Changing molecular epidemiology of rotavirus infection after introduction of monovalent rotavirus vaccination in Scotland

Publication date: Available online 18 November 2016
Source:Vaccine
Author(s): Indrani Mukhopadhya, Heather Murdoch, Susan Berry, Alison Hunt, Miren Iturriza-Gomara, Alison Smith-Palmer, J. Claire Cameron, Georgina L. Hold
BackgroundRotaviruses (RV) are the leading cause of gastroenteritis in children less than five years of age worldwide. Rotarix®, a live attenuated monovalent vaccine containing a RV strain of G1P[8] specificity has been included in the childhood immunisation schedule from June 2013 in Scotland. This study aimed to characterise the prevalent RV strains in Scotland before and after the introduction of the RV vaccine.MethodsRV positive faecal samples from Scottish virology laboratories covering the years 2012–2015 were genotyped. Viral RNA was extracted from faecal suspensions. VP7 and VP4 gene specific primers were used for multiplex hemi-nested PCRs and sequencing. Mann-Whitney U test and Chi-square test were used for statistical comparison.ResultsThere was a decrease in RV positive samples from the Scottish virology laboratories from 7409 samples in the pre-vaccination years (2009–2013) to 760 in 2014–2015, with an annual reduction of RV infections by 74.4% (RR-3.95; 95%-CI, 3.53–4.42, p<0.001). 362 samples from the pre-vaccination period and 278 samples from the post-vaccination were genotyped. There was a drop in prevalence of G1P[8] strains (72.1%, 95%-CI, 67.42–76.33 to 15%, 95%-CI, 11.38–19.79) after introduction of the vaccine. In the post-vaccination period G2P[4] was the dominant strain in Scotland (21.9%, 95%-CI, 17.48–27.17) with increase in G9P[8] (12.9%, 95%-CI, 9.50–7.41), G12P[8] (12.2%, 95%-CI, 8.89–16.60) and G3P[8] (11.9%, 95%-CI, 8.58–16.20) infections. Phylogenetic analysis of the VP7 and VP4 genes showed no major differences between the pre and post-vaccination G1P[8] strains.ConclusionThis laboratory based surveillance study shows significant reduction in reported RV cases and a shift in proportion from G1P[8] to G2P[4] strains after introduction of RV vaccination in Scotland. The genotyping data from a subset of the total reported RV cases will be used to ascertain cross protection against strains and identify vaccine induced RV strain shifts in the years to come.



http://ift.tt/2fbj2PA

Dual function of Ixr1 in transcriptional regulation and recognition of cisplatin-DNA adducts is caused by differential binding through its two HMG-boxes

Publication date: Available online 19 November 2016
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): A. Vizoso-Vázquez, M. Lamas-Maceiras, R. Fernández-Leiro, A. Rico-Díaz, M. Becerra, M.E. Cerdán
Ixr1 is a transcriptional factor involved in the response to hypoxia, which is also related to DNA repair. It binds to DNA through its two in-tandem high mobility group box (HMG-box) domains. Each function depends on recognition of different DNA structures, B-form DNA at specific consensus sequences for transcriptional regulation, or distorted DNA, like cisplatin-DNA adducts, for DNA repair. However, the contribution of the HMG-box domains in the Ixr1 protein to the formation of different protein-DNA complexes is poorly understood. We have biophysically and biochemically characterized these interactions with specific DNA sequences from the promoters regulated by Ixr1, or with cisplatin-DNA adducts. Both HMG-boxes are necessary for transcriptional regulation, and they are not functionally interchangeable. The in-tandem arrangement of their HMG-boxes is necessary for functional folding and causes sequential cooperative binding to specific DNA sequences, with HMG-box A showing a higher contribution to DNA binding and bending than the HMG-box B. Binding of Ixr1 HMG boxes to specific DNA sequences is entropy driven, whereas binding to platinated DNA is enthalpy driven for HMG-box A and entropy driven for HMG-box B. This is the first proof that HMG-box binding to different DNA structures is associated with predictable thermodynamic differences. Based on our study, we present a model to explain the dual function of Ixr1 in the regulation of gene expression and recognition of distorted DNA structures caused by cisplatin treatment.



http://ift.tt/2g8sXYv

Infrequent mismatch repair protein loss in gallbladder cancer patients in Japan

http://ift.tt/2g58l1V

Detection of mutations in the BRAF gene in patients with KIT and PDGFRA wild-type gastrointestinal stromal tumors

Abstract

Gastrointestinal stromal tumors (GISTs) are characterized by mutations in exons 9, 11, 13, and 17 of KIT or exons 12, 14, and 18 of PDGFRA gene. However, approximately 10 to 15 % of GISTs lack the mutations in KIT and PDGFRA, and these are referred to as wild-type GISTs which are less sensitive to tyrosine-kinase inhibitors. The aim of this study was to detect BRAF mutations in patients with wild-type GISTs. We applied a sensitive allele-specific PCR, which was optimized using the V600E mutation-harboring cell line RKO, followed by verification of the results by dideoxy sequencing. We selected 149 GIST patients without detectable mutations in KIT and PDGFRA genes from the Slovak national GIST register and analyzed biopsy specimens for the presence of BRAF mutations in exon 15. We identified nine patients with the V600E mutation. The BRAF-driven GISTs were primary gastric (n = 3), small intestinal (n = 3), colon (n = 1), and of uncertain origin (n = 1). We also included a liver metastasis of a patient with a simultaneous KIT exon 11-mutated intra-abdominal metastasis. We conclude that genome analysis of wild-type GISTs for mutations should include the BRAF gene, as its mutation status contributes to understanding of pathogenesis and might be important for decisions on therapy.

http://ift.tt/2fetKIu

Epstein–Barr virus infection and gene promoter hypermethylation in rheumatoid arthritis patients with methotrexate-associated B cell lymphoproliferative disorders

Abstract

We analyzed CpG-island hypermethylation status in 12 genes of paraffin-embedded tissues from 38 rheumatoid arthritis (RA) patients with methotrexate (MTX)-associated large B cell lymphoproliferative disorder (BLPD), 11 RA patients with non-MTX-associated BLPD (non-MTX-BLPD), 22 controls with diffuse large B cell lymphoma (DLBCL), and 10 controls with Epstein–Barr virus (EBV)⁺ DLBCL. Among them, tumor cells from EBV⁺ MTX-BLPD patients and control EBV⁺ DLBCL patients had significantly lower median incidence of CpG island methylator phenotype (CIMP) than those from non-MTX-BLPD and control DLBCL groups (2.3 and 1.7 vs. 4.3 and 4.4; P < 0.01 for each). In the MTX-BLPD group, EBV⁺ patients showed lower median CIMP than EBV⁻ patients (2.3 vs. 3.2); they also had significantly lower hypermethylation incidence in four apoptosis-related genes, especially death-associated protein kinase (14 vs. 55 %), higher incidence of massive tumor necrosis (86 vs. 27 %), and lower BCL2 protein expression (19 vs. 86 %) than did the control DLBCL group (P < 0.01 for all). In all clinical stages, EBV⁺ MTX-BLPD patients had better prognoses than the EBV⁻ MTX-BLPD (P = 0.011), non-MTX-BLPD (P = 0.002), and control DLBCL groups (P = 0.015). MTX-BLPD patients without hypermethylated RAS-associated domain family-1A (RASSF1A) or O ⁶-methyl guanine-DNA methyltransferase (MGMT) had significantly better prognosis than those with hypermethylation of those genes (P = 0.033). We conclude that in RA patients with MTX-BLPD, EBV infection is associated with a lower incidence of CIMP, apoptosis-related gene hypermethylation, and BCL2 expression, which can induce tumor regression by MTX withdrawal and lead to better prognoses.

http://ift.tt/2g56pWY

Effective use of 20% subcutaneous immunoglobulin therapy in a man with preexisting thrombi

Publication date: Available online 18 November 2016
Source:Annals of Allergy, Asthma & Immunology
Author(s): Carla Duff, Mandel R. Sher, Jennifer W. Leiding




http://ift.tt/2g7HyDe

Drug-induced pyoderma gangrenosum: a model to understand the pathogenesis of pyoderma gangrenosum

Summary

Pyoderma gangrenosum (PG) is a rare auto-inflammatory condition in which the alteration of neutrophil function and the innate immune response play key roles in its pathogenesis. Cases of PG have been reported in patients being treated with certain medications, which may help us to understand some of the possible pathways involved in the etiology of PG. The aim of this review is to review the cases of PG triggered by certain drugs and try to thoroughly understand the pathogenesis of the disease. To accomplish this, a PubMed search was completed using the following words: pyoderma gangrenosum, neutrophilic dermatosis, pathophysiology, drug-induced pyoderma gangrenosum. In total, we found 43 cases of drug-induced pyoderma gangrenosum. Most of them were caused by colony stimulating factors and small molecule inhibitors of tyrosine kinase. We propose that drugs induce PG through various mechanisms such as dysfunctional neutrophil migration and function, dysregulated inflammatory response, promotion of keratinocyte apoptosis and alteration of epigenetics mechanism. PG is a rare condition with complex pathophysiology and drug-induced cases are even more scarce; this is the main limitation of this review. Understanding the possible mechanisms of drug-induced PG, via abnormal neutrophil migration and function, abnormal inflammation, keratinocyte apoptosis and alteration of epigenetic mechanisms would help to better understand the pathogenesis of PG and ultimately to optimize targeted therapy.

This article is protected by copyright. All rights reserved.

http://ift.tt/2fPabEB

Atopic dermatitis patients with filaggrin loss-of-function mutations show good but lower responses to immunosuppressive treatment

Abstract

Filaggrin (FLG) mutations are a strong risk factor to develop atopic dermatitis (AD). However, the relationship between FLG mutations and treatment outcome in AD has not been thoroughly studied. To investigate whether FLG mutations influence immunosuppressive treatment outcome in AD, we studied the effect of FLG mutations in patients with severe AD participating in a single blinded randomized controlled trial (RCT) with methotrexate (MTX) or azathioprine (AZA) during a 24 weeks treatment regimen.⁽¹⁾ Two years after randomization buccal mucosa swabs were collected from 36 of the 42 RCT patients (86%) to determine the FLG genotype status (R501X, 2282del4, R2447X, S3247X and 3321delA mutations).

This article is protected by copyright. All rights reserved.

http://ift.tt/2g6gsyZ

Drug-induced pyoderma gangrenosum: a model to understand the pathogenesis of pyoderma gangrenosum

Summary

Pyoderma gangrenosum (PG) is a rare auto-inflammatory condition in which the alteration of neutrophil function and the innate immune response play key roles in its pathogenesis. Cases of PG have been reported in patients being treated with certain medications, which may help us to understand some of the possible pathways involved in the etiology of PG. The aim of this review is to review the cases of PG triggered by certain drugs and try to thoroughly understand the pathogenesis of the disease. To accomplish this, a PubMed search was completed using the following words: pyoderma gangrenosum, neutrophilic dermatosis, pathophysiology, drug-induced pyoderma gangrenosum. In total, we found 43 cases of drug-induced pyoderma gangrenosum. Most of them were caused by colony stimulating factors and small molecule inhibitors of tyrosine kinase. We propose that drugs induce PG through various mechanisms such as dysfunctional neutrophil migration and function, dysregulated inflammatory response, promotion of keratinocyte apoptosis and alteration of epigenetics mechanism. PG is a rare condition with complex pathophysiology and drug-induced cases are even more scarce; this is the main limitation of this review. Understanding the possible mechanisms of drug-induced PG, via abnormal neutrophil migration and function, abnormal inflammation, keratinocyte apoptosis and alteration of epigenetic mechanisms would help to better understand the pathogenesis of PG and ultimately to optimize targeted therapy.

This article is protected by copyright. All rights reserved.

http://ift.tt/2fPabEB

Atopic dermatitis patients with filaggrin loss-of-function mutations show good but lower responses to immunosuppressive treatment

Abstract

Filaggrin (FLG) mutations are a strong risk factor to develop atopic dermatitis (AD). However, the relationship between FLG mutations and treatment outcome in AD has not been thoroughly studied. To investigate whether FLG mutations influence immunosuppressive treatment outcome in AD, we studied the effect of FLG mutations in patients with severe AD participating in a single blinded randomized controlled trial (RCT) with methotrexate (MTX) or azathioprine (AZA) during a 24 weeks treatment regimen.⁽¹⁾ Two years after randomization buccal mucosa swabs were collected from 36 of the 42 RCT patients (86%) to determine the FLG genotype status (R501X, 2282del4, R2447X, S3247X and 3321delA mutations).

This article is protected by copyright. All rights reserved.

http://ift.tt/2g6gsyZ

Oxidatively generated base modifications in DNA: Not only carcinogenic risk factor but also regulatory mark?

Publication date: Available online 18 November 2016
Source:Free Radical Biology and Medicine
Author(s): Marco Seifermann, Bernd Epe
The generation of DNA modifications in cells is in most cases accidental and associated with detrimental consequences such as increased mutation rates and an elevated risk of malignant transformation. Accordingly, repair enzymes involved in the removal of the modifications have primarily a protective function. Among the well-established exceptions of this rule are 5-methylcytosine and uracil, which are generated in DNA enzymatically under controlled conditions and fulfill important regulatory functions in DNA as epigenetic marks and in antibody diversification, respectively. More recently, considerable evidence has been obtained that also 8-oxo-7,8-dihydroguanine (8-oxoG), a frequent pro-mutagenic DNA modification generated by endogenous or exogenous reactive oxygen species (ROS), has distinct roles in the regulation of both transcription and signal transduction. Thus, the activation of transcription by the estrogen receptor, NF-κB, MYC and other transcription factors was shown to depend on the presence of 8-oxoG in the promoter regions and its recognition by the DNA repair glycosylase OGG1. The lysine-specific histone demethylase LSD1, which produces H2O2 as a by-product, was indentified as a local generator of 8-oxoG in some of these cases. In addition, a complex of OGG1 with the excised free substrate base was demonstrated to act as a guanine nucleotide exchange factor (GEF) for small GTPases such as Ras, Rac and Rho, thus stimulating signal transduction. The various findings and intriguing novel mechanisms suggested will be described and compared in this review.

Graphical abstract

http://ift.tt/2fFJEfE

Change and Continuity at JBMT

Publication date: Available online 18 November 2016
Source:Journal of Bodywork and Movement Therapies
Author(s): Leon Chaitow




http://ift.tt/2feqGfe

Massive lamotrigine poisoning. A case report

Publication date: Available online 19 November 2016
Source:Brain and Development
Author(s): Salvatore Grosso, Silvia Ferranti, Carla Gaggiano, Elisabetta Grande, Barbara Loi, Rosanna Di Bartolo
Lamotrigine (LTG) represents the most commonly prescribed of the so-called new generation antiepileptic drugs. We describe a child who was admitted to the emergency room because of generalized tonic–clonic status epilepticus followed by a complex neurological picture with hyperkinesia and acute ataxia as a result of a LTG intoxication. The experience on acute LTG intoxication is very limited in pediatrics. The present case provides information on the clinical picture related to LTG overdose and confirms that drug intoxications should be considered in the differential diagnosis strategy when severe and polymorphic neurological symptoms occur acutely.



http://ift.tt/2eR3bum

Postnatal irradiation-induced hippocampal neuropathology, cognitive impairment and aging

Publication date: Available online 19 November 2016
Source:Brain and Development
Author(s): Feng Ru Tang, Weng Keong Loke, Boo Cheong Khoo
Irradiation of the brain in early human life may set abnormal developmental events into motion that last a lifetime, leading to a poor quality of life for affected individuals. While the effect of irradiation at different early developmental stages on the late human life has not been investigated systematically, animal experimental studies suggest that acute postnatal irradiation with ⩾0.1Gy may significantly reduce neurogenesis in the dentate gyrus and endotheliogenesis in cerebral vessels and induce cognitive impairment and aging. Fractionated irradiation also reduces neurogenesis. Furthermore, irradiation induces hippocampal neuronal loss in CA1 and CA3 areas, neuroinflammation and reduces gliogenesis. The hippocampal neurovascular niche and the total number of microvessels are also changed after radiation exposures. Each or combination of these pathological changes may cause cognitive impairment and aging. Interestingly, acute irradiation of aged brain with a certain amount of radiation has also been reported to induce brain hormesis or neurogenesis. At molecular levels, inflammatory cytokines, chemokines, neural growth factors, neurotransmitters, their receptors and signal transduction systems, reactive oxygen species are involved in radiation-induced adverse effect on brain development and functions. Further study at different omics levels after low dose/dose rate irradiation may not only unravel the mechanisms of radiation-induced adverse brain effect or hormesis, but also provide clues for detection or diagnosis of radiation exposure and for therapeutic approaches to effectively prevent radiation-induced cognitive impairment and aging. Investigation focusing on radiation-induced changes of critical brain development events may reveal many previously unknown adverse effects.



http://ift.tt/2frv3Be

Anatomical, animal, and cellular evidence for Zika-induced pathogenesis of fetal microcephaly

Publication date: Available online 19 November 2016
Source:Brain and Development
Author(s): Jing-Zhang Wang, Xin-Hua Guo, Dian-Guo Xu
Several recent articles published by Brain and Development in 2016 demonstrated some rare, but innovative, genetic mechanisms for microcephaly. This concise mini-review presented another novel pathogenic mechanism for microcephaly, which has actually been a worldwide medical challenge since the World Health Organization (WHO) defined the outbreak of the Zika virus (ZIKV) as an International Public Health Emergency on 1 Feb, 2016. As a recent noteworthy clinical phenomenon, the ZIKV outbreak was accompanied by a dramatically increased number of microcephalus fetuses. However, no direct evidence supporting the suspected pathogenic effects of ZIKV on fetal microcephaly was shown previously before 2016. Herein, we evaluated the most important human pathological, animal developmental, and neuro-cytotoxic findings released in 2016, and highlighted the original experimental evidence that strengthens the potential link between ZIKV and the high incidence of microcephaly in new-born babies. Because killing mosquitoes via insecticides is currently the only effective way to suppress ZIKV-induced disorders, the animal and cellular models described in this mini-review are very beneficial to anti-ZIKV drug development and vaccine assessment.



http://ift.tt/2eR2ZLn

The Cingulate Cortex of Older Adults with Excellent Memory Capacity

Publication date: Available online 19 November 2016
Source:Cortex
Author(s): Feng Lin, Ping Ren, Mark Mapstone, Steven P. Meyers, Anton Porsteinsson, Timothy M. Baran
Memory deterioration is the earliest and most devastating cognitive deficit in normal aging and Alzheimer's disease. Some older adults, known as "Supernormals", maintain excellent memory. This study examined relationships between cerebral amyloid deposition and functional connectivity (FC) within the cingulate cortex (CC) and between CC and other regions involved in memory maintenance between Supernormals, healthy controls, and those at risk for Alzheimer's disease (amnestic mild cognitive impairment). Supernormals had significantly stronger FC between anterior CC and R-hippocampus, middle CC (MCC) and L-superior temporal gyrus, and posterior CC and R-precuneus, while weaker FC between MCC and R-middle frontal gyrus and MCC and R-thalamus than other groups. All of these FC were significantly related to memory and global cognition in all participants. Supernormals had less amyloid deposition than other groups. Relationships between global cognition and FC were stronger among amyloid positive participants. Relationships between memory and FC remained regardless of amyloid level. This revealed how CC-related neural function participates in cognitive maintenance in the presence of amyloid deposition, potentially explaining excellent cognitive function among Supernormals.



http://ift.tt/2guxTKH

Disentangling meaning in the brain: left temporal involvement in agreement processing

Publication date: Available online 18 November 2016
Source:Cortex
Author(s): S. Mancini, I. Quiñones, N. Molinaro, J.A. Hernandez-Cabrera, M. Carreiras
Sentence comprehension is successfully accomplished by means of a form-to-meaning mapping procedure that relies on the extraction of morphosyntactic information from the input and its mapping to higher-level semantic-discourse representations. In this study, we sought to determine whether neuroanatomically distinct brain regions are involved in the processing of different types of information contained in the propositional meaning of a sentence, namely person and number. While person information indexes the role that an individual has in discourse (i.e. the speaker, the addressee or the entity being talked about by speaker and addressee), number indicates its cardinality (i.e. a single entity vs. a multitude of entities). An event-related fMRI experiment was run using agreement-correct and person- and number-violated sentences in Spanish, to disentangle the processing mechanisms and neural substrates associated with the building of discourse and cardinality representations. The contrast between person and number violations showed qualitative and quantitative differences. A greater response for person compared to number was found in the left middle temporal gyrus (LMTG). However, critically, a posterior-to-anterior functional gradient emerged within this region. While the posterior portion of the LMTG was sensitive to both person and number violations, the anterior portion of this region showed selective response for person violations. These results confirm that the comprehension of the propositional meaning of a sentence results from a composite, feature-sensitive mechanism of form-to-meaning mapping in which the nodes of the language network are differentially involved.



http://ift.tt/2g7B9Ik

Left inferior frontal gyrus mediates morphosyntax: ERP evidence from verb processing in left-hemisphere damaged patients

Publication date: Available online 18 November 2016
Source:Cortex
Author(s): Stefanie Regel, Sonja A. Kotz, Ilona Henseler, Angela D. Friederici
Neurocognitive models of language comprehension have proposed different mechanisms with different neural substrates mediating human language processing. Whether the left inferior frontal gyrus (LIFG) is engaged in morpho-syntactic information processing is currently still controversially debated. The present study addresses this issue by examining the processing of irregular verb inflection in real words (e.g., swim>swum>swam) and pseudowords (e.g., frim>frum>fram) by using event-related brain potentials (ERPs) in neurological patients with lesions in the LIFG involving Broca's area as well as healthy controls. Different ERP patterns in response to the grammatical violations were observed in both groups. Controls showed a biphasic negativity-P600 pattern in response to incorrect verb inflections whereas patients with LIFG lesions displayed a N400. For incorrect pseudoword inflections, a late positivity was found in controls, no ERP effects were obtained in patients. These findings of different ERP patterns in the two groups strongly indicate an involvement of LIFG in morphosyntactic processing, thereby suggesting brain regions' specialization for different language functions.



http://ift.tt/2guwLXB

Déjà vecu for news events but not personal events: A dissociation between autobiographical and non-autobiographical episodic memory processing

Publication date: Available online 18 November 2016
Source:Cortex
Author(s): Martha S. Turner, E. Arthur Shores, Nora Breen, Max Coltheart
In déjà vu, the feeling that what we are currently experiencing we have experienced before is fleeting and is not accepted as true. In contrast, in déjà vecu or "recollective confabulation", the sense of déjà vu is persistent and convincing, and patients genuinely believe that they have lived through the current moment at some previous time. In previous reports of cases of déjà vecu, both personal events and non-personal, world events gave rise to this experience. In this paper we describe a patient whose déjà vecu experiences are entirely restricted to non-personal events, suggesting that autobiographical and non-autobiographical episodic memory processing can dissociate. We suggest that this dissociation is secondary to differences in the degree to which personal and emotional associations are formed for these two different types of event, and offer a two-factor theory of déjà vecu.



http://ift.tt/2gusGCT

Highly sensitive detection of cancer cells with an electrochemical cytosensor based on boronic acid functional polythiophene

Publication date: 15 April 2017
Source:Biosensors and Bioelectronics, Volume 90
Author(s): Muamer Dervisevic, Mehmet Senel, Tugba Sagir, Sevim Isik
The detection of cancer cells through important molecular recognition target such as sialic acid is significant for the clinical diagnosis and treatment. There are many electrochemical cytosensors developed for cancer cells detection but most of them have complicated fabrication processes which results in poor reproducibility and reliability. In this study, a simple, low-cost, and highly sensitive electrochemical cytosensor was designed based on boronic acid-functionalized polythiophene. In cytosensors fabrication simple single-step procedure was used which includes coating pencil graphite electrode (PGE) by means of electro-polymerization of 3-Thienyl boronic acid and Thiophen. Electrochemical impedance spectroscopy and cyclic voltammetry were used as an analytical methods to optimize and measure analytical performances of PGE/P(TBA0.5Th0.5) based electrode. Cytosensor showed extremely good analytical performances in detection of cancer cells with linear rage of 1×10¹ to 1×10⁶ cellsmL⁻¹ exhibiting low detection limit of 10 cellsmL⁻¹ and incubation time of 10min. Next to excellent analytical performances, it showed high selectivity towards AGS cancer cells when compared to HEK 293 normal cells and bone marrow mesenchymal stem cells (BM-hMSCs). This method is promising for future applications in early stage cancer diagnosis.



http://ift.tt/2farFdf

Multimodal plasmonic biosensing nanostructures prepared by DNA-directed immobilization of multifunctional DNA-gold nanoparticles

Publication date: 15 April 2017
Source:Biosensors and Bioelectronics, Volume 90
Author(s): Nuria Tort, J.-Pablo Salvador, M.-Pilar Marco
Biofunctional multimodal plasmonic nanostructures suitable for multiplexed localized surface plasmon resonance (LSPR) biosensing have been created by DNA-directed immobilization (DDI) of two distinct multifunctional biohybrid gold nanoparticles. Gold nanoparticles (AuNP) of distinct sizes, and therefore showing distinct plasmon resonant peaks (RP), have been biofunctionalized and codified with two different single stranded-DNA (ssDNA) chains. One of these oligonucleotide chains has been specifically designed to direct each AuNP to a distinct location of the surface of a DNA microarray chip through specific hybridization with complementary oligonucleotide strands. Scanning Electron Microscopy (SEM) has been used to demonstrate selective immobilization of each AuNP on distinct spots. The second ssDNA chain of the AuNPs provides the possibility to introduce by hybridization distinct types of bioactive molecules or bioreceptors, on a reversible manner. In this work, hapten-oligonucleotide bioconjugate probes, with sequences complementary to the second ssDNA linked to the AuNP, have been synthesized and used to create multiplexed hapten-biofuncionalized plasmonic nanostructures. The oligonucleotide probes consist on anabolic androgenic steroid haptens (AAS) covalently linked to specifically designed oligonucleotide sequences. The biofunctionality of these plasmonic nanostructures has been demonstrated by fluorescent microarray immunoassay and LSPR measurements, recording the shift of the RP produced after the antibody binding to the corresponding hapten-oligonucleotide probes immobilized on the nanostructured surface. Preliminary data show that this approach could allow manufacturing multifunctional multimodal LSPR chips for multiplexed analysis of different substances reaching very good detectability. Thus, small molecular weigh, analytes such as stanozolol (ST,) could be detected at concentrations in the low nM range. The results here presented open the door for an easy way to construct site-encoded multiplexed multimodal LSPR sensor transducers, combining the DDI strategies with multimodal biohybrid nanoparticles showing distinct optical properties.



http://ift.tt/2gq3SuW

Recombinant azurin-CdSe/ZnS hybrid structures for nanoscale resistive random access memory device

Publication date: 15 April 2017
Source:Biosensors and Bioelectronics, Volume 90
Author(s): Ajay Kumar Yagati, Sang-Uk Kim, Taek Lee, Junhong Min, Jeong-Woo Choi
In the present study, we developed a biohybrid material composed of recombinant azurin and CdSe-ZnS quantum dot to perform as a resistive random access memory (ReRAM) device. Site specific amino acid sequences were introduced in azurin to bind with the surface of CdSe-ZnS nanoparticle allowing the formation of a hybrid and voltage-driven switching enabled to develop a resistive random access memory (ReRAM) device. The analytical measurements confirmed that the azurin and CdSe-ZnS nanoparticles were well conjugated and formed into a single hybrid. Further, reversible, bistable switching along with repeatable writing-reading-erasing processes on individual azurin/CdSe-ZnS hybrid at nanoscale was achieved on the hybrid device. The device was programmed tested for 50 cycles with an ON/OFF ratio and measured to be of three orders of magnitude. The developed device shown good stability and repeatability and operates at low voltages thus makes it promising candidate for future memory device applications.



http://ift.tt/2g5k58c

A novel label-free electrochemical immunosensor based on functionalized nitrogen-doped graphene quantum dots for carcinoembryonic antigen detection

Publication date: 15 April 2017
Source:Biosensors and Bioelectronics, Volume 90
Author(s): Yuying Yang, Qing Liu, Yan Liu, Jianjian Cui, Hui Liu, Ping Wang, Yueyun Li, Lei Chen, Zengdian Zhao, Yunhui Dong
A novel and ultrasensitive label-free electrochemical immunosensor was fabricated for quantitative detection of carcino-embryonic antigen (CEA). The nitrogen-doped graphene quantum dots (N-GQDs) supported PtPd bimetallic nanoparticles (PtPd/N-GQDs) were synthesized by a simple and green hydrothermal procedure. Subsequently, PtPd/N-GQDs functionalized Au nanoparticles (PtPd/N-GQDs@Au) were prepared successfully via a self-assembly approach. Because of the synergetic effect present in PtPd/N-GQDs@Au, this novel nanocomposites has shown excellent electrocatalytic activity towards hydrogen peroxide (H2O2) reduction. Featuring good biocompatibility, excellent conductivity and large surface area, PtPd/N-GQDs@Au was applied as transducing materials to efficiently conjugate capture antibodies and amplify electrochemical signal. Under the optimal conditions, the proposed immunosensor was used for the detection of CEA with wide dynamic range in the range from 5 fg/mL to 50ng/mL with a low detection limit of 2fg/mL (S/N=3). Furthermore, this label-free immunosensor possesses high sensitivity, special selectivity and long-term stability, which shows promising application in bioassay analysis.



http://ift.tt/2fayYSb

Construction of a highly sensitive non-enzymatic sensor for superoxide anion radical detection from living cells

Publication date: 15 April 2017
Source:Biosensors and Bioelectronics, Volume 90
Author(s): Yuelin Liu, Xiuhui Liu, Yidan Liu, Guoan Liu, Lan Ding, Xiaoquan Lu
A novel non-enzymatic superoxide anion (O2•⁻) sensor was fabricated based on Ag nanoparticles (NPs)/L-cysteine functioned carbon nanotubes (Cys-MWCNTs) nanocomposites and used to measure the release of O2•⁻ from living cells. In this strategy, AgNPs could be uniformly electrodeposited on the MWCNTs surface with average diameter of about 20nm as exhibited by scanning electronmicroscopy (SEM). Electrochemical study demonstrated that the AgNPs/Cys-MWCNTs modified glassy carbon electrode exhibited excellent catalytic activity toward the reduction of O2•⁻ with a super wide linear range from 7.00×10^–11 to 7.41×10^-5M and a low detection limit (LOD) of 2.33×10^-11M (S/N=3). Meanwhile, the mechanism for O2•⁻ reduction was also proposed for the first time. Importantly, this novel non-enzymatic O2•⁻ sensor can detect O2•⁻ release from cancer cells under both the external stimulation and the normal condition, which has the great potential application in clinical diagnostics to assess oxidative stress of living cells.

Graphical abstract

http://ift.tt/2gq55lW

A pH Indicator-linked Immunosorbent assay following direct amplification strategy for colorimetric detection of protein biomarkers

Publication date: 15 April 2017
Source:Biosensors and Bioelectronics, Volume 90
Author(s): Fengying Shao, Lei Jiao, Luyang Miao, Qin Wei, He Li
A new pH indicator-linked immunosorbent assay (PILISA) reached pg/mL sensitivity based on pH indicator molecules loaded carbon nitride nanosheets as signal enhancer has been developed for colorimetric detection of protein biomarkers. As the secondary antibody binds to the carbon nitride nanosheets, the carbon nitride nanosheets and pH indicator complex as the signal amplification platform for colour change by detecting absorbance of pH indicator. The colour change was resulted from the releasing of pH indicator molecules from carbon nitride nanosheets triggered by alkali solution (AS). In this novel PILISA, the intensity absorbance of pH indicator is proportional to the concentration of the disease marker. The outstanding detection performance of the PILISA can be attributed to the following reasons: (1) ultrathin carbon nitride nanosheets with a larger surface area could adsorb abundant phenolphthalein (PP) molecules through hydrophobic interactions as well as the resulted PP anions can be free easily released into aqueous solution, leading to an obvious allochroic response; (2) the signal intensity is precisely determined by the amount of PP molecules loading onto the carbon nitride nanosheets surface, which ensures simple, low-cost and stable colorimetric detection. As expected, this new PILISA method offered an enzyme-free approach followed enzyme-linked immunosorbent assay format, which showed great promising potential as an innovative robust assay method for practical clinical applications.



http://ift.tt/2gpZPib

All-in-one dual-aptasensor capable of rapidly quantifying carcinoembryonic antigen

Publication date: 15 April 2017
Source:Biosensors and Bioelectronics, Volume 90
Author(s): Harriet Khang, Kelly Cho, Stephanie Chong, Ji Hoon Lee
Using a dual DNA aptamer (CEA aptamer linked to hemin aptamer), capable of rapidly capturing carcinoembryonic antigen (CEA) and hemin, an all-in-one dual-aptasensor with 1,1′-oxalyldiimidazole (ODI) chemiluminescence detection was developed for the early diagnosis of human cancer. CEA and hemin competitively bound with the dual DNA aptamer while the mixture in a detection cell was incubated for 30min at room temperature. When Amplex Red and H2O2 were added in the detection cell after the incubation, the yield of resorufin formed from the reaction Amplex Red and H2O2 depended on the concentration of HRP-mimicking G-quardruplex DNAzyme formed from the binding interaction between hemin and the dual DNA aptamer. Bright red light was observed with the addition of ODI and H2O2 in the detection cell containing resorufin. Relative CL intensity of all-in-one dual-aptasensor, operated with the competitive reaction of CEA and hemin in the presence of the dual aptamer, was exponentially decreased with the increase of CEA concentration in human serum. The limit of detection (LOD=3σ) of the all-in-one dual-aptasensor which operated with excellent accuracy, precision, and reproducibility was as low as 0.58ng/ml. The good correlation between the easy to use all-in-one dual-aptasensor and conventional enzyme-linked immunosorbent assay (ELISA), operated with time consuming procedures (e.g., long incubations and multiple washings), indicates that the rapid all-in-one dual-aptasensor can be applied as a novel clinical tool for the early diagnosis of breast cancer.

Graphical abstract

http://ift.tt/2gq02Sq

Toxicity evaluation of e-juice and its soluble aerosols generated by electronic cigarettes using recombinant bioluminescent bacteria responsive to specific cellular damages

Publication date: 15 April 2017
Source:Biosensors and Bioelectronics, Volume 90
Author(s): Shiv Bharadwaj, Robert J. Mitchell, Anjum Qureshi, Javed H. Niazi
Electronic-cigarettes (e-cigarette) are widely used as an alternative to traditional cigarettes but their safety is not well established. Herein, we demonstrate and validate an analytical method to discriminate the deleterious effects of e-cigarette refills (e-juice) and soluble e-juice aerosol (SEA) by employing stress-specific bioluminescent recombinant bacterial cells (RBCs) as whole-cell biosensors. These RBCs carry luxCDABE-operon tightly controlled by promoters that specifically induced to DNA damage (recA), superoxide radicals (sodA), heavy metals (copA) and membrane damage (oprF). The responses of the RBCs following exposure to various concentrations of e-juice/SEA was recorded in real-time that showed dose-dependent stress specific-responses against both the e-juice and vaporized e-juice aerosols produced by the e-cigarette. We also established that high doses of e-juice (4-folds diluted) lead to cell death by repressing the cellular machinery responsible for repairing DNA-damage, superoxide toxicity, ion homeostasis and membrane damage. SEA also caused the cellular damages but the cells showed enhanced bioluminescence expression without significant growth inhibition, indicating that the cells activated their global defense system to repair these damages. DNA fragmentation assay also revealed the disintegration of total cellular DNA at sub-toxic doses of e-juice. Despite their state of matter, the e-juice and its aerosols induce cytotoxicity and alter normal cellular functions, respectively that raises concerns on use of e-cigarettes as alternative to traditional cigarette. The ability of RBCs in detecting both harmful effects and toxicity mechanisms provided a fundamental understanding of biological response to e-juice and aerosols.



http://ift.tt/2gq01Om

Right ventricular function assessment in single LAD lesion patients using strain and strain rate imaging

Publication date: December 2016
Source:Alexandria Journal of Medicine, Volume 52, Issue 4
Author(s): Rania Gaber
BackgroundStrain and strain rate imaging is currently the most popular echocardiographic technique that reveals subclinical myocardial damage, and data are not available on this imaging method with regard to assessing right ventricular involvement in single LAD lesion.AimTo evaluate right ventricular regional functions using strain and strain rate imaging tissue Doppler method in patients with single LAD lesion.MethodsThe patient group was composed of 60 patients who had experienced first anterior myocardial infarction and had undergone successful percutaneous coronary intervention for LAD lesion. Twenty patients were selected for the control group. The right ventricular myocardial samplings were performed in three regions: the basal, mid, and apical segments of the lateral wall. The individual myocardial velocity, strain, and strain rate values of each basal, mid, and apical segment were obtained.ResultsThe right ventricular tissue Doppler parameters (Sm, E, A, E/A ratio, IVA, E/E″) of the patients group were significantly decreased than controls. In addition, changes in the right ventricular mean strain and strain rate values were significantly lower in patient group than controls.ConclusionRight ventricular involvement in LAD lesion patient is significant even after PCI and recanalization of LAD. TDI, strain and strain rate are new, useful imaging techniques for detection of subclinical RV dysfunction in patients with LAD lesion.



http://ift.tt/2fau3k4

A study of serum magnesium, calcium and phosphorus level, and cognition in the elderly population of South India

Publication date: December 2016
Source:Alexandria Journal of Medicine, Volume 52, Issue 4
Author(s): M.P. Basheer, K.M. Pradeep Kumar, E. Sreekumaran, T. Ramakrishna
IntroductionDifferent studies have shown the role of micro and macronutrients on cognitive function. Macronutrients have been involved in many metabolic activities of the body including oxidation and reduction reactions in the central nervous system. This involvement of macronutrients in the activities of central nervous system indicates its role in cognition. The present study is designed to know the role of macronutrients and its relation with cognition by using biological samples.Materials and methodsA total of 337 subjects with a mean age of 49 participated in the cross sectional study from different parts of Kerala state in India. Individuals participating in this study were administered a series of neuropsychological test batteries with major emphasis on 7-min screen test. All test procedures were administered by standard protocol after a written consent was obtained from the participating subjects. Analysis of macronutrients level of magnesium, calcium and phosphorus was done by using serum samples and the data obtained were then statistically analyzed using SPSS software version 17.ResultsThe macronutrients magnesium, calcium and phosphorus were found to be significantly related to the cognitive score. Increasing magnesium and calcium level was associated with higher cognitive score (P<0.0031 and 0.001 respectively), while lower phosphorus level was significantly associated with lower composite score (P<0.001).ConclusionThe results of our study give us an expression that macronutrients such as calcium, magnesium and phosphorus may be associated with cognitive function in elderly population of our state. But further studies on a larger population are required to come out with a definite conclusion.



http://ift.tt/2gpZ4FZ

Promoting effect of adipocytokine, apelin, on hepatic injury in caerulein-induced acute pancreatitis in rats

Publication date: December 2016
Source:Alexandria Journal of Medicine, Volume 52, Issue 4
Author(s): Marwa N. Emam, Rehab E. Abo El gheit
ObjectiveTo evaluate the potential apelin effect on hepatic injury in caerulein (Cn) -induced AP in rats.Experimental protocolThirty male albino rats were divided into three groups, 10 rats each: control group: received 0.9% NaCl solution. AP group: received (Cn, 50μg/kg/h, i.p.) for 6h. Apelin-13 treated AP group: received apelin 13, 50nmol/kg/h, i.p, immediately after each Cn injection, starting after the second Cn dose. 12h after the last Cn injection, the rats were sacrificed, and serum amylase, lipase, phospholipase A2 (PLA2), interleukin (IL)-6, IL-1β, IL-10, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactic dehydrogenase activity (LDH) were assayed. The hepatic malondialdehyde (MDA), reduced glutathione (GSH) and catalase (CAT) levels, caspase-3 activity and tumor necrosis factor-alpha (TNF-α) were assessed, while myeloperoxidase (MPO) was determined in pancreatic and hepatic tissues.ResultsCn injection caused severe AP, with marked hepatic damage. The exogenous apelin reduced Cn-induced pancreatic and hepatic injury with reduction in hepatic oxidative, apoptotic and inflammatory markers, pancreatic and hepatic MPO activity with modulation of inflammatory cytokines.ConclusionApelin could be protective in AP associated liver damage, possibly through anti-oxidant, anti-apoptotic mechanisms with modulating the inflammatory mediators.



http://ift.tt/2gq4aBX

MDCT angiography and transcatheter embolization in management of acute gastrointestinal bleeding

Publication date: December 2016
Source:Alexandria Journal of Medicine, Volume 52, Issue 4
Author(s): Hassan Abdelsalam, Mohamed Saied Abdelgawad
Acute gastrointestinal (GI) bleeding is an important cause of emergency hospital admissions, with its related morbidity and mortality. The availability of endoscopic equipment has had an important effect on the rapid identification and treatment of the bleeding source. Multidetector computed tomography (MDCT) allows direct demonstration and visualization of the bleeding source and its characterization. The information provided by MDCT angiography before attempts at therapeutic angiographic procedures leads to faster selective catheterization of bleeding vessels.The purpose of this study was to show the role of MDCT and catheter embolization in management of acute GI bleeding.Materials and methodsThis is a retrospective study that included 57 patients referred in 4years with active gastrointestinal bleeding.MDCT was performed in 43 cases, while 14 patients didn't have CT angiography and proceeded straight to angiography.Results37 patients had positive MDCT findings, of which 27 cases had positive bleed on angiography, and 10 did not show active bleeding on angiography. 6 patients had a negative MDCT and did not proceed to angiography. 14 patients did not have a MDCT and proceeded straight to angiography; 6 of them showed active bleeding on angiography.ConclusionMDCT is an excellent technique before angiography and embolization in cases with acute gastrointestinal bleeding. Transcatheter embolization is an effective tool for control of GI bleed.



http://ift.tt/2faDBeT

The potential protective effects of erythropoietin and estrogen on renal ischemia reperfusion injury in ovariectomized rats

Publication date: December 2016
Source:Alexandria Journal of Medicine, Volume 52, Issue 4
Author(s): Noha I. Hussien, Hanan T. Emam
BackgroundRenal ischemia–reperfusion (RIR) is an important etiopathological mechanism of acute renal failure (ARF). Erythropoietin (EPO) has been candidate as a nephroprotectant agent. However, its nephroprotective effect when it is accompanied with estrogen has not been studied in female.MethodsFifty-six female rats were divided into seven groups. Each formed of 8 rats. Group I: control group. Group II: Female rats exposed to RIR (named RIR group).Group III: Female rats exposed to RIR and pretreated with EPO (named RIR+EPO group). Group IV: ovariectomized rats exposed to RIR (named OVR+RIR group). Group V: ovariectomized rats received estrogen (E) then exposed to RIR (named OVR+RIR+E group). Group VI: ovariectomized rats received EPO before RIR (named OVR+RIR+EPO group). Group VII: ovariectomized rats received E then received EPO before RIR (named OVR+RIR+E+EPO group).Serum creatinine, blood urea nitrogen (BUN) and renal blood flow (RBF) were measured. Tumor necrosis factor-α (TNF-α), Myeloperoxidase activity (MPO), nitric oxide (NO), endothelin-1(ET-1) and EPO levels were assessed in the renal tissue. Histopathology was assessed to detect renal damage score.ResultsRIR significantly increased the serum levels of creatinine and BUN with decrease in RBF. In addition it significantly increased TNF-α, MPO and endothelin-1 levels with decrease in NO and EPO levels in renal tissue. However, these parameters significantly reversed by EPO except RBF. Combination of E and EPO leads to significant decrease in the protective effect of EPO.ConclusionIt seems that EPO could protect the kidney against RIR, while this protective effect was decreased when E was supplemented.



http://ift.tt/2gq56GH

Editorial Board

Publication date: December 2016
Source:Alexandria Journal of Medicine, Volume 52, Issue 4





http://ift.tt/2fay7Rg

Chronic pain in hemodialysis patients: Role of bone mineral metabolism

Publication date: December 2016
Source:Alexandria Journal of Medicine, Volume 52, Issue 4
Author(s): Tarek A. Ghonemy, Hala M. Allam, Amir M. Elokely, Yosef A. Kadry, Hesham M. Omar
BackgroundPain is one of the most common complaints in clinical practice because it is a symptom for a myriad of physical and mental problems. The high prevalence of pain in the chronic kidney disease (CKD) population is particularly concerning because pain has been shown to adversely affect quality of life. The aim of this study was to evaluate the prevalence and possible causes of chronic pain in patients with end stage renal disease on long-term hemodialysis (HD).MethodsWe prospectively enrolled 100 patients who were undergoing maintenance HD for at least 6months or more. Pain was evaluated using the Brief Pain Inventory (BPI). Data collected on each participant included age, gender, body mass index (BMI), time on dialysis and biochemical findings.ResultsThe average age was 42.06years ranged from 22 to 58years; the average duration on dialysis was 4.97years. 52 patients were males and 48 were females. Although 52% of patients experienced chronic pain, only 25% described the pain as severe, 28% described pain as moderate while 52% of patients described as mild. Musculoskeletal pain was the most frequent form of chronic pain reported by patients who were on HD (54%). Malnutrition and high CRP were highly statistically associated with chronic pain (p<0.001). High statistical significant correlation was found between lower calcium, lower 25(OH) D3 levels, higher parathyroid hormone (PTH) levels and experienced chronic pain (p<0.001).ConclusionChronic pain is highly experienced in long-term hemodialysis patients. Malnutrition, high CRP and disturbed bone mineral metabolism are highly correlated with the incident of this pain.



http://ift.tt/2gq5sgg

Isolated cutaneous leishmaniasis over face – A diagnostic dilemma

Publication date: December 2016
Source:Alexandria Journal of Medicine, Volume 52, Issue 4
Author(s): Santosh K. Swain, Ishwar C. Behera, Mahesh C. Sahu, Maitreyee Panda
Cutaneous Leishmaniasis (CL) is a disease caused by an intracellular protozoa belong to the genus Leishmania, transmitted by the bite of a sandfly. It has diverse clinical presentation and may create a public health problem in endemic countries. CL is often confused with lepromatous leprosy, pimples and fungal dermatitis. This case is an isolated cutaneous variety in facial region which was mistaken and treated initially for fungal dermatitis and then for leprosy by local physicians. Smears examined from the skin lesion confirmed Leishmania amastigotes. The isolated localized CL may create confusion and its many differential diagnoses made delaying in the diagnosis.



http://ift.tt/2fay5sC

Esthetic rhinoplasty as an adjunctive technique in nasal oncoplastic surgery

Publication date: December 2016
Source:Alexandria Journal of Medicine, Volume 52, Issue 4
Author(s): Adham Farouk
BackgroundThe nose is a prime esthetic focus of the human face and it is a common site for nonmelanoma skin cancers. Esthetic reconstruction of nasal skin after tumor resection remains a problem. Beside conservative surgical excision of the skin tumor, this article presents a tactic for decreasing the size of the skin defect and optimizing its shape to facilitate reconstruction.MethodsThroughout a period of seven years, thirty-five patients with nonmelanoma cancer of nasal skin were managed by a one stage surgical operation, which entails conservative tumor resection followed by performing an esthetic rhinoplasty that remodels the nasal skeleton in order to shrink the skin defect; making it more amenable to reconstruction by adjacent skin.ResultsResults were satisfactory for all patients in terms of adequate tumor resection and pleasant appearance of their noses.ConclusionsEsthetic rhinoplasty is a useful adjunctive technique in nasal oncoplastic surgery.



http://ift.tt/2gq309D

Antimicrobial susceptibility pattern of genital Mycoplasmas among a group of pregnant women

Publication date: December 2016
Source:Alexandria Journal of Medicine, Volume 52, Issue 4
Author(s): Safaa M. Abdel Rahman, Rania A. Hassan, Noha A. Sakna
Mycoplasma hominis (MH) and Ureaplasma urealyticum (UU) are important members of genital Mycoplasmas. They are implicated in urogenital infections and complicated pregnancy (chorioamnionitis, preterm delivery, abortion, and preterm birth) as well as bacterial vaginosis and cervicitis. The administration of antimicrobial agents to pregnant women with preterm rupture of the membranes (PROM) may extend the gestation period and decrease the risks of associated complications and neonatal infections. Despite empirical therapy is the rule in cases suspected to have genital infection in Egypt, the surveillance of the susceptibilities of used antibiotics is mandatory to ensure treatment efficacy and good prevention of any possible complications. This study aimed to assess the infection rate of genital Mycoplasmas (MH and UU) among pregnant females and their antimicrobial susceptibility pattern to provide a provisional idea about the effectiveness of antibiotics used empirically to treat cases of genital infections in pregnant women. High vaginal swabs of 50 pregnant females were examined using Mycoplasma IES kit, for identification of UU and MH. The kit also provides the antimicrobial susceptibility results for 12 antimicrobials of five different classes. UU and MH were detected in 26/50 (52%), and 7/50 (14%) of cases respectively, of which 5 cases showed mixed infection with both organisms. UU was most sensitive to quinolones (90–95%), followed by tetracyclines (80–85%). The least sensitivity was detected with chloramphenicol and clindamycin (40% and 30% respectively). The two MH isolates (100%) were sensitive to the three tested quinolones in addition to clindamycin and thiamphenicol. MH showed 100% sensitivity to clindamycin and 75% of UU isolates were sensitive to azithromycin. Further studies are needed to detect any future changes in the susceptibility pattern for these drugs or other antibiotics.



http://ift.tt/2faD4cR

Scanning electron microscopic study of the effect of chlorpyrifos on the developing neural tube in comparison with Arsenic in mouse embryo

Publication date: December 2016
Source:Alexandria Journal of Medicine, Volume 52, Issue 4
Author(s): Miriam R.R.F. Abdelmalek, Eman Elazab Beheiry, Rasha Mohammed El-Shinety, Amina Tolba Farag, Shawky Mahmoud Tayel
BackgroundArsenic is an important environmental toxicant which is usually found in drinking water in inorganic form. Arsenic exposure in pregnant mice causes neural tube defects (NTDs). Chlorpyrifos, an organophosphorus insecticide, recommended universally and in Egypt to control various pests, was evaluated for its potential developmental toxicity. Studies have shown increasing evidence to suggest an association between environmental exposure to this agricultural pesticides and adverse reproductive outcomes. The hypothesis tested in this investigation is chlorpyrifos causes significant defects on the developing central nervous system compared to the proven Arsenic.ObjectivesThe aim of this work was to assess congenital malformations induced by the organophosphorus insecticide chlorpyrifos on the neural tube and brain development in comparison with the positive control Arsenic.MethodsVirgin female ICR (CD-1) mice, approximately 10weeks old were mated with adult males. The day the vaginal plug was found was considered day 0 of gestation. It consisted of 320mice. They were subdivided into four groups of 80bred mice each. Each group was divided into 4 subgroups, and 20mice per each were treated by gavage as follows: 30mg/kg/day chlorpyrifos (tested group), 40mg/kg/day sodium Arsenite (positive control group), and corn oil and distilled water (negative control groups) on days 6–15 of gestation. Maternal observations throughout gestation were reported. In each subgroup the mice proved to be pregnant were sacrificed on gestational days; GD 10, 11, 12 and 16. The day of scarification was determined according to the neural tube developmental stages. The conceptus extraction was done and their number reported to be subjected to the SEM study.After mice scarification, the uteri were opened and a total of 30 embryos and fetuses, randomly selected from each subgroup were processed for scanning electron microscopy investigating the neural tube developmental defects.ResultsCPF ingested by gravid mice at dose of 30mg/kg/day started from 6th day of gestation proved to produce NTDs as compared to Arsenite.ConclusionNeural tube defects are due to chlorpyrifos that may directly influence brain cell replication and differentiation.



http://ift.tt/2gq2nNk

The response of pre-inflammatory cytokines factors to different exercises (endurance, resistance, concurrent) in overweight men

Publication date: December 2016
Source:Alexandria Journal of Medicine, Volume 52, Issue 4
Author(s): Khalid Mohamadzadeh Salamat, Mohammad Ali Azarbayjani, Ashril Yusof, Firouzeh Dehghan
Applying several energy systems and concurrent performing of various training models have a more effective role in preventing precocious occurrence of many diseases compared to training single energy system. This can be seen in case of physiologic and metabolic adaptations of the human body too. The present study attempted to investigate the effect of endurance, resistance and concurrent (endurance–resistance) training on pre-inflammatory cytokines in overweight men. Accordingly, 43 healthy overweight (BMI=28.56±2.67) young (23.7±3.3yr) students were volunteered to participate and randomly divided into three experimental (n=11) and one control (n=10) groups. The experimental groups performed 3days/wk endurance, resistance and concurrent training for 8weeks. Also, prior to and after the training, a blood sample was collected from the subjects in order to measure pre-inflammatory cytokines (IL-1β, IL-6 and TNF-α). Following 8week training, repeated measure ANOVA results showed a significant difference in IL-1β (P=0.046) and IL-6 (P=0.009) compared to baseline. However, this was not the case with the TNF-α. Furthermore, between group comparisons showed significant difference in IL-6 (P=0.020) between endurance and resistance groups. Within group comparisons (depended t student test) also showed a significant difference in IL-1β and IL-6 of endurance and concurrent groups compared to baseline. Generally, it can be concluded that endurance and concurrent exercise training in part has a positive effect on pre-inflammatory cytokines.



http://ift.tt/2faDfVP

Facial rejuvenation: Serial fat graft transfer

Publication date: December 2016
Source:Alexandria Journal of Medicine, Volume 52, Issue 4
Author(s): Saad Mohamed Saad Ibrahiem, Adham Farouk, Iman Labib Salem
Autologous fat transfer is a century-old method for both aesthetic and reconstructive purposes. It is considered by many plastic surgeons the ideal body filler. The only disadvantage is its variable degree of resorption, which ranged from 45% to 80%. Various groups have studied the effects of cryo-preservation for fat storage, the advantage being that fat harvesting need only be performed once, and thereafter fat injections can be performed using stored fat as an outpatient service. This a clinical study carried out to test the aesthetic outcome of serial injection of the cryo-preserved fat cells for both aesthetic and reconstructive purposes.MethodsClinical evaluation was performed under standardized condition for serial lipofilling between October 2003 and May 2012, and 364 autologous fat transfers were performed in 104 patients ranging in age from 18 to 69years (mean age 34years).ResultsThe postoperative clinical results favored the use of serial fat transfer because the aesthetic and structural results were stable up to 90% of the initial volume more than a year after initial transfer.ConclusionOur data suggest that serial transfer of the cryo-preserved fat leads to better cosmetic results on the basis of outpatient service without increasing the financial burden for our patients.



http://ift.tt/2fauECn

Enhanced mechanical properties, water stability and repeatable shape recovery behavior of Ca2+ crosslinking graphene oxide-based nacre-mimicking hybrid film

Publication date: 5 February 2017
Source:Materials & Design, Volume 115
Author(s): Weiyi Xing, Bihe Yuan, Xin Wang, Yuan Hu
Artificial nacre-like inorganic-organic hybrid films are fabricated by a facile evaporation-induced self-assembly method using graphene oxide (GO) nanosheets as rigid bricks and a natural polysaccharide of sodium alginate (SA) as soft mortar. To further improve tensile mechanical properties of the GO/SA films, Ca²⁺ is utilized as a substitute for the most widely used glutaraldehyde to crosslink the films. Owing to the high chelation affinity for metal ions, the Ca²⁺ modified (Ca-GO/SA) films show higher tensile mechanical properties than those of the original samples. Water uptake in the Ca-GO/SA film is greatly decreased and water stability is improved by the introduction of Ca²⁺. The Ca-GO/SA films exhibit water-triggered shape recovery behavior. The films show two-way shape memory effect and possess two original shapes, which can be reversibly transformed by immersion in water and removal of the absorbed moisture. This advanced hybrid film will broaden the applications for biomimetic materials and shows potential for applications in the fields of water-sensitive actuators and sensors.

Graphical abstract

http://ift.tt/2feoEf1

Effect of water depth on weld quality and welding process in underwater fiber laser welding

Publication date: 5 February 2017
Source:Materials & Design, Volume 115
Author(s): Ning Guo, Xiao Xing, Hongyun Zhao, Caiwang Tan, Jicai Feng, Zongquan Deng
A series of experiments under various water depths were performed using an optical fiber laser without draining the welding zone to study the effect of water depth on the laser welding. The ULBW processes were also monitored using a camera. Firstly, welding experiments were performed with laser power 3.0kW, welding speed 0.6m/min, focal position 0mm. It was found that water has a slight effect on the ULBW, particularly when the water depth is less than 3mm; however, when the water depth is greater than 7mm, water has a strong hindering effect on ULBW and leads it to failure. In the process of direct ULBW, the 'beam channel' is formed in the water environment between the incident laser beam and the target surface as a result of the gas pressure inside the plasma exceed the water pressure depending on the water depth. The stability of the 'beam channel', which gradually worsens with increasing water depth, have an important influence on the weld bead quality and the welding process stability. Additionally, laser power has the greatest effect on the available water depth, followed by the welding speed, while focal position has little effect on it.

Graphical abstract

http://ift.tt/2fecCm6

Fabrication of oriented UHMWPE films using low solvent concentration

Publication date: 5 February 2017
Source:Materials & Design, Volume 115
Author(s): A.V. Maksimkin, A.P. Kharitonov, S.G. Nematulloev, S.D. Kaloshkin, M.V. Gorshenkov, D.I. Chukov, I.V. Shchetinin
The method of oriented films fabrication from the ultrahigh molecular weight polyethylene (UHMWPE) and small amount of solvent (1.6ml of solvent per 1g of UHMWPE) is described. This method excludes UHMWPE solution because the solvent acts as a plasticity agent. The UHMWPE structure formed due to plasticization favoured to drawability increase. Multi-stage hot orientation method with a draw ratio up to 35 was used to fabricate UHMWPE films. The reactor powders and fabricated films were tested by SEM, DSC and XRD. The degree of crystallinity was increased up to 94% determined by DSC and 93% determined by XRD for films with draw ratio 26 and 35. The achieved tensile strength and modulus was 0.9GPa and 35GPa respectively for films with draw ratio 35. Orientation of the films proceeded via two different mechanisms: (i) macromolecules deployment and their crystallization below draw ratio 26 and (ii) slipping of the fibrils above draw ratio 26. Slipping of the fibrils results in a taut tie molecules amount increase and consequently favour the tensile strength and especially modulus increase.

Graphical abstract

http://ift.tt/2feeMCi

Enhanced and selective acetone sensing properties of SnO2-MWCNT nanocomposites: Promising materials for diabetes sensor

Publication date: 5 February 2017
Source:Materials & Design, Volume 115
Author(s): M. Narjinary, P. Rana, A. Sen, M. Pal
Achieving good sensitivity toward low ppm acetone with pronounced resolution is a challenging, yet very much required task for the development of breath analyzer to monitor diabetes in a non-invasive way. We were able to achieve high sensitivity, stability, ultrafast response toward sub-ppm acetone with a good resolution just by using MWCNTs as a substrate for nanocrystalline SnO2 prepared through a facile sol-gel technique. The composites were well characterized using XRD and TEM/HRTEM which revealed not only the structure and purity of the samples but also indicates the successful integration of MWCNT with SnO2 nanoparticles. The composite sensor showed much better performance at the lower temperature than pure SnO2. Enhancement of adsorption ability of SnO2 due to the addition of MWCNTs, and the difference between their work function, could be collectively responsible for the improvement of sensing activity. Besides, these nanocomposite sensors also showed much-reduced cross-sensitivity toward moisture, which is a major component of human exhale breath. This will be an extra-advantage of MWCNT incorporation for developing breath analyzer to monitor diabetes using SnO2 nanocomposites based sensor.

Graphical abstract

http://ift.tt/2fegKSZ

Nb segregation at prior austenite grain boundaries and defects in high strength low alloy steel during cooling

Publication date: 5 February 2017
Source:Materials & Design, Volume 115
Author(s): Xianglong Li, Ping Wu, Ruijie Yang, Shoutian Zhao, Shiping Zhang, Sen Chen, Xingzhong Cao, Xuemin Wang
The segregation of Nb at prior austenite grain boundary during cooling was investigated. Auger electron spectroscopy and electron backscattering diffraction were performed to characterize the segregation of Nb, while positron annihilation lifetime spectroscopy was applied to analyze the behavior of defects within the material. The formation energy of vacancy and the activation energy of the climb or glide of dislocations coincide well with reported results. The segregation of Nb at the grain boundaries increases with the decreasing defects during the cooling process. The diffusion of vacancy and the climb or glide of dislocations may both contribute to the segregation of Nb.

Graphical abstract

http://ift.tt/2fekNPn

An update on the current management of head and neck mucosal melanoma

Abstract

Primary mucosal melanomas of the head and neck are rare and aggressive tumours that arise in the nasal cavity, paranasal sinuses and more rarely, in the oral cavity. The current treatment options include radical surgical resection with adjuvant external beam radiotherapy being offered in high risk patients. Although the latter can improve regional control, it does not reduce overall survival. Elective neck dissection is recommended for nodular oral mucosal melanoma but its role in the clinically node negative neck is controversial.

Systemic therapies including the use of tyrosine kinase inhibitors for tumours with c-KIT mutations are suitable for patients with advanced loco-regional and/or metastatic disease but current results are variable. Patients with head and neck mucosal melanoma have a poor prognosis due to the high incidence of metastatic disease. This review assesses the latest evidence in the diagnosis and management of primary oral and head and neck mucosal melanoma including details of systemic therapies.

This article is protected by copyright. All rights reserved.

http://ift.tt/2g80zWN

An open prospective single cohort multicenter study evaluating the novel, tapered, conical connection implants supporting single crowns in the anterior and premolar maxilla: interim 1-year results

Abstract

Objectives

The aim of this multicenter prospective clinical study was to evaluate anodized tapered implants with a conical connection and integrated platform shifting placed in the anterior and premolar maxilla.

Materials and methods

The study enrolled patients requiring single-tooth restorations in healed sites of maxillary anterior and premolar teeth. All implants were immediately temporized. Clinical and radiographic evaluations were conducted at implant insertion, 6 months, and 1 year. Outcome measures included bone remodeling, cumulative survival rate (CSR), success rate, soft-tissue health and esthetics, and patient satisfaction. Bone remodeling and pink esthetic score were analyzed using Wilcoxon signed-rank tests. CSR was calculated using life table analysis. Other soft-tissue outcomes were analyzed using sign tests.

Results

Out of 97 enrolled patients (102 implants), 87 patients (91 implants) completed the 1-year visit. Marginal bone remodeling was −0.85 ± 1.36 mm. After the expected initial bone loss, a mean bone gain of 0.11 ± 1.05 mm was observed between 6 months and 1 year. The CSR was 99.0%, and the cumulative success rate was 97.0%. Partial or full papilla was observed at 30.8% of sites at baseline, 87.2% at 6 months, and 90.5% at 1 year. Soft-tissue response, esthetics, and patient satisfaction all improved during the study period.

Conclusions

Bone gain was observed following the expected initial bone loss, and soft-tissue outcomes improved suggesting favorable tissue response using anodized tapered conical connection implants.

Clinical relevance

Rapid stabilization of bone remodeling and robust papilla regeneration indicate favorable tissue healing promoted by the conical connection, platform-shift design.

Trial registration

clinicaltrials.gov NCT02175550

http://ift.tt/2g7l2dz

Cardiac Fibroblasts Adopt Osteogenic Fates and Can Be Targeted to Attenuate Pathological Heart Calcification

Publication date: Available online 17 November 2016
Source:Cell Stem Cell
Author(s): Indulekha C.L. Pillai, Shen Li, Milagros Romay, Larry Lam, Yan Lu, Jie Huang, Nathaniel Dillard, Marketa Zemanova, Liudmilla Rubbi, Yibin Wang, Jason Lee, Ming Xia, Owen Liang, Ya-Hong Xie, Matteo Pellegrini, Aldons J. Lusis, Arjun Deb
Mammalian tissues calcify with age and injury. Analogous to bone formation, osteogenic cells are thought to be recruited to the affected tissue and induce mineralization. In the heart, calcification of cardiac muscle leads to conduction system disturbances and is one of the most common pathologies underlying heart blocks. However the cell identity and mechanisms contributing to pathological heart muscle calcification remain unknown. Using lineage tracing, murine models of heart calcification and in vivo transplantation assays, we show that cardiac fibroblasts (CFs) adopt an osteoblast cell-like fate and contribute directly to heart muscle calcification. Small-molecule inhibition of ENPP1, an enzyme that is induced upon injury and regulates bone mineralization, significantly attenuated cardiac calcification. Inhibitors of bone mineralization completely prevented ectopic cardiac calcification and improved post injury heart function. Taken together, these findings highlight the plasticity of fibroblasts in contributing to ectopic calcification and identify pharmacological targets for therapeutic development.

Graphical abstract

Teaser

Pillai et al. demonstrate that cardiac fibroblasts adopt bone-forming cell fates and induce ectopic calcification. ENPP1, an enzyme that regulates bone mineralization, is induced in cardiac fibroblasts after injury. Administration of ENPP1 inhibitors or inhibitors of bone mineralization significantly decreased pathologic cardiac calcification and augmented cardiac function.


http://ift.tt/2g4c7Kr

DNA Methylation Dynamics of Human Hematopoietic Stem Cell Differentiation

Publication date: Available online 17 November 2016
Source:Cell Stem Cell
Author(s): Matthias Farlik, Florian Halbritter, Fabian Müller, Fizzah A. Choudry, Peter Ebert, Johanna Klughammer, Samantha Farrow, Antonella Santoro, Valerio Ciaurro, Anthony Mathur, Rakesh Uppal, Hendrik G. Stunnenberg, Willem H. Ouwehand, Elisa Laurenti, Thomas Lengauer, Mattia Frontini, Christoph Bock
Hematopoietic stem cells give rise to all blood cells in a differentiation process that involves widespread epigenome remodeling. Here we present genome-wide reference maps of the associated DNA methylation dynamics. We used a meta-epigenomic approach that combines DNA methylation profiles across many small pools of cells and performed single-cell methylome sequencing to assess cell-to-cell heterogeneity. The resulting dataset identified characteristic differences between HSCs derived from fetal liver, cord blood, bone marrow, and peripheral blood. We also observed lineage-specific DNA methylation between myeloid and lymphoid progenitors, characterized immature multi-lymphoid progenitors, and detected progressive DNA methylation differences in maturing megakaryocytes. We linked these patterns to gene expression, histone modifications, and chromatin accessibility, and we used machine learning to derive a model of human hematopoietic differentiation directly from DNA methylation data. Our results contribute to a better understanding of human hematopoietic stem cell differentiation and provide a framework for studying blood-linked diseases.

Graphical abstract

Teaser

As part of the IHEC consortium, Bock and colleagues present genome-wide reference maps of DNA methylation dynamics during human blood development. The characteristic DNA methylation patterns they see in the different cell types allow data-driven inference of an epigenome-based model of hematopoietic differentiation. Explore the IHEC web portal at http://ift.tt/2gczkgR.


http://ift.tt/2g4ksxD

Two-Way Conversion between Lipogenic and Myogenic Fibroblastic Phenotypes Marks the Progression and Resolution of Lung Fibrosis

Publication date: Available online 17 November 2016
Source:Cell Stem Cell
Author(s): Elie El Agha, Alena Moiseenko, Vahid Kheirollahi, Stijn De Langhe, Slaven Crnkovic, Grazyna Kwapiszewska, Djuro Kosanovic, Felix Schwind, Ralph T. Schermuly, Ingrid Henneke, BreAnne MacKenzie, Jennifer Quantius, Susanne Herold, Aglaia Ntokou, Katrin Ahlbrecht, Rory E. Morty, Andreas Günther, Werner Seeger, Saverio Bellusci
Idiopathic pulmonary fibrosis (IPF) is a form of progressive interstitial lung disease with unknown etiology. Due to a lack of effective treatment, IPF is associated with a high mortality rate. The hallmark feature of this disease is the accumulation of activated myofibroblasts that excessively deposit extracellular matrix proteins, thus compromising lung architecture and function and hindering gas exchange. Here we investigated the origin of activated myofibroblasts and the molecular mechanisms governing fibrosis formation and resolution. Genetic engineering in mice enables the time-controlled labeling and monitoring of lipogenic or myogenic populations of lung fibroblasts during fibrosis formation and resolution. Our data demonstrate a lipogenic-to-myogenic switch in fibroblastic phenotype during fibrosis formation. Conversely, we observed a myogenic-to-lipogenic switch during fibrosis resolution. Analysis of human lung tissues and primary human lung fibroblasts indicates that this fate switching is involved in IPF pathogenesis, opening potential therapeutic avenues to treat patients.

Graphical abstract

Teaser

El Agha et al. use genetic engineering in mice to identify precursor cells for activated myofibroblasts and investigate their fate in a reversible model of lung fibrosis. Their findings emphasize the phenotypic plasticity of lipogenic and myogenic lung fibroblasts and indicate that PPARγ agonists might be beneficial in treating IPF.


http://ift.tt/2g49GYe