. , Arthur Kathryn A. , D’Lugos Andrew C. , Sørensen Mikkel A. , Magnusson S. Peter , Dickinson Jared M. , Hale Taben M. , Carroll Chad C.
Published: December 2016

The purpose of this study was to evaluate the role of TGF-β1in regulating tendon extracellular matrix after acute exercise. Wistar rats exercised ( n = 15) on a treadmill for four consecutive days (60 min/day) or maintained normal cage activity. After each exercise bout, the peritendinous space of each Achilles tendon was injected with a TGF-β1receptor inhibitor or sham. Independent of group, tendons injected with inhibitor exhibited ~50% lower Smad 3 (Ser423/425) ( P < 0.05) and 2.5-fold greater ERK1/2 phosphorylation ( P < 0.05) when compared with sham ( P < 0.05). Injection of the inhibitor did not alter collagen content in either group ( P > 0.05). In exercised rats, hydroxylyslpyridinoline content and collagen III expression were lower ( P < 0.05) in tendons injected with inhibitor when compared with sham. In nonexercised rats, collagen I and lysyl oxidase (LOX) expression was lower ( P < 0.05) in tendons injected with inhibitor when compared with sham. Decorin expression was not altered by inhibitor in either group ( P > 0.05). On the basis of evaluation of hematoxylin and eosin (H&E) stained cross sections, cell numbers were not altered by inhibitor treatment in either group ( P > 0.05). Evaluation of H&E-stained sections revealed no effect of inhibitor on collagen fibril morphology. In contrast, scores for regional variation in cellularity decreased in exercised rats ( P < 0.05). No differences in fiber arrangement, structure, and nuclei form were noted in either group ( P > 0.05). Our findings suggest that TGF-β1signaling is necessary for the regulation of tendon cross-link formation, as well as collagen and LOX gene transcription in an exercise-dependent manner.
DNA repair in ischemic acute kidney injury
Authors: Pressly Jeffrey D. , Park Frank
Published: December 2016

Ischemia-reperfusion injury (IRI) is a common cause of acute kidney injury leading to an induction of oxidative stress, cellular dysfunction, and loss of renal function. DNA damage, including oxidative base modifications and physical DNA strand breaks, is a consequence of renal IRI. Like many other organs in the body, a redundant and highly conserved set of endogenous repair pathways have evolved to selectively recognize the various types of cellular DNA damage and combat its negative effects on cell viability. Severe damage to the DNA, however, can trigger cell death and elimination of the injured tubular epithelial cells. In this minireview, we summarize the state of the current field of DNA damage and repair in the kidney and provide some expected and, in some cases, unexpected effects of IRI on DNA damage and repair in the kidney. These findings may be applicable to other forms of acute kidney injury and could provide new opportunities for renal research.
Knockdown of Add3 impairs the myogenic response of renal afferent arterioles and middle cerebral arteries
Authors: Fan Fan , Pabbidi Mallikarjuna R. , Ge Ying , Li Longyang , Wang Shaoxun , Mims Paige N. , Roman Richard J.
Published: December 2016

We have reported that the myogenic response of the renal afferent arteriole (Af-art) and middle cerebral artery (MCA) and autoregulation of renal and cerebral blood flow are impaired in Fawn-Hooded Hypertensive (FHH) rats. Transfer of a region of chromosome 1 containing γ-adducin (Add3) from the Brown Norway rat rescued the vascular dysfunction and the development of renal disease. To examine whether Add3 is a viable candidate gene altering renal and cerebral hemodynamics in FHH rats, we knocked down the expression of Add3 in rat Af-arts and MCAs cultured for 36-h using a 27-mer Dicer-substrate short interfering RNA (DsiRNA). Control Af-arts constricted by 10 ± 1% in response to an elevation in pressure from 60 to 120 mmHg but dilated by 4 ± 3% when treated with Add3 DsiRNA. Add3 DsiRNA had no effect on the vasoconstrictor response of the Af-art to norepinephrine (10−7M). Add3 DsiRNA had a similar effect on the attenuation of the myogenic response in the MCA. Peak potassium currents were threefold higher in smooth muscle cells isolated from Af-arts or MCAs transfected with Add3 DsiRNA than in nontransfected cells isolated from the same vessels. This is the first study demonstrating that Add3 plays a role in the regulation of potassium channel function and vascular reactivity. It supports the hypothesis that sequence variants in Add3, which we previously identified in FHH rats, may play a causal role in the impaired myogenic response and autoregulation in the renal and cerebral circulation.
Expression of sodium-dependent dicarboxylate transporter 1 (NaDC1/SLC13A2) in normal and neoplastic human kidney
Authors: Lee Hyun-Wook , Handlogten Mary E. , Osis Gunars , Clapp William L. , Wakefield Dara N. , Verlander Jill W. , Weiner I. David
Published: December 2016

Regulated dicarboxylate transport is critical for acid-base homeostasis, prevention of calcium nephrolithiasis, regulation of collecting duct sodium chloride transport, and the regulation of blood pressure. Although luminal dicarboxylate reabsorption via NaDC1 (SLC13A2) is believed to be the primary mechanism regulating renal dicarboxylate transport, the specific localization of NaDC1 in the human kidney is currently unknown. This study’s purpose was to determine NaDC1's expression in normal and neoplastic human kidneys. Immunoblot analysis demonstrated NaDC1 expression with an apparent molecular weight of ~61 kDa. Immunohistochemistry showed apical NaDC1 immunolabel in the proximal tubule of normal human kidney tissue; well-preserved proximal tubule brush border was clearly labeled. Apical NaDC1 expression was evident throughout the entire proximal tubule, including the initial proximal convoluted tubule, as identified by origination from the glomerular tuft, and extending through the terminal of the proximal tubule, the proximal straight tubule in the outer medulla. We confirmed proximal tubule localization by colocalization with the proximal tubule specific protein, NBCe1. NaDC1 immunolabel was not detected other than in the proximal tubule. In addition, NaDC1 immunolabel was not detected in tumors of presumed proximal tubule origin, clear cell and papillary renal cell carcinoma, or in tumors of nonproximal tubule origin, oncocytoma and chromophobe carcinoma. In summary, 1) in the human kidney, apical NaDC1 immunolabel is present throughout the entire proximal tubule, and is not detectable in other renal cells; and 2) NaDC1 immunolabel is not present in renal tumors. These studies provide important information regarding NaDC1’s role in human dicarboxylate metabolism.
Are there sex differences in the capillary blood volume and diffusing capacity response to exercise?
Authors: Bouwsema Melissa M. , Tedjasaputra Vincent , Stickland Michael K.
Published: December 2016

Previous work suggests that women may exhibit a greater respiratory limitation in exercise compared with height-matched men. Diffusion capacity (DlCO) increases with incremental exercise, and the smaller lungs of women may limit membrane diffusing capacity (Dm) and pulmonary capillary blood volume (Vc) in response to the increased oxygen demand. We hypothesized that women would have lower DlCO, DlCO relative to cardiac output (DlCO/Q̇), Dm, Vc, and pulmonary transit time, secondary to lower Vc at peak exercise. Sixteen women (112 ± 12% predicted relative V̇o2peak) and sixteen men (118 ± 22% predicted relative V̇o2peak) were matched for height and weight. Hemoglobin-corrected diffusing capacity (DlCO), Vc, and Dm were determined via the multiple-[Formula: see text] DlCO technique at rest and during incremental exercise up to 90% of V̇o2peak. Both groups increased DlCO, Vc, and Dm with exercise intensity, but women had 20% lower DlCO ( P < 0.001), 18% lower Vc ( P = 0.002), and 22% lower Dm ( P < 0.001) compared with men across all workloads, and neither group exhibited a plateau in Vc. When expressed relative to alveolar volume (Va), the between-sex difference was eliminated. The drop in DlCO/Q̇ was proportionally less in women than men, and mean pulmonary transit time did not drop below 0.3 s in either group. Women demonstrate consistently lower DlCO, Vc, and Dm compared with height-matched men during exercise; however, these differences disappear with correction for lung size. These results suggest that after differences in lung volume are accounted for there is no intrinsic sex difference in the DlCO, Vc, or Dm response to exercise.

NEW & NOTEWORTHY Women demonstrate lower diffusing capacity-to-cardiac output ratio (DlCO/Q̇), pulmonary capillary blood volume (Vc), and membrane diffusing capacity (Dm) compared with height-matched men during exercise. However, these differences disappear after correction for lung size. The drop in DlCO/Q̇ was proportionally less in women, and pulmonary transit time did not drop below 0.3 s in either group. After differences in lung volume are accounted for, there is no intrinsic sex difference in DlCO, Vc, or Dm response to exercise.
The effects of voluntary exercise and prazosin on capillary rarefaction and metabolism in streptozotocin-induced diabetic male rats
Authors: Dunford Emily C. , Leclair Erwan , Aiken Julian , Mandel Erin R. , Haas Tara L. , Birot Olivier , Riddell Michael C.
Published: December 2016

Type-1 diabetes mellitus (T1D) causes impairments within the skeletal muscle microvasculature. Both regular exercise and prazosin have been shown to improve skeletal muscle capillarization and metabolism in healthy rats through distinct angiogenic mechanisms. The aim of this study was to evaluate the independent and additive effects of voluntary exercise and prazosin treatment on capillary-to-fiber ratio (C:F) in streptozotocin (STZ)-treated diabetic rats. STZ (65 mg/kg) was intraperitoneally administered to male Sprague-Dawley rats ( n = 36) to induce diabetes, with healthy, nondiabetic, sedentary rats ( n = 10) as controls. The STZ-treated rats were then divided into sedentary (SED) or exercising (EX; 24-h access to running wheels) groups and then further subdivided into prazosin (Praz) or water (H2O) treatment groups: nondiabetic-SED-H2O, STZ-SED-H2O, STZ-EX-H2O, STZ-SED-Praz, and STZ-EX-Praz. After 3 wk, untreated diabetes significantly reduced the C:F in tibialis anterior (TA) and soleus muscles in the STZ-SED-H2O animals (both P < 0.05). Voluntary exercise and prazosin treatment independently resulted in a normalization of C:F within the TA (1.86 ± 0.12 and 2.04 ± 0.03 vs 1.71 ± 0.09, P < 0.05) and the soleus (2.36 ± 0.07 and 2.68 ± 0.14 vs 2.13 ± 0.12, P < 0.05). The combined STZ-EX-Praz group resulted in the highest C:F within the TA (2.26 ± 0.07, P < 0.05). Voluntary exercise volume was negatively correlated with fed blood glucose levels ( r2 = −0.7015, P < 0.01) and, when combined with prazosin, caused further enhanced nonfasted glucose ( P < 0.01). Exercise and prazosin reduced circulating nonesterified fatty acids more than either stimulus alone ( P < 0.05). These results suggest that the distinct stimulation of angiogenesis, with both regular exercise and prazosin treatment, causes a cooperative improvement in the microvascular complications associated with T1D.

NEW & NOTEWORTHY It is currently well established that poorly controlled diabetes reduces both skeletal muscle mass and muscle capillarization. These muscle-specific features of diabetes may, in turn, compromise insulin sensitivity and glucose control. Using a model of streptozotocin-induced diabetes, we show the vascular complications linked with disease and how chronic exposure to exercise and prazosin (an α1-adrenergic antagonist) can reduce these complications and improve glycemic control.
Suite of clinically relevant functional assays to address therapeutic efficacy and disease mechanism in the dystrophic mdx mouse
Authors: Song Yafeng , Rosenblum Shira T. , Morales Leon , Petrov Mihail , Greer Christopher , Globerman Samantha , Stedman Hansell H.
Published: December 2016

Duchenne muscular dystrophy (DMD) is a progressive primary myodegenerative disease caused by a genetic deficiency of the 427-kDa cytoskeletal protein dystrophin. Despite its single-gene etiology, DMD’s complex pathogenesis remains poorly understood, complicating the extrapolation from results of preclinical studies in genetic homologs to the design of informative clinical trials. Here we describe novel phenotypic assays which when applied to the mdx mouse resemble recently used primary end points for DMD clinical trials. By coupling force transduction, high-precision motion tracking, and respiratory measurements, we have achieved a suite of integrative physiological tests that provide novel insights regarding normal and pathological responses to muscular exertion. A common feature of these physiological assays is the precise tracking and analysis of volitional movement, thereby optimizing the relevance to clinical tests. Unexpectedly, the measurable biological distinction between dystrophic and control mice at early time points in the disease process is better resolved with these tests than with the majority of previously used, labor-intensive studies of individual muscle function performed ex vivo. For example, the dramatic loss of volitional movement following a novel, standardized grip test distinguishes control mice from mdx mice by a 17.4-fold difference of the means (3.5 ± 2.2 vs. 60.9 ± 12.1 units of activity, respectively; effect size 1.99). The findings have both mechanistic and translational implications of potential significance to the fields of basic myology and neuromuscular therapeutics.

NEW & NOTEWORTHY This study uses novel phenotypic assays which when applied to the mdx mouse resemble recently used primary end points for DMD clinical trials. A measurable distinction between dystrophic and control mice was seen at early time points in vivo compared with invasive muscle studies performed ex vivo. These assays shed light on normal and pathological responses to muscular exertion and have significant mechanistic and translational implications for the fields of basic myology and neuromuscular therapeutics.
Efficient and Secure Top-k Query Processing on Hybrid Sensed Data
Authors: Wu Haiqin , Wang Liangmin
Published: December 2016

The ubiquity of mobile devices equipped with various sensors has promoted the advent of a novel data sensing paradigm. Based on the traditional static sensing mode, the mobile sensing (sensor) nodes collaboratively collect data with the static sensor nodes. This large volume of hybrid sensed data is then sent to the storage nodes for flexible management and top-k query services. One crucial security issue is that the compromised storage node may falsify or drop some data during the query processing, which returns fake or incorrect result to the query users. In this paper, we propose an efficient and verifiable scheme (EVTopk) for secure top-k query processing on hybrid sensed data, which is suitable for the tiered hybrid sensing network where mobile nodes exist. The basic idea is to bind each data record, generated by static or mobile sensing nodes, with the corresponding location where it is sensed. Then some verification information is created sequentially, which is submitted along with the encrypted locations and hybrid sensed data for user’s verification. The security and efficiency of EVTopk are thoroughly analyzed in theory and evaluated in our experiments, respectively.
Patterns of Early Rejection in Renal Retransplantation: A Single-Center Experience
Authors: Zhu Lan , Fu Cheng , Lin Kailin , Wang Zhiqiang , Guo Hui , Chen Song , Lin Zhengbin , Chen Zhishui , Chen Gang
Published: December 2016

It has been reported that kidney retransplant patients had high rates of early acute rejection due to previous sensitization. In addition to the acute antibody-mediated rejection (ABMR) that has received widespread attention, the early acute T-cell-mediated rejection (TCMR) may be another important issue in renal retransplantation. In the current single-center retrospective study, we included 33 retransplant patients and 90 first transplant patients with similar protocols of induction and maintenance therapy. Analysis focused particularly on the incidence and patterns of early acute rejection episodes, as well as one-year graft and patient survival. Excellent short-term clinical outcomes were obtained in both groups, with one-year graft and patient survival rates of 93.9%/100% in the retransplant group and 92.2%/95.6% in the first transplant group. Impressively, with our strict immunological selection and desensitization criteria, the retransplant patients had a very low incidence of early acute ABMR (6.1%), which was similar to that in the first transplant patients (4.4%). However, a much higher rate of early acute TCMR was observed in the retransplant group than in the first transplant group (30.3% versus 5.6%, P<0.001). Acute TCMR that develops early after retransplantation should be monitored in order to obtain better transplant outcomes.
Theory and Implementation of a Two-Step Unconditionally Stable Explicit Integration Algorithm for Vibration Analysis of Structures
Authors: Changqing Li , Junping Jie , Lizhong Jiang , Yang T. Y.
Published: December 2016

Time history analysis is becoming the routine process to quantify the response of the structure under dynamic loads. In this paper, a novel two-step unconditionally stable explicit integration algorithm, named Unconditional Stable Two-Step Explicit Displacement Method (USTEDM), is proposed for vibration analysis of structure. USTEDM is unconditionally stable, requires low memory, produces no overshoot, and is third order accurate. The accuracy and efficiency of USTEDM are presented and compared with other commonly used integration algorithms. The result shows that the proposed algorithm has superior performance and can be used efficiently in solving vibration response of civil engineering structure.
Antiepileptic Drug Nonadherence and Its Predictors among People with Epilepsy
Authors: Getnet Asmamaw , Woldeyohannes Solomon Meseret , Bekana Lulu , Mekonen Tesfa , Fekadu Wubalem , Menberu Melak , Yimer Solomon , Assaye Adisu , Belete Amsalu , Belete Habte
Published: December 2016

Introduction. Antiepileptic drugs are effective in the treatment of epilepsy to the extent that about 70% of people with epilepsy can be seizure-free, but poor adherence to medication is major problem to sustained remission and functional restoration. The aim of this study was to assess the prevalence and associated factors of antiepileptic drug nonadherence. Methods. Cross-sectional study was conducted on 450 individuals who were selected by systematic random sampling method. Antiepileptic drug nonadherence was measured by Morisky Medication Adherence Scale (MMAS) and logistic regression was used to look for significant associations. Result. The prevalence of AEDs nonadherence was 37.8%. Being on treatment for 6 years and above [AOR = 3.47, 95% CI: 1.88, 6.40], payment for AEDs [AOR = 2.76, 95% CI: 1.73, 4.42], lack of health information [AOR = 2.20, 95% CI: 1.41,3.43], poor social support [AOR = 1.88, 95%, CI: 1.01, 3.50], perceived stigma [AOR = 2.27, 95% CI: 1.45, 3.56], and experience side effect [AOR = 1.70, 95% CI: 1.06, 2.72] were significantly associated with antiepileptic drug nonadherence. Conclusion. More than one-third of people with epilepsy were not compliant with their AEDs. Giving health information about epilepsy and its management and consequent reduction in stigma will help for medication adherence.
Macroautophagy and Selective Mitophagy Ameliorate Chondrogenic Differentiation Potential in Adipose Stem Cells of Equine Metabolic Syndrome: New Findings in the Field of Progenitor Cells Differentiation
Authors: Marycz Krzysztof , Kornicka Katarzyna , Grzesiak Jakub , Śmieszek Agnieszka , Szłapka Jolanta
Published: December 2016

Equine metabolic syndrome (EMS) is mainly characterized by insulin resistance, obesity, and local or systemic inflammation. That unfriendly environment of adipose tissue has huge impact on stem cells population (ASC) residing within. In the present study, using molecular biology techniques and multiple imaging techniques (SEM, FIB‐SEM, and confocal microscopy), we evaluated the impact of EMS on ASC viability and chondrogenic differentiation. Moreover, we visualized the mitochondrial network and dynamics in ASCCTRL and ASCEMS during control and chondrogenic conditions. In control conditions, ASCEMS were characterized by increased mitochondrial fission in comparison to ASCCTRL. We found that extensive remodeling of mitochondrial network including fusion and fission occurs during early step of differentiation. Moreover, we observed mitochondria morphology deterioration in ASCEMS. These conditions seem to cause autophagic shift in ASCEMS, as we observed increased accumulation of LAMP2 and formation of multiple autophagosomes in those cells, some of which contained dysfunctional mitochondria. “Autophagic” switch may be a rescue mechanism allowing ASCEMS to clear impaired by ROS proteins and mitochondria. Moreover it provides a precursors‐to‐macromolecules synthesis, especially during chondrogenesis. Our data indicates that autophagy in ASCEMS would be crucial for the quality control mechanisms and maintenance of cellular homeostasis ASCEMS allowing them to be in “stemness” status.
The Impact of Cocreation on the Student Satisfaction: Analysis through Structural Equation Modeling
Authors: Pantoja Díaz Odette , Ribes-Giner Gabriela , Perello-Marin María Rosario
Published: December 2016

The objective of this study is to apply the cocreation initiative as a marketing tool in the context of university undergraduate programs. Considering that cocreation is a practice that involves stakeholders in different phases of product production or service, this research analyzes the interactions between some of the factors during the cocreation process as students collaborate with the university. These factors are participation, communication, cocreation, and satisfaction, and this study focuses on how they fuse together at the moment of cocreation. After a literature review, which supplied the basis for creating a model, we used exploratory and confirmatory factor analysis and structural equation modeling to validate the hypothesized relations between the variables; finally, the proposed cocreation model was verified. The results could empower academic institutions to develop managerial strategies in order to increase students’ collaboration and satisfaction.
Compound Control Strategy for MDF Continuous Hot Pressing Electrohydraulic Servo System with Uncertainties and Input Saturation
Authors: Liang-kuan Zhu , Zi-bo Wang , Ya-qiu Liu
Published: December 2016

A compound control strategy is investigated for Medium Density Fiberboard (MDF) continuous hot pressing electrohydraulic servo system (EHSS) with uncertainties and input saturation. Firstly, a hyperbolic tangent function is applied to approximate saturation nonlinearity in the system. And thus the mathematical model is continuous and differentiable. Subsequently, the slab thickness tracking controller is constructed by using a dynamic surface control (DSC) method, which introduces first-order low-pass filters to calculate derivatives of virtual control input in each step. Compared with the conventional backstepping controller, complexity of the design procedure is alleviated obviously. Moreover, a composite disturbance of uncertainties and input saturation is estimated by a nonlinear disturbance observer for compensation of the control law. Finally, an appropriate Lyapunov function is chosen to prove that all signals of the closed-loop system are semiglobally uniformly ultimately bounded and the tracking error converges to zero asymptotically. Numerical simulation results are also exhibited to authenticate and validate the benefits of the proposed control scheme.
Estimating the Proportion of True Null Hypotheses in Multiple Testing Problems
Authors: Oyeniran Oluyemi , Chen Hanfeng
Published: December 2016

The problem of estimating the proportion,π0, of the true null hypotheses in a multiple testing problem is important in cases where large scale parallel hypotheses tests are performed independently. While the problem is a quantity of interest in its own right in applications, the estimate ofπ0can be used for assessing or controlling an overall false discovery rate. In this article, we develop an innovative nonparametric maximum likelihood approach to estimateπ0. The nonparametric likelihood is proposed to be restricted to multinomial models and an EM algorithm is also developed to approximate the estimate ofπ0. Simulation studies show that the proposed method outperforms other existing methods. Using experimental microarray datasets, we demonstrate that the new method provides satisfactory estimate in practice.
Cardiovascular Autonomic Dysfunction in Patients of Nonalcoholic Fatty Liver Disease
Authors: Kumar Mavidi Sunil , Singh Akanksha , Jaryal Ashok Kumar , Ranjan Piyush , Deepak K. K. , Sharma Sanjay , Lakshmy R. , Pandey R. M. , Vikram Naval K.
Published: December 2016

Aim. The present study was designed to evaluate the heart rate variability (HRV) in nonalcoholic fatty liver disease (NAFLD) and to assess the effect of grade of NAFLD and diabetic status on HRV. Methods. This cross-sectional study included 75 subjects (25 NAFLD without diabetes, 25 NAFLD with diabetes, and 25 controls). Measurements included anthropometry, body composition analysis, estimation of plasma glucose, serum lipids, hsCRP, and serum insulin. HRV analysis was performed in both time and frequency domains. Results. The time and frequency domain indices of overall variability (SDNN, total power) were significantly lower in NAFLD with diabetes as compared to the controls. However, the LF : HF ratio did not differ among the three groups. The variables related to obesity, lipid profile, and glucose metabolism were also higher in NAFLD with diabetes and those with Grade II NAFLD without diabetes, as compared to controls. Multivariate stepwise regression analysis showed a negative correlation between HRV and total cholesterol and fat percentage. Conclusion. The grade of NAFLD as well as diabetic status contributes to the decrease in the cardiovascular autonomic function, with diabetic status rather than grade of NAFLD playing a critical role. Serum lipids and adiposity may also contribute to cardiac autonomic dysfunction.
Appearances Are Deceiving: Observing the World as It Looks and How It Really Is—Theory of Mind Performances Investigated in 3-, 4-, and 5-Year-Old Children
Authors: Bigozzi Lucia , Di Cosimo Alessandra , Vettori Giulia
Published: December 2016

Appearance-reality (AR) distinction understanding in preschoolers is worth of further consideration. This also goes for its relationship with false-belief (FB) understanding. This study helped fill these gaps by assessing 3-, 4-, and 5-year-old children’s performances on an appearance-reality distinction task and by investigating relationships with unexpected location, deceptive content, and deception comprehension task performances. 91 preschoolers participated in this study divided into 3 groups: (1) 37 children, M-age 3.4 years; (2) 23 children, M-age 4.5 years; (3) 31 children, M-age 5.4 years. A developmental trend was found where appearance-reality distinction understanding was significantly influenced by age. If wrong answers were particularly high by 3-year-old children, they greatly decreased by 4- and 5-year-old children. 3-year-old children also tended to fail in FB tasks; instead 4- and 5-year-old children performed AR tasks better than FB tasks. Theoretical and practical implications were discussed.
Pharmacological Inhibition of NLRP3 Inflammasome Attenuates Myocardial Ischemia/Reperfusion Injury by Activation of RISK and Mitochondrial Pathways
Authors: Mastrocola Raffaella , Penna Claudia , Tullio Francesca , Femminò Saveria , Nigro Debora , Chiazza Fausto , Serpe Loredana , Collotta Debora , Alloatti Giuseppe , Cocco Mattia , Bertinaria Massimo , Pagliaro Pasquale , Aragno Manuela , Collino Massimo
Published: December 2016

Although the nucleotide‐binding oligomerization domain‐ (NOD‐) like receptor pyrin domain containing 3 (NLRP3) inflammasome has been recently detected in the heart, its role in cardiac ischemia/reperfusion (IR) is still controversial. Here, we investigate whether a pharmacological modulation of NLRP3 inflammasome exerted protective effects in an ex vivo model of IR injury. Isolated hearts from male Wistar rats (5‐6 months old) underwent ischemia (30 min) followed by reperfusion (20 or 60 min) with and without pretreatment with the recently synthetized NLRP3 inflammasome inhibitor INF4E (50 μM, 20 min before ischemia). INF4E exerted protection against myocardial IR, shown by a significant reduction in infarct size and lactate dehydrogenase release and improvement in postischemic left ventricular pressure. The formation of the NLRP3 inflammasome complex was induced by myocardial IR and attenuated by INF4E in a time‐dependent way. Interestingly, the hearts of the INF4E‐pretreated animals displayed a marked improvement of the protective RISK pathway and this effect was associated increase in expression of markers of mitochondrial oxidative phosphorylation. Our results demonstrate for the first time that INF4E protected against the IR‐induced myocardial injury and dysfunction, by a mechanism that involves inhibition of the NLRP3 inflammasome, resulting in the activation of the prosurvival RISK pathway and improvement in mitochondrial function.
Hypertension, an Emerging Problem in Rural Cameroon: Prevalence, Risk Factors, and Control
Authors: Arrey Walters Tabi , Dimala Christian Akem , Atashili Julius , Mbuagbaw Josephine , Monekosso Gottlieb Lobe
Published: December 2016

Background. Despite the increasing trends suggesting that hypertension is a growing public health problem in developing countries, studies on its prevalence, associated risk factors, and extent of blood pressure control have been inequitably done in urban and rural communities in these countries. We therefore aimed to determine the prevalence of hypertension and extent of blood pressure control in rural Cameroon. Methods. This was a community-based cross-sectional study conducted in rural Cameroon (the Moliwe Health Area). Participants aged 21 years and above were recruited by a probability proportional to size multistage sampling method, using systematic sampling for household selection and random sampling for participant selection. Blood pressure, weight, and height were measured by standard methods. Hypertension was defined as BP ≥ 140/90 mmHg. Results. The prevalence of hypertension among the 733 participants recruited was 31.1% (95% CI: 27.8–34.6) and 71% (95% CI: 58.7–81.7) of these hypertensive patients were newly diagnosed. Only 21.2% (95% CI: 12.1–33.3) of known hypertensives had a well controlled BP. Age, obesity, low educational status, and being married were associated with HTN after adjusting for confounders. Conclusions. The high prevalence of hypertension and inadequate BP control among known hypertensives in rural Cameroon warrants greater sensitization and regular screening to reduce hypertension-related morbidity and mortality.
Immunosuppression Induced by Chronic Inflammation and the Progression to Oral Squamous Cell Carcinoma
Authors: Sun Yujuan , Liu Nan , Guan Xiaobing , Wu Hongru , Sun Zheng , Zeng Hui
Published: December 2016

Oral squamous cell carcinoma (OSCC) is an aggressive, invasive malignancy of epithelial origin. The progression from premalignant lesions—oral leukoplakia (OLK) and oral lichen planus (OLP)—to OSCC involves complex inflammatory processes that have not been elucidated. We investigated the roles of inflammatory mediators and infiltrating immunocytes in the pathogenic progression of OLK and OLP to OSCC. The occurrence of regulatory T-cells (Tregs) and tumor-associated macrophages (TAMs) and the expression of anti-inflammatory cytokines and proinflammatory cytokines were investigated in OLK, OLP, and OSCC tissues. Immunohistochemical staining of CD4, FOXP3, CD68, TGF-β1, IL-10, IL-4, IFN-γ, and MCP-1 showed that the occurrence of Tregs and TAMs increased in parallel with disease progression in OLK and OSCC. IL-10 gradually increased during the early stages of OLK and in OSCC. Infiltrating IL-4+macrophages were seen with increasing frequency in OLK tissue during the progression of oral dysplasia. Fewer TGF-β1+macrophages were seen in OSCC than in OLK and OLP. The expression of IFN-γdecreased gradually with the OLK development and had the lowest expression in OSCC. MCP-1 expression did not change significantly during the development of OSCC. The results suggested that the immunosuppression induced by chronic inflammation promotes tumorigenesis in OSCC, rather than initiating it.
Nanoscale Continuum Modelling of Carbon Nanotubes by Polyhedral Finite Elements
Authors: Perumal Logah , Leng Lim Thong , Tso C. P.
Published: December 2016

As the geometry of a cell of carbon nanotube is hexagonal, a new approach is presented in modelling of single-walled carbon nanotubes using polyhedral finite elements. Effect of varying length, diameter, and thickness of carbon nanotubes on Young’s modulus is studied. Both armchair and zigzag configurations are modelled and simulated in Mathematica. Results from current approach found good agreement with the other published data.
Synthesis of Novel Heterocyclic Imine Type UV Absorbers for Application on Cotton Based Textile Materials
Authors: Ocal Nuket , Aker Acelya , Ergindemir Hikmet Nil , Hamitbeyli Agamirze
Published: December 2016

Novel Schiff bases with the potential to exhibit biologically active and UV absorption properties were synthesized. Their application on cotton based textile materials was performed and the UV protection factor (UPF) values and the antibacterial features of the treated fabrics were measured.
Cotard’s Syndrome in a Patient with Schizophrenia: Case Report and Review of the Literature
Authors: Huarcaya-Victoria Jeff , Ledesma-Gastañadui Mario , Huete-Cordova Maria
Published: December 2016

Jules Cotard described, in 1880, the case of a patient characterized by delusions of negation, immortality, and guilt as well as melancholic anxiety among other clinical features. Later this constellation of symptoms was given the eponym Cotard’s syndrome, going through a series of theoretical vicissitudes, considering itself currently as just the presence of nihilistic delusions. The presentation of the complete clinical features described by Cotard is a rare occurrence, especially in the context of schizophrenia. Here we present the case of a 50-year-old male patient with schizophrenia who developed Cotard’s syndrome. The patient was treated with aripiprazole, showing improvement after two weeks of treatment. A review of the literature is performed about this case.
Deciphering the Translation Initiation Factor 5A Modification Pathway in Halophilic Archaea
Authors: Prunetti Laurence , Graf Michael , Blaby Ian K. , Peil Lauri , Makkay Andrea M. , Starosta Agata L. , Papke R. Thane , Oshima Tairo , Wilson Daniel N. , de Crécy-Lagard Valérie
Published: December 2016

Translation initiation factor 5A (IF5A) is essential and highly conserved in Eukarya (eIF5A) and Archaea (aIF5A). The activity of IF5A requires hypusine, a posttranslational modification synthesized in Eukarya from the polyamine precursor spermidine. Intracellular polyamine analyses revealed that agmatine and cadaverine were the main polyamines produced inHaloferax volcaniiin minimal medium, raising the question of how hypusine is synthesized in this halophilic Archaea. Metabolic reconstruction led to a tentative picture of polyamine metabolism and aIF5A modification inHfx. volcaniithat was experimentally tested. Analysis of aIF5A fromHfx. volcaniiby LC-MS/MS revealed it was exclusively deoxyhypusinylated. Genetic studies confirmed the role of the predicted arginine decarboxylase gene(HVO_1958)in agmatine synthesis. The agmatinase-like gene(HVO_2299)was found to be essential, consistent with a role in aIF5A modification predicted by physical clustering evidence. Recombinant deoxyhypusine synthase (DHS) fromS. cerevisiaewas shown to transfer 4-aminobutyl moiety from spermidine to aIF5A fromHfx. volcanii in vitro.However, at least under conditions tested, this transfer was not observed with theHfx. volcaniiDHS. Furthermore, the growth ofHfx. volcaniiwas not inhibited by the classical DHS inhibitor GC7. We propose a model of deoxyhypusine synthesis inHfx. volcaniithat differs from the canonical eukaryotic pathway, paving the way for further studies.
Sociocultural Determinants to Adoption of Safe Water, Sanitation, and Hygiene Practices in Nyakach, Kisumu County, Kenya: A Descriptive Qualitative Study
Authors: Wasonga Job , Okowa Mark , Kioli Felix
Published: December 2016

Provision of safe water, adequate sanitation, and hygiene has been lauded as one way of preventing diarrheal infections and improving health especially in developing countries. However, lack of safe water, inadequate sanitation, and poor hygiene practices in most parts of rural Kenya have posed a challenge that exposes the populace to diarrhea cases and possible deaths. In this regard, many nongovernmental organizations and governmental agencies have tried to provide water, sanitation, and hygiene services with poor results. This study was conducted using qualitative research methods in Central Nyakach in Kisumu County, Kenya. The methods were focus group discussions (FGD), key informant interviews (KII), and observation of homesteads. The data were then analyzed thematically. Findings revealed that water issues are gendered and its use is socially and culturally categorized. Water storage is affected by traditions such as use of a clay pot, while sanitation and hygiene issues are ritualized and bound by taboos. Latrines are majorly constructed by men and sharing the same with in-laws and older children is prohibited. Children faeces are thrown out in the open fields as a means of disposal and hand washing with soap is nonexistent, since it is believed that doing so would make a person lose the ability to rear livestock. The implications of these findings are that some of these sociocultural practices have a profound effect on health of the population. This affects health care delivery through high incidence rates of disease, encourages “unhealthy” environments through open defecation and pollution, and negates the government’s commitment to national and international policies on universal health care provision.
Complications, Not Minimally Invasive Surgical Technique, Are Associated with Increased Cost after Esophagectomy
Authors: Fu Sue J. , Ho Vanessa P. , Ginsberg Jennifer , Perry Yaron , Delaney Conor P. , Linden Philip A. , Towe Christopher W.
Published: December 2016

Background. Minimally invasive esophagectomy (MIE) techniques offer similar oncological and surgical outcomes to open methods. The effects of MIE on hospital costs are not well documented. Methods. We reviewed the electronic records of patients who underwent esophagectomy at a single academic institution between January 2012 and December 2014. Esophagectomy techniques were grouped into open, hybrid, MIE, and transhiatal (THE) esophagectomy. Univariate and multivariate analyses were performed to assess the impact of surgery on total hospital cost after esophagectomy. Results. 80 patients were identified: 11 THE, 11 open, 41 hybrid, and 17 MIE. Median total cost of the hospitalization was $31,375 and was similar between surgical technique groups. MIE was associated with higher intraoperative costs, but not total hospital cost. Multivariable analysis revealed that the presence of a complication, increased age, American Society of Anesthesiologists class IV (ASA4), and preoperative coronary artery disease (CAD) were associated with significantly increased cost. Conclusions. Despite the association of MIE with higher operation costs, the total hospital cost was not different between surgical technique groups. Postoperative complications and severe preoperative comorbidities are significant drivers of hospital cost associated with esophagectomy. Surgeons should choose technique based on clinical factors, rather than cost implications.
Comparisons of Curative Effects of Chlorophyll fromSauropus androgynus(L) Merr Leaf Extract and Cu-Chlorophyllin on Sodium Nitrate-Induced Oxidative Stress in Rats
Authors: Suparmi Suparmi , Fasitasari Minidian , Martosupono Martanto , Mangimbulude Jubhar Christian
Published: December 2016

Sodium nitrate (NaNO2) widely used as food additive for coloring and preserving meat has been reported to induce oxidative stress and cause histopathologic changes, nitrosative tissue damage, and lipid peroxidation in liver and kidney. Therefore, the present study compared the curative effect of chlorophyll fromSauropus androgynus(L) Merr and Cu-chlorophyllin as antioxidant in NaNO2-induced female Wistar rats based on haematological, serum biochemical, and histological evaluation. Thirty male Wistar rats were randomly assigned into six groups of five rats each. NaNO2were given at a subacute dose of 50 mg/kg bw intraperitoneally for 10 days. Chlorophyll fromS. androgynusand Cu-chlorophyllin from K-Liquid™ were given in the following 14 days at the two doses: 0,016 mg/mL and 0.008 mg/mL. NaNO2exposure resulted in significant reductions (p<0.05) in values of packed cell volume (PCV), haemoglobin (Hb) concentration and red blood cell (RBC) count, transferrin, and ferritin and elevation in malondialdehyde (MDA) level and schistocytes percentage with insignificant reductions in serum albumin and transferrin levels. Histology of kidney and liver were changed insignificantly (p>0.05) to normal values. Chlorophyll fromS. androgynusand Cu-chlorophyllin possess antioxidant potentials to protect against toxicities induced by sodium nitrate.
Pain Induced during Both the Acquisition and Retention Phases of Locomotor Adaptation Does Not Interfere with Improvements in Motor Performance
Authors: Bouffard Jason , Bouyer Laurent J. , Roy Jean-Sébastien , Mercier Catherine
Published: December 2016

Cutaneous pain experienced during locomotor training was previously reported to interfere with retention assessed in pain-free conditions. To determine whether this interference reflects consolidation deficits or a difficulty to transfer motor skills acquired in the presence of pain to a pain-free context, this study evaluated the effect of pain induced during both the acquisition and retention phases of locomotor learning. Healthy participants performed a locomotor adaptation task (robotized orthosis perturbing ankle movements during swing) on two consecutive days. Capsaicin cream was applied around participants’ ankle on both days for the Pain group, while the Control group was always pain-free. Changes in movement errors caused by the perturbation were measured to assess global motor performance; temporal distribution of errors and electromyographic activity were used to characterize motor strategies. Pain did not interfere with global performance during the acquisition or the retention phases but was associated with a shift in movement error center of gravity to later in the swing phase, suggesting a reduction in anticipatory strategy. Therefore, previously reported retention deficits could be explained by contextual changes between acquisition and retention tests. This difficulty in transferring skills from one context to another could be due to pain-related changes in motor strategy.
CXCL4 Contributes to the Pathogenesis of Chronic Liver Allograft Dysfunction
Authors: Li Jing , Liu Bin , Shi Yuan , Xie Ke-Liang , Yin Hai-Fang , Yan Lu-nan , Lau Wan-yee , Wang Guo-Lin
Published: December 2016

Chronic liver allograft dysfunction (CLAD) remains the most common cause of patient morbidity and allograft loss in liver transplant patients. However, the pathogenesis of CLAD has not been completely elucidated. By establishing rat CLAD models, in this study, we identified the informative CLAD-associated genes using isobaric tags for relative and absolute quantification (iTRAQ) proteomics analysis and validated these results in recipient rat liver allografts. CXCL4, CXCR3, EGFR, JAK2, STAT3, and Collagen IV were associated with CLAD pathogenesis. We validated that CXCL4 is upstream of these informative genes in the isolated hepatic stellate cells (HSC). Blocking CXCL4 protects against CLAD by reducing liver fibrosis. Therefore, our results indicated that therapeutic approaches that neutralize CXCL4, a newly identified target of fibrosis, may represent a novel strategy for preventing and treating CLAD after liver transplantation.