Anaplastic Lymphoma Kinase Protein Positive Diffuse Large B cell Lymphoma; A developing world experience

Publication date: Available online 6 March 2017
Source:Pathology - Research and Practice
Author(s): Huzaifah Salat, Nasir Ud Din, Tariq Moatter, Naila Kayani, Arsalan Ahmed
Anaplastic lymphoma kinase (ALK) positive diffuse large B-cell lymphoma (ALK+DLBCL) is a rare, distinct and aggressive subtype of non-Hodgkin's lymphoma (NHL). These tumors are considered to be derived from post-germinal center B cells but peculiarly their distinction is based on the fact that they are ALK-positive neoplastic B cells but lack expression of B cell markers (CD19,CD20, CD79a), T cell markers (CD3, CD5) and CD30. Its broad differential diagnosis and similarities to plasmablastic lymphoma, immunoblastic DLBCL, Anaplastic large-cell lymphoma (ALCL) of T-null cell lineage, and poorly differentiated/anaplastic carcinoma pose a grave challenge to physicians with conventional costly treatment for DLBCL failing to yield any clinical or prognostic significance in ALK+DLBCL. In this article we present 7 cases which were reported at Aga Khan University Hospital, Department of Pathology and Laboratory Medicine from 2009 to 2015 and a review of literature on ALK+ DLBCL, which according to the best of our knowledge is the second largest reported series and the first from South Asian subcontinent.



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IOP-details

Publication date: April 2017
Source:International Journal of Psychophysiology, Volume 114





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Editorial board

Publication date: April 2017
Source:International Journal of Psychophysiology, Volume 114





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Instructions to Authors

Publication date: April 2017
Source:International Journal of Psychophysiology, Volume 114





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Inscuteable maintains type I neuroblast lineage identity via Numb/Notch signaling in the Drosophila larval brain

Publication date: Available online 6 March 2017
Source:Journal of Genetics and Genomics
Author(s): Huanping An, Wanzhong Ge, Yongmei Xi, Xiaohang Yang
In the Drosophila larval brain, type I and type II neuroblasts (NBs) undergo a series of asymmetric divisions which give rise to distinct progeny lineages. The intermediate neural progenitors (INPs) exist only in type II NB lineages. In this study, we reveal a novel function of Inscuteable (Insc) that acts to maintain type I NB lineage identity. In insc type I NB clones of mosaic analyses with a repressible cell marker (MARCM), the formation of extra Deadpan (Dpn)⁺ NB-like and GMC-like cells is observed. The lack of Insc leads to the defective localization and segregation of Numb during asymmetric cell division. By the end of cytokinesis this results in insufficient Numb in ganglion mother cells (GMCs). The formation of extra Deadpan (Dpn)⁺ cells in insc clones is prevented by the attenuation of Notch activity. This suggests that Insc functions through the Numb/Notch signaling pathway. We also show that in the absence of Insc in type I NB lineages, the cellular identity of GMCs is altered where they adopt an INP-like cell fate as indicated by the initiation of Dpn expression accompanied by a transient presence of Earmuff (Erm). These INP-like cells have the capacity to divide multiple times. We conclude that Insc is necessary for the maintenance of type I NB lineage identity. Genetic manipulations to eliminate most type I NBs with overproliferating type II NBs in the larval brain lead to altered circadian rhythms and defective phototaxis in adult flies. This indicates that the homeogenesis of NB lineages is important for the adult's brain function.



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First Molecular Cytogenetic Characterization of Murine Malignant Mesothelioma Cell Line AE17 and In Silico Translation to the Human Genome

Background: Mesothelial cells can be malignantly transformed e.g. due to previous asbestos exposure and form a clinically aggressive tumor called malignant mesothelioma (MM). Presently, there is extensive ongoing research in MM with the goal to identify prognostic factors and new therapeutic targets. Accordingly, well studied model systems, like cell lines, are urgently needed. Interestingly, murine MM cell lines models were established in the 1990s; however, they were not characterized genetically in any detail, yet. <p></p> Objective: Provide first genetic characterization of murine MM cell line AE17, translate into human genome and characterize the human subtype of MM AE17 is suited as a model. <p></p> Method: AE17 was studied on chromosomal level by molecular cytogenetics and array comparative genomic hybridization. <p></p> Results and Conclusion: AE17 did not tetraploidize yet, has a basic karyotype of 40 chromosomes with only 3 balanced inversions, one balanced translocation and five chromosomes with simple to complex rearrangements, leading in the end to partial chromosomal deletions. Besides one stemline, three additional subclones could be observed. The obtained data was, by means of bioinformatics based on silico translation of the detected imbalances and observed chromosomal breakpoints, translated to the human genome. The obtained data suggests that AE17 is a well suited cell line model for MM with (cyto)genetic changes characteristic for sarcomatoid MM form. Furthermore, genes ESR2 and BAK1 seem to be activated in one of the subclones of AE17, which also could be of interest for future studies. Overall, the present data could only be obtained through bioinformatics based on silico analyses, to cope with the microarray data and also for browser based translation of murine into human genome. <p></p>

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D Allele Frequency in Insertion/Deletion Polymorphism of the Angiotensin Converting Enzyme (ACE) Gene is Associated with Development of Breast Cancer Risk in Indian Women

Aims: Breast cancer is the second most common cancer in the world and, by far, the most frequent cancer among women. Scientific literature has hypothesized the association of ACE I/D polymorphism with breast cancer for several decades. Unfortunately the outcomes of studies are inconsistent. Thus the present study was designed to evaluate the association of ACE gene (I/D) polymorphism with breast cancer in Indian population. <p></p> Methods: Genotyping was performed by PCR (polymerase chain reaction), using genomic DNA extracted from peripheral blood of subjects, with (213 cases) or without (213 controls) breast cancer. <p></p> Findings: The distribution of ACE genotype frequencies i.e. II, DD and ID in patients was 43.19%, 16.43% and 40.38% respectively. In healthy control group II, DD and ID frequencies were 52.58%, 11.27% and 36.15% respectively. The frequencies of D and I alleles were 29.34% and 70.66% in the healthy subjects, while 36.62% and 63.38% among the patient group. Frequency of D allele was significantly different (p=0.0287) between control and case subjects. <p></p> Significance: The present study showed an association of D allele of ACE gene with increased genetic risk factor for breast cancer in Indian women. 0.2% increased disease risk was found in patients carrying D allele. <p></p>

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Copper sulfide nanoparticle-based localized drug delivery system as an effective cancer synergistic treatment and theranostic platform

Publication date: Available online 6 March 2017
Source:Acta Biomaterialia
Author(s): Lin Hou, Xiaoning Shan, Lisha Hao, Qianhua Feng, Zhenzhong Zhang
Localized cancer treatment with combination therapy has attracted increasing attention for effective inhibition of tumor growth. In this work, we introduced diffusion molecular retention (DMR) tumor targeting effect, a new strategy that employed transferrin (Tf) modified hollow mesoporous CuS nanoparticles (HMCuS NPs) to undergo extensive diffuse through the interstitium and tumor retention after a peritumoral (PT) injection. Herein, HMCuS NPs with strong near-infrared (NIR) absorption and photothermal conversion efficiency could serve as not only a drug carrier but also a powerful contrast agent for photoacoustic imaging to guide chemo-phototherapy. The iron-dependent artesunate (AS), which possessed profound cytotoxicity against tumor cell, was used as model drug. As a result, this AS loaded Tf-HMCuS NPs (AS/Tf-HMCuS NPs) system could specially target to tumor cells and synchronously deliver AS as well as irons into tumor to achieve enhanced antitumor activity. It was found that AS/Tf-HMCuS NPs was taken up by MCF-7 cells via Tf-mediated endocytosis, and could effectively convert NIR light into heat for photothermal therapy as well as generated high levels of reactive oxygen species (ROS) for photodynamic therapy. In addition, in vivo antitumor efficacy studies showed that tumor-bearing mice treated with AS/Tf-HMCuS NPs through peritumoral (PT) injection under NIR laser irradiation displayed the strongest inhibition rate of about 74.8%, even with the reduced frequency of administration. Furthermore, to demonstrate DMR, the optical imaging, photoacoustic tomography and immunofluorescence after PT injection were adopted to track the behavior of AS/Tf-HMCuS NPs in vivo. The results exhibited that Tf-HMCuS NPs prolonged the local accumulation and retention together with slow vascular uptake and extensive interstitial diffusion, which was consistent with the biodistribution studies of AS/Tf-HMCuS NPs. Therefore, the approach of localized delivery through DMR combined with multi-mechanism therapy may be a promising method for cancer treatment.Statement of SignificanceIn recent years, localized cancer treatment using different biomaterials has attracted increasing attention for effective inhibition of tumor growth. However, it is still challenging for this kind of system to achieve a high drug loading, overcome biological barriers from the site of injection to the site of action, and combine synergetic therapy with diagnosis without adversely affecting the formation process. This study provides a localized diffusion molecular retention (DMR) tumor targeting drug delivery system based on hollow mesoporous copper sulfide nanoparticles (HMCuS NPs) entrapment of anticancer drug for the first time, which can achieve high drug loading, improve local drug accumulation and retention, accomplish synergistic combination of chemo-phototherapy, and finally enhance antitumor effect. In addition, HMCuS NPs also possesses the property suitable for photoacoustic imaging, which could offer us a theranostic platform.

Graphical abstract

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Engineering Mechanical Gradients in Next Generation Biomaterials - Lessons Learned from Medical Textile Design

Publication date: Available online 6 March 2017
Source:Acta Biomaterialia
Author(s): Joanna L. Ng, Ciara E. Collins, Melissa L. Knothe Tate
Nonwoven and textile membranes have been applied both externally and internally to prescribe boundary conditions for medical conditions as diverse as oedema and tissue defects. Incorporation of mechanical gradients in next generation medical membrane design offers great potential to enhance function in a dynamic, physiological context. Yet the gradient properties and resulting mechanical performance of current membranes are not well described. To bridge this knowledge gap, we tested and compared the mechanical properties of bounding membranes used in both external (compression sleeves for oedema, exercise bands) and internal (surgical membranes) physiological contexts. We showed that anisotropic compression garment textiles, isotropic exercise bands and surgical membranes exhibit similar ranges of resistance to tension under physiologic strains. However, their mechanical gradients and resulting stress-strain relationships show differences in work capacity and energy expenditure. Exercise bands' moduli of elasticity and respective thicknesses allow for controlled, incremental increases in loading to facilitate healing as injured tissues return to normal structure and function. In contrast, the gradients intrinsic to compression sleeve design exhibit gaps in the middle range of physiological strains and also inconsistencies along the length of the sleeve, resulting in less than optimal performance of these devices. These current shortcomings in compression textile and garment design may be addressed in the future through implementation of novel approaches. For example, patterns, fibre compositions, and fibre anisotropy can be incorporated into biomaterial design to achieve seamless mechanical gradients in structure and resulting dynamic function, which would be particularly useful in physiological contexts. These concepts can be applied further to biomaterial design to deliver pressure gradients during movement of oedematous limbs (compression garments) and facilitate transport of molecules and cells during tissue genesis within tissue defects (surgical membranes).Statement of significanceExternal and internal biomaterial membranes prescribe boundary conditions for treatment of medical disorders, from oedema to tissue defects. Studies are needed to guide the design of next generation biomaterials and devices that incorporate gradient engineering approaches, which offer great potential to enhance function in a dynamic and physiological context. Mechanical gradients intrinsic to currently implemented biomaterials such as medical textiles and surgical interface membranes are poorly understood. Here we characterise quantitatively the mechanics of textile and nonwoven biomaterial membranes for external and internal use. The lack of seamless gradients in compression medical textiles contrasts with the graded mechanical effects achieved by elastomeric exercise bands, which are designed to deliver controlled, incremental increases in loading to facilitate healing as injured tissues return to normal structure and function. Engineering textiles with a prescient choice of fibre composition/size, type of knit/weave and inlay fibres, and weave density/anisotropy will enable creation of fabrics that can deliver spatially and temporally controlled mechanical gradients to maintain force balances at tissue boundaries, e.g. to treat oedema or tissue defects.

Graphical abstract

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Design Strategies and Applications of Nacre – based Biomaterials

Publication date: Available online 6 March 2017
Source:Acta Biomaterialia
Author(s): Ethan Gerhard, Wei Wang, Caiyan Li, Jinshan Guo, Ibrahim Ozbolat, Kevin Rahn, April Armstrong, Jingfen Xia, Guoying Qian, Jian Yang
The field of tissue engineering and regenerative medicine relies heavily on materials capable of implantation without significant foreign body reactions and with the ability to promote tissue differentiation and regeneration. The field of bone tissue engineering in particular requires materials capable of providing enhanced mechanical properties and promoting osteogenic cell lineage commitment. While bone repair has long relied almost exclusively on inorganic, calcium phosphate ceramics such as hydroxyapatite and their composites or on non- degradable metals, the organically derived shell and pearl nacre generated by mollusks has emerged as a promising alternative. Nacre is a naturally occurring composite material composed of inorganic, calcium carbonate plates connected by a framework of organic molecules. Similar to mammalian bone, the highly organized microstructure of nacre endows the composite with superior mechanical properties while the organic phase contributes to significant bioactivity. Studies, both in vitro and in vivo, have demonstrated nacre's biocompatibility, biodegradability, and osteogenic potential, which are superior to pure inorganic minerals such as hydroxyapatite or non-degradable metals. Nacre can be used directly as a bulk implant or as part of a composite material when combined with polymers or other ceramics. While nacre has demonstrated its effectiveness in multiple cell culture and animal models, it remains a relatively underexplored biomaterial. This review introduces the formation, structure, and characteristics of nacre, and discusses the present and future uses of this biologically-derived material as a novel biomaterial for orthopedic and other tissue engineering applications.Statement of SignificanceMussel derived nacre, a biological composite composed of mineralized calcium carbonate platelets and interplatelet protein components, has recently gained interest as a potential alternative ceramic material in orthopedic biomaterials, combining the integration and mechanical capabilities of calcium phosphates with increased bioactivity derived from proteins and biomolecules; however, there is limited awareness of this material's potential. Herein, we present, to our knowledge, the first comprehensive review of nacre as a biomaterial. Nacre is a highly promising yet overlooked biomaterial for orthopedic tissue engineering with great potential in a wide variety of material systems. It is our hope that publication of this article will lead to increased community awareness of the potential of nacre as a versatile, bioactive ceramic capable of improving bone tissue regeneration and will elicit increased research effort and innovation utilizing nacre.

Graphical abstract

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Computational smart polymer design based on elastin protein mutability

Publication date: May 2017
Source:Biomaterials, Volume 127
Author(s): Anna Tarakanova, Wenwen Huang, Anthony S. Weiss, David L. Kaplan, Markus J. Buehler
Soluble elastin-like peptides (ELPs) can be engineered into a range of physical forms, from hydrogels and scaffolds to fibers and artificial tissues, finding numerous applications in medicine and engineering as "smart polymers". Elastin-like peptides are attractive candidates as a platform for novel biomaterial design because they exhibit a highly tunable response spectrum, with reversible phase transition capabilities. Here, we report the design of the first virtual library of elastin-like protein models using methods for enhanced sampling to study the effect of peptide chemistry, chain length, and salt concentration on the structural transitions of ELPs, exposing associated molecular mechanisms. We describe the behavior of the local molecular structure under increasing temperatures and the effect of peptide interactions with nearest hydration shell water molecules on peptide mobility and propensity to exhibit structural transitions. Shifts in the magnitude of structural transitions at the single-molecule scale are explained from the perspective of peptide-ion-water interactions in a library of four unique elastin-like peptide systems. Predictions of structural transitions are subsequently validated in experiment. This library is a valuable resource for recombinant protein design and synthesis as it elucidates mechanisms at the single-molecule level, paving a feedback path between simulation and experiment for smart material designs, with applications in biomedicine and diagnostic devices.



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Protein-free formation of bone-like apatite: New insights into the key role of carbonation

Publication date: May 2017
Source:Biomaterials, Volume 127
Author(s): Alix C. Deymier, Arun K. Nair, Baptiste Depalle, Zhao Qin, Kashyap Arcot, Christophe Drouet, Claude H. Yoder, Markus J. Buehler, Stavros Thomopoulos, Guy M. Genin, Jill D. Pasteris
The nanometer-sized plate-like morphology of bone mineral is necessary for proper bone mechanics and physiology. However, mechanisms regulating the morphology of these mineral nanocrystals remain unclear. The dominant hypothesis attributes the size and shape regulation to organic-mineral interactions. Here, we present data supporting the hypothesis that physicochemical effects of carbonate integration within the apatite lattice control the morphology, size, and mechanics of bioapatite mineral crystals. Carbonated apatites synthesized in the absence of organic molecules presented plate-like morphologies and nanoscale crystallite dimensions. Experimentally-determined crystallite size, lattice spacing, solubility and atomic order were modified by carbonate concentration. Molecular dynamics (MD) simulations and density functional theory (DFT) calculations predicted changes in surface energy and elastic moduli with carbonate concentration. Combining these results with a scaling law predicted the experimentally observed scaling of size and energetics with carbonate concentration. The experiments and models describe a clear mechanism by which crystal dimensions are controlled by carbonate substitution. Furthermore, the results demonstrate that carbonate substitution is sufficient to drive the formation of bone-like crystallites. This new understanding points to pathways for biomimetic synthesis of novel, nanostructured biomaterials.



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Near-infrared light activation of quenched liposomal Ce6 for synergistic cancer phototherapy with effective skin protection

Publication date: May 2017
Source:Biomaterials, Volume 127
Author(s): Liangzhu Feng, Danlei Tao, Ziliang Dong, Qian Chen, Yu Chao, Zhuang Liu, Meiwan Chen
Current photodynamic therapy (PDT) is suffering from limited efficacy towards hypoxia tumors and severe post-treatment photo-toxicity such as light-induced skin damages. To make PDT more effective in cancer treatment while being patient-comfortable, herein, a hexylamine conjugated chlorin e6 (hCe6) as the photosensitizer together with a lipophilic near-infrared (NIR) dye 1,1'-dioctadecyl-3,3,3′,3'-tetramethylindotricarbocyanine iodide (DiR) are co-encapsulated into polyethylene glycol (PEG) shelled liposomes. In the obtained DiR-hCe6-liposome, the photosensitizing effect of hCe6 is quenched by DiR via fluorescence resonance energy transfer (FRET). Interestingly, upon irradiation with a 785-nm NIR laser to photobleach DiR, both fluorescence and photodynamic effect of hCe6 in DiR-hCe6-liposome would be activated. Meanwhile, such NIR irradiation applied on tumors of mice with intravenous injection of DiR-hCe6-liposome could result in mild photothermal heating, which in turn would promote intra-tumor blood flow and relieve tumor hypoxia, contributing to the enhanced photodynamic tumor treatment. Importantly, compared to hCe6-loaded liposomes, DiR-hCe6-liposome without being activated by the 785-nm laser shows much lower skin photo-toxicity, demonstrating its great skin protection effect. This work demonstrates a promising yet simple strategy to prepare NIR-light-activatable photodynamic theranostics for synergistic cancer phototherapy, which is featured high specificity/efficacy in tumor treatment with minimal photo-toxicity towards the skin.



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Biomaterial-enabled delivery of SDF-1α at the ventral side of breast cancer cells reveals a crosstalk between cell receptors to promote the invasive phenotype

Publication date: May 2017
Source:Biomaterials, Volume 127
Author(s): Xi Qiu Liu, Laure Fourel, Fabien Dalonneau, Rabia Sadir, Salome Leal, Hugues Lortat-Jacob, Marianne Weidenhaupt, Corinne Albiges-Rizo, Catherine Picart
The SDF-1α chemokine (CXCL12) is a potent bioactive chemoattractant known to be involved in hematopoietic stem cell homing and cancer progression. The associated SDF-1α/CXCR4 receptor signaling is a hallmark of aggressive tumors, which can metastasize to distant sites such as lymph nodes, lung and bone. Here, we engineered a biomimetic tumoral niche made of a thin and soft polyelectrolyte film that can retain SDF-1α to present it, in a spatially-controlled manner, at the ventral side of the breast cancer cells. Matrix-bound SDF-1α but not soluble SDF-1α induced a striking increase in cell spreading and migration in a serum-containing medium, which was associated with the formation of lamellipodia and filopodia in MDA-MB231 cells and specifically mediated by CXCR4. Other Knockdown and inhibition experiments revealed that CD44, the major hyaluronan receptor, acted in concert, via a spatial coincidence, to drive a specific matrix-bound SDFα-induced cell response associated with ERK signaling. In contrast, the β1 integrin adhesion receptor played only a minor role on cell polarity. The CXCR4/CD44 mediated cellular response to matrix-bound SDF-1α involved the Rac1 RhoGTPase and was sustained solely in the presence of matrix-bound SDFα, in contrast with the transient signaling observed in response to soluble SDF-1α. Our results highlight that a biomimetic tumoral niche enables to reveal potent cellular effects and so far hidden molecular mechanisms underlying the breast cancer response to chemokines. These results open new insights for the design of future innovative therapies in metastatic cancers, by inhibiting CXCR4-mediated signaling in the tumoral niche via dual targeting of receptors (CXCR4 and CD44) or of associated signaling molecules (CXCR4 and Rac1).



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Active targeting theranostic iron oxide nanoparticles for MRI and magnetic resonance-guided focused ultrasound ablation of lung cancer

Publication date: May 2017
Source:Biomaterials, Volume 127
Author(s): Zhongling Wang, Ruirui Qiao, Na Tang, Ziwei Lu, Han Wang, Zaixian Zhang, Xiangdong Xue, Zhongyi Huang, Siruo Zhang, Guixiang Zhang, Yuanpei Li
Despite its great promise in non-invasive treatment of cancers, magnetic resonance-guided focused ultrasound surgery (MRgFUS) is currently limited by the insensitivity of magnetic resonance imaging (MRI) for visualization of small tumors, low efficiency of in vivo ultrasonic energy deposition, and damage to surrounding tissues. We hereby report the development of an active targeting nano-sized theranostic superparamagnetic iron oxide (SPIO) platform for significantly increasing the imaging sensitivity and energy deposition efficiency using a clinical MRgFUS system. The surfaces of these PEGylated SPIO nanoparticles (NPs) were decorated with anti-EGFR (epidermal growth factor receptor) monoclonal antibodies (mAb) for targeted delivery to lung cancer with EGFR overexpression. The potential of these targeted nano-theranostic agents for MRI and MRgFUS ablation was evaluated in vitro and in vivo in a rat xenograft model of human lung cancer (H460). Compared with nontargeting PEGylated SPIO NPs, the anti-EGFR mAb targeted PEGylated SPIO NPs demonstrated better targeting capability to H460 tumor cells and greatly improved the MRI contrast at the tumor site. Meanwhile, this study showed that the targeting NPs, as synergistic agents, could significantly enhance the efficiency for in vivo ultrasonic energy deposition in MRgFUS. Moreover, we demonstrated that a series of MR methods including T2-weighted image (T2WI), T1-weighted image (T1WI), diffusion-weighted imaging (DWI) and contrast-enhanced T1WI imaging, could be utilized to noninvasively and conveniently monitor the therapeutic efficacy in rat models by MRgFUS.



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Personalized medicine and follow-up of therapeutic delivery through exploitation of quantum dot toxicity

Publication date: May 2017
Source:Biomaterials, Volume 127
Author(s): Bella B. Manshian, Julio Jiménez, Uwe Himmelreich, Stefaan J. Soenen
Tumor therapy using nanoparticles (NPs) is mainly aimed at using the NPs as carriers for therapeutic drugs or as mediators for external stimuli to generate heat. Recent studies have shown that the toxicity of NPs can also be specifically exploited to kill cancer cells. In the present work, we employ core-only CdTe quantum dots and study their cytotoxicity using a validated high-content screening approach. The data revealed a clear correlation between toxicity and quantum dot degradation, which could be monitored through loss of fluorescence intensity. Based on the in vitro data obtained, the in vivo dose was calculated relative to the estimated number of tumor cells based on luminescence measurements. The obtained results show a clear increase in reproducibility of the therapeutic effect compared to normal conditions, where a set dose of quantum dots was administered regardless of the tumor size. The therapeutic delivery could also be monitored in vivo, where the loss of fluorescence intensity correlated with the anticancer efficacy. The present work highlights the benefits of noninvasive imaging to monitor therapeutic delivery and to optimize treatment via personalized medicine.



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Highly potent antimicrobial polyionenes with rapid killing kinetics, skin biocompatibility and in vivo bactericidal activity

Publication date: May 2017
Source:Biomaterials, Volume 127
Author(s): Shaoqiong Liu, Robert J. Ono, Hong Wu, Jye Yng Teo, Zhen Chang Liang, Kaijin Xu, Musan Zhang, Guansheng Zhong, Jeremy P.K. Tan, Michelle Ng, Chuan Yang, Julian Chan, Zhongkang Ji, Chang Bao, Kiran Kumar, Shujun Gao, Ashlynn Lee, Mareva Fevre, Huihui Dong, Jackie Y. Ying, Lanjuan Li, Weimin Fan, James L. Hedrick, Yi Yan Yang
Effective antimicrobial agents are important arsenals in our perennial fight against communicable diseases, hospital-acquired and surgical site multidrug-resistant infections. In this study, we devise a strategy for the development of highly efficacious and skin compatible yet inexpensive water-soluble macromolecular antimicrobial polyionenes by employing a catalyst-free, polyaddition polymerization using commercially available monomers. A series of antimicrobial polyionenes are prepared through a simple polyaddition reaction with both polymer-forming reaction and charge installation occurring simultaneously. The compositions and structures of polymers are modulated to study their effects on antimicrobial activity against a broad spectrum of pathogenic microbes. Polymers with optimized compositions have potent antimicrobial activity with low minimum inhibitory concentrations of 1.95–7.8 μg/mL and high selectivity over mammalian cells. In particular, a killing efficiency of more than 99.9% within 2 min is obtained. Moreover, the polymers demonstrate high antimicrobial efficacy against various clinically-isolated multidrug-resistant microbes, yet exhibit vastly superior skin biocompatibility in mice as compared to other clinically used surgical scrubs (chlorhexidine and betadine). Microbicidal activity of the polymer is mediated via membrane lysis as demonstrated by confocal microscopy. Unlike small molecular antibiotics, repeated use of the polymer does not induce drug resistance. More importantly, the polymer shows excellent bactericidal activity in a P. aeruginosa-contaminated mouse skin model. Given their rapid and efficacious microbicidal activity and skin compatibility, these polymers have tremendous potential to be developed as surgical scrubs/hand sanitizers to prevent multidrug-resistant infections.

Graphical abstract

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Cerebral Microbleeds and risk of Incident Dementia: The Framingham Heart Study

Publication date: Available online 6 March 2017
Source:Neurobiology of Aging
Author(s): José R. Romero, Alexa Beiser, Jayandra J. Himali, Ashkan Shoamanesh, Charles DeCarli, Sudha Seshadri
Cerebral microbleeds (CMB) are MRI markers attributed to the most common cerebral angiopathies in the elderly and in patients with dementia: hypertensive and cerebral amyloid angiopathy (CAA). CMB detection in asymptomatic persons may help identify those at risk for dementia, and may influence preventive strategies and design of clinical trials testing treatments for dementia. We studied the association of CMB with risk of incident dementia in community dwelling individuals. 1296 dementia-free Framingham Heart Study participants (mean age 72years; 54% women) with available brain MRI and incident dementia data during a mean follow-up period of 6.7 years were included. Using Cox-proportional hazards models we related CMB presence to incident dementia. Multivariable models were adjusted for age, sex, APOE status, and education, with additional models adjusting for vascular risk factors and MRI markers of ischemic brain injury. CMB were observed in 10.8% and incident dementia in 85 participants (6.6% over study period). Participants with any CMB had 1.74 times higher risk of dementia (HR 1.74, 95% CI 1.00-3.01), while those with deep and mixed CMB had a three-fold increased risk (HR 2.99, 95% CI 1.52-5.90). The associations were independent of vascular risk factors, and for deep and mixed CMB also independent of MRI markers of ischemia (HR 2.44, 95% CI 1.22-4.88). Purely lobar CMB were not associated with incident dementia. Our findings support a role for hypertensive vasculopathy and the interplay of hypertensive and CAA in risk of dementia, and suggest that CMB presence can identify individuals at risk of dementia.



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Removal of subcutaneous lipomas: Interest of liposuction

Summary

Subcutaneous lipomas are very common tumors. We report our experience of treatment by liposuction in carefully selected patients, initially referred for conventional surgical excision.

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Sugar 3D Printing: Additive Manufacturing with Molten Sugar for Investigating Molten Material Fed Printing

3D Printing and Additive Manufacturing , Vol. 0, No. 0.


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