Scientifica http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. Invasive Mold Infections in Solid Organ Transplant Recipients Sun, 23 Nov 2014 12:35:43 +0000 http://www.hindawi.com/journals/scientifica/2014/821969/ Invasive mold infections represent an increasing source of morbidity and mortality in solid organ transplant recipients. Whereas there is a large literature regarding invasive molds infections in hematopoietic stem cell transplants, data in solid organ transplants are scarcer. In this comprehensive review, we focused on invasive mold infection in the specific population of solid organ transplant. We highlighted epidemiology and specific risk factors for these infections and we assessed the main clinical and imaging findings by fungi and by type of solid organ transplant. Finally, we attempted to summarize the diagnostic strategy for detection of these fungi and tried to give an overview of the current prophylaxis treatments and outcomes of these infections in solid organ transplant recipients. Yoann Crabol and Olivier Lortholary Copyright © 2014 Yoann Crabol and Olivier Lortholary. All rights reserved. The Role of RaxST, a Prokaryotic Sulfotransferase, and RaxABC, a Putative Type I Secretion System, in Activation of the Rice XA21-Mediated Immune Response Sun, 19 Oct 2014 00:00:00 +0000 http://www.hindawi.com/journals/scientifica/2014/532816/ Tyrosine sulfation is an important posttranslational modification that determines the outcome of serious diseases in plants and animals. We have recently demonstrated that the plant pathogen Xanthomonas oryzae pv. oryzae (Xoo) carries a functional sulfotransferase (RaxST). raxST is required for activation of rice Xa21-mediated immunity indicating the critical, but unknown, function of raxST in mediating the Xoo/rice interaction. The raxST gene resides in the same operon (raxSTAB) as components of a predicted type I secretion and processing system (RaxA and RaxB). These observations suggest a model where RaxST sulfates a molecule that contains a leader peptide, which is cleaved by the peptidase domain of the RaxB protein and secreted outside the bacterial cell by the RaxABC T1SS. Pamela C. Ronald Copyright © 2014 Pamela C. Ronald. All rights reserved. The Preventable Risk Integrated ModEl and Its Use to Estimate the Health Impact of Public Health Policy Scenarios Thu, 25 Sep 2014 11:05:18 +0000 http://www.hindawi.com/journals/scientifica/2014/748750/ Noncommunicable disease (NCD) scenario models are an essential part of the public health toolkit, allowing for an estimate of the health impact of population-level interventions that are not amenable to assessment by standard epidemiological study designs (e.g., health-related food taxes and physical infrastructure projects) and extrapolating results from small samples to the whole population. The PRIME (Preventable Risk Integrated ModEl) is an openly available NCD scenario model that estimates the effect of population-level changes in diet, physical activity, and alcohol and tobacco consumption on NCD mortality. The structure and methods employed in the PRIME are described here in detail, including the development of open source code that will support a PRIME web application to be launched in 2015. This paper reviews scenario results from eleven papers that have used the PRIME, including estimates of the impact of achieving government recommendations for healthy diets, health-related food taxes and subsidies, and low-carbon diets. Future challenges for NCD scenario modelling, including the need for more comparisons between models and the improvement of future prediction of NCD rates, are also discussed. Peter Scarborough, Richard A. Harrington, Anja Mizdrak, Lijuan Marissa Zhou, and Aiden Doherty Copyright © 2014 Peter Scarborough et al. All rights reserved. Immune Response in Thyroid Cancer: Widening the Boundaries Thu, 25 Sep 2014 00:00:00 +0000 http://www.hindawi.com/journals/scientifica/2014/125450/ The association between thyroid cancer and thyroid inflammation has been repeatedly reported and highly debated in the literature. In fact, both molecular and epidemiological data suggest that these diseases are closely related and this association reinforces that the immune system is important for thyroid cancer progression. Innate immunity is the first line of defensive response. Unlike innate immune responses, adaptive responses are highly specific to the particular antigen that induced them. Both branches of the immune system may interact in antitumor immune response. Major effector cells of the immune system that directly target thyroid cancer cells include dendritic cells, macrophages, polymorphonuclear leukocytes, mast cells, and lymphocytes. A mixture of immune cells may infiltrate thyroid cancer microenvironment and the balance of protumor and antitumor activity of these cells may be associated with prognosis. Herein, we describe some evidences that immune response may be important for thyroid cancer progression and may help us identify more aggressive tumors, sparing the vast majority of patients from costly unnecessary invasive procedures. The future trend in thyroid cancer is an individualized therapy. Laura Sterian Ward Copyright © 2014 Laura Sterian Ward. All rights reserved. Regulation of TGF-β Signal Transduction Tue, 23 Sep 2014 00:00:00 +0000 http://www.hindawi.com/journals/scientifica/2014/874065/ Transforming growth factor-β (TGF-β) signaling regulates diverse cellular processes, including cell proliferation, differentiation, apoptosis, cell plasticity, and migration. TGF-β signaling can be mediated by Smad proteins or other signaling proteins such as MAP kinases and Akt. TGF-β signaling is tightly regulated at different levels along the pathways to ensure its proper physiological functions in different cells and tissues. Deregulation of TGF-β signaling has been associated with various kinds of diseases, such as cancer and tissue fibrosis. This paper focuses on our recent work on regulation of TGF-β signaling. Bing Zhao and Ye-Guang Chen Copyright © 2014 Bing Zhao and Ye-Guang Chen. All rights reserved. Computational Insights into Substrate and Site Specificities, Catalytic Mechanism, and Protonation States of the Catalytic Asp Dyad of β-Secretase Thu, 18 Sep 2014 09:14:00 +0000 http://www.hindawi.com/journals/scientifica/2014/598728/ In this review, information regarding substrate and site specificities, catalytic mechanism, and protonation states of the catalytic Asp dyad of β-secretase (BACE1) derived from computational studies has been discussed. BACE1 catalyzes the rate-limiting step in the generation of Alzheimer amyloid beta peptide through the proteolytic cleavage of the amyloid precursor protein. Due to its biological functioning, this enzyme has been considered as one of the most important targets for finding the cure for Alzheimer’s disease. Molecular dynamics (MD) simulations suggested that structural differences in the key regions (inserts A, D, and F and the 10s loop) of the enzyme are responsible for the observed difference in its activities towards the WT- and SW-substrates. The modifications in the flap, third strand, and insert F regions were found to be involved in the alteration in the site specificity of the glycosylphosphatidylinositol bound form of BACE1. Our QM and QM/MM calculations suggested that BACE1 hydrolyzed the SW-substrate more efficiently than the WT-substrate and that cleavage of the peptide bond occurred in the rate-determining step. The results from molecular docking studies showed that the information concerning a single protonation state of the Asp dyad is not enough to run an in silico screening campaign. Arghya Barman and Rajeev Prabhakar Copyright © 2014 Arghya Barman and Rajeev Prabhakar. All rights reserved. Adipose Tissue and Adipokines: The Association with and Application of Adipokines in Obesity Wed, 17 Sep 2014 11:28:43 +0000 http://www.hindawi.com/journals/scientifica/2014/328592/ 2014 marks the 20th anniversary of adipokines. Through the identification of leptin, our perceived understanding of adipose tissue was changed instantaneously. From a simple dormant site of energy storage, adipose tissue is now recognized as an integral hub of various hormones known as adipokines. Although great strides have been made in characterizing these hormones in health, research also shows they are significantly implicated in a series of pathologies. One such condition is obesity. Defined as an excess of adipose tissue, obesity remains one of the greatest healthcare epidemics of the 21st century. With no definitive treatment, attention has shifted to understanding the role of adipokines in obesity. This review provides an introduction to the salient obesity-related adipokines and their possible application as a treatment for obesity. Muhammad Khan and Frank Joseph Copyright © 2014 Muhammad Khan and Frank Joseph. All rights reserved. Walking along the Fibroblast Growth Factor 10 Route: A Key Pathway to Understand the Control and Regulation of Epithelial and Mesenchymal Cell-Lineage Formation during Lung Development and Repair after Injury Thu, 11 Sep 2014 07:45:33 +0000 http://www.hindawi.com/journals/scientifica/2014/538379/ Basic research on embryonic lung development offers unique opportunities to make important discoveries that will impact human health. Developmental biologists interested in the molecular control of branching morphogenesis have intensively studied the developing lung, with its complex and seemingly stereotyped ramified structure. However, it is also an organ that is linked to a vast array of clinical problems in humans such as bronchopulmonary dysplasia in premature babies and emphysema, chronic obstructive pulmonary disease, fibrosis, and cancer in adults. Epithelial stem/progenitor cells reside in niches where they interact with specific extracellular matrices as well as with mesenchymal cells; the latter are still poorly characterized. Interactions of epithelial stem/progenitor cells with their microenvironments are usually instructive, controlling quiescence versus activation, proliferation, differentiation, and migration. During the past 18 years, Fgf10 has emerged not only as a marker for the distal lung mesenchyme during early lung development, but also as a key player in branching morphogenesis and a critical component of the niche for epithelial stem cells. In this paper, we will present the current knowledge regarding the lineage tree in the lung, with special emphasis on cell-lineage decisions in the lung mesenchyme and the role of Fgf10 in this context. Elie El Agha and Saverio Bellusci Copyright © 2014 Elie El Agha and Saverio Bellusci. All rights reserved. A New Approach in Risk Stratification by Coronary CT Angiography Mon, 01 Sep 2014 00:00:00 +0000 http://www.hindawi.com/journals/scientifica/2014/278039/ For a decade, coronary computed tomographic angiography (CCTA) has been used as a promising noninvasive modality for the assessment of coronary artery disease (CAD) as well as cardiovascular risks. CCTA can provide more information incorporating the presence, extent, and severity of CAD; coronary plaque burden; and characteristics that highly correlate with those on invasive coronary angiography. Moreover, recent techniques of CCTA allow assessing hemodynamic significance of CAD. CCTA may be potentially used as a substitute for other invasive or noninvasive modalities. This review summarizes risk stratification by anatomical and hemodynamic information of CAD, coronary plaque characteristics, and burden observed on CCTA. Rine Nakanishi and Matthew J. Budoff Copyright © 2014 Rine Nakanishi and Matthew J. Budoff. All rights reserved. Using the Neurofibromatosis Tumor Predisposition Syndromes to Understand Normal Nervous System Development Thu, 28 Aug 2014 00:00:00 +0000 http://www.hindawi.com/journals/scientifica/2014/915725/ Development is a tightly regulated process that involves stem cell self-renewal, differentiation, cell-to-cell communication, apoptosis, and blood vessel formation. These coordinated processes ensure that tissues maintain a size and architecture that is appropriate for normal tissue function. As such, tumors arise when cells acquire genetic mutations that allow them to escape the normal growth constraints. In this regard, the study of tumor predisposition syndromes affords a unique platform to better understand normal development and the process by which normal cells transform into cancers. Herein, we review the processes governing normal brain development, discuss how brain cancer represents a disruption of these normal processes, and highlight insights into both normal development and cancer made possible by the study of tumor predisposition syndromes. Cynthia Garcia and David H. Gutmann Copyright © 2014 Cynthia Garcia and David H. Gutmann. All rights reserved. Speech Evoked Auditory Brainstem Response in Stuttering Tue, 19 Aug 2014 08:17:15 +0000 http://www.hindawi.com/journals/scientifica/2014/328646/ Auditory processing deficits have been hypothesized as an underlying mechanism for stuttering. Previous studies have demonstrated abnormal responses in subjects with persistent developmental stuttering (PDS) at the higher level of the central auditory system using speech stimuli. Recently, the potential usefulness of speech evoked auditory brainstem responses in central auditory processing disorders has been emphasized. The current study used the speech evoked ABR to investigate the hypothesis that subjects with PDS have specific auditory perceptual dysfunction. Objectives. To determine whether brainstem responses to speech stimuli differ between PDS subjects and normal fluent speakers. Methods. Twenty-five subjects with PDS participated in this study. The speech-ABRs were elicited by the 5-formant synthesized syllable/da/, with duration of 40 ms. Results. There were significant group differences for the onset and offset transient peaks. Subjects with PDS had longer latencies for the onset and offset peaks relative to the control group. Conclusions. Subjects with PDS showed a deficient neural timing in the early stages of the auditory pathway consistent with temporal processing deficits and their abnormal timing may underlie to their disfluency. Ali Akbar Tahaei, Hassan Ashayeri, Akram Pourbakht, and Mohammad Kamali Copyright © 2014 Ali Akbar Tahaei et al. All rights reserved. Atrial Fibrillation: A Review of Recent Studies with a Focus on Those from the Duke Clinical Research Institute Tue, 19 Aug 2014 05:59:26 +0000 http://www.hindawi.com/journals/scientifica/2014/901586/ Atrial fibrillation is the most common arrhythmia and accounts for one-third of hospitalizations for rhythm disorders in the United States. The prevalence of atrial fibrillation averages 1% and increases with age. With the aging of the population, the number of patients with atrial fibrillation is expected to increase 150% by 2050, with more than 50% of atrial fibrillation patients being over the age of 80. This increasing burden of atrial fibrillation will lead to a higher incidence of stroke, as patients with atrial fibrillation have a five- to sevenfold greater risk of stroke than the general population. Strokes secondary to atrial fibrillation have a worse prognosis than in patients without atrial fibrillation. Vitamin K antagonists (e.g., warfarin), direct thrombin inhibitors (dabigatran), and factor Xa inhibitors (rivaroxaban and apixaban) are all oral anticoagulants that have been FDA approved for the prevention of stroke in atrial fibrillation. This review will summarize the experience of anticoagulants in patients with atrial fibrillation with a focus on the experience at the Duke Clinic Research Institute. Meena P. Rao, Sean D. Pokorney, and Christopher B. Granger Copyright © 2014 Meena P. Rao et al. All rights reserved. Absorbed Radiation Dose in Radiosensitive Organs Using 64- and 320-Row Multidetector Computed Tomography: A Comparative Study Wed, 06 Aug 2014 09:16:30 +0000 http://www.hindawi.com/journals/scientifica/2014/305942/ Aim. To determine absorbed radiation dose (ARD) in radiosensitive organs during prospective and full phase dose modulation using ECG-gated MDCTA scanner under 64- and 320-row detector modes. Methods. Female phantom was used to measure organ radiation dose. Five DP-3 radiation detectors were used to measure ARD to lungs, breast, and thyroid using the Aquilion ONE scanner in 64- and 320-row modes using both prospective and dose modulation in full phase acquisition. Five measurements were made using three tube voltages: 100, 120, and 135 kVp at 400 mA at heart rate (HR) of 60 and 75 bpm for each protocol. Mean acquisition was recorded in milligrays (mGy). Results. Mean ARD was less for 320-row versus 64-row mode for each imaging protocol. Prospective EKG-gated imaging protocol resulted in a statistically lower ARD using 320-row versus 64-row modes for midbreast (6.728 versus 19.687 mGy, ), lung (6.102 versus 21.841 mGy, ), and thyroid gland (0.208 versus 0.913 mGy; ). Retrospective imaging using 320- versus 64-row modes showed lower ARD for midbreast (10.839 versus 43.169 mGy, ), lung (8.848 versus 47.877 mGy, ), and thyroid gland (0.057 versus 2.091 mGy; ). ARD reduction was observed at lower kVp and heart rate. Conclusions. Dose reduction to radiosensitive organs is achieved using 320-row compared to 64-row modes for both prospective and retrospective gating, whereas 64-row mode is equivalent to the same model 64-row MDCT scanner. Atif N. Khan, Waqas Shuaib, Boris Nikolic, Mohammad K. Khan, Jian Kang, and Faisal Khosa Copyright © 2014 Atif N. Khan et al. All rights reserved. Detection of β-Lactamases and Outer Membrane Porins among Klebsiella pneumoniae Strains Isolated in Iran Sun, 03 Aug 2014 11:39:59 +0000 http://www.hindawi.com/journals/scientifica/2014/726179/ This descriptive study was accomplished on 83 K. pneumoniae strains isolated from two hospitals in Tehran, Iran. Antibiotic susceptibility tests were performed by disc diffusion and broth microdilution methods. ESBLs, MBL, Amp-C, and KPC producing strains were detected by phenotypic confirmatory test, combination disk diffusion test (CDDT), Amp-C detection kit, and modified Hodge test, respectively. OXA-48, NDM-1, and CTX-M-15 genes were detected by PCR and sequencing methods. The outer membrane porins such as OmpK35 and OmpK36 were analysed by SDS-PAGE, PCR, and sequencing methods. From 83 K. pneumoniae isolates, 48 (57.5%), 3 (3.5%), 23 (28%), and 5 (6%) were ESBL, MBL, Amp-C, and KPC positive, respectively. The CTX-M-15 gene was detected in 30 (62.5%) and OXA-48 gene was found in 2 (4.1%) of the 48 ESBL-producing isolates. Two isolates harboured both OXA-48 and CTX-M-15; NDM-1 gene was not detected in this study. Outer membrane porin, OmpK35, was detected in 30 (62.5%) of 48 ESBL-producing isolates while OmpK36 was found in 35 (72.91%) of 48 ESBL-producing isolates. In this study, fosfomycin and tigecycline were more effective than other antibiotics. The high prevalence of β-lactamase-producing K. pneumoniae detected in this study is of great concern, which requires infection control measures including antibacterial management and identification of β-lactamases-producing isolates. Ali Hashemi, Fatemeh Fallah, Soroor Erfanimanesh, Parastu Hamedani, Shadi Alimehr, and Hossein Goudarzi Copyright © 2014 Ali Hashemi et al. All rights reserved. Relationship between Nutrition Knowledge and Physical Fitness in Semiprofessional Soccer Players Mon, 21 Jul 2014 11:41:26 +0000 http://www.hindawi.com/journals/scientifica/2014/180353/ Whereas nutrition has a crucial role on sport performance, it is not clear to what extent nutrition knowledge is associated with physical fitness. The aim of this study was to examine the current level of nutrition knowledge of soccer players and whether this level is associated with physical fitness. Soccer players (, aged  yr, weight  kg, and height  cm) performed a battery of physical fitness tests (sit-and-reach test, SAR; physical working capacity in heart rate 170, PWC170; and Wingate anaerobic test, WAnT) and completed an 11-item nutrition knowledge questionnaire (NKQ). Low to moderate Pearson correlations (, ) of NKQ with age, weight, height, fat free mass (FFM), SAR, peak power, and mean power of WAnT were observed. Soccer players with high score in NKQ were older (4.4 yr (2.2; 6.6), mean difference (95% confidence intervals)) and heavier (4.5 kg (0.6; 8.3)) with higher FFM (4.0 kg (1.1; 6.8)) and peak power (59 W (2; 116)) than their counterparts with low score. The moderate score in the NKQ suggests that soccer players should be targeted for nutrition education. Although the association between NKQ and physical fitness was low to moderate, there were indications that better nutrition knowledge might result in higher physical fitness and, consequently, soccer performance. P. T. Nikolaidis and E. Theodoropoulou Copyright © 2014 P. T. Nikolaidis and E. Theodoropoulou. All rights reserved. Understanding Thoracic Outlet Syndrome Sun, 20 Jul 2014 11:54:49 +0000 http://www.hindawi.com/journals/scientifica/2014/248163/ The diagnosis of thoracic outlet syndrome was once debated in the world of vascular surgery. Today, it is more understood and surprisingly less infrequent than once thought. Thoracic outlet syndrome (TOS) is composed of three types: neurogenic, venous, and arterial. Each type is in distinction to the others when considering patient presentation and diagnosis. Remarkable advances have been made in surgical approach, physical therapy, and rehabilitation of these patients. Dedicated centers of excellence with multidisciplinary teams have been developed and continue to lead the way in future research. Julie Freischlag and Kristine Orion Copyright © 2014 Julie Freischlag and Kristine Orion. All rights reserved. Ionotropic GABA Receptors and Distal Retinal ON and OFF Responses Sun, 20 Jul 2014 06:55:01 +0000 http://www.hindawi.com/journals/scientifica/2014/149187/ In the vertebrate retina, visual signals are segregated into parallel ON and OFF pathways, which provide information for light increments and decrements. The segregation is first evident at the level of the ON and OFF bipolar cells in distal retina. The activity of large populations of ON and OFF bipolar cells is reflected in the b- and d-waves of the diffuse electroretinogram (ERG). The role of gamma-aminobutyric acid (GABA), acting through ionotropic GABA receptors in shaping the ON and OFF responses in distal retina, is a matter of debate. This review summarized current knowledge about the types of the GABAergic neurons and ionotropic GABA receptors in the retina as well as the effects of GABA and specific GABAA and GABAC receptor antagonists on the activity of the ON and OFF bipolar cells in both nonmammalian and mammalian retina. Special emphasis is put on the effects on b- and d-waves of the ERG as a useful tool for assessment of the overall function of distal retinal ON and OFF channels. The role of GABAergic system in establishing the ON-OFF asymmetry concerning the time course and absolute and relative sensitivity of the ERG responses under different conditions of light adaptation in amphibian retina is also discussed. E. Popova Copyright © 2014 E. Popova. All rights reserved. Night-Time Decibel Hell: Mapping Noise Exposure Zones and Individual Annoyance Ratings in an Urban Environment in Ghana Thu, 17 Jul 2014 08:11:40 +0000 http://www.hindawi.com/journals/scientifica/2014/892105/ Although accumulating evidence over the past thirty years indicates that noise is an environmental stressor in residential settings, much of the data emanated from studies in high-intensity, noise impact zones around airports or major roads. Little is known about religious noise, especially at night, which is increasingly a growing concern for both the general public and policy-makers in sub-Saharan Africa. Using geographical information systems (GIS), this study measured and mapped exposure to religious noise in a rapidly urbanising municipality in Ghana. Quantitative noise risk assessment was used to evaluate the risk of religious noise-induced hearing loss to residents in the exposed neighbourhoods. The results show that all neighbourhoods where churches were situated had at least one location with significant risk of noise-induced hearing loss. However, there was no statistically significant relationship between neighbourhoods where religious noise exposure was the highest and where noise annoyance was the highest. The magnitude of the noise values for night-time exposure is remarkable particularly given that excessive night-time noise exposure has the greatest detrimental effect on public health. There is the need to focus on vulnerable groups, sensitive hours of the night, and possible confounding with air pollution in order to wholly address this potential hazard. Rachel N. Zakpala, Frederick Ato Armah, Brigid M. Sackey, and Opoku Pabi Copyright © 2014 Rachel N. Zakpala et al. All rights reserved. Detection of Circulating Tumor Cells Tue, 15 Jul 2014 07:49:48 +0000 http://www.hindawi.com/journals/scientifica/2014/819362/ The increasing number of treatment options for patients with metastatic carcinomas has created an accompanying need for methods to determine if the tumor will be responsive to the intended therapy and to monitor its effectiveness. Ideally, these methods would be noninvasive and provide quantitative real-time analysis of tumor activity in a variety of carcinomas. Assessment of circulating tumor cells shed into the blood during metastasis may satisfy this need. Here we review the CellSearch technology used for the detection of circulating tumor cells and discuss potential future directions for improvements. Sanne de Wit, Guus van Dalum, and Leon W. M. M. Terstappen Copyright © 2014 Sanne de Wit et al. All rights reserved. Prevalence of blaNDM, blaPER, blaVEB, blaIMP, and blaVIM Genes among Acinetobacter baumannii Isolated from Two Hospitals of Tehran, Iran Tue, 15 Jul 2014 00:00:00 +0000 http://www.hindawi.com/journals/scientifica/2014/245162/ Background and Objectives. The aim of this study was to determine the frequency of blaNDM, blaPER, blaVEB, blaIMP, and blaVIM type genes among A. baumannii isolates from hospitalized patients in two hospitals in Tehran, Iran. Patients and Methods. Antibiotic susceptibility tests were performed by Kirby-Bauer disc diffusion and Broth microdilution methods. The frequency of MBL (metallo-beta-lactamase) and ESBL (extended-spectrum-beta-lactamase) producers was evaluated by CDDT. The β-lactamases genes were detected by PCR and sequencing methods. Results. The resistance of A. baumannii isolates against tested antibiotics was as follows: 103 (95.4%) to ceftazidime, 108 (100%) to cefotaxime, 105 (95.7%) to cefepime, 99 (91.7%) to imipenem, 99 (91.7%) to meropenem, 87 (80.6%) to amikacin, 105 (97.2%) to piperacillin, 100 (92.6%) to ciprofloxacin, 103 (95.4%) to piperacillin/tazobactam, 44 (40.7%) to gentamicin, 106 (98.1%) to ampicillin/sulbactam, 106 (98.1%) to co-trimoxazole, 87 (80.6%) to tetracycline, and 1 (1.8%) to colistin. Using combined disk diffusion test, 91 (84.2%) and 86 (86.86%) were ESBL and MBL producers, respectively. The prevalence of blaPER-1, blaVEB-1, blaIMP-1, and blaVIM-1 genes was 71 (78.03%), 36 (39.5%), 3 (3.48%), and 15 (17.44%), respectively. Conclusions. The prevalence of ESBLs and MBLs-producing A. baumannii strains detected in this study is a major concern and highlights the need of infection control measures. Fatemeh Fallah, Maryam Noori, Ali Hashemi, Hossein Goudarzi, Abdollah Karimi, Soroor Erfanimanesh, and Shadi Alimehr Copyright © 2014 Fatemeh Fallah et al. All rights reserved. Development of the Rat Model of Lapatinib-Induced Diarrhoea Mon, 07 Jul 2014 11:31:58 +0000 http://www.hindawi.com/journals/scientifica/2014/194185/ Targeted therapy of cancer is often associated with clinically significant diarrhoea; however, the mechanisms underpinning this adverse effect are currently unknown. Diarrhoea following treatment with tyrosine kinase inhibitors (TKIs) of EGFR is particularly troublesome. Until recently, understanding of EGFR TKI-induced diarrhoea has been limited to clinical observation. However, our group has recently developed the first rat model of EGFR TKI-induced diarrhoea. This paper reviews the published and unpublished findings. Joanne M. Bowen Copyright © 2014 Joanne M. Bowen. All rights reserved. Does B Cell Receptor Signaling in Chronic Lymphocytic Leukaemia Cells Differ from That in Other B Cell Types? Wed, 02 Jul 2014 00:00:00 +0000 http://www.hindawi.com/journals/scientifica/2014/208928/ Chronic lymphocytic leukaemia (CLL) is an incurable malignancy of mature B cells. CLL is important clinically in Western countries because of its commonality and because of the significant morbidity and mortality associated with the progressive form of this incurable disease. The B cell receptor (BCR) expressed on the malignant cells in CLL contributes to disease pathogenesis by providing signals for survival and proliferation, and the signal transduction pathway initiated by engagement of this receptor is now the target of several therapeutic strategies. The purpose of this review is to outline current understanding of the BCR signal cascade in normal B cells and then question whether this understanding applies to CLL cells. In particular, this review studies the phenomenon of anergy in CLL cells, and whether certain adaptations allow the cells to overcome anergy and allow full BCR signaling to take place. Finally, this review analyzes how BCR signals can be therapeutically targeted for the treatment of CLL. Joseph R. Slupsky Copyright © 2014 Joseph R. Slupsky. All rights reserved. Anti-Inflammatory and Antimicrobial Actions of Vitamin D in Combating TB/HIV Wed, 02 Jul 2014 00:00:00 +0000 http://www.hindawi.com/journals/scientifica/2014/903680/ Tuberculosis (TB) disease activation is now believed to arise due to a lack of inflammatory homeostatic control at either end of the spectrum of inflammation: either due to immunosuppression (decreased antimicrobial activity) or due to immune activation (excess/aberrant inflammation). Vitamin D metabolites can increase antimicrobial activity in innate immune cells, which, in the context of HIV-1 coinfection, have insufficient T cell-mediated help to combat Mycobacterium tuberculosis (MTB) infection. Moreover, maintaining vitamin D sufficiency prior to MTB infection enhances the innate antimicrobial response to T cell-mediated interferon-γ. Conversely, vitamin D can act to inhibit expression and secretion of a broad range of inflammatory mediators and matrix degrading enzymes driving immunopathology during active TB and antiretroviral- (ARV-) mediated immune reconstitution inflammatory syndrome (IRIS). Adjunct vitamin D therapy during treatment of active TB may therefore reduce lung pathology and TB morbidity, accelerate resolution of cavitation and thereby decrease the chance of transmission, improve lung function following therapy, prevent relapse, and prevent IRIS in those initiating ARVs. Future clinical trials of vitamin D for TB prevention and treatment must be designed to detect the most appropriate primary endpoint, which in some cases should be anti-inflammatory and not antimicrobial. Anna K. Coussens, Adrian R. Martineau, and Robert J. Wilkinson Copyright © 2014 Anna K. Coussens et al. All rights reserved. Therapy of Hypoparathyroidism by Replacement with Parathyroid Hormone Tue, 01 Jul 2014 07:51:02 +0000 http://www.hindawi.com/journals/scientifica/2014/765629/ Hypoparathyroidism (HypoPT) is a state of hypocalcemia due to inappropriate low levels of parathyroid hormone (PTH). HypoPT is normally treated by calcium supplements and activated vitamin D analogues. Although plasma calcium is normalized in response to conventional therapy, quality of life (QoL) seems impaired and patients are at increased risk of renal complications. A number of studies have suggested subcutaneous injections with PTH as an alternative therapy. By replacement with the missing hormone, urinary calcium may be lowered and QoL may improve. PTH replacement therapy (PTH-RT) possesses, nevertheless, a number of challenges. If PTH is injected only once a day, fluctuations in calcium levels may occur resulting in hypercalcemia in the hours following an injection. Twice-a-day injections seem to cause less fluctuation in plasma calcium but do stimulate bone turnover to above normal. Most recently, continuous delivery of PTH by pump has appeared as a feasible alternative to injections. Plasma calcium levels do not fluctuate, urinary calcium is lowered, and bone turnover is only stimulated modestly (into the normal range). Further studies are needed to assess the long-term effects. If beneficial, it seems likely that standard treatment of HypoPT in the future will change into replacement therapy with the missing hormone. Lars Rejnmark, Line Underbjerg, and Tanja Sikjaer Copyright © 2014 Lars Rejnmark et al. All rights reserved. Staphylococcus aureus: Screening for Nasal Carriers in a Community Setting with Special Reference to MRSA Wed, 25 Jun 2014 11:31:13 +0000 http://www.hindawi.com/journals/scientifica/2014/479048/ Introduction. Emergence of MRSA infections among previously healthy persons in community settings (without exposure to health care facilities) has been noted recently. MRSA infections are now classified as health care-associated MRSA (HA-MRSA) and community-associated MRSA (CA-MRSA) infections. Its colonization is an important risk factor for subsequent MRSA infection. Aims and Objectives. The aim was to screen patients and health care workers for staphylococcal carriage, identify risk factors for MRSA colonization, and determine the sensitivity pattern. Materials and Methods. A total of 200 subjects were screened for nasal carriage after obtaining verbal consent. These were both healthy subjects attending various outpatient departments and health care workers. Specimens were collected from the anterior nares using premoistened sterile cotton swabs and inoculated onto blood agar and mannitol salt agar and incubated at 37°C for 24–48 h. Results. Staphylococcus aureus colonisation was found to be 12% (). MRSA was identified in 5% () which represents 41.66% of SA. A total of 10 strains of MRSA were isolated from 200 subjects, giving an overall positivity rate of 5%. Discussion. Staphylococcal colonization was found to be 12% (MRSA 5%). Fluoroquinolone resistance was remarkable whereas all strains were sensitive to vancomycin, teicoplanin, linezolid, quinupristin-dalfopristin. Yukti Sharma, Sanjay Jain, Harshvardhan Singh, and Vasudha Govil Copyright © 2014 Yukti Sharma et al. All rights reserved. Patent Foramen Ovale and Closure Technique with the Amplatzer Occluder Wed, 25 Jun 2014 08:18:27 +0000 http://www.hindawi.com/journals/scientifica/2014/129196/ Proof that percutaneous closure of the patent foramen ovale (PFO) is superior to medical treatment is still incomplete. Paradoxical embolism is a rare event occurring over decades rather than years. None of the 4 randomized trials published carried enough patients or was followed up for long enough to reach superiority endpoints. All data, however, point to a benefit of PFO closure. Free wall erosion (exceedingly rare) and triggering of atrial fibrillation (in about 1% of patients) are the only noteworthy complications. They are outweighed by the supposedly prevented events of paradoxical embolisms, such as stroke, transient ischemic attacks, myocardial infarctions, or other systemic embolisms. Medical treatment with perhaps the exception of lifelong oral anticoagulation provides less protection. During a 10-year follow-up of a comparative study the annual mortality was significantly lower in the patients with PFO closure (0.4%) than in those with medical treatment (1.1%, ). PFO closure can be accomplished in less than 1 hour with immediate resumption of physical activity. It represents thus a kind of mechanical vaccination. Bernhard Meier Copyright © 2014 Bernhard Meier. All rights reserved. Utilizing Cytokines to Function-Enable Human NK Cells for the Immunotherapy of Cancer Wed, 25 Jun 2014 05:49:29 +0000 http://www.hindawi.com/journals/scientifica/2014/205796/ Natural killer (NK) cells are innate lymphoid cells important for host defense against pathogens and mediate antitumor immunity. Cytokine receptors transduce important signals that regulate proliferation, survival, activation status, and trigger effector functions. Here, we review the roles of major cytokines that regulate human NK cell development, survival, and function, including IL-2, IL-12, IL-15, IL-18, and IL-21, and their translation to the clinic as immunotherapy agents. We highlight a recent development in NK cell biology, the identification of innate NK cell memory, and focus on cytokine-induced memory-like (CIML) NK cells that result from a brief, combined activation with IL-12, IL-15, and IL-18. This activation results in long lived NK cells that exhibit enhanced functionality when they encounter a secondary stimulation and provides a new approach to enable NK cells for enhanced responsiveness to infection and cancer. An improved understanding of the cellular and molecular aspects of cytokine-cytokine receptor signals has led to a resurgence of interest in the clinical use of cytokines that sustain and/or activate NK cell antitumor potential. In the future, such strategies will be combined with negative regulatory signal blockade and enhanced recognition to comprehensively enhance NK cells for immunotherapy. Rizwan Romee, Jeffrey W. Leong, and Todd A. Fehniger Copyright © 2014 Rizwan Romee et al. All rights reserved. Suppression of the Oncogenic Transcription Factor FOXM1 by Proteasome Inhibitors Tue, 24 Jun 2014 13:29:15 +0000 http://www.hindawi.com/journals/scientifica/2014/596528/ The oncogenic transcription factor FOXM1 is one of the key regulators of tumorigenesis. We found that FOXM1 upregulates its own transcription and its protein stability depends on its interaction with the chaperone nucleophosmin. We also determined that FOXM1 is negatively regulated by the tumor suppressor p53. We identified the thiazole antibiotics Siomycin A and thiostrepton as inhibitors of transcriptional activity and FOXM1 expression via proteasome inhibition. In addition, we found that all tested proteasome inhibitors target FOXM1. We showed synergy between thiostrepton and bortezomib in different human cancer cell lines and in vivo. We generated isogenic human cancer cell lines of different origin with wild-type p53 or p53 knockdown and we demonstrated that proteasome inhibitors induce p53-independent apoptosis in these cells. Using RNA-interference or proteasome inhibitors to inhibit FOXM1 we found that suppression of FOXM1 sensitized human cancer cells to apoptosis induced by DNA-damaging agents or oxidative stress. We encapsulated thiostrepton into micelle-nanoparticles and after injection we detected accumulation of nanoparticles in tumors and in the livers of treated mice. This treatment led to inhibition of human xenograft tumor growth in nude mice. Our data indicate that targeting FOXM1 increases apoptosis and inhibits tumor growth. Andrei L. Gartel Copyright © 2014 Andrei L. Gartel. All rights reserved. The Cardioprotective Actions of Hydrogen Sulfide in Acute Myocardial Infarction and Heart Failure Sun, 22 Jun 2014 09:02:34 +0000 http://www.hindawi.com/journals/scientifica/2014/768607/ It has now become universally accepted that hydrogen sulfide (H2S), previously considered only as a lethal toxin, has robust cytoprotective actions in multiple organ systems. The diverse signaling profile of H2S impacts multiple pathways to exert cytoprotective actions in a number of pathological states. This paper will review the recently described cardioprotective actions of hydrogen sulfide in both myocardial ischemia/reperfusion injury and congestive heart failure. David J. Polhemus, John W. Calvert, Javed Butler, and David J. Lefer Copyright © 2014 David J. Polhemus et al. All rights reserved. Radiosensitivity and Induction of Apoptosis by High LET Carbon Ion Beam and Low LET Gamma Radiation: A Comparative Study Sun, 15 Jun 2014 08:54:46 +0000 http://www.hindawi.com/journals/scientifica/2014/438030/ Cancer treatment with high LET heavy ion beam, especially, carbon ion beam (12C), is becoming very popular over conventional radiotherapy like low LET gamma or X-ray. Combination of Poly(ADP-ribose) polymerase (PARP) inhibitor with xenotoxic drugs or conventional radiation (gamma or X-ray) is the newer approach for cancer therapy. The aim of our study was to compare the radiosensitivity and induction of apoptosis by high LET 12C and low LET gamma radiation in HeLa and PARP-1 knocked down cells. We did comet assay to detect DNA breaks, clonogenic survival assay, and cell cycle analysis to measure recovery after DNA damage. We measured apoptotic parameters like nuclear fragmentation and caspase-3 activation. DNA damage, cell killing, and induction of apoptosis were significantly higher for 12C than gamma radiation in HeLa. Cell killing and apoptosis were further elevated upon knocking down of PARP-1. Both 12C and gamma induced G2/M arrest although the 12C had greater effect. Unlike the gamma, 12C irradiation affects DNA replication as detected by S-phase delay in cell cycle analysis. So, we conclude that high LET 12C has greater potential over low LET gamma radiation in killing cells and radiosensitization upon PARP-1 inhibition was several folds greater for 12C than gamma. Atanu Ghorai, Nitai P. Bhattacharyya, Asitikantha Sarma, and Utpal Ghosh Copyright © 2014 Atanu Ghorai et al. All rights reserved.