Scientifica The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. Speech Evoked Auditory Brainstem Response in Stuttering Tue, 19 Aug 2014 08:17:15 +0000 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 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 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 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, and Shadi Alimehr 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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. Perfluorocarbon Nanoparticles: Evolution of a Multimodality and Multifunctional Imaging Agent Thu, 12 Jun 2014 10:46:38 +0000 Perfluorocarbon nanoparticles offer a biologically inert, highly stable, and nontoxic platform that can be specifically designed to accomplish a range of molecular imaging and drug delivery functions in vivo. The particle surface can be decorated with targeting ligands to direct the agent to a variety of biomarkers that are associated with diseases such as cancer, cardiovascular disease, obesity, and thrombosis. The surface can also carry a high payload of imaging agents, ranging from paramagnetic metals for MRI, radionuclides for nuclear imaging, iodine for CT, and florescent tags for histology, allowing high sensitivity mapping of cellular receptors that may be expressed at very low levels in the body. In addition to these diagnostic imaging applications, the particles can be engineered to carry highly potent drugs and specifically deposit them into cell populations that display biosignatures of a variety of diseases. The highly flexible and robust nature of this combined molecular imaging and drug delivery vehicle has been exploited in a variety of animal models to demonstrate its potential impact on the care and treatment of patients suffering from some of the most debilitating diseases. Patrick M. Winter Copyright © 2014 Patrick M. Winter. All rights reserved. XB130—A Novel Adaptor Protein: Gene, Function, and Roles in Tumorigenesis Thu, 05 Jun 2014 08:52:38 +0000 Several adaptor proteins have previously been shown to play an important role in the promotion of tumourigenesis. XB130 (AFAP1L2) is an adaptor protein involved in many cellular functions, such as cell survival, cell proliferation, migration, and gene and miRNA expression. XB130’s functional domains and motifs enable its interaction with a multitude of proteins involved in several different signaling pathways. As a tyrosine kinase substrate, tyrosine phosphorylated XB130 associates with the p85α regulatory subunit of phosphoinositol-3-kinase (PI3K) and subsequently affects Akt activity and its downstream signalling. Tumourigenesis studies show that downregulation of XB130 expression by RNAi inhibits tumor growth in mouse xenograft models. Furthermore, XB130 affects tumor oncogenicity by regulating the expression of specific tumour suppressing miRNAs. The expression level and pattern of XB130 has been studied in various human tumors, such as thyroid, esophageal, and gastric cancers, as well as, soft tissue tumors. Studies show the significant effects of XB130 in tumourigenesis and suggest its potential as a diagnostic biomarker and therapeutic target for cancer treatments. Xiao-Hui Bai, Hae-Ra Cho, Serisha Moodley, and Mingyao Liu Copyright © 2014 Xiao-Hui Bai et al. All rights reserved. Inducible Protective Processes in Animal Systems XIII: Comparative Analysis of Induction of Adaptive Response by EMS and MMS in Ehrlich Ascites Carcinoma Cells Wed, 04 Jun 2014 11:51:31 +0000 In order to investigate the presence of adaptive response in cancerous cells, two monofunctional alkylating agents, namely, ethyl methanesulfonate (EMS) and methyl methanesulfonate (MMS), were employed to treat Ehrlich ascites carcinoma (EAC) cells in vivo. Conditioning dose of 80 mg/kg body weight of EMS or 50 mg/kg body weight of MMS and challenging dose of 240 mg/kg body weight of EMS or 150 mg/kg body weight of MMS were selected by pilot toxicity studies. Conditioned EAC cells when challenged after 8 h time lag resulted in significant reduction in chromosomal aberrations compared to challenging dose of respective agents. As has been proved in earlier studies with normal organisms, even in cancerous cells (EAC), there is presence of adaptive response to methylating and ethylating agents. Furthermore, it is also interesting to note in the present studies that the methylating agent, MMS, is a stronger inducer of the adaptive response than the ethylating agent, EMS. Periyapatna Vishwaprakash Mahadimane and Venkateshaiah Vasudev Copyright © 2014 Periyapatna Vishwaprakash Mahadimane and Venkateshaiah Vasudev. All rights reserved. Improving the Performance of Phase-Change Perfluorocarbon Droplets for Medical Ultrasonography: Current Progress, Challenges, and Prospects Sun, 01 Jun 2014 12:34:23 +0000 Over the past two decades, perfluorocarbon (PFC) droplets have been investigated for biomedical applications across a wide range of imaging modalities. More recently, interest has increased in “phase-change” PFC droplets (or “phase-change” contrast agents), which can convert from liquid to gas with an external energy input. In the field of ultrasound, phase-change droplets present an attractive alternative to traditional microbubble agents for many diagnostic and therapeutic applications. Despite the progress, phase-change PFC droplets remain far from clinical implementation due to a number of challenges. In this review, we survey our recent work to enhance the performance of phase-change agents for ultrasound through a variety of techniques in order to provide increased efficacy in therapeutic applications of ultrasound and enable previously unexplored applications in diagnostic and molecular imaging. Paul S. Sheeran and Paul A. Dayton Copyright © 2014 Paul S. Sheeran and Paul A. Dayton. All rights reserved. Clostridium difficile Infection: Epidemiology, Pathogenesis, Risk Factors, and Therapeutic Options Sun, 01 Jun 2014 11:02:53 +0000 The incidence and mortality rate of Clostridium difficile infection have increased remarkably in both hospital and community settings during the last two decades. The growth of infection may be caused by multiple factors including inappropriate antibiotic usage, poor standards of environmental cleanliness, changes in infection control practices, large outbreaks of C. difficile infection in hospitals, alteration of circulating strains of C. difficile, and spread of hypervirulent strains. Detection of high-risk populations could be helpful for prompt diagnosis and consequent treatment of patients suffering from C. difficile infection. Metronidazole and oral vancomycin are recommended antibiotics for the treatment of initial infection. Current treatments for C. difficile infection consist of supportive care, discontinuing the unnecessary antibiotic, and specific antimicrobial therapy. Moreover, novel approaches include fidaxomicin therapy, monoclonal antibodies, and fecal microbiota transplantation mediated therapy. Fecal microbiota transplantation has shown relevant efficacy to overcome C. difficile infection and reduce its recurrence. Mehdi Goudarzi, Sima Sadat Seyedjavadi, Hossein Goudarzi, Elnaz Mehdizadeh Aghdam, and Saeed Nazeri Copyright © 2014 Mehdi Goudarzi et al. All rights reserved. Reproductive Dynamics of Sterna hirundinacea Lesson, 1831 in Ilha dos Cardos, Santa Catarina, Brazil Wed, 28 May 2014 11:00:18 +0000 In this work, we intend to describe the reproductive dynamics of Sterna hirundinacea in an island from South Brazil. We studied the reproductive biology of this species in its natural environment and provide data on their growth, survival, and reproductive success in Ilha dos Cardos, Santa Catarina, South Brazil. Samplings were carried out daily on the island throughout the reproductive seasons of 2003, 2005, and 2006 and the different stages of development of the chicks were characterized according to age, length of the beak, and plumage characteristics. We provide a basic equation to determine the approximate age of individuals using their body mass. The main cause of chick mortality on the island was natural (63.17% in 2003, 81.41% in 2005, and 79.96% in 2006), whereas predation contributed to mortality in a proportion of 38.83% in 2003, 18.59% in 2005, and 20.04% in 2006. The absence in the area of the chicks’ main predator, Kelp gull (Larus dominicanus), the large number of chicks that reached the final stages of development, and their reproductive success demonstrate that Ilha dos Cardos is an important breeding site for the species in southern Brazil. Hélio Augusto Alves Fracasso, Joaquim Olinto Branco, Márcio Amorim Efe, and João Pedro Barreiros Copyright © 2014 Hélio Augusto Alves Fracasso et al. All rights reserved. Paediatric Inflammatory Bowel Disease: A Mechanistic Approach to Investigate Exclusive Enteral Nutrition Treatment Wed, 21 May 2014 13:16:45 +0000 The inflammatory bowel diseases (IBD) include Crohn’s disease (CD) and ulcerative colitis. The disease may present at any age although the peak of presentation is the second and third decades of life. The incidences of these diseases are increasing around the world with the age of presentation getting younger. At present CD is incurable with colectomy being the treatment for severe UC. Although several pharmacological approaches are used to modulate the inflammatory response in IBD, few lead to histological healing and most have side effects. An alternative approach is to use enteral formulae given exclusively (EEN) to treat IBD. EEN requires the consumption of an elemental or polymeric formula, with the exclusion of all other nutrients, for a period of up to 12 weeks. The introduction of EEN as a therapeutic option for IBD was through prudent observation; however, EEN has become an established and reliable option for the treatment of paediatric IBD. Despite this, the mechanisms through which EEN induces disease remission are unknown and remain hypothetical. This review will discuss recent research into EEN both describing clinical features of EEN therapy and discussing the most up-to-date understanding of the mechanisms through which EEN may be reducing intestinal inflammation and inducing disease remission. Lily Nahidi, Andrew S. Day, Daniel A. Lemberg, and Steven T. Leach Copyright © 2014 Lily Nahidi et al. All rights reserved. Bcl2 Family Functions as Signaling Target in Nicotine-/NNK-Induced Survival of Human Lung Cancer Cells Tue, 20 May 2014 12:45:38 +0000 Lung cancer is the leading cause of cancer death and has a strong etiological association with cigarette smoking. Nicotine and nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) are two major components in cigarette smoke that significantly contribute to the development of human lung cancer. Nicotine is able to stimulate survival of both normal human lung epithelial and lung cancer cells. In contrast to nicotine, NNK is a more potent carcinogen that not only induces single-strand DNA breaks and oxidative DNA damage but also stimulates survival and proliferation of normal lung epithelial and lung cancer cells. However, the molecular mechanism(s) by which nicotine and NNK promote cell survival, proliferation, and lung tumor development remains elusive. The fate of cells (i.e., survival or death) is largely decided by the Bcl2 family members. In the past several years, multiple signaling links between nicotine/NNK and Bcl2 family members have been identified that regulate survival and proliferation. This review provides a concise, systematic overview of the current understanding of the role of the pro- or antiapoptotic proteins in cigarette smoking, lung cancer development, and treatment resistance. Xingming Deng Copyright © 2014 Xingming Deng. All rights reserved. Phage Therapy: Eco-Physiological Pharmacology Tue, 20 May 2014 11:02:23 +0000 Bacterial virus use as antibacterial agents, in the guise of what is commonly known as phage therapy, is an inherently physiological, ecological, and also pharmacological process. Physiologically we can consider metabolic properties of phage infections of bacteria and variation in those properties as a function of preexisting bacterial states. In addition, there are patient responses to pathogenesis, patient responses to phage infections of pathogens, and also patient responses to phage virions alone. Ecologically, we can consider phage propagation, densities, distribution (within bodies), impact on body-associated microbiota (as ecological communities), and modification of the functioning of body “ecosystems” more generally. These ecological and physiological components in many ways represent different perspectives on otherwise equivalent phenomena. Comparable to drugs, one also can view phages during phage therapy in pharmacological terms. The relatively unique status of phages within the context of phage therapy as essentially replicating antimicrobials can therefore result in a confluence of perspectives, many of which can be useful towards gaining a better mechanistic appreciation of phage therapy, as I consider here. Pharmacology more generally may be viewed as a discipline that lies at an interface between organism-associated phenomena, as considered by physiology, and environmental interactions as considered by ecology. Stephen T. Abedon Copyright © 2014 Stephen T. Abedon. All rights reserved. The Association of −330 Interleukin-2 Gene Polymorphism with Its Plasma Concentration in Iranian Multiple Sclerosis Patients Mon, 19 May 2014 00:00:00 +0000 Multiple sclerosis (MS) is a chronic neuroinflammatory demyelinating disease of the central nervous system. The cytokine genes are involved in autoimmune diseases such as MS. In this study, we report the influence of −330 interleukin-2 (IL2) gene polymorphism on its plasma levels in a group of Iranian MS patients. In this study 100 MS patients and 100 ethnically, age, and sex matched healthy controls were selected from Medical Genetics Department of Sarem Women Hospital. Blood samples of all individuals were collected in EDTA tubes. The restriction fragment length polymorphism PCR (RFLP) method was applied to determine various alleles and genotypes in these individuals. Plasma concentration of IL2 was measured in all the samples using human IL2 kit. The frequency of −330 T/T IL2 genotype was higher in MS patients compared to normal individuals. Accordingly, the plasma levels of IL2 were significantly higher () in patients when compared to the control group. In conclusion, in case of MS patients the −330 T/T IL2 genotype is associated with higher plasma levels of IL2. Arezou Sayad and Abolfazl Movafagh Copyright © 2014 Arezou Sayad and Abolfazl Movafagh. All rights reserved.