bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Characterization of a Recombinant Manganese Superoxide Dismutase fromLactococcus lactisM4
Authors: Tan Boon Hooi , Chor Leow Thean , Foo Hooi Ling , Abdul Rahim Raha
Published: January 2014

A superoxide dismutase (SOD) gene ofLactococcus lactisM4 was cloned and expressed in a prokaryotic system. Sequence analysis revealed an open reading frame of 621 bp which codes for 206 amino acid residues. Expression ofsodAunder T7 promoter exhibited a specific activity of 4967 U/mg when induced with 1 mM of isopropyl-β-D-thiogalactopyranoside. The recombinant SOD was purified to homogeneity by immobilised metal affinity chromatography and Superose 12 gel filtration chromatography. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and western blot analyses of the recombinant SOD detected a molecular mass of approximately 27 kDa. However, the SOD was in dimer form as revealed by gel filtration chromatography. The purified recombinant enzyme had a pI of 4.5 and exhibited maximal activity at 25°C and pH 7.2. It was stable up to 45°C. The insensitivity of this lactococcal SOD to cyanide and hydrogen peroxide established that it was a MnSOD. Although it has 98% homology to SOD ofL. lactisIL1403, this is the first elucidated structure of lactococcal SOD revealing active sites containing the catalytic manganese coordinated by four ligands (H-27, H-82, D-168, and H-172).
The Implications of Diagnosis of Small for Gestational Age Fetuses Using European and South Asian Growth Charts: An Outcome-Based Comparative Study
Authors: Maso Gianpaolo , Jayawardane Mathota A. M. M. , Alberico Salvatore , Piccoli Monica , Senanayake Hemantha M.
Published: January 2014

The antenatal condition of small for gestational age (SGA) is significantly associated with perinatal morbidity and mortality and it is known that there are significant differences in birth weight and fetal size among different populations. The aim of our study was to assess the impact on outcomes of the diagnosis of SGA according to Bangladeshi and European antenatal growth charts in Sri Lankan population. The estimated fetal weight before delivery was retrospectively reviewed according to Bangladeshi and European growth references. Three groups were identified: Group 1-SGA according to Bangladeshi growth chart; Group 2-SGA according to European growth chart but not having SGA according to Bangladeshi growth chart; Group 3-No SGA according to both charts. There was a difference in prevalence of SGA between Bangladeshi and European growth charts: 12.7% and 51.7%, respectively. There were statistically significant higher rates in emergency cesarean section, fetal distress in labour, and intrauterine death (P<0.001) in Group 1 compared with Group, 2 and 3. No differences of outcomes occurred between Groups 2 and 3. Our study demonstrated that only cases diagnosed as SGA according to population-based growth charts are at risk of adverse outcome. The use of inappropriate prenatal growth charts might lead to misdiagnosis and potential unnecessary interventions.
Long-Term Results of Reconstruction with Pelvic Allografts after Wide Resection of Pelvic Sarcomas
Authors: Ayvaz Mehmet , Bekmez Senol , Mermerkaya M. Ugur , Caglar Omur , Acaroglu Emre , Tokgozoglu A. Mazhar
Published: January 2014

Reconstruction after the resection of a pelvic tumor is a challenging procedure in orthopedic oncology. The main advantage of allograft reconstruction is restoration of the bony architecture of the complex pelvic region. However, high complication rates such as infection and allograft resorption had been reported in the literature. In this study, we aimed to retrospectively review nine patients treated with pelvic resection and structural pelvic allograft reconstruction. Functional results, complications, and survival of the patients and the allografts were evaluated. At a mean follow-up of 79 months, three patients were dead. Major complications were detected in eight of the nine patients. Infection (four of the nine patients) and allograft resorption (three of the nine patients) were the most common causes of failure. The cumulative survival of the patients was 66.7 percent at 70 months. However, allograft survival was only 26.7 percent at 60 months. Mean MSTS score was 69. In conclusion, we suggest that other reconstruction options should be preferred after pelvic resections because of the high complication rates associated with massive allograft reconstruction.
Modelling Socio-Environmental Sensitivities: How Public Responses to Low Carbon Energy Technologies Could Shape the UK Energy System
Authors: Moran Jay Brighid , Howard David , Hughes Nick , Whitaker Jeanette , Anandarajah Gabrial
Published: January 2014

Low carbon energy technologies are not deployed in a social vacuum; there are a variety of complex ways in which people understand and engage with these technologies and the changing energy system overall. However, the role of the public’s socio-environmental sensitivities to low carbon energy technologies and their responses to energy deployments does not receive much serious attention in planning decarbonisation pathways to 2050. Resistance to certain resources and technologies based on particular socio-environmental sensitivities would alter the portfolio of options available which could shape how the energy system achieves decarbonisation (the decarbonisation pathway) as well as affecting the cost and achievability of decarbonisation. Thus, this paper presents a series of three modelled scenarios which illustrate the way that a variety of socio-environmental sensitivities could impact the development of the energy system and the decarbonisation pathway. The scenarios represent risk aversion (DREAD) which avoids deployment of potentially unsafe large-scale technology, local protectionism (NIMBY) that constrains systems to their existing spatial footprint, and environmental awareness (ECO) where protection of natural resources is paramount. Very different solutions for all three sets of constraints are identified; some seem slightly implausible (DREAD) and all show increased cost (especially in ECO).
Milestones in Software Engineering and Knowledge Engineering History: A Comparative Review
Authors: del Águila Isabel M. , Palma José , Túnez Samuel
Published: January 2014

We present a review of the historical evolution of software engineering, intertwining it with the history of knowledge engineering because “those who cannot remember the past are condemned to repeat it.” This retrospective represents a further step forward to understanding the current state of both types of engineerings; history has also positive experiences; some of them we would like to remember and to repeat. Two types of engineerings had parallel and divergent evolutions but following a similar pattern. We also define a set of milestones that represent a convergence or divergence of the software development methodologies. These milestones do not appear at the same time in software engineering and knowledge engineering, so lessons learned in one discipline can help in the evolution of the other one.
On the Exponential Inequality for Weighted Sums of a Class of Linearly Negative Quadrant Dependent Random Variables
Authors: Xing Guodong , Yang Shanchao
Published: January 2014

The exponential inequality for weighted sums of a class of linearly negative quadrant dependent random variables is established, which extends and improves the corresponding ones obtained by Ko et al. (2007) and Jabbari et al. (2009). In addition, we also give the relevant precise asymptotics.
Efficacy and Clinical Determinants of Antipsychotic Polypharmacy in Psychotic Patients Experiencing an Acute Relapse and Admitted to Hospital Stay: Results from a Cross-Sectional and a Subsequent Longitudinal Pilot Study
Authors: Iasevoli Felice , Buonaguro Elisabetta F. , Marconi Massimo , Di Giovambattista Emanuela , Rapagnani Maria Paola , De Berardis Domenico , Martinotti Giovanni , Mazza Monica , Balletta Raffaele , Serroni Nicola , Di Giannantonio Massimo , de Bartolomeis Andrea , Valchera Alessandro
Published: January 2014

Background. Antipsychotic polypharmacy is used in several psychiatric disorders, despite poor evidence existing to support this practice. Aim. We evaluated whether psychotic patients in acute relapse exposed to antipsychotic polypharmacy (AP + AP) showed different demographic, clinical, or psychopathological features compared to those exposed to one antipsychotic (AP) and whether AP + AP patients showed significantly higher improvement compared to AP patients after a 4-week treatment. Methods. Inpatients were subdivided into AP + AP and AP ones. In the cross-sectional step, patients were compared according to demographics, clinical variables, and scores on rating scales. In the longitudinal step, patients remained for 4 weeks under admission medications and were compared for clinical improvement. Results. AP + AP patients were more frequently diagnosed with schizophrenia and mental retardation as a comorbid illness. AP + AP patients were more frequently under first-generation antipsychotics and had worse clinical presentation. After 4 weeks of treatment, both AP + AP and AP patients improved compared to the baseline. However, AP patients scored significantly less than AP + AP patients at the Clinical Global Impression Scale at the 4-week time point but not at the baseline, indicating a treatment-specific improvement. Conclusions. Antipsychotic polypharmacy may be offered to specific types of psychotic patients. However, efficacy of this strategy is limited at best.
Feasibility of a Hybrid Brain-Computer Interface for Advanced Functional Electrical Therapy
Authors: Savić Andrej M. , Malešević Nebojša M. , Popović Mirjana B.
Published: January 2014

We present a feasibility study of a novel hybrid brain-computer interface (BCI) system for advanced functional electrical therapy (FET) of grasp. FET procedure is improved with both automated stimulation pattern selection and stimulation triggering. The proposed hybrid BCI comprises the two BCI control signals: steady-state visual evoked potentials (SSVEP) and event-related desynchronization (ERD). The sequence of the two stages, SSVEP-BCI and ERD-BCI, runs in a closed-loop architecture. The first stage, SSVEP-BCI, acts as a selector of electrical stimulation pattern that corresponds to one of the three basic types of grasp: palmar, lateral, or precision. In the second stage, ERD-BCI operates as a brain switch which activates the stimulation pattern selected in the previous stage. The system was tested in 6 healthy subjects who were all able to control the device with accuracy in a range of 0.64–0.96. The results provided the reference data needed for the planned clinical study. This novel BCI may promote further restoration of the impaired motor function by closing the loop between the “will to move” and contingent temporally synchronized sensory feedback.
Microstructural Characterization and Corrosion Behavior of Electroless Ni-Zn-P Thin Films
Authors: Constantin Ionuţ
Published: January 2014

Ternary Ni-Zn-P alloy thin films were electrolessly deposited on a carbon steel substrate from sulphate alkaline baths. The effect of deposition bath composition and process duration on the physical-chemical and corrosion characteristics of the obtained thin films was investigated. The thin films were characterized by EDAX analysis techniques and scanning electronic microscopy. Corrosion tests were performed in 3.5% sodium chloride solution and the corrosion current values were determined to be 4–12 μA, comparative to 15 μA for the uncoated steel sample.
Evolution of Microstructure and Residual Stress under Various Vibration Modes in 304 Stainless Steel Welds
Authors: Hsieh Chih-Chun , Wang Peng-Shuen , Wang Jia-Siang , Wu Weite
Published: January 2014

Simultaneous vibration welding of 304 stainless steel was carried out with an eccentric circulating vibrator and a magnetic telescopic vibrator at subresonant (362 Hz and 59.3 Hz) and resonant (376 Hz and 60.9 Hz) frequencies. The experimental results indicate that the temperature gradient can be increased, accelerating nucleation and causing grain refinement during this process. During simultaneous vibration welding primaryδ-ferrite can be refined and the morphologies of retainedδ-ferrite become discontinuous so thatδ-ferrite contents decrease. The smallest content ofδ-ferrite (5.5%) occurred using the eccentric circulating vibrator. The diffraction intensities decreased and the FWHM widened with both vibration and no vibration. A residual stress can obviously be increased, producing an excellent effect on stress relief at a resonant frequency. The stress relief effect with an eccentric circulating vibrator was better than that obtained using a magnetic telescopic vibrator.
Antimicrobial Resistance Trends among Community-Acquired Respiratory Tract Pathogens in Greece, 2009–2012
Authors: Maraki Sofia , Papadakis Ioannis S.
Published: January 2014

The aim of the present study was to determine the antimicrobial resistance trends of respiratory tract pathogens isolated from patients with community-acquired respiratory tract infections (CARTIs) in Crete, Greece, over a 4-year period (2009–2012). A total of 588 community-acquired respiratory pathogens were isolated during the study period.Streptococcus pneumoniaewas the most common organism responsible for 44.4% of CARTIs, followed byHaemophilus influenzae(44.2%) andMoraxella catarrhalis(11.4%). AmongS. pneumoniae, the prevalence of isolates with intermediate- and high-level resistance to penicillin was 27.2% and 12.3%, respectively. Macrolide resistance slightly decreased from 29.4% over the period 2009-2010 to 28.8% over the period 2011-2012. Multiresistance was observed among 56 (54.4%) penicillin nonsusceptible isolates. A nonsignificant increase in resistance ofH. influenzaeisolates was noted forβ-lactams, cotrimoxazole, and tetracycline. Among the 67M. catarrhalistested, 32 produced beta-lactamase and were resistant to ampicillin. Macrolide resistance decreased over the study period. All isolates were susceptible to amoxicillin + clavulanic acid, chloramphenicol, rifampicin, and the fluoroquinolones. Although a decreasing trend in the prevalence of resistance of the three most common pathogens involved in CARTIs was noted, continuous surveillance of antimicrobial susceptibility at the local and national level remains important, in order to guide appropriate empirical antimicrobial therapy.
Diverse Roles of Prostaglandins in Blastocyst Implantation
Authors: Salleh Naguib
Published: January 2014

Prostaglandins (PGs), derivatives of arachidonic acid, play an indispensable role in embryo implantation. PGs have been reported to participate in the increase in vascular permeability, stromal decidualization, blastocyst growth and development, leukocyte recruitment, embryo transport, trophoblast invasion, and extracellular matrix remodeling during implantation. Deranged PGs syntheses and actions will result in implantation failure. This review summarizes up-to-date literatures on the role of PGs in blastocyst implantation which could provide a broad perspective to guide further research in this field.
Coronary Spasm in Neurosurgical Patients and Role of Trigeminocardiac Reflex
Authors: Chowdhury Tumul , Meuwly Cyrill , Sandu Nora , Cappellani Ronald B. , Schaller Bernhard
Published: January 2014

Background.Coronary artery spasm (CAS) is a rarely reported complication in neurosurgical patients and its main causative mechanism was attributed to vagal mediated responses. However, these may be the unusual manifestations of trigeminal cardiac reflex (TCR) which is a well established brain stem reflex observed in various neurosurgical patients.Methods and Results.In this review, we have searched for the case reports/papers related to intraoperative coronary spasm in neurosurgical patients and described the role of TCR in this regard. TCR is a possible mechanism in producing CAS in most of the cases in which stimulation occurred at or near the vicinity of trigeminal nerve. It is likely that TCR mediated coronary spasm may be a physiological mechanism and not related to actual myocardial insult apparent by cardiac enzymes or echocardiography studies in most of the cases. Some common risk factors may also exist related to occurrence of CAS as well as TCR.Conclusions.In conclusion, neurosurgical procedures occurring at the vicinity of trigeminal nerve may produce CAS even in previously healthy patients and may produce catastrophic consequences. There is a need for future reports and experimental studies on the interaction of TCR and pathophysiological mechanisms related to CAS.
Validation of Nomograms Predicting Lymph Node Involvement in Patients with Prostate Cancer Undergoing Extended Pelvic Lymph Node Dissection
Authors: Hinev Alexander I. , Anakievski Deyan , Kolev Nikolay H. , Hadjiev Vesselin I.
Published: January 2014

Our aim was to validate Briganti's nomograms predicting the probability of lymph node involvement (LNI) in prostate cancer (PCa). Clinicopathological data of 256 PCa patients who underwent extended pelvic lymph node dissection (ePLND) and radical prostatectomy (RP) were obtained from two Bulgarian institutions. Predicted probabilities of LNI were assessed using Briganti's nomograms based on ePLND. In addition to the established basic LNI predictors, Briganti's nomograms included the number of lymph nodes removed (version 2006) and the number and percentage of positive biopsy cores (versions 2007 and 2012). The accuracy of these nomograms was compared with the updated Memorial Sloan-Kettering Cancer Center (MSKCC) nomogram (version 2011). Receiver-operating characteristics analysis was done to assess the discriminative ability of each of the nomograms applied. All of Briganti's nomograms showed a higher predictive accuracy as compared with the updated MSKCC nomogram. The respective AUC values were calculated as 0.847, 0.837, 0.858 and 0.875 for the four Briganti nomograms, and 0.770 for the updated MSKCC nomogram, respectively. Despite the potential for heterogeneity in patient selection and management, all predictions demonstrated high concordance with actual observations. Compared with other similar prognostic tools the updated Briganti nomogram (version 2012) showed the highest predictive accuracy and should therefore be preferred.
Painful Orgasm in an Adolescent after Seminal-Sparing Cystoprostatectomy: A Puzzling Symptom
Authors: Angelini Lorenzo , Castagnetti Marco , Rigamonti Waifro
Published: January 2014

An 18-year-old boy, followed up after seminal-sparing cystectomy for bladder rhabdomyosarcoma, presented complaining of recurrent episodes of left scrotal/inguinal pain arising after orgasms. Full work-up ruled out disease recurrence, but showed enlarged seminal vesicles. Ligation of the vas deferens was unsuccessful. The patient was started on α-blockers to reduce vas contractions with improvement of symptoms. The possible pathophysiology and treatments of this symptom are discussed.
Successful Endourological Management of the ‘Forgotten' Stent in a Transplanted Kidney
Authors: Wu Fiona Mei Wen , Lim Mark , Deng Zhaolong , Heng Chin Tiong , Tiong Ho Yee
Published: January 2014

Background: Ureteric stents are used to prevent urological complications like ureteric fistulas and obstruction in kidney transplants. Despite its advantages, complications arising from delayed removal of a double J (DJ) stent include urinary tract infections, stone encrustation, and migration of the DJ stent [Sansalone et al.: Transplant Proc 2005;37:2511-2515]. Encrustation of the stent makes removal difficult and risks injury to the transplanted kidney. Case Presentation: We report a case of retained DJ stent for 19 years presenting with recurrent urinary tract infections. A radiograph revealed a retained ureteric stent extending from the right iliac fossa transplant kidney to the urinary bladder with multiple foci of large calcification along its length. Two sessions of extracorporeal shockwave lithotripsy along the stent were performed after a percutaneous nephrostomy tube had been placed in the transplanted kidney. Subsequently, the retained DJ stent was removed endoscopically after laser lithotripsy to remnant calcifications. Remnant stone fragments were removed with another session of ureteroscopy and laser lithotripsy. The patient achieved complete stent and stone clearance with a functioning graft. Conclusion: This case illustrates that significant stone encrustation of the retained stent in a transplanted kidney can be treated successfully with a combination of endourological techniques.
Unusual Intracytoplasmic Crystalline Inclusions in Chronic Myelomonocytic Leukemia with Double Minute Chromosomes and MYC Amplification: A Rare Case
Authors: Miyazaki Kanji , Suzuki Kenshi
Published: January 2014

Chronic myelomonocytic leukemia (CMML) is a clonal hematological disease characterized by the presence of peripheral blood monocytosis and bone marrow dysplasia. Double minute chromosomes (dmin) are rare and intracytoplasmic crystalline inclusions are very rare in hematologic malignancies. We present a case of CMML with dmin and unusual intracytoplasmic crystalline inclusions. To our knowledge, no such case has previously been reported.
New Self-Reporting Questionnaire to Assess Urinary Tract Infections and Differential Diagnosis: Acute Cystitis Symptom Score
Authors: Alidjanov Jakhongir F. , Abdufattaev Ulugbek A. , Makhsudov Saidamin A. , Pilatz Adrian , Akilov Farkhad A. , Naber Kurt G. , Wagenlehner Florian M.
Published: January 2014

Objective: Development and validation of a simple and standardized self-reporting questionnaire for acute uncomplicated cystitis (AUC) assessing typical and differential symptoms, quality of life and possible changes after therapy in female patients with AUC. Materials and Methods: Literature research, development and evaluation of the Acute Cystitis Symptom Score (ACSS), an 18-item self-reporting questionnaire including (a) six questions about ‘typical' symptoms of AUC, (b) four questions regarding differential diagnoses, (c) three questions on quality of life and (d) five questions on additional conditions which may affect therapy. The ACSS was evaluated in 286 women (mean age 32.3 ± 12.3 years) in the Russian and Uzbek language. Measurements of reliability, validity, predictive ability and responsiveness were performed. Results: Cronbach's alpha for the ACSS was 0.89, split-half reliability was 0.92 and correlation between halves was 0.85. Mann-Whitney test revealed significant difference scores of the ‘typical' domain between patients and controls (10.75 vs. 2.02, p < 0.001). The optimal threshold score was 6 points, with a 94% sensitivity and 90% specificity to predict AUC. The symptom score decreased significantly when comparing before and after therapy (10.7 vs. 2.1, p < 0.001). Conclusion: The new validated ACSS is accurate enough and can be recommended for clinical studies and practice for initial diagnosis and monitoring treatment of AUC. Evaluation in other languages is in progress. © 2014 S. Karger AG, Basel
Regional Atrophy of the Insular Cortex Is Associated with Neuropsychiatric Symptoms in Alzheimer's Disease Patients
Authors: Moon Yeonsil , Moon Won-Jin , Kim Heejin , Han Seol-Heui
Published: January 2014

Background: Alzheimer's disease (AD) is a devastating illness that results in progressive cognitive decline and neuropsychiatric symptoms. The neuropsychiatric symptoms are associated with a rapid decline in cognition and activities of daily living and increased mortality, however the neuroanatomical localisation involved in the development of neuropsychiatric symptoms remains poorly understood. The aim of this study was to identify the association with the regional volume of the insular cortex and each neuropsychiatric symptom in patients with AD. Methods: Subjects diagnosed with AD (n = 40) were evaluated. Magnetic resonance images were obtained and the insular cortex was subdivided into four subregions through the central sulcus of the insula and bilaterally: right anterior insular cortex, right posterior insular cortex, left anterior insular cortex and left posterior insular cortex. The neuropsychiatric symptoms were assessed using the Neuropsychiatric Inventory. A partial correlation analysis was performed. Results: A significant negative correlation existed between apathy, the irritability subscale score and the volume ratio of the bilateral anterior insular cortex and right posterior insular cortex (r = -0.457, -0.433 and -0.572, respectively, p = 0.032, 0.044 and 0.005, respectively). Conclusion: The findings suggest that the regional atrophy of the insular cortex is associated with neuropsychiatric symptoms in AD patients.
Juvenile ‘Cryptogenic' Stroke from Noncompaction in a Neuromuscular Disease
Authors: Finsterer Josef , Stöllberger Claudia
Published: January 2014

Juvenile, ‘cryptogenic' stroke from left-ventricular hypertrabeculation/noncompaction (LVHT) missed on transthoracic echocardiography (TTE) but present on transesophageal echocardiography (TEE) has not been reported before. A 31-year-old Caucasian male experienced a small acute embolic ischemic stroke in the anterior territory of the left median-cerebral artery. He had a history of epilepsy until the age of 12 years with rare seizures, headache 6 weeks prior to admission and a speech disturbance lasting 2 h. He smoked 20 cigarettes per day. An intensive diagnostic work-up including TTE did not reveal the cause of the stroke. Upon TEE, however, LVHT was found. Cardiac MRI did not reveal intraventricular thrombi. There were mild indications for a neuromuscular disorder. LVHT may be a risk factor for cardioembolic stroke. Patients with cryptogenic stroke and normal TTE should undergo TEE. Patients with LVHT should undergo neurological investigation to look for neuromuscular disorders.
Patients' Understanding of How Genotype Variation Affects Benefits of Tamoxifen Therapy for Breast Cancer
Authors: Brewer N.T. , DeFrank J.T. , Chiu W.K. , Ibrahim J.G. , Walko C.M. , Rubin P. , Olajide O.A. , Moore S.G. , Raab R.E. , Carrizosa D.R. , Corso S.W. , Schwartz G. , Peppercorn J.M. , McLeod H.L. , Carey L.A. , Irvin Jr. W.J.
Published: January 2014

Background: CYP2D6 is a critical enzyme in the metabolism of tamoxifen and potentially a key determinant in breast cancer outcomes. Our study examined patients' beliefs about how the CYP2D6 genotype would affect their prognoses. Methods: Women enrolled in a pharmacogenomic clinical trial and on tamoxifen for prevention or treatment of breast cancer underwent CYP2D6 genotyping (EM = extensive, IM = intermediate, PM = poor metabolizing alleles). The informed consent said that the purpose of the trial was to examine effects of dose adjustment based on genotype, but that clinical benefits were uncertain. Our embedded sub-study surveyed 320 patients prior to receiving their genotypes. We experimentally manipulated 6 vignettes to describe hypothetical tamoxifen treatment (no or yes) and hypothetical genotype (EM, IM or PM). For each vignette, women gave their perceived recurrence risk (RR; 0-100%). Results: Women believed that genotype would not affect their RR if they did not take tamoxifen (p = 0.06). However, women believed that if prescribed tamoxifen, genotype would affect their RR (22% if EM, 30% if IM and 40% if PM, p < 0.001). Conclusion: Women believed that extensive tamoxifen metabolizers had better prognoses, despite study materials stating uncertainty about any benefit. The rapidly changing nature of genomic science calls for caution when communicating clinical utility.
Prenatal Exposure to Alcohol and 3,4-Methylenedioxymethamphetamine (Ecstasy) Alters Adult Hippocampal Neurogenesis and Causes Enduring Memory Deficits
Authors: Canales Juan J. , Ferrer-Donato Agueda
Published: January 2014

Recreational drug use among pregnant women is a source of concern due to potential harmful effects of drug exposure on prenatal and infant development. The simultaneous abuse of ecstasy [3,4-methylenedioxymethamphetamine (MDMA)] and alcohol is prevalent among young adults, including young expectant mothers. Here, we used a rat model to study the potential risks associated with exposure to alcohol and MDMA during pregnancy. Pregnant rats received alcohol, MDMA, or both alcohol and MDMA by gavage at E13 through E15 twice daily. Female offspring treated prenatally with the combination of alcohol and MDMA, but not those exposed to either drug separately, showed at 3 months of age decreased exploratory activity and impaired working memory function. Prenatal treatment with the combination of alcohol and MDMA decreased proliferation of neuronal precursors in the adult dentate gyrus of the hippocampus, as measured by 5-bromo-2-deoxyuridine labelling, and adult neurogenesis, assessed by quantifying doublecortin expression. These results provide the first evidence that the simultaneous abuse of alcohol and ecstasy during pregnancy, even for short periods of time, may cause significant abnormalities in neurocognitive development.
Fiber Type-Specific Expression of Low-Density Lipoprotein Receptor-Related Protein 6 in Human Skeletal Muscles
Authors: Takeda Ikuko , Takahashi Tetsuya , Ochi Kazuhide , Kurashige Takashi , Shinozaki Yukari , Nakamori Masahiro , Arihiro Koji , Maruyama Hirofumi , Matsumoto Masayasu
Published: January 2014

Objective: Gene expression patterns differ in the two types of skeletal muscle fiber. The Wnt signaling pathway, which includes low-density lipoprotein receptor-related protein 6 (LRP6), has been associated with cell differentiation and glucose metabolism in skeletal muscles. We examined the relationships between muscle fiber types and LRP6 expression. Methods: Adenosine triphosphatase was assayed histochemically, and the levels of expression of LRP6 and myosin were analyzed immunohistochemically, in frozen sections of muscle fiber obtained from 16 muscle biopsy samples. The expression pattern of LRP6 in C2C12 cells was assayed by immunocytochemistry. Results: LRP6 was expressed only in type II fibers. Type IIc fibers showed variations in LRP6 expression. Expression of LRP6 was observed at the stage of myoblast differentiation. Conclusion: Antibody to LRP6 may be useful for identifying type II skeletal muscle fibers. LRP6 may influence glucose metabolism in type II fibers of human skeletal muscles.
Mapping of CD8 T Cell Epitopes in Human Respiratory Syncytial Virus L Protein
Authors: Medina-Armenteros Yordanka , Farinha-Arcieri Luis E. , Braga Catarina J.M. , Carromeu Cassiano , Tamura Rodrigo E. , Ventura Armando M.
Published: January 2014

Objectives: Since it has been reported that in humans there is a relationship between human respiratory syncytial virus (hRSV)-specific cytotoxic T lymphocytes and symptom reduction, and that the polymerase (structural L protein) is highly conserved among different strains, this work aimed to identify the CD8 T cell epitopes H-2d restricted within the L sequence for immunization purposes. Methods: We screened the hRSV strain A2 L protein sequence using two independent algorithms, SYFPEITHI and PRED/BALB/c, to predict CD8 T cell epitopes. The selected peptides were synthesized and used to immunize BALB/c mice for the evaluation of T cell response. The production of IFN-γ from splenocytes of hRSV-infected animals stimulated by these peptides was assayed by ELISPOT. Results: Nine peptides showing the best binding scores to the BALB/c MHC-I molecules (H-2Kd, Ld and Dd) were selected. Sequence homology analysis showed that these sequences are conserved among different hRSV strains. Two of these peptides induced significant IFN-γ production by ex vivo-stimulated T cells. Conclusions: Our results indicate that the hRSV L protein contains H-2d-restricted epitopes.
Low-Density Lipoprotein and Intracerebral Hematoma Expansion in Daily Alcohol Users
Authors: Pletsch Gayle R. , Boehme Amelia K. , Albright Karen C. , Burns Christopher , Beasley T. Mark , Martin-Schild Sheryl
Published: January 2014

Background: Epidemiological studies suggest that the intracerebral hemorrhage (ICH) rate correlates with alcohol consumption. Alcohol leads to elevated blood pressure (BP) and inhibition of platelet aggregation. These factors could promote excessive bleeding. To our knowledge, in the setting of normal liver function tests, there are no studies that have systematically evaluated the relationship between daily alcohol use and hematoma expansion. The aim of this study is to compare the baseline ICH characteristics, frequency of hematoma expansion, and outcomes in patients with ICH who are daily alcohol users with those who are not daily alcohol users. Methods: A retrospective chart review was performed on consecutive patients who presented from July 2008 to July 2013 to the Tulane University Hospital in New Orleans, La., USA, with a spontaneous ICH. Ninety-nine patients who met these criteria were admitted. Patients who underwent hematoma evacuation were excluded. Hemorrhage volumes were calculated based on the ABC/2 method. Low-density lipoprotein (LDL) was dichotomized into low (<100 mg/dl) and high (≥100 mg/dl) values. Comparisons were made using t tests, χ2 and nonparametric equivalents where appropriate. ICH growth in 24 h and LDL were evaluated using linear regression. Results: Of the 226 patients who met inclusion criteria, 20.4% had a history of daily alcohol use. The average age was 61 years (range 19-94), 55.6% of the patients were males, and 67.1% were of African American origin. Daily alcohol use was associated with male gender, lower rate of home antihypertensive, higher presenting BP, and lower platelet counts, but there was no difference in ICH characteristics, ICH growth, or clinical outcome. Daily alcohol use in patients with a low LDL level was associated with supratentorial location and trends for lower baseline Glasgow Coma Scale score, higher ICH score, and follow-up ICH volume, but no significant difference in significant hematoma expansion or clinical outcome except for a trend for higher mortality was found (25 vs. 9.5%, p = 0.1311) compared to patients with high LDL values. Conclusions: Our data suggest that neither chronic daily alcohol use nor a low LDL level in combination with daily alcohol use can be used to predict ICH growth. Daily alcohol use was associated with untreated hypertension and higher BP on presentation. A low LDL level in combination with daily alcohol use may be linked with larger and more severe ICH, but we were unable to demonstrate a relationship with hematoma expansion or poor clinical outcome. The role of LDL in vessel fragility and clot stabilization needs to be further explored before concluding that a low LDL level confers risk of bleeding.
A Staphylococcus aureus TIR Domain Protein Virulence Factor Blocks TLR2-Mediated NF-κB Signaling
Authors: Askarian Fatemeh , van Sorge Nina M. , Sangvik Maria , Beasley Federico C. , Henriksen Jørn R. , Sollid Johanna U.E. , van Strijp Jos A.G. , Nizet Victor , Johannessen Mona
Published: January 2014

Signaling through Toll-like receptors (TLRs), crucial molecules in the induction of host defense responses, requires adaptor proteins that contain a Toll/interleukin-1 receptor (TIR) domain. The pathogen Staphylococcus aureus produces several innate immune-evasion molecules that interfere with the host's innate immune response. A database search analysis suggested the presence of a gene encoding a homologue of the human TIR domain in S. aureus MSSA476 which was named staphylococcal TIR domain protein (TirS). Ectopic expression of TirS in human embryonic kidney, macrophage and keratinocyte cell lines interfered with signaling through TLR2, including MyD88 and TIRAP, NF-κB and/or mitogen-activated protein kinase pathways. Moreover, the presence of TirS reduced the levels of cytokines MCP-1 and G-CSF secreted in response to S. aureus. The effects on NF-κB pathway were confirmed using S. aureus MSSA476 wild type, an isogenic mutant MSSA476ΔtirS, and complemented MSSA476ΔtirS +pTirS in a Transwell system where bacteria and host cells were physically separated. Finally, in a systematic mouse infection model, TirS promoted bacterial accumulation in several organs 4 days postinfection. The results of this study reveal a new S. aureus virulence factor that can interfere with PAMP-induced innate immune signaling in vitro and bacterial survival in vivo.
Effects of Selective Activation of M1 and M4 Muscarinic Receptors on Object Recognition Memory Performance in Rats
Authors: Galloway Claire R. , Lebois Evan P. , Shagarabi Shezza L. , Hernandez Norma A. , Manns Joseph R.
Published: January 2014

Acetylcholine signaling through muscarinic receptors has been shown to benefit memory performance in some conditions, but pan-muscarinic activation also frequently leads to peripheral side effects. Drug therapies that selectively target M1 or M4 muscarinic receptors could potentially improve memory while minimizing side effects mediated by the other muscarinic receptor subtypes. The ability of three recently developed drugs that selectively activate M1 or M4 receptors to improve recognition memory was tested by giving Long-Evans rats subcutaneous injections of three different doses of the M1 agonist VU0364572, the M1 positive allosteric modulator BQCA or the M4 positive allosteric modulator VU0152100 before performing an object recognition memory task. VU0364572 at 0.1 mg/kg, BQCA at 1.0 mg/kg and VU0152100 at 3.0 and 30.0 mg/kg improved the memory performance of rats that performed poorly at baseline, yet the improvements in memory performance were the most statistically robust for VU0152100 at 3.0 mg/kg. The results suggested that selective M1 and M4 receptor activation each improved memory but that the likelihood of obtaining behavioral efficacy at a given dose might vary between subjects even in healthy groups depending on baseline performance. These results also highlighted the potential of drug therapies that selectively target M1 or M4 receptors to improve memory performance in individuals with impaired memory.
Postmortem Pump-Driven Reperfusion of the Vascular System of Porcine Lungs: Towards a New Model for Surgical Training
Authors: Willaert W. , Van Hoof T. , De Somer F. , Grabherr S. , D'Herde K. , Ceelen W. , Pattyn P.
Published: January 2014

Purpose: The objective of this experiment is to establish a continuous postmortem circulation in the vascular system of porcine lungs and to evaluate the pulmonary distribution of the perfusate. This research is performed in the bigger scope of a revascularization project of Thiel embalmed specimens. This technique enables teaching anatomy, practicing surgical procedures and doing research under lifelike circumstances. Methods: After cannulation of the pulmonary trunk and the left atrium, the vascular system was flushed with paraffinum perliquidum (PP) through a heart-lung machine. A continuous circulation was then established using red PP, during which perfusion parameters were measured. The distribution of contrast-containing PP in the pulmonary circulation was visualized on computed tomography. Finally, the amount of leak from the vascular system was calculated. Results: A reperfusion of the vascular system was initiated for 37 min. The flow rate ranged between 80 and 130 ml/min throughout the experiment with acceptable perfusion pressures (range: 37-78 mm Hg). Computed tomography imaging and 3D reconstruction revealed a diffuse vascular distribution of PP and a decreasing vascularization ratio in cranial direction. A self-limiting leak (i.e. 66.8% of the circulating volume) towards the tracheobronchial tree due to vessel rupture was also measured. Conclusions: PP enables circulation in an isolated porcine lung model with an acceptable pressure-flow relationship resulting in an excellent recruitment of the vascular system. Despite these promising results, rupture of vessel walls may cause leaks. Further exploration of the perfusion capacities of PP in other organs is necessary. Eventually, this could lead to the development of reperfused Thiel embalmed human bodies, which have several applications.
Creativity and Psychopathology: A Systematic Review
Authors: Thys Erik , Sabbe Bernard , De Hert Marc
Published: January 2014

Background: The possible link between creativity and psychopathology has been a long-time focus of research up to the present day. However, the research results in this field are heterogeneous and contradictory. Links between creativity and specific psychiatric disorders have been confirmed and refuted in different studies. This disparity is partly explained by the methodological challenges peculiar to this field. Methods: In this systematic review of the literature from 1950, research articles in the field of creativity and psychopathology are presented, focusing on the methodology and results of the collected studies. Results: This review confirms the methodological problems and the heterogeneity of the study designs and results. The assessment of psychopathology, but more so of creativity, remains a fundamental challenge. On the whole, study results cautiously confirm an association between creativity and both bipolar disorder and schizotypy. Conclusion: The research on creativity and psychopathology is hampered by serious methodological problems. Study results are to be interpreted with caution and future research needs more methodological rigor.
Effects of Mesenchymal Stem Cells Transplanted at Different Time Points in a Rat Remnant Kidney Model
Authors: Bian Xiaohui , Zhang Beiru , Guo Wei , Liu Na , Bai Yu , Miao Jianing , Zhao Guifeng , Liu Bo , Wang Shubao , Ma Li , Zheng Liqiang , Zhao Yueyang , Li Detian , Feng Jiangmin
Published: January 2014

Aims: The optimal time for mesenchymal stem cell (MSCs) transplantation remains an unresolved issue. We compared the effects of MSCs on a rat remnant kidney model. Methods: Male Sprague-Dawley rats were randomly divided and treated with a corresponding reagent at 4, 8, 12 and 16 weeks, respectively. A remnant kidney model was established and MSCs were injected into rats. The migration of MSCs was then assessed by using cell-tracking experiments. Renal function and histological analyses were performed 4 weeks after MSC transplantation. Immunohistochemistry, Western blotting and real-time polymerase chain reaction were used to detect the TGF-β1 and α-SMA levels. Results: Four weeks after MSC injection, MSCs were found to migrate to the injured kidney. Significant histological damage improvement was observed after the treatment of MSCs at 4 and 8 weeks. The functional benefits of MSC treatment were observed in the 5/6 nephrectomy (Nx) + MSC group and the benefits were significantly higher at 4 and 8 weeks than at other time points (p < 0.05). Meanwhile, serum creatinine and urea levels as well as glomerular sclerosis and tubulointerstitial injury indexes were decreased at 4 and 8 weeks. Compared with the 5/6 Nx + PBS group, TGF-β1 and α-SMA levels were decreased in the 5/6 Nx + MSC group. Conclusion: These data can be used to optimize the MSC transplantation time point as a therapeutic modality.
Management of Liver Trauma in Kuwait
Authors: Asfar Sami , Khoursheed Mousa , Al-Saleh Mervat , Alfawaz Abdullah A. , Farghaly Medhat M. , Nur Ali M. ,   on behalf of the Liver Trauma Registry Group
Published: January 2014

Objectives: The aim of this study was to introduce the concept of non-operative management (NOM) for blunt liver trauma by establishing a protocol and a prospective Liver Trauma Registry in Kuwait. Subjects and Methods: A prospective Liver Trauma Registry was started in 4 hospitals and it included 117 patients who had sustained blunt liver trauma (94 men and 23 women). Unstable patients were taken to surgery while stable patients were managed conservatively regardless of the grade of liver injury. High-grade (III-VI) liver injuries were managed in collaboration with the liver surgery specialist. Results: The mean age of the 117 patients was 29.02 ± 11.18 years (range 7-63). NOM was successful in 94 (96%) patients and failed in 4 (4%) (these 4 then underwent successful surgery). Nineteen (16.2%) were unstable and underwent surgery immediately; 15 (79%) of them survived (they had had grade III-V injuries) and 4 died (2 with grade V injuries and 2 with grade VI injuries). Perihepatic packing was necessary in 8/19 (42%) patients. The overall mortality was 3.4% (4/117). Conclusions: This study showed that NOM was successful in a majority of patients with blunt liver trauma. In addition, it confirmed that the magnitude of liver injury and haemoperitoneum did not preclude NOM as long as the patient was haemodynamically stable.
An Unexpected Complication of Bone Marrow Aspiration and Trephine Biopsy: Arteriovenous Fistula
Authors: Berber Ilhami , Erkurt Mehmet Ali , Kuku Irfan , Kaya Emin , Kutlu Ramazan , Koroglu Mustafa , Yigit Ali , Unlu Serkan
Published: January 2014

Objective: To report a case of arteriovenous fistula (AVF) following bone marrow aspiration and trephine biopsy. Clinical Presentation and Intervention: A 76-year-old man was diagnosed with acute myeloblastic leukemia. Pain and hematoma were detected in his left leg and hip 4 days after bone marrow aspiration and trephine biopsy. A pelvic arteriography was performed, and a diagnosis of AVF was made. Conclusion: This case shows that clinicians should be aware of AVF, especially in cases with refractory bleeding after bone marrow aspiration and trephine biopsy despite normal blood coagulation parameters.
Subglottic Chondrosarcoma Presenting Only Mild Acute-Onset Dyspnea: A Case Report and Review of the Literature
Authors: Tsai Su-wei , Ou Chun-yen
Published: January 2014

Chondrosarcoma is categorized as a malignant cartilaginous tumor, which occurs rarely in the craniofacial region. We report the case of a 68-year-old man with chondrosarcoma in the subglottic area. His chief symptoms were hoarseness and mild dysphagia. A computed tomography scan revealed a lesion with expansion of the cricoid cartilage and marked reduction of the airway. After biopsy, histological inspection showed that chondrocytes are multi-nucleus, their size does not differ much and mitosis is not obvious. These are all characteristics of a low-grade chondrosarcoma. We performed an organ-preserving operation by debulking the low-grade malignant tumor in order to keep a patent airway. No further metastasis or airway compromise was evident during the 1-year follow-up visit.
Two Case Reports of Resensitization to Previous Chemotherapy with the Novel Hypoxia-Activated Hypomethylating Anticancer Agent RRx-001 in Metastatic Colorectal Cancer Patients
Authors: Reid T. , Dad S. , Korn R. , Oronsky B. , Knox S. , Scicinski J.
Published: January 2014

The development of chemoresistance is a persistent problem during the treatment of cancer. Although reversion or modification of acquired chemoresistance has been previously observed, no systematic exploration has been undertaken. Here, we report a case study of 2 male patients, 62 and 66 years old, both with histologically proven, radiologically progressing, extensively pretreated, metastatic and refractory (≥2 conventional regimens and drug therapy) colorectal adenocarcinoma that was previously treated with FOLFIRI. The patients were resensitized to FOLFIRI after exposure to RRx-001 in the context of a phase-1 study. RRx-001 is a novel, hypomethylating and free-radical-inducing anticancer agent that activates nitrite reduction to NO under hypoxia and has an impact on epigenetic pathways. The repression of DNA methyltransferase 1 by RRx-001 may lead to demethylation and reexpression of silenced tumor suppressor genes, leading to resensitization. These examples provide insight into a nascent strategy to improve the prognosis in heavily pretreated cancer patients and suggest routes for further exploration.