bluuebunny/crossref_metadata_2025 huggingface dataset:
Sildenafil reduces polyuria in rats with lithium-induced NDI
Authors: Sanches Talita Rojas , Volpini Rildo Aparecido , Massola Shimizu Maria H. , Bragança Ana Carolina de , Oshiro-Monreal Fabíola , Seguro Antonio Carlos , Andrade Lúcia
Published: October 2011

Lithium (Li)-treated patients often develop urinary concentrating defect and polyuria, a condition known as nephrogenic diabetes insipidus (NDI). In a rat model of Li-induced NDI, we studied the effect that sildenafil (Sil), a phosphodiesterase 5 (PDE5) inhibitor, has on renal expression of aquaporin-2 (AQP2), urea transporter UT-A1, Na+/H+exchanger 3 (NHE3), Na+-K+-2Cl−cotransporter (NKCC2), epithelial Na channel (ENaC; α-, β-, and γ-subunits), endothelial nitric oxide synthase (eNOS), and inducible nitric oxide synthase. We also evaluated cGMP levels in medullary collecting duct cells in suspension. For 4 wk, Wistar rats received Li (40 mmol/kg food) or no treatment (control), some receiving, in weeks 2–4, Sil (200 mg/kg food) or Li and Sil (Li+Sil). In Li+Sil rats, urine output and free water clearance were markedly lower, whereas urinary osmolality was higher, than in Li rats. The cGMP levels in the suspensions of medullary collecting duct cells were markedly higher in the Li+Sil and Sil groups than in the control and Li groups. Semiquantitative immunoblotting revealed the following: in Li+Sil rats, AQP2 expression was partially normalized, whereas that of UT-A1, γ-ENaC, and eNOS was completely normalized; and expression of NKCC2 and NHE3 was significantly higher in Li rats than in controls. Inulin clearance was normal in all groups. Mean arterial pressure and plasma arginine vasopressin did not differ among the groups. Sil completely reversed the Li-induced increase in renal vascular resistance. We conclude that, in experimental Li-induced NDI, Sil reduces polyuria, increases urinary osmolality, and decreases free water clearance via upregulation of renal AQP2 and UT-A1.
Coding of sound direction in the auditory periphery of the lake sturgeon,Acipenser fulvescens
Authors: Meyer Michaela , Popper Arthur N. , Fay Richard R.
Published: October 2011

The lake sturgeon, Acipenser fulvescens, belongs to one of the few extant nonteleost ray-finned fishes and diverged from the main vertebrate lineage about 250 million years ago. The aim of this study was to use this species to explore the peripheral neural coding strategies for sound direction and compare these results to modern bony fishes (teleosts). Extracellular recordings were made from afferent neurons innervating the saccule and lagena of the inner ear while the fish was stimulated using a shaker system. Afferents were highly directional and strongly phase locked to the stimulus. Directional response profiles resembled cosine functions, and directional preferences occurred at a wide range of stimulus intensities (spanning at least 60 dB re 1 nm displacement). Seventy-six percent of afferents were directionally selective for stimuli in the vertical plane near 90° (up down) and did not respond to horizontal stimulation. Sixty-two percent of afferents responsive to horizontal stimulation had their best axis in azimuths near 0° (front back). These findings suggest that in the lake sturgeon, in contrast to teleosts, the saccule and lagena may convey more limited information about the direction of a sound source, raising the possibility that this species uses a different mechanism for localizing sound. For azimuth, a mechanism could involve the utricle or perhaps the computation of arrival time differences. For elevation, behavioral strategies such as directing the head to maximize input to the area of best sensitivity may be used. Alternatively, the lake sturgeon may have a more limited ability for sound source localization compared with teleosts.
Contribution of intrinsic properties and synaptic inputs to motoneuron discharge patterns: a simulation study
Authors: Powers Randall K. , ElBasiouny Sherif M. , Rymer W. Zev , Heckman C. J.
Published: October 2011

Motoneuron discharge patterns reflect the interaction of synaptic inputs with intrinsic conductances. Recent work has focused on the contribution of conductances mediating persistent inward currents (PICs), which amplify and prolong the effects of synaptic inputs on motoneuron discharge. Certain features of human motor unit discharge are thought to reflect a relatively stereotyped activation of PICs by excitatory synaptic inputs; these features include rate saturation and de-recruitment at a lower level of net excitation than that required for recruitment. However, PIC activation is also influenced by the pattern and spatial distribution of inhibitory inputs that are activated concurrently with excitatory inputs. To estimate the potential contributions of PIC activation and synaptic input patterns to motor unit discharge patterns, we examined the responses of a set of cable motoneuron models to different patterns of excitatory and inhibitory inputs. The models were first tuned to approximate the current- and voltage-clamp responses of low- and medium-threshold spinal motoneurons studied in decerebrate cats and then driven with different patterns of excitatory and inhibitory inputs. The responses of the models to excitatory inputs reproduced a number of features of human motor unit discharge. However, the pattern of rate modulation was strongly influenced by the temporal and spatial pattern of concurrent inhibitory inputs. Thus, even though PIC activation is likely to exert a strong influence on firing rate modulation, PIC activation in combination with different patterns of excitatory and inhibitory synaptic inputs can produce a wide variety of motor unit discharge patterns.
Distribution of eye position information in the monkey inferior colliculus
Authors: Bulkin David A. , Groh Jennifer M.
Published: October 2011

The inferior colliculus (IC) is thought to have two main subdivisions, a central region that forms an important stop on the ascending auditory pathway and a surrounding shell region that may play a more modulatory role. In this study, we investigated whether eye position affects activity in both the central and shell regions. Accordingly, we mapped the location of eye position-sensitive neurons in six monkeys making spontaneous eye movements by sampling multiunit activity at regularly spaced intervals throughout the IC. We used a functional map based on auditory response patterns to estimate the anatomical location of recordings, in conjunction with structural MRI and histology. We found eye position-sensitive sites throughout the IC, including at 27% of sites in tonotopically organized recording penetrations (putatively the central nucleus). Recordings from surrounding tissue showed a larger proportion of sites indicating an influence of eye position (33–43%). When present, the magnitude of the change in activity due to eye position was often comparable to that seen for sound frequency. Our results indicate that the primary ascending auditory pathway is influenced by the position of the eyes. Because eye position is essential for visual-auditory integration, our findings suggest that computations underlying visual-auditory integration begin early in the ascending auditory pathway.
Endothelin Receptor Antagonists for the Treatment of Raynaud's Phenomenon and Digital Ulcers in Systemic Sclerosis
Authors: Arefiev Kait , Fiorentino David F. , Chung Lorinda
Published: October 2011

Systemic sclerosis is a connective tissue disease characterized by fibrosis of the skin, internal organs, and widespread vasculopathy. Raynaud's phenomenon and digital ulcers are vascular manifestations of this disease and cause significant morbidity. Current treatments are only moderately effective in reducing the severity of Raynaud's in a portion of patients and typically do not lead to substantial benefit in terms of the healing or prevention of digital ulcers. Several studies have evaluated the efficacy of targeting the vasoconstrictor endothelin-1 for the treatment of systemic sclerosis-associated vascular disease. The purpose of this paper is to summarize the published studies and case reports evaluating the efficacy of endothelin receptor antagonists in the treatment of Raynaud's phenomenon and digital ulcers associated with systemic sclerosis.
Convergence and Divergence of the Solutions of a Neutral Difference Equation
Authors: Chatzarakis G. E. , Miliaras G. N.
Published: October 2011

We investigate the asymptotic behavior of the solutions of a neutral type difference equation of the form Δ[x(n) + cx(τ(n))] + p(n)x(σ(n)) = 0, where τ(n) is a general retarded argument, σ(n) is a general deviated argument (retarded or advanced), c ∈ ℝ, (p(n)) n≥0 is a sequence of positive real numbers such that p(n) ≥ p, p ∈ ℝ+, and Δ denotes the forward difference operator Δx(n) = x(n + 1) − x(n). Also, we examine the asymptotic behavior of the solutions in case they are
continuous and differentiable with respect to c.
P‐Stable Higher Derivative Methods with Minimal Phase‐Lag for Solving Second Order Differential Equations
Authors: Hendi Fatheah A.
Published: October 2011

Some new higher algebraic order symmetric various‐step methods are introduced. For these methods a direct formula for the computation of the phase‐lag is given. Basing on this formula, calculation of free parameters is performed to minimize the phase‐lag. An explicit symmetric multistep method is presented. This method is of higher algebraic order and is fitted both exponentially and trigonometrically. Such methods are needed in various branches of natural science, particularly in physics, since a lot of physical phenomena exhibit a pronounced oscillatory behavior. Many exponentially‐fitted symmetric multistepmethods for the second‐order differential equation are already developed. The stability properties of several existing methods are analyzed, and a new P‐stable method is proposed, to establish the existence of methods to which our definition applies and to demonstrate its relevance to stiff oscillatory problems. The work is mainly concerned with two‐stepmethods but extensions tomethods of larger step‐number are also considered. To have an idea about its accuracy, we examine their phase properties. The efficiency of the proposed method is demonstrated by its application to well‐known periodic orbital problems. The new methods showed better stability properties than the previous ones.
Effect of Precuring Warming on Mechanical Properties of Restorative Composites
Authors: Nada Kareem , El-Mowafy Omar
Published: October 2011

To investigate the effect of prepolymerization warming on composites' mechanical properties, three composites were evaluated: Clearfil Majesty (CM) (Kuraray), Z-100 (3M/ESPE), and Light-Core (LC) (Bisco). Specimens were prepared from each composite at room temperature as control and 2 higher temperatures (37∘Cand54∘C) to test surface hardness (SH), compressive strength (CS), and diametral tensile strength (DTS). Data were statistically analyzed using ANOVA and Fisher's LSD tests. Results revealed that prewarming CM and Z100 specimens significantly improved their SH mean values (P<0.05). Prewarming also improved mean CS values of Z100 specimens (P<0.05). Furthermore, DTS mean value of CM prepared at52∘was significantly higher than that of room temperature specimens (P<0.05). KHN, CS, and DTS mean values varied significantly among the three composites. In conclusion, Prewarming significantly enhanced surface hardness of 2 composites. Prewarming also improved bulk properties of the composites; however, this improvement was significant in only some of the tested materials.
Molecular and Immunological Characterization ofStaphylococcus aureusin Pediatric Atopic Dermatitis: Implications for Prophylaxis and Clinical Management
Authors: Pascolini Chiara , Sinagra JoLinda , Pecetta Simone , Bordignon Valentina , De Santis Alessandra , Cilli Laura , Cafiso Viviana , Prignano Grazia , Capitanio Bruno , Passariello Claudio , Stefani Stefania , Cordiali-Fei Paola , Ensoli Fabrizio
Published: October 2011

S. aureusrepresents a critical cofactor in atopic dermatitis (AD). In this paper, the prevalence ofS. aureusinfection/colonization was evaluated in 117 children as well as in their cohabitants, in order to assess the value ofS. aureuscharacterization in predicting disease onset and severity and in providing indications for prophylaxis. Results showed that children with AD as well as their cohabitants had a significantly greater incidence ofS. aureusinfection/colonization as compared to controls. The genetic characterization showed a virtual identity of the bacteria strains collected at different sites of the patients with those found in the cohabitants, suggesting both a direct transmission between the nasal reservoir and the lesions in the same atopic subject and a risk for reinfection within family cohabitants. These data stress the need of preliminary laboratory assessment and posttherapy control in both AD patients and their close contacts for effectiveS. aureuseradication.
Successful Management of Pregnancy Complicated by Klippel-Trenaunay Syndrome Using MR Angiography-Based Evaluation
Authors: Tanaka Reiko , Fujita Yasuyuki , Ishibashi Hiasa Kana , Yumoto Yasuo , Hidaka Nobuhiro , Fukushima Kotaro , Wake Norio
Published: October 2011

Klippel-Trenaunay syndrome (KTS) is a rare congenital disease, and extensive cutaneous hemangiomas and abnormal venous vessels are characteristic. In our case, to manage her pregnancy with KTS, whole-body MRA was performed before delivery. A 29-year-old woman was referred at 28 weeks because of prominent vulvovaginal varicosities due to KTS. At 35 weeks, hypertrophy and multiple venous varicosities of her leg as well as massive vulvovaginal varicosities became prominent with a normal coagulation profile. Systematic MRAs revealed hemangiomas and varicosities in the right leg, the lower abdomen, and the pubic region, while no obvious AVM was detected around the bronchial tube and spine. We decided to deliver her baby by cesarean section at 37 weeks under general anesthesia, and a healthy baby was delivered. No blood transfusion was required. Prophylaxis against thrombosis was performed after the operation. She was discharged with her baby. Her vulvovaginal varicosities shrunk considerably one month later.
Periodicity in a Class of Systems of Delay Difference Equations
Authors: Wei Zhijian
Published: October 2011

We study a system of delay difference equations modeling four‐dimensional discrete‐time delayed neural networks with no internal decay. Such a discrete‐time system can be regarded as the discrete analog of a differential equation with piecewise constant argument. By using semicycle analysis method, it is shown that every bounded solution of this discrete‐time system is eventually periodic. The obtained results are new, and they complement previously known results.
Influence of Maternal Glycemia on Intrauterine Fetal Adiposity Distribution after a Normal Oral Glucose Tolerance Test at 28 Weeks Gestation
Authors: Farah Nadine , Hogan Jennifer , O'Dwyer Vicky , Stuart Bernard , Kennelly Mairead , Turner Michael J.
Published: October 2011

Objective. To examine the relationship between maternal glucose levels and intrauterine fetal adiposity distribution in women with a normal oral glucose tolerance test (OGTT) at 28 weeks gestation.Study Design. We recruited 231 women with a singleton pregnancy. At 28 and 37 weeks gestation, sonographic measurements of fetal body composition were performed. Multiple regression analysis was used to study the influence of different maternal variables on fetal adiposity distribution.Results. Maternal glucose levels correlated with the fetal abdominal subcutaneous tissue measurements (; ) and with birth weight (; ). Maternal glucose levels did not correlate with the fetal mid-thigh muscle thickness and mid-thigh subcutaneous tissue measurements.Conclusion. We found that in nondiabetic women maternal glucose levels not only influence fetal adiposity and birth weight, but also influence the distribution of fetal adiposity. This supports previous evidence that maternal glycemia is a key determinant of intrauterine fetal programming.
Diagnosis and Evaluation of Nonalcoholic Fatty Liver Disease
Authors: Obika Mikako , Noguchi Hirofumi
Published: October 2011

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of elevated liver function tests results, after the commonly investigated causes have been excluded, and frequently coexists with type 2 diabetes mellitus (T2DM) because the conditions have common risk factors. As both T2DM and NAFLD are related to adverse outcomes of the other, diagnosis and valuation of fatty liver is an important part of the management of diabetes. Although noninvasive methods, such as biomarkers, panel markers, and imaging, may support a diagnostic evaluation of NAFLD patients, accurate histopathological findings cannot be achieved without a liver biopsy. As it is important to know whether steatohepatitis and liver fibrosis are present for the management of NAFLD, liver biopsy remains the gold standard for NAFLD diagnosis and evaluation. Therefore, new investigations of the pathogenesis of NAFLD are necessary to develop useful biomarkers that could provide a reliable noninvasive alternative to liver biopsy.
Reduced Central Memory CD4+ T Cells and Increased T-Cell Activation Characterise Treatment-Naive Patients Newly Diagnosed at Late Stage of HIV Infection
Authors: Bai Francesca , Tincati Camilla , Merlini Esther , Pacioni Carlotta , Sinigaglia Elisabetta , Carpani Giovanni , d’Arminio Monforte Antonella , Marchetti Giulia
Published: October 2011

Objectives. We investigated immune phenotypes of HIV+ patients who present late, considering late presenters (LPs, CD4+ < 350/μL and/or AIDS), advanced HIV disease (AHD, CD4+ < 200/μL and/or AIDS), and AIDS presenters (AIDS-defining condition at presentation, independently from CD4+).Methods. Patients newly diagnosed with HIV at our clinic between 2007–2011 were enrolled. Mann-Whitney/Chi-squared tests and logistic regression were used for statistics.Results. 275 patients were newly diagnosed with HIV between January/2007–March/2011. 130 (47%) were LPs, 79 (29%) showed AHD, and 49 (18%) were AIDS presenters. LP, AHD, and AIDS presenters were older and more frequently heterosexuals. Higher CD8+%, lower CD127+CD4+%, higher CD95+CD8+%, CD38+CD8+%, and CD45R0+CD38+CD8+% characterized LP/AHD/AIDS presentation. In multivariate analysis, older age, heterosexuality, higher CD8+%, and lower CD127+CD4+% were confirmed associated with LP/AHD. Lower CD4+ and higher CD38+CD8+% resulted independently associated with AIDS presentation.Conclusions. CD127 downregulation and immune activation characterize HIV+ patients presenting late and would be studied as additional markers of late presentation.
Development of Mucosal Immunity in Children: A Rationale for Sublingual Immunotherapy?
Authors: Szczawinska-Poplonyk Aleksandra
Published: October 2011

The mucosal immune system has bidirectional tasks to mount an effective defense against invading harmful pathogens and to suppress the immune response to alimentary antigens and commensal bacterial flora. Oral tolerance is a suppression of the mucosal immune pathway related to a specific immunophenotype of the dendritic cells and an induction of the regulatory T cells as well as with the silencing of the effector T cell response by anergy and deletion. The physiological dynamic process of the anatomical and functional maturation of the immune system occurring in children during pre- and postnatal periods is a significant factor, having an impact on the fine balance between the activation and the suppression of the immune response. In this paper, mechanisms of mucosal immunity and tolerance induction in terms of maturational issues are discussed with a special emphasis on the implications for a novel therapeutic intervention in allergic diseases via the sublingual route.
Premature Coronary Artery Disease and Familial Hypercholesterolemia: Need for Early Diagnosis and Cascade Screening in the Indian Population
Authors: Setia N. , Verma I. C. , Khan B. , Arora A.
Published: October 2011

Cardiovascular disease (CVD) is the leading cause of death in India, accounting for 28% of mortality. The average age of onset of CVD is younger (below 55 years) among Indians than in other populations. This may be due to bad lifestyle, genetic factors, or both. Hypertension, smoking, diabetes, and physical inactivity have been identified as modifiable risk factors for heart disease. Hypercholesterolemia is the most common and treatable cause of heart disease. Genetic factors that lead to hypercholesterolemia have not been fully studied in India. Familial Hypercholesterolemia results from mutations in the LDL receptor, ApoB, PCSK9, and ApoE genes. There is an urgent need to screen subjects with premature CAD and their relatives in India for the presence of FH, identify the mutations that lead to high cholesterol, and carry out cascade screening in the at-risk relatives. Those harbouring mutations in the above genes can be treated to lower the cholesterol levels, prevent early CVD, and avoid death. A programme based on these lines has been initiated in Delhi.
Suppressive Effect of Juzentaihoto on Vascularization Induced by B16 Melanoma CellsIn VitroandIn Vivo
Authors: Ishikawa Shintaro , Ishikawa Takako , Asano Kazuhito , Fujiwara Hiroshi , Okada Mayumi , Sunagawa Masataka , Hisamitsu Tadashi
Published: October 2011

Juzentaihoto (JTT) is well known to be one of Japanese herbal medicines, and used for the supplemental therapy of cancer patients with remarkable success. The present study, therefore, was undertaken to examine the possible therapeutic mechanisms of JTT on cancer using B16 melanoma cell (B16 cell)/experimental mouse system. JTT was well mixed with rodent chow at 3.0% concentrations, and was administered orally ad libitum. Administration of JTT was started one week before tumor cell injection and continued throughout the experiment. Administration of JTT into mice significantly inhibited tumor metastasis in lungs after intravenous injection of2×105B16 cells in a volume of 50 μL. JTT also significantly suppressed enlargement of tumor size in hind footpad after the subcutaneous injection of2×105(50 μL) B16 cells. In the second part of experiments, the chamber that containing B16 cells was buried in the murine back. In JTT administrated group, vascular endothelial growth factor (VEGF) of chamber internal fluid significantly decreased, and vascularization of chamber circumference was also inhibited. These results strongly suggest that oral administration of JTT caused decrease in the generation of VEGF, which is responsible for vascularization, and results in inhibition of B16 cell metastasis.
miRNA Expression Profiling Enables Risk Stratification in Archived and Fresh Neuroblastoma Tumor Samples
Authors: De Preter Katleen , Mestdagh Pieter , Vermeulen Joëlle , Zeka Fjoralba , Naranjo Arlene , Bray Isabella , Castel Victoria , Chen Caifu , Drozynska Elzbieta , Eggert Angelika , Hogarty Michael D. , Iżycka-Swieszewska Ewa , London Wendy B. , Noguera Rosa , Piqueras Marta , Bryan Kenneth , Schowe Benjamin , van Sluis Peter , Molenaar Jan J. , Schramm Alexander , Schulte Johannes H. , Stallings Raymond L. , Versteeg Rogier , Laureys Geneviève , Van Roy Nadine , Speleman Frank , Vandesompele Jo
Published: October 2011

Purpose: More accurate assessment of prognosis is important to further improve the choice of risk-related therapy in neuroblastoma (NB) patients. In this study, we aimed to establish and validate a prognostic miRNA signature for children with NB and tested it in both fresh frozen and archived formalin-fixed paraffin-embedded (FFPE) samples.

Experimental Design: Four hundred-thirty human mature miRNAs were profiled in two patient subgroups with maximally divergent clinical courses. Univariate logistic regression analysis was used to select miRNAs correlating with NB patient survival. A 25-miRNA gene signature was built using 51 training samples, tested on 179 test samples, and validated on an independent set of 304 fresh frozen tumor samples and 75 archived FFPE samples.

Results: The 25-miRNA signature significantly discriminates the test patients with respect to progression-free and overall survival (P < 0.0001), both in the overall population and in the cohort of high-risk patients. Multivariate analysis indicates that the miRNA signature is an independent predictor of patient survival after controlling for current risk factors. The results were confirmed in an external validation set. In contrast to a previously published mRNA classifier, the 25-miRNA signature was found to be predictive for patient survival in a set of 75 FFPE neuroblastoma samples.

Conclusions: In this study, we present the largest NB miRNA expression study so far, including more than 500 NB patients. We established and validated a robust miRNA classifier, able to identify a cohort of high-risk NB patients at greater risk for adverse outcome using both fresh frozen and archived material. Clin Cancer Res; 17(24); 7684–92. ©2011 AACR.
Abnormal MicroRNA Expression in Ts65Dn Hippocampus and Whole Blood: Contributions to Down Syndrome Phenotypes
Authors: Keck-Wherley Jennifer , Grover Deepak , Bhattacharyya Sharmistha , Xu Xiufen , Holman Derek , Lombardini Eric D. , Verma Ranjana , Biswas Roopa , Galdzicki Zygmunt
Published: October 2011

Down syndrome (DS; trisomy 21) is one of the most common genetic causes of intellectual disability, which is attributed to triplication of genes located on chromosome 21. Elevated levels of several microRNAs (miRNAs) located on chromosome 21 have been reported in human DS heart and brain tissues. The Ts65Dn mouse model is the most investigated DS model with a triplicated segment of mouse chromosome 16 harboring genes orthologous to those on human chromosome 21. Using ABI TaqMan miRNA arrays, we found a set of miRNAs that were significantly up- or downregulated in the Ts65Dn hippocampus compared to euploid controls. Furthermore, miR-155 and miR-802 showed significant overexpression in the Ts65Dn hippocampus, thereby confirming results of previous studies. Interestingly, miR-155 and miR-802 were also overexpressed in the Ts65Dn whole blood but not in lung tissue. We also found overexpression of the miR-155 precursors, pri- and pre-miR-155 derived from the miR-155 host gene, known as B cell integration cluster, suggesting enhanced biogenesis of miR-155. Bioinformatic analysis revealed that neurodevelopment, differentiation of neuroglia, apoptosis, cell cycle, and signaling pathways including ERK/MAPK, protein kinase C, phosphatidylinositol 3-kinase, m-TOR and calcium signaling are likely targets of these miRNAs. We selected some of these potential gene targets and found downregulation of mRNA encoding Ship1, Mecp2 and Ezh2 in Ts65Dn hippocampus. Interestingly, the miR-155 target gene Ship1 (inositol phosphatase) was also downregulated in Ts65Dn whole blood but not in lung tissue. Our findings provide insights into miRNA-mediated gene regulation in Ts65Dn mice and their potential contribution to impaired hippocampal synaptic plasticity and neurogenesis, as well as hemopoietic abnormalities observed in DS.
Inhibition of X-Linked Inhibitor of Apoptosis with Embelin Differentially Affects Male versus Female Behavioral Outcome following Neonatal Hypoxia-Ischemia in Rats
Authors: Hill C.A. , Alexander M.L. , McCullough L.D. , Fitch R.H.
Published: October 2011

Hypoxia-ischemia (HI; concurrent oxygen/blood deficiency) and associated encephalopathy represent a common cause of neurological injury in premature/low-birth-weight infants and term infants with birth complications. Resulting behavioral impairments include cognitive and/or sensory processing deficits, as well as language disabilities, and clinical evidence shows that male infants with HI exhibit more severe cognitive deficits compared to females with equivalent injury. Evidence also demonstrates activation of sex-dependent apoptotic pathways following HI events, with males preferentially activating a caspase-independent cascade of cell death and females preferentially activating a caspase-dependent cascade following neonatal hypoxic and/or ischemic insults. Based on these combined data, the ‘female protection’ following HI injury may reflect the endogenous X-linked inhibitor of apoptosis (XIAP), which effectively binds effector caspases and halts downstream cleavage of effector caspases (thus reducing cell death). To test this theory, the current study utilized neonatal injections of vehicle or embelin (a small molecule inhibitor of XIAP) in male and female rats with or without induced HI injury on postnatal day 7 (P7). Subsequent behavioral testing using a clinically relevant task revealed that the inhibition of XIAP exacerbated HI-induced persistent behavioral deficits in females, with no effect on HI males. These results support sex differences in mechanisms of cell death following early HI injuries, and suggest a potential clinical benefit from the development of sex-specific neuroprotectants for the treatment of HI.
Quality of life in patients with systemic lupus erythematosus (SLE) compared with related controls within a unique African American population
Authors: Barnado A , Wheless L , Meyer AK , Gilkeson GS , Kamen DL
Published: October 2011

The patient’s perspective of how their health affects their function is health-related quality of life (HRQOL). HRQOL is poorer in patients with systemic lupus erythematosus (SLE). Few HRQOL studies in SLE patients have focused on African Americans despite an increased disease burden compared with Caucasians. The African American Gullah population of South Carolina has a homogeneous genetic and environmental background and a high prevalence of multi-patient families with SLE. Demographics, medical history, and Short-Form 36 (SF-36) were measured within a cohort of Gullah SLE cases and related controls. Compared with related controls ( n = 37), cases ( n = 89) had a lower Physical Component Summary (PCS, 41.8 vs. 52.3, p < 0.01), but not Mental Component Summary (MCS, 55.0 vs. 56.0, p = 0.70). The difference in PCS was no longer significant upon adjustment for working status, disability, and medical conditions. None of the 11 SLE American College of Rheumatology criteria, disease duration, or Systemic Lupus International Collaborating Clinics Damage Index were associated with either PCS or MCS. Cases and controls had similar MCS scores. We hypothesize that this lack of effect of SLE on MCS may be due to disease-coping mechanisms interplaying with cultural factors unique to the Gullah.
ASXL1 mutations identify a high-risk subgroup of older patients with primary cytogenetically normal AML within the ELN Favorable genetic category
Authors: Metzeler Klaus H. , Becker Heiko , Maharry Kati , Radmacher Michael D. , Kohlschmidt Jessica , Mrózek Krzysztof , Nicolet Deedra , Whitman Susan P. , Wu Yue-Zhong , Schwind Sebastian , Powell Bayard L. , Carter Thomas H. , Wetzler Meir , Moore Joseph O. , Kolitz Jonathan E. , Baer Maria R. , Carroll Andrew J. , Larson Richard A. , Caligiuri Michael A. , Marcucci Guido , Bloomfield Clara D.
Published: October 2011

The associations of mutations in the enhancer of trithorax and polycomb family gene ASXL1 with pretreatment patient characteristics, outcomes, and gene-/microRNA-expression profiles in primary cytogenetically normal acute myeloid leukemia (CN-AML) are unknown. We analyzed 423 adult patients for ASXL1 mutations, other prognostic gene mutations, and gene-/microRNA-expression profiles. ASXL1 mutations were 5 times more common in older (≥ 60 years) patients (16.2%) than those younger than 60 years (3.2%; P < .001). Among older patients, ASXL1 mutations associated with wild-type NPM1 (P < .001), absence of FLT3-internal tandem duplications (P = .002), mutated CEBPA (P = .01), and with inferior complete remission (CR) rate (P = .04), disease-free survival (DFS; P = .03), overall survival (OS; P = .006), and event-free survival (EFS; P = .002). Within the European LeukemiaNet (ELN) genetic categories of older CN-AML, ASXL1 mutations associated with inferior CR rate (P = .02), OS (P < .001), and EFS (P < .001) among ELN Favorable, but not among ELN Intermediate-I patients. Multivariable analyses confirmed associations of ASXL1 mutations with unfavorable CR rate (P = .03), DFS (P < .001), OS (P < .001), and EFS (P < .001) among ELN Favorable patients. We identified an ASXL1 mutation-associated gene-expression signature, but no microRNA-expression signature. This first study of ASXL1 mutations in primary CN-AML demonstrates that ASXL1mutated older patients, particularly within the ELN Favorable group, have unfavorable outcomes and may be candidates for experimental treatment approaches.
BioN∅T: A searchable database of biomedical negated sentences
Authors: Agarwal Shashank , Yu Hong , Kohane Issac
Published: October 2011

Background

Negated biomedical events are often ignored by text-mining applications; however, such events carry scientific significance. We report on the development of BioN∅T, a database of negated sentences that can be used to extract such negated events.

Description

Currently BioN∅T incorporates ≈32 million negated sentences, extracted from over 336 million biomedical sentences from three resources: ≈2 million full-text biomedical articles in Elsevier and the PubMed Central, as well as ≈20 million abstracts in PubMed. We evaluated BioN∅T on three important genetic disorders: autism, Alzheimer's disease and Parkinson's disease, and found that BioN∅T is able to capture negated events that may be ignored by experts.

Conclusions

The BioN∅T database can be a useful resource for biomedical researchers. BioN∅T is freely available at http://bionot.askhermes.org/ In future work, we will develop semantic web related technologies to enrich BioN∅T.
Exploring the contribution of efflux on the resistance to fluoroquinolones in clinical isolates of Staphylococcus aureus
Authors: Costa Sofia Santos , Falcão Celeste , Viveiros Miguel , Machado Diana , Martins Marta , Melo-Cristino José , Amaral Leonard , Couto Isabel
Published: October 2011

Background

Antimicrobial resistance mediated by efflux systems is still poorly characterized in Staphylococcus aureus, despite the description of several efflux pumps (EPs) for this bacterium. In this work we used several methodologies to characterize the efflux activity of 52 S. aureus isolates resistant to ciprofloxacin collected in a hospital in Lisbon, Portugal, in order to understand the role played by these systems in the resistance to fluoroquinolones.

Results

Augmented efflux activity was detected in 12 out of 52 isolates and correlated with increased resistance to fluoroquinolones. Addition of efflux inhibitors did not result in the full reversion of the fluoroquinolone resistance phenotype, yet it implied a significant decrease in the resistance levels, regardless of the type(s) of mutation(s) found in the quinolone-resistance determining region of grlA and gyrA genes, which accounted for the remaining resistance that was not efflux-mediated. Expression analysis of the genes coding for the main efflux pumps revealed increased expression only in the presence of inducing agents. Moreover, it showed that not only different substrates can trigger expression of different EP genes, but also that the same substrate can promote a variable response, according to its concentration. We also found isolates belonging to the same clonal type that showed different responses towards drug exposure, thus evidencing that highly related clinical isolates may diverge in the efflux-mediated response to noxious agents. The data gathered by real-time fluorometric and RT-qPCR assays suggest that S. aureus clinical isolates may be primed to efflux antimicrobial compounds.

Conclusions

The results obtained in this work do not exclude the importance of mutations in resistance to fluoroquinolones in S. aureus, yet they underline the contribution of efflux systems for the emergence of high-level resistance. All together, the results presented in this study show the potential role played by efflux systems in the development of resistance to fluoroquinolones in clinical isolates of S. aureus.
A large sustained endemic outbreak of multiresistant Pseudomonas aeruginosa: a new epidemiological scenario for nosocomial acquisition
Authors: Suarez Cristina , Peña Carmen , Arch Olga , Dominguez M Angeles , Tubau Fe , Juan Carlos , Gavaldá Laura , Sora Mercedes , Oliver Antonio , Pujol Miquel , Ariza Javier
Published: October 2011

Background

Studies of recent hospital outbreaks caused by multiresistant P.aeruginosa (MRPA) have often failed to identify a specific environmental reservoir. We describe an outbreak due to a single clone of multiresistant (MR) Pseudomonas aeruginosa (PA) and evaluate the effectiveness of the surveillance procedures and control measures applied.

Methods

Patients with MRPA isolates were prospectively identified (January 2006-May 2008). A combined surveillance procedure (environmental survey, and active surveillance program in intensive care units [ICUs]) and an infection control strategy (closure of ICU and urology wards for decontamination, strict compliance with cross-transmission prevention protocols, and a program restricting the use of carbapenems in the ICUs) was designed and implemented.

Results

Three hundred and ninety patients were identified. ICU patients were the most numerous group (22%) followed by urology patients (18%). Environmental surveillance found that 3/19 (16%) non-ICU environmental samples and 4/63 (6%) ICU samples were positive for the MRPA clonal strain. In addition, active surveillance found that 19% of patients were fecal carriers of MRPA. Significant changes in the trends of incidence rates were noted after intervention 1 (reinforcement of cleaning procedures): -1.16 cases/1,000 patient-days (95%CI -1.86 to -0.46; p = 0.003) and intervention 2 (extensive decontamination): -1.36 cases/1,000 patient-days (95%CI -1.88 to -0.84; p < 0.001) in urology wards. In addition, restricted use of carbapenems was initiated in ICUs (January 2007), and their administration decreased from 190-170 DDD/1,000 patient-days (October-December 2006) to 40-60 DDD/1,000 patient-days (January-April 2007), with a reduction from 3.1 cases/1,000 patient-days in December 2006 to 2.0 cases/1,000 patient-days in May 2007. The level of initial carbapenem use rose again during 2008, and the incidence of MRPA increased progressively once more.

Conclusions

In the setting of sustained MRPA outbreaks, epidemiological findings suggest that patients may be a reservoir for further environmental contamination and cross-transmission. Although our control program was not successful in ending the outbreak, we think that our experience provides useful guidance for future approaches to this problem.
Sequential thrombosis and bleeding in a woman with a prolonged activated partial thromboplastin time
Authors: Spencer Akpan , Pearce Michael I , Ames Paul RJ
Published: October 2011

Simultaneous or sequential haemorrhage and thrombosis in the presence of a prolonged activated partial thromboplastin time (aPTT) is a rare occurrence: we describe the case a 37 year old lady who developed post-delivery deep vein thrombosis treated with low molecular heparin and warfarin followed a week later by extensive bruising over legs and forearms, a significant drop in haemoglobin and a very prolonged aPTT. Further tests revealed an acquired factor VIII inhibitor at 35 Bethesda Units. We discuss the clinical and laboratory implications and provide a literature review of simultaneous thrombophilia and haemophilia in the presence of a prolonged aPTT.
The role of Pax6 in regulating the orientation and mode of cell division of progenitors in the mouse cerebral cortex
Authors: Asami Maki , Pilz Gregor A. , Ninkovic Jovica , Godinho Leanne , Schroeder Timm , Huttner Wieland B. , Götz Magdalena
Published: October 2011

Successful brain development requires tight regulation of sequential symmetric and asymmetric cell division. Although Pax6 is known to exert multiple roles in the developing nervous system, its role in the regulation of cell division is unknown. Here, we demonstrate profound alterations in the orientation and mode of cell division in the cerebral cortex of mice deficient in Pax6 function (Pax6Sey/Sey) or after acute induced deletion of Pax6. Live imaging revealed an increase in non-vertical cellular cleavage planes, resulting in an increased number of progenitors with unequal inheritance of the apical membrane domain and adherens junctions in the absence of Pax6 function. This phenotype appears to be mediated by the direct Pax6 target Spag5, a microtubule-associated protein, reduced levels of which result in the replication of the Pax6 phenotype of altered cell division orientation. In addition, lack of Pax6 also results in premature delamination of progenitor cells from the apical surface due to an overall decrease in proteins mediating anchoring at the ventricular surface. Moreover, continuous long-term imaging in vitro revealed that Pax6-deficient progenitors generate daughter cells with asymmetric fates at higher frequencies. These data demonstrate a cell-autonomous role for Pax6 in regulating the mode of cell division independently of apicobasal polarity and cell-cell interactions. Taken together, our work reveals several direct effects that the transcription factor Pax6 has on the machinery that mediates the orientation and mode of cell division.
Dynamic Behavior of Sand/Rubber Mixtures, Part II: Effect of Rubber Content on G/GO-γ-DT Curves and Volumetric Threshold Strain
Authors: Senetakis Kostas , Anastasiadis Anastasios , Pitilakis Kyriazis , Souli Argiro
Published: October 2011

This paper examines the strain-dependent dynamic properties (G/GO-logγ-DT curves) of dry and saturated sand–recycled rubber mixtures in a range of shearing strain amplitudes from (5 × 10−4) % to (6 × 10−1) % using a fixed-free torsional resonant column device. The effect of the rubber content on the pore water pressure buildup and volumetric threshold strain γtv of saturated mixtures, as well as the effect of specimens’ geometry on the experimental data, are also presented and discussed. Based on a comprehensive set of experimental results, a modified hyperbolic model, frequently used in practice, has been proposed. An increase in the rubber content leads to a more linear shape of the G/GO-logγ and DT-logγ curves and a reduction in the pore water pressure buildup. Damping is expressed in terms of DT-DTO, which eliminates the effect of the rubber content and the mean confining pressure. The final aim is to propose appropriate design G/GO-logγ-DT curves for sand–rubber mixtures currently used in practice.
Pilot Evaluation of a Biopsychosocial Integrated Standardized Patient Examination in a Family Medicine Clerkship
Authors: Morley Christopher P. , Flad Jennifer R. , Arthur Melissa , Recker-Hughes Carol , Barzee Kathleen A. , Bailey R. Eugene , Manyon Andrea T.
Published: October 2011

Objective:

A new biopsychosocial Integrated Standardized Patient Examination (ISPE) was implemented to assess communication skills for medical students participating in a family medicine clerkship.

Method:

Mixed method, multi-level evaluation.

Results:

Pilot ISPE scores were significantly higher than previous Objective Structured Clinical Examination (OSCE) ( p < .01). Family Physician and Social/Behavioral Scientist rater scores were correlated ( p < .001), and Cronbach's a statistics were acceptable (FM: α = .837; BH: α = .768). Preceptor scores on “relations with professionals” (β = .694, p = .008) significantly predicted ISPE scores, but other clerkship assignment grades were inversely associated with ISPE. Qualitative focus group themes included lack of readiness, divergence in beliefs on scope of physician practice, and focus on grade.

Conclusions:

This pilot project describes the process and demonstrates the possibility of implementing a complex standardized patient case to assess students' management of complicated primary care patients with medical, psychological, and social issues.
Pathohistological study of tumors in canine testes and ovarian in the period 1999-2003
Authors: Marinkovic Darko , Pavlovic Nebojsa , Magas Vladimir , Aleksic-Kovacevic Sanja
Published: October 2011

Testes and ovarian tumors are tumors which appear in small percentages in dogs. They rarely lead to a lethal outcome in animals, but, due to the different clinical manifestations that can accompany these tumors, their timely diagnosis is significant because it often determines the treatment of the animal in which such tumors were diagnosed. During the period from 1999 until 2003, the Department for Pathological Morphology of the Belgrade Faculty of Veterinary Medicine examined macroscopically and pathohistologically 5 ovaries with macroscopic signs of neoplastic changes from 5 female and 25 neoplastically altered testes from 18 male dogs. In the testes, seminom, collision tumor (Sertoli cell tumor), Sertoli cell tumor, Leydig cell tumor, and lymphosarcoma were diagnozed. In the ovaries, granulosa cell tumor and dysgerminoma were diagnozed.
Investigations of hemadsorption characteristics of glycoprotein HN and F antigens of Newcastle Disease virus envelope in vitro
Authors: Nisavic Jakov , Milic Nenad
Published: October 2011

The objective of these investigations was to examine the hemadsorption characteristics of glycoprotein HN and F antigens of the Newcastle Disease virus envelope. Six hours following inoculation of the cell line with the Newcastle Disease Vero virus, previously activated with 0.025 g/dl trypsin-versene, the appearance of hemadsorption was established in a smaller intensity in antigens diluted in ratios from 1:8 to 1:16. Hemadsorption was also determined in the mentioned cell lines 12 hours following inoculation in viruses diluted 1:64, while hemadsorption was present in virus dilutions of 1:256 after 24 hours. Inhibition of hemadsorption in inoculated cells with immune serum dilutions of 1:64 was established 24 hours following inoculation of the cell line with Vero samples of the Newcastle Disease virus, activated with trypsin-versene and the addition of specific immune serum.
Influence of puerperal gonadoreline application on reproductive parameter values in cows
Authors: Sabanovic Mustafa , Mutavelic Tarik , Suljkanovic Ahmet , Lazarevic Miodrag
Published: October 2011

This paper presents results of investigations conducted in order to investigate the influence of gonadoreline application 14-16, 17-20 and 21-25 days postpartum on reproductive parameters values in cows. A total of 241 cows was included in the study. Out of this number, 126 cows were treated with gonadoreline while 115 animals were placebo treated and served as controls. The estimation of progesterone concentration was conducted on 43 animals selected randomly from the first two groups of treated cows. Analyses of the results in cows that gave normal birth, revealed that mean anoestrus period, open day's period and intervals between calving were significantly lower in the gonadoreline treated groups. Reproductive parameter values in cows with different progesterone concentrations did not differ significantly. The period from gonadoreline application until conception, was shorter by 30, 30 and 14 days, respectively, compared to the controls. The total conception rate from the first three artificial inseminations was 88. 8% in gonadoreline treated groups and 83.47 % in the control groups.