Publication date: Available online 9 September 2017
Source:Human Pathology
Author(s): Michelle Moh, Ankur Sangoi, Joseph T. Rabban
Angiomyomatous hamartoma of lymph nodes (AMH-LN) is an uncommon benign proliferation of smooth muscle, blood vessels, collagenous stroma and adipocytes, most commonly affecting inguinal LN. A similar constellation of cell types constitutes various members of the perivascular epithelioid cell tumor (PEComa) family, including lymphangioleiomyomatosis (LAM) which can involve LN in women. Because some LN-LAM patients have tuberous sclerosis complex (TSC) and/or other PEComa family lesions, it is clinically relevant to distinguish LN-LAM from AMH-LN. Given their similar features, however, the possibility that AMH-LN is a morphologic variant of LN-LAM merits inquiry. The dual melanocytic and myoid immunophenotype distinguishes the PEComa family from its mimics. Cathepsin K has recently emerged as a more sensitive marker for the PEComa family than HMB-45, which can be weak and focal,but cathepsin K has not been studied in AMH-LN. This study evaluated 21 AMH-LN for clinical, morphologic and immunophenotypic features of LN-LAM. None (0/21) had TSC or PEComas. Thirteen (62%) were male, unlike LN-LAM which is restricted to women. All cases exhibited intraparenchymal proliferation of variable size, thick-walled blood vessels within collagenous stroma containing a sparse to focally cellular population of haphazardly distributed smooth muscle cells. Admixed adipocytes were commonly present. None exhibited classical features of LN-LAM such as subcapsular localization, extranodal extension, intralymphatic growth, compact nests, branching lymphatic channels, plump cell shape or foamy / clear cytoplasm. None exhibited any staining for cathepsin K, HMB45, or MiTF. There is no clinical, morphologic or immunohistochemical evidence to suggest that AMH-LN is a variant of LN-LAM.
http://ift.tt/2wRK7S8
Σάββατο 9 Σεπτεμβρίου 2017
Angiomyomatous Hamartoma of Lymph Nodes, Revisited: Clinico-pathologic Study of 21 Cases, Emphasizing Its Distinction from Lymphangioleiomyomatosis of Lymph Nodes
Characterization of genome-wide copy number aberrations in colonic mixed adenoneuroendocrine carcinoma and neuroendocrine carcinoma reveals recurrent amplification of PTGER4 and MYC genes
Publication date: Available online 9 September 2017
Source:Human Pathology
Author(s): Namita Sinha, Daniel Gaston, Daniel Manders, Marissa Goudie, Makoto Matsuoka, Tao Xie, Weei-Yuarn Huang
Colonic Mixed adenoneuroendocrine Carcinoma (MANEC) is an aggressive neoplasm with worse prognosis compared to adenocarcinoma. To gain a better understanding of the molecular features of colonic MANEC, we characterized the genome-wide copy number aberrations (CNA) of 14 MANECs and 5 neuroendocrine carcinomas using the OncoScan FFPE assay. Compared to 269 colonic adenocarcinomas, 19 of 42 chromosomal arms of MANEC exhibited a similar frequency of major aberrant events as adenocarcinomas, and 13 chromosomal arms exhibited a higher frequency of copy number gains. Among them, the most significant chromosomal arms were 5p (77% vs. 13%, P=1.2E-05) and 8q (85% vs. 33%, P=0.0018). The genomic identification of significant targets in cancers (GISTIC) algorithm identified seven peaks that drive the tumorgenesis of MANEC. For all except 5p13.1, the peaks largely overlapped with those of adenocarcinoma. Two tumors exhibited MYC amplification localized in 8q24.21 and two tumors exhibited PTGER4 amplification localized in 5p13.1. A total of eight tumors exhibited high copy number gain of PTGER4 and/or MYC. While the frequency of MYC amplification was similar to adenocarcinoma (10.5% vs. 4%, P=0.2), the frequency of PTGER4 amplification was higher than adenocarcinoma (10.5% vs. 0.3%, P=0.01). Our study demonstrates similar, but also distinct, CNAs in MANEC compared to adenocarcinoma and suggests an important role for the MYC pathway of colonic carcinoma with neuroendocrine differentiation. The discovery of recurrent PTGER4 amplification implies a potential of exploring targeting therapy to the prostaglandin synthesis pathways in a subset of these tumors.
http://ift.tt/2vWecTv
Histone 3.3 Mutations in Giant Cell Tumor and Giant Cell-Rich Sarcomas of Bone
Publication date: Available online 9 September 2017
Source:Human Pathology
Author(s): Alberto Righi, Irene Mancini, Marco Gambarotti, Piero Picci, Gabriella Gamberi, Cristina Marraccini, Angelo Paolo Dei Tos, Lisa Simi, Pamela Pinzani, Alessandro Franchi
Mutually exclusive histone 3.3 gene mutations have been recognized in chondroblastoma and giant cell tumor of bone (GCTB), which may be useful for differential diagnostic purposes in morphologically ambiguous cases. While over 90% of GCTB presents histone 3.3 variants exclusively in the H3F3A gene, chondroblastoma is mutated mainly in H3F3B. In this study we examined a series of giant cell rich primary bone tumors, aiming to evaluate the possible diagnostic role of histone 3.3 mutations in the differential diagnosis between GCTB and giant cell rich sarcomas. Sixteen cases of non-metastatic GCTB, 9 GCTB with lung metastases, and 35 giant cell-rich sarcomas were selected from our institutional archives. Eight chondroblastomas were used as controls. Direct sequencing for the presence of H3F3A and H3F3B variants in coding region between codons 1 and 42, including the hot spot codons (28, 35 and 37) was performed on DNA extracted from formalin-fixed paraffin-embedded tissue using conventional polymerase chain reaction (PCR) and fast COamplification at Lower Denaturation temperature-PCR (COLD-PCR). Overall, 24 GCTB (96%) presented a mutation in the H3F3A gene (15 of 16 non metastatic and 9 of 9 metastatic). Five sarcomas harbored a H3F3A mutation (3 p.G35 W, 1 p.G35 L and 1 p.G35E), and these were all secondary malignant GCTB. In conclusion, we confirm that H3F3A mutational testing may be a useful adjunct to differentiate GCTB from giant cell rich sarcomas. Although the presence of H3F3A mutations does not exclude with certainty a diagnosis of sarcoma, the possibility of a malignant evolution of GCTB should also be considered.
http://ift.tt/2wRQFk5
Expression of YES-associated protein (YAP) and its clinical significance in breast cancer tissues
Publication date: Available online 9 September 2017
Source:Human Pathology
Author(s): Lanqing Cao, Ping-Li Sun, Min Yao, Meng Jia, Hongwen Gao
The transcriptional co-activator YES-associated protein (YAP) has been reported to act as both an oncogene and tumor suppressor in breast cancers. In this study, we evaluated YAP expression immunohistochemically in 324 breast cancer tissues and correlated the expression with clinicopathological findings and patient survival data. Additionally, we reviewed the literature to clarify the role of YAP in breast cancer. We detected YAP, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth receptor-2 (HER2) expression and a Ki67 labeling index >20% in 53.4%, 49.0%, 45.0%, 28.3%, and 57.4% of invasive ductal carcinoma (IDC) tissues, respectively. YAP is mainly localized within the tumor cell nuclei, and its expression was associated with the PR status and Luminal A subtype. YAP expression also inversely correlated with the HER2 and Ki67 levels and lymph node metastasis. Kaplan–Meier curves revealed associations of YAP expression with favorable disease-free survival (DFS) and overall survival (OS) in patients with Luminal A subtype breast cancer and with favorable DFS association among patients with IDC, Luminal B (HER2-) and Luminal B (HER2+) subtype breast cancers. A multivariate Cox analysis revealed that YAP expression and PR status were independent favorable predictors of DFS and OS, respectively, among patients with breast cancer, whereas TNM stage and an old age were independent predictors of a poor DFS. Our results, together with the literature review findings, suggest that YAP could be a prognostic marker in patients with breast cancer.
http://ift.tt/2vWeael
Small bowel stenosis: a manifestation of chronic graft-versus-host disease in children?
Publication date: Available online 9 September 2017
Source:Human Pathology
Author(s): Mickael Tordjman, Marie Ouachee, Arnaud Bonnard, Bogdana Tilea, Karima Yakouben, Jerome Viala, Michel Peuchmaur, Dominique Berrebi
Digestive graft versus host disease (GVHD) is a frequent complication after bone marrow transplantation (BMT), but small bowel obstruction is an extremely rare event. We present herein the first pediatric series of 4 cases of small bowel obstruction after BMT with detailed gross, histological data and their genetic status of the NOD2 gene. All patients had a history of severe acute GVHD treated by immunosuppressive agents and/or infliximab (in 3 cases). Acute or progressively worsening abdominal pain accompanied by small bowel occlusion occurred 5–16months after graft and CT-scan revealed multiple small intestinal stenosis. Failure of intensive medical treatment led to surgical resection of affected loops. Stigmata of acute (apoptosis of crypts and satellitosis) and chronic GVHD features (submucosal fibrosis and serosae sclerolipomatosis), as well as extensive ulcerations, were observed in all ileal specimens. NOD2 mutation was found in only one patient. The follow up showed successful outcome after surgery.
http://ift.tt/2wRBasf
Copyright
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 5
http://ift.tt/2fazHWa
Contributors
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 5
http://ift.tt/2wPiZFP
Contents
Publication date: October 2017
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 5
http://ift.tt/2fblZ5z
Forthcoming Issues
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 5
http://ift.tt/2wPqsVz
Gene Therapy
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 5
Author(s): Daniel E. Bauer, Donald B. Kohn
http://ift.tt/2fb0UrS
Historical Perspective on the Current Renaissance for Hematopoietic Stem Cell Gene Therapy
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 5
Author(s): Donald B. Kohn
Teaser
Gene therapy using hematopoietic stem cells (HSC) has developed over the past 3 decades, with progressive improvements in the efficacy and safety. Autologous transplantation of HSC modified with murine gammaretroviral vectors first showed clinical benefits for patients with several primary immune deficiencies, but some of these patients suffered complications from vector-related genotoxicity. Lentiviral vectors have been used recently for gene addition to HSC and have yielded clinical benefits for primary immune deficiencies, metabolic diseases, and hemoglobinopathies, without vector-related complications. Gene editing using site-specific endonucleases is emerging as a promising technology for gene therapy and is moving into clinical trials.http://ift.tt/2wPiyeF
Integrating Vectors for Gene Therapy and Clonal Tracking of Engineered Hematopoiesis
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 5
Author(s): Luca Biasco, Michael Rothe, Juliane W. Schott, Axel Schambach
Teaser
Gene therapy using autologous or allogeneic cells offers promising possibilities to treat inherited and acquired diseases, ideally leading to a long-lasting therapeutic correction. This article summarizes efforts that use integrating vectors derived from retroviruses and transposons, and briefly explains integrating vector biology and integration site analysis and recent successful application of this technology in clinical trials. Moreover, outlined is how these vectors can be used for cancer gene discovery and clonal tracking of benign and malignant hematopoiesis to gain insights into the dynamics of hematopoiesis.http://ift.tt/2fb0TUQ
Nonintegrating Gene Therapy Vectors
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 5
Author(s): Takis Athanasopoulos, Mustafa M. Munye, Rafael J. Yáñez-Muñoz
Teaser
Gene delivery vectors that do not rely on host cell genome integration offer several advantages for gene transfer, chiefly the avoidance of insertional mutagenesis and position effect variegation. However, unless engineered for replication and segregation, nonintegrating vectors will dilute progressively in proliferating cells, and are not exempt of epigenetic effects. This article provides an overview of the main nonintegrating viral (adenoviral, adeno-associated viral, integration-deficient retro-lentiviral, poxviral), and nonviral (plasmid vectors, artificial chromosomes) vectors used for preclinical and clinical cell and gene therapy applications. Particular emphasis is placed on their use in hematologic disease.http://ift.tt/2wPkmV3
In Vivo Hematopoietic Stem Cell Transduction
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 5
Author(s): Maximilian Richter, Daniel Stone, Carol Miao, Olivier Humbert, Hans-Peter Kiem, Thalia Papayannopoulou, André Lieber
Teaser
Current protocols for hematopoietic stem cell (HSC) gene therapy, involving the transplantation of ex vivo lentivirus vector-transduced HSCs into myeloablated recipients, are complex and not without risk for the patient. In vivo HSC gene therapy can be achieved by the direct modification of HSCs in the bone marrow after intraosseous injection of gene delivery vectors. A recently developed approach involves the mobilization of HSCs from the bone marrow into peripheral the blood circulation, intravenous vector injection, and re-engraftment of genetically modified HSCs in the bone marrow. We provide examples for in vivo HSC gene therapy and discuss advantages and disadvantages.http://ift.tt/2fbaoTS
Gene Editing
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 5
Author(s): Dale Ando, Kathleen Meyer
Teaser
The clinical application and regulatory strategy of genome editing for ex vivo cell therapy is derived from the intersection of two fields of study: viral vector gene therapy trials; and clinical trials with ex vivo purification and engraftment of CD34+ hematopoietic stem cells, T cells, and tumor cell vaccines. This article covers the regulatory and translational preclinical activities needed for a genome editing clinical trial modifying hematopoietic stem cells and the genesis of this current strategy based on previous clinical trials using genome-edited T cells. The SB-728 zinc finger nuclease platform is discussed because this is the most clinically advanced genome editing technology.http://ift.tt/2wPI83v
Gene Therapy Approaches to Hemoglobinopathies
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 5
Author(s): Giuliana Ferrari, Marina Cavazzana, Fulvio Mavilio
Teaser
Gene therapy for hemoglobinopathies is currently based on transplantation of autologous hematopoietic stem cells genetically modified with a lentiviral vector expressing a globin gene under the control of globin transcriptional regulatory elements. Preclinical and early clinical studies showed the safety and potential efficacy of this therapeutic approach as well as the hurdles still limiting its general application. In addition, for both beta-thalassemia and sickle cell disease, an altered bone marrow microenvironment reduces the efficiency of stem cell harvesting as well as engraftment. These hurdles need be addressed for gene therapy for hemoglobinopathies to become a clinical reality.http://ift.tt/2fbfb84
Gene Therapy for Hemophilia
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 5
Author(s): Amit C. Nathwani, Andrew M. Davidoff, Edward G.D. Tuddenham
Teaser
The best currently available treatments for hemophilia A and B (factor VIII or factor IX deficiency, respectively) require frequent intravenous infusion of highly expensive proteins that have short half-lives. Factor levels follow a saw-tooth pattern that is seldom in the normal range and falls so low that breakthrough bleeding occurs. Most hemophiliacs worldwide do not have access to even this level of care. In stark contrast, gene therapy holds out the hope of a cure by inducing continuous endogenous expression of factor VIII or factor IX following transfer of a functional gene to replace the hemophilic patient's own defective gene.http://ift.tt/2wPnzE8
Gene Therapy Approaches to Human Immunodeficiency Virus and Other Infectious Diseases
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 5
Author(s): Geoffrey L. Rogers, Paula M. Cannon
Teaser
Advances in gene therapy technologies, particularly in gene editing, are suggesting new avenues for the treatment of human immunodeficiency virus and other infectious diseases. This article outlines recent developments in antiviral gene therapies, including those based on the disruption of entry receptors or that target viral genomes using targeted nucleases, such as the CRISPR/Cas9 system. In addition, new ways to express circulating antiviral factors, such as antibodies, and approaches to harness and engineer the immune system to provide an antiviral effect that is not naturally achieved are described.http://ift.tt/2faAsPh
Hematopoietic Stem Cell Approaches to Cancer
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 5
Author(s): Jennifer E. Adair, Sara P. Kubek, Hans-Peter Kiem
Teaser
Hematopoietic stem cells (HSCs) are unique in their ability to self-renew and generate all blood lineages for the entire life. HSC modification affects red blood cells, platelets, lymphocytes, and myeloid cells. Chemotherapy can result in myelosuppression, limiting effective chemotherapy administration. For diseases like glioblastoma, high expression of methlylguanine methyltransferase can inactivate alkylating agent chemotherapy. Here we discuss how HSCs can be modified to overcome this resistance, permitting sensitization of tumors to chemotherapy while simultaneously protecting the hematopoietic system. We also discuss how HSCs can be harnessed to produce powerful tumor killing T cells, potentially benefitting and complementing T-cell–based immunotherapies.http://ift.tt/2wPNICG
Gene Modified T Cell Therapies for Hematological Malignancies
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 5
Author(s): Ulrike Abramowski-Mock, Juliette M. Delhove, Waseem Qasim
Teaser
This article focuses on clinical applications of T cells transduced to express recombinant T cell receptor and chimeric antigen receptor constructs directed toward hematological malignancies, and considers newer strategies incorporating gene-editing technologies to address GvHD and host-mediated rejection. Recent data from clinical trials are reviewed, and an overview is provided of current and emerging manufacturing processes; consideration is also given to new developments in the pipeline.http://ift.tt/2faAqH9
Blockage of regulatory T cells augments induction of protective immune responses by influenza virus-like particles in aged mice
Source:Microbes and Infection
Author(s): Zhiyuan Wen, Xi Wang, Ke Dong, Huizhong Zhang, Zhigao Bu, Ling Ye, Chinglai Yang
Elderly humans over 65 years old are at great risk to pathogenesis by influenza virus infection. However, although influenza vaccines provide effective protection in healthy young adults, protection of elderly adults is substantially lower even with a good match between the vaccine and the circulating influenza virus. To gain insight of the underlying mechanism for the reduced immunogenicity of influenza vaccines in the aged population, we investigated immunogenicity of influenza virus-like particle vaccines in aged mice, which represent a useful model for studying aging associated impairment in immune responses. Specifically, we investigated the effect of inhibiting regulatory T cells in aged mice on induction of protective immune responses by influenza vaccines. Our results showed that injecting anti-CD25 antibodies could down-regulate CD25 on the surface of regulatory T cells and significantly increase the levels of antibody responses induced by VLP immunization in aged mice. Further, the profiles of antibody responses were also changed towards Th1 type by regulatory T cell blockage in aged mice. Moreover, aged mice that were treated by anti-CD25 antibodies prior to vaccination were more effectively protected against lethal influenza virus challenge.
http://ift.tt/2xm0HwG
Single immunization with MF59-adjuvanted inactivated whole-virion H7N9 influenza vaccine provides early protection against H7N9 virus challenge in mice
Source:Microbes and Infection
Author(s): Haiyan Chang, Jie Duan, Peng Zhou, Ling Su, Dan Zheng, Fenghua Zhang, Fang Fang, Xiaoman Li, Ze Chen
H7N9 influenza infection in humans would result in severe respiratory illness. Vaccination is the best way to prevent influenza virus. In this paper, we investigated the effect of early protection provided by inactivated whole-virion H7N9 influenza vaccine in a mouse model.Mice were immunized intramuscularly once with different doses of inactivated whole-virion H7N9 influenza vaccine alone or in combination with MF59 adjuvant. Specific IgM and IgG antibody titers in sera of mice were detected by ELISA 3, 5 and 7days after immunization. To evaluate the early protection provided by the vaccine, mice were challenged with lethal dose (40LD50) of homologous virus 3, 5 and 7 days after immunization respectively. The survival rate and body weight change of mice during 21 days after challenge and the residual lung virus titer on 3rd day after challenge were determined. The results demonstrated that mice could obtain effective protection 3 days after immunization with the vaccine at a high dose, and 5-7 days after immunization even at a low dose. Thus early immune responses induced by inactivated whole-virion H7N9 vaccine could provide effective protection.
http://ift.tt/2whoxoe
The caspase-8/Bid/cytochrome c axis links signals from death receptors to mitochondrial reactive oxygen species production
Publication date: November 2017
Source:Free Radical Biology and Medicine, Volume 112
Author(s): Wan-Sung Kim, Kwang-Soon Lee, Ji-Hee Kim, Chun-Ki Kim, Gwangsoo Lee, Jongseon Choe, Moo-Ho Won, Tae-Hyoung Kim, Dooil Jeoung, Hansoo Lee, Ji-Yoon Kim, Mi Ae Jeong, Kwon-Soo Ha, Young-Guen Kwon, Young-Myeong Kim
Ligation of the death receptors for TNF-α, FasL, and TRAIL triggers two common pathways, caspase-dependent intrinsic apoptosis and intracellular reactive oxygen species (ROS) generation. The apoptotic pathway is well characterized; however, a signaling linker between the death receptor and ROS production has not been clearly elucidated. Here, we found that death receptor-induced ROS generation was strongly inhibited by mitochondrial complex I and II inhibitors, but not by inhibitors of NADPH oxidase, lipoxygenase, cyclooxygenase or xanthine oxidase, indicating that ROS are mostly generated by the impairment of the mitochondrial respiratory chain. ROS generation was accompanied by caspase-8 activation, Bid cleavage, and cytochrome c release; it was blocked in FADD- and caspase-8-deficient cells, as well as by caspase-8 knockdown and inhibitor. Moreover, Bid knockdown abrogated TNF-α- or TRAIL-induced ROS generation, whereas overexpression of truncated Bid (tBid) or knockdown of cytochrome c spontaneously elevated ROS production. In addition, p53-overexpressing cells accumulated intracellular ROS via cytochrome c release mediated by the BH3-only protein Noxa induction. In a cell-free reconstitution system, caspase-8-mediated Bid cleavage and recombinant tBid induced mitochondrial cytochrome c release and ROS generation, which were blocked by Bcl-xL and antioxidant enzymes. These data suggest that anti-apoptotic Bcl-2 proteins play an important role in mitochondrial ROS generation by preventing cytochrome c release. These data provide evidence that the FADD/caspase-8/Bid/cytochrome c axis is a crucial linker between death receptors and mitochondria, where they play a role in ROS generation and apoptosis.
Graphical abstract
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Immune mechanisms of food allergy and its prevention by early intervention
Source:Current Opinion in Immunology, Volume 48
Author(s): Victor Turcanu, Helen A Brough, George Du Toit, Ru-Xin Foong, Tom Marrs, Alexandra F Santos, Gideon Lack
The environmental factors driving the increase in food allergies are unclear and possibly involve dual exposure to allergens, microbiome-driven effects or other mechanisms. Until they can be better understood, early intervention aiming at establishing oral tolerance provides an effective way to decrease the window-of-risk when children may develop allergic sensitisation to foods due to the absence of a protective immune response. Thus, the recent LEAP (Learning Early About Peanut allergy) and LEAP-On studies achieved a high level of peanut allergy prevention by early introduction of peanuts in the infants diet and conveyed more information regarding the evolution of IgE and IgG4 antibody responses to food antigens over time.
http://ift.tt/2fbmyMR
Skin burns following cryotherapy in misdiagnosed pediatric injuries
Publication date: Available online 8 September 2017
Source:Journal of Bodywork and Movement Therapies
Author(s): N.K. Sferopoulos
Superficial local cryotherapy is frequently and safely used for pain relief following musculoskeletal injury or disease. However, serious skin complications have been reported in adults following inappropriate application. Skin burns following superficial local cryotherapy have not been previously reported in children.The consequences of inappropriate use of various forms of cryotherapy in four children following sport injuries are presented. They were all primarily misdiagnosed with a soft tissue injury. The incorrect usage was due to the high severity of the local symptoms and signs. They were all referred with partial thickness skin burns. Diagnosis on referral indicated a bone injury in all of them. The value of the initial clinical examination is emphasized considering that fractures, including physeal injuries, are more common than ligamentous lesions, and the high incidence of the radiographically occult acute injuries in children. The use of superficial local cryotherapy following injuries in children should always follow the rules of proper usage and should be avoided in cases that the clinical examination cannot exclude a potential sprain or fracture to prevent further ligament, joint or bone damaging.
http://ift.tt/2wR5JzR
Pilates Reformer exercises for fall risk reduction in older adults: A randomized controlled trial
Publication date: Available online 9 September 2017
Source:Journal of Bodywork and Movement Therapies
Author(s): Margaret Roller, Aimie Kachingwe, Janna Beling, Dawn-Marie Ickes, Allyson Cabot, Gabrielle Shrier
ObjectiveTo investigate the effects of Pilates exercises using a Reformer on measures of fall risk, balance and mobility, self-efficacy, and active range of motion in adults age 65 and over at risk for falls compared to a control group.DesignRandomized Controlled Trial.Methods55 subjects (27 Pilates intervention, 28 control; 38 females, 17 males; mean age 77.6 years, range 65–95) were randomly assigned to either a Pilates Reformer intervention group or a control group (no intervention). Subjects in the intervention group attended a Pilates Reformer exercise program in a group format once a week over a 10-week period. The primary outcome measures were the Sensory Organization Test (SOT) composite scores on the NeuroCom® system, Timed Up-and-Go (TUG), and Activities-specific Balance Confidence (ABC) scale. The secondary outcome measures were the Adaptation Test (ADT), straight leg raise, hip extension, and ankle dorsiflexion active range of motion (AROM), Berg Balance Scale (BBS), and 10 Meter Walk Test (10MWT).ResultsThere was a significant interaction between group and time on the TUG, BBS, 10MWT, and SLR, hip extension, and ankle dorsiflexion AROM measurements. Over time, subjects in the Pilates intervention group improved their scores significantly on all mentioned measures, whereas subjects in the control group did not (P ≤ 0.05). Significantly improved AROM was found between groups following the Pilates intervention for hip extension, left SLR, and right ankle dorsiflexion.ConclusionPilates Reformer exercises performed once per week for 10 weeks resulted in reduced fall risk and significant improvements in static and dynamic balance, functional mobility, balance self-efficacy, and lower extremity AROM in adults age 65 and older at risk for falling, whereas the control group did not significantly improve in any measures. Pilates Reformer exercises are more effective compared to no exercise intervention at improving hip and ankle AROM.
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Stress-Activated Chaperones: A First Line of Defense
Publication date: Available online 8 September 2017
Source:Trends in Biochemical Sciences
Author(s): Wilhelm Voth, Ursula Jakob
Proteins are constantly challenged by environmental stress conditions that threaten their structure and function. Especially problematic are oxidative, acid, and severe heat stress which induce very rapid and widespread protein unfolding and generate conditions that make canonical chaperones and/or transcriptional responses inadequate to protect the proteome. We review here recent advances in identifying and characterizing stress-activated chaperones which are inactive under non-stress conditions but become potent chaperones under specific protein-unfolding stress conditions. We discuss the post-translational mechanisms by which these chaperones sense stress, and consider the role that intrinsic disorder plays in their regulation and function. We examine their physiological roles under both non-stress and stress conditions, their integration into the cellular proteostasis network, and their potential as novel therapeutic targets.
http://ift.tt/2wRFN5o
Neuropeptide discovery in Proasellus cavaticus: prediction of the first large-scale peptidome for a member of the Isopoda using a publicly accessible transcriptome
Source:Peptides
Author(s): Andrew E. Christie
In silico transcriptome mining is one of the most effective methods for neuropeptide discovery in crustaceans, particularly for species that are small, rare or from geographically inaccessible habitats that make obtaining the large pools of tissue needed for other peptide discovery platforms impractical. Via this approach, large peptidomes have recently been described for members of many of the higher crustacean taxa, one notable exception being the Isopoda; no peptidome has been predicted for any member of this malacostracan order. Using a publicly accessible transcriptome for the isopod Proasellus cavaticus, a subcentimeter subterranean ground water dweller, the first in silico-predicted peptidome for a member of the Isopoda is presented here. BLAST searches employing known arthropod neuropeptide pre/preprohormone queries identified 49 transcripts as encoding putative homologs within the P. cavaticus transcriptome. The proteins deduced from these transcripts allowed for the prediction of 171 distinct mature neuropeptides. The P. cavaticus peptidome includes members of the adipokinetic hormone-corazonin-like peptide, allatostatin A, allatostatin B, allatostatin C, allatotropin, bursicon α, bursicon β, CCHamide, crustacean cardioactive peptide, crustacean hyperglycemic hormone/molt-inhibiting hormone, diuretic hormone 31, eclosion hormone, elevenin, FMRFamide-like peptide, glycoprotein hormone α2, leucokinin, myosuppressin, neuroparsin, neuropeptide F, pigment dispersing hormone, pyrokinin, red pigment concentrating hormone, RYamide, short neuropeptide F, sulfakinin, tachykinin-related peptide and trissin families, as well as many linker/precursor-related sequences that may or may not represent additional bioactive molecules. Interestingly, many of the predicted P. cavaticus neuropeptides possess structures identical (or nearly so) to those previously described from members of several other malacostracan orders, i.e., the Decapoda, Amphipoda and Euphausiacea, a finding that suggests broad phylogenetic conservation of bioactive peptide structures, and possibly functions, may exist within the Malacostraca.
http://ift.tt/2vMS7m7
Hypothyroidism in the “Arnolfini Portrait” (1434) by Jan Van Eyck (1390–1441)
Abstract
Background
The Arnolfini portrait painted by Jan van Eyck in 1434 remains one of the most puzzling yet alluring paintings of prerenaissance western art.
Purpose
The painting is renowned for its exactitude in brush strokes, textures and the distinctive morphology of the main character Arnolfini. The nature of these requires pathological consideration.
Methods
Diagnostic and pathological analysis of the painting.
Results
A number of pathological abnormalities are noted in the face of the main character including loss of outer third of the eyebrow (Sign of Hertoghe), bilateral ptosis and melasma of the forehead. These together support a diagnosis of hypothyroidism.
Conclusions
This novel diagnosis offers an additional perspective to this enigmatic portrait, and can add to the comprehension of the method, origin and pathological associations of this prominent painting from a genius artist.
http://ift.tt/2xThLGq
Are children playgrounds safe play areas? Inorganic analysis and lead isotope ratios for contamination assessment in recreational (Brazilian) parks
Abstract
In city playgrounds, there is a potential risk of harming children's health by contamination coming from anthropogenic activities. With the aim to determinate the sources and the risk of hazardous elements, soil samples were collected in 19 selected playgrounds of different urban and rural areas from the Rio Grande do Sul state (Brazil). The concentration of 23 metals and metalloids and lead isotopic ratios were determined by ICP-MS. The methodology proposed here, firstly, classified the parks according to the average metal content by means of the NWACs (Normalized-and-Weighted Average Concentrations) and assess the contamination risk determining the Contamination Factors (CFs). Finally, statistical tools (correlation analysis and principal component analysis) were used to identify the most important contamination sources. The statistical tools used, together with lead isotopic composition analysis of the samples, revealed that coal combustion is the main source of contamination in the area. Vegetation was identified as a barrier for the contamination coming from the city. Nonetheless, some of the soils present a possible toxicological risk for humans. In fact, Cr, Sb, and Pb concentrations were higher than the Residential Intervention Values (VIRs) defined by the Environmental Protection Agency of the State of São Paulo, also in Brazil.
http://ift.tt/2wQRKu1
The dissipation and risk assessment of 2,4-D sodium, a preharvest anti-fruit-drop plant hormone in bayberries
Abstract
Preharvest fruit-drop is a challenge to bayberry production. 2,4-D sodium as a commonly used anti-fruit-drop hormone on bayberry can reduce the yield loss caused by preharvest fruit-drop. The persistence and risk assessment of 2,4-D sodium after applying on bayberries were investigated. A method for determining 2,4-D sodium in bayberry was established based on LC-MS-MS. The average recoveries of 2,4-D sodium were at the range of 93.7–95.8% with relative standard deviations (RSDs) ranging from 0.9 to 2.8%. The dissipation rates of 2,4-D sodium were described using first-order kinetics, and its half-life ranged from 11.2 to 13.8 days. A bayberry consumption survey was carried out for Chinese adults for the first time. The safety assessments of 2,4-D sodium were conducted by using field trail data as well as monitoring data. Results showed that the chronic risk quotient and the acute risk quotient were calculated to be 0.23–0.59 and 0.02–0.05%, respectively, for Chinese adults, indicating low dietary risk for adults and children. In the end, the household cleaning steps were compared, and results showed that water rinsing for 1 min can remove 49.9% 2,4-D sodium residue, which provides pesticide removal suggestion for consumers.
http://ift.tt/2wh75Ae
Brevibacillus laterosporus isolated from the digestive tract of honeybees has high antimicrobial activity and promotes growth and productivity of honeybee’s colonies
Abstract
The development of novel antimicrobial drugs, as well as the discovery of novel compounds able to promote honeybee's growth, represents major challenges for modern entomology. The main aim of this study was to investigate whether Brevibacillus laterosporus isolated from the digestive tract of Saudi honeybees, Apis mellifera, was able to stimulate colony strength parameters of honeybees and to evaluate its ability to produce antimicrobial agents. Honeybees were collected in Dirab, Riyadh Region, Saudi Arabia, and microorganisms were isolated and identified by 16S ribosomal RNA analysis. Microscopic identification of the microorganism in its native state was facilitated by atomic force microscopy at high-resolution imaging. Active biological compounds were produced by submerged fermentation with B. laterosporus. The fermented broth was subjected to extraction and purification, and then semi-pure compounds were analyzed by gas chromatography–mass spectrometry. The effectiveness of the crude extract and semi-pure compounds as antimicrobial agents was evaluated by susceptibility assays. More than 22% of the microorganisms isolated from the digestive tract of healthy honeybees have been identified as B. laterosporus, this kind of species has a unique shape and morphological structure. The cyclic dipeptide cyclo(Leu-Pro) produced by B. laterosporus showed biological activity against several pathogenic microorganisms. Furthermore, the total counts of workers, closed brood, and open brood, as well as the production of bee pollen and honey, were better in honeybees treated with a B. laterosporus suspension. The data indicated that the B. laterosporus strain isolated from a healthy honeybee might be a novel probiotic and a producer of important biological compounds.
http://ift.tt/2wgAT0b
Morphology evolution of nanorods decorated on electrospun nanofibers and their applications in SERS and catalysis
Publication date: 5 December 2017
Source:Materials & Design, Volume 135
Author(s): Lu Bai, Zhaodong Yan, Lu Jia, Zhicheng Liu, Yaqing Liu
Understanding the structure-property relationships of functional materials with changing nanostructures is essential for their practical applications. In this work, the nanorods-decorated electrospun nanofibers underwent a morphology evolution upon simple thermal treatment. The nanorods became short, and finally round with the increasing thermal treating time. As results of the morphology evolution, the SERS properties and the catalytic properties of the changing nanostructures showed different trends. The SERS activity firstly increased and then decreased with the thermal treating time. However, the catalytic property decreased with the thermal treating time. The revealed connections between the practical performance and the morphology evolution might be helpful for the control of functionality of nanomaterials under certain conditions.
Graphical abstract
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The Ice Test to Differentiate Essential tremor from Parkinson’s disease tremor
Source:Clinical Neurophysiology
Author(s): Aparna Wagle Shukla, Michael Okun, David Vaillancourt, Lisa Warren
http://ift.tt/2wS8rDK
Standard computerized EEG reporting - it’s time to even the score
Source:Clinical Neurophysiology
Author(s): William O. Tatum
http://ift.tt/2eUBjGD
Processing of visual food cues during bitter taste perception in female patients with binge-eating symptoms: a cross-modal ERP study
Source:Clinical Neurophysiology
Author(s): Anne Schienle, Wilfried Scharmüller, Daniela Schwab
ObjectiveIn healthy individuals, the perception of an intense bitter taste decreased the reward value of visual food cues, as reflected by the reduction of a specific event-related brain potential (ERP), frontal late positivity. The current cross-modal ERP study investigated responses of female patients with binge-eating symptoms (BES) to this type of visuo-gustatory stimulation.MethodsWomen with BES (n = 36) and female control participants (n = 38) viewed food images after they rinsed their mouth with either bitter wormwood tea or water.ResultsRelative to controls, the patients showed elevated late positivity (LPP: 400-700 ms) to the food images in the bitter condition. The LPP source was located in the medial prefrontal cortex. Both groups did not differ in the ratings for the fluids (intensity, bitterness, disgust).ConclusionsThis ERP study showed that a bitter taste did not decrease late positivity to visual food cues (reflecting food reward) in women with BES.SignificanceThe atypical bitter responding might be a biological marker of this condition and possibly contributes to overeating. Future studies should additionally record food intake behavior to further investigate this mechanism.
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Frontal EEG asymmetry and later behavior vulnerability in infants with congenital visual impairment
Source:Clinical Neurophysiology
Author(s): Michelle A. O'Reilly, Joe Bathelt, Elena Sakkalou, Hanna Sakki, Alison Salt, Naomi Dale, Michelle de Haan
ObjectiveYoung children with congenital visual impairment (VI) are at increased risk of behavioral vulnerabilities. Studies on 'at risk' populations suggest that frontal EEG asymmetry may be associated with behavioral risk. We investigated frontal asymmetry at 1 year (Time 1), behavior at 2 years (Time 2) and their longitudinal associations within a sample of infants with VI. Frontal asymmetry in the VI sample at 1 year was also compared cross-sectionally to an age-matched typically sighted (TS) group.MethodsAt Time 1, 22 infants with VI and 10 TS infants underwent 128-channel EEG recording. Frontal asymmetry ratios were calculated from power spectral density values in the alpha frequency band. At Time 2, Achenbach Child Behavior Checklist data was obtained for the VI sample.Results63.6% of the VI sample and 50% of the TS sample showed left frontal asymmetry; no significant difference in frontal asymmetry was found between the two groups. 22.7% of the VI sample had subclinical to clinical range 'internalizing' behavior difficulties. Greater left frontal asymmetry at one year was significantly associated with greater emotionally reactive scores at two years within the VI sample (r=.50, p=.02).ConclusionsLeft frontal asymmetry correlates with later behavior risk within this vulnerable population. Significance: These findings make an important first contribution regarding the utility of frontal EEG asymmetry as a method to investigate risk in infants with VI.
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Protection against infectious bronchitis virus by spike ectodomain subunit vaccine
Source:Vaccine
Author(s): Fatma Eldemery, Kellye S. Joiner, Haroldo Toro, Vicky L. van Santen
The avian coronavirus infectious bronchitis virus (IBV) S1 subunit of the spike (S) glycoprotein mediates viral attachment to host cells and the S2 subunit is responsible for membrane fusion. Using IBV Arkansas-type (Ark) S protein histochemistry, we show that extension of S1 with the S2 ectodomain improves binding to chicken tissues. Although the S1 subunit is the major inducer of neutralizing antibodies, vaccination with S1 protein has been shown to confer inadequate protection against challenge. The demonstrated contribution of S2 ectodomain to binding to chicken tissues suggests that vaccination with the ectodomain might improve protection compared to vaccination with S1 alone. Therefore, we immunized chickens with recombinant trimeric soluble IBV Ark-type S1 or S-ectodomain protein produced from codon-optimized constructs in mammalian cells. Chickens were primed at 12days of age with water-in-oil emulsified S1 or S-ectodomain proteins, and then boosted 21days later. Challenge was performed with virulent Ark IBV 21days after boost. Chickens immunized with recombinant S-ectodomain protein showed statistically significantly (P<0.05) reduced viral loads 5days post-challenge in both tears and tracheas compared to chickens immunized with recombinant S1 protein. Consistent with viral loads, significantly reduced (P<0.05) tracheal mucosal thickness and tracheal lesion scores revealed that recombinant S-ectodomain protein provided improved protection of tracheal integrity compared to S1 protein. These results indicate that the S2 domain has an important role in inducing protective immunity. Thus, including the S2 domain with S1 might be promising for better viral vectored and/or subunit vaccine strategies.
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Cost-effectiveness of HPV vaccination in the context of high cervical cancer incidence and low screening coverage
Source:Vaccine
Author(s): Triin Võrno, Katrin Lutsar, Anneli Uusküla, Lee Padrik, Terje Raud, Rainer Reile, Oliver Nahkur, Raul-Allan Kiivet
BackgroundEstonia has high cervical cancer incidence and low screening coverage. We modelled the impact of population-based bivalent, quadrivalent or nonavalent HPV vaccination alongside cervical cancer screening.MethodsA Markov cohort model of the natural history of HPV infection was used to assess the cost-effectiveness of vaccinating a cohort of 12-year-old girls with bivalent, quadrivalent or nonavalent vaccine in two doses in a national, school-based vaccination programme. The model followed the natural progression of HPV infection into subsequent genital warts (GW); premalignant lesions (CIN1–3); cervical, oropharyngeal, vulvar, vaginal and anal cancer. Vaccine coverage was assumed to be 70%. A time horizon of 88years (up to 100years of age) was used to capture all lifetime vaccination costs and benefits. Costs and utilities were discounted using an annual discount rate of 5%.ResultsVaccination of 12-year-old girls alongside screening compared to screening alone had an incremental cost-effectiveness ratio (ICER) of €14,007 (bivalent), €14,067 (quadrivalent) and €11,633 (nonavalent) per quality-adjusted life-year (QALY) in the base-case scenario and ranged between €5367–21,711, €5142–21,800 and €4563–18,142, respectively, in sensitivity analysis. The results were most sensitive to changes in discount rate, vaccination regimen, vaccine prices and cervical cancer screening coverage.ConclusionVaccination of 12-year-old girls alongside current cervical cancer screening can be considered a cost-effective intervention in Estonia. Adding HPV vaccination to the national immunisation schedule is expected to prevent a considerable number of HPV infections, genital warts, premalignant lesions, HPV related cancers and deaths. Although in our model ICERs varied slightly depending on the vaccine used, they generally fell within the same range. Cost-effectiveness of HPV vaccination was found to be most dependent on vaccine cost and duration of vaccine immunity, but not on the type of vaccine used.
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Bioreactor culture duration of engineered constructs influences bone formation by mesenchymal stem cells
Source:Biomaterials, Volume 146
Author(s): Debika Mitra, Jacklyn Whitehead, Osamu W. Yasui, J. Kent Leach
Perfusion culture of mesenchymal stem cells (MSCs) seeded in biomaterial scaffolds provides nutrients for cell survival, enhances extracellular matrix deposition, and increases osteogenic cell differentiation. However, there is no consensus on the appropriate perfusion duration of cellular constructs in vitro to boost their bone forming capacity in vivo. We investigated this phenomenon by culturing human MSCs in macroporous composite scaffolds in a direct perfusion bioreactor and compared their response to scaffolds in continuous dynamic culture conditions on an XYZ shaker. Cell seeding in continuous perfusion bioreactors resulted in more uniform MSC distribution than static seeding. We observed similar calcium deposition in all composite scaffolds over 21 days of bioreactor culture, regardless of pore size. Compared to scaffolds in dynamic culture, perfused scaffolds exhibited increased DNA content and expression of osteogenic markers up to 14 days in culture that plateaued thereafter. We then evaluated the effect of perfusion culture duration on bone formation when MSC-seeded scaffolds were implanted in a murine ectopic site. Human MSCs persisted in all scaffolds at 2 weeks in vivo, and we observed increased neovascularization in constructs cultured under perfusion for 7 days relative to those cultured for 1 day within each gender. At 8 weeks post-implantation, we observed greater bone volume fraction, bone mineral density, tissue ingrowth, collagen density, and osteoblastic markers in bioreactor constructs cultured for 14 days compared to those cultured for 1 or 7 days, and acellular constructs. Taken together, these data demonstrate that culturing MSCs under perfusion culture for at least 14 days in vitro improves the quantity and quality of bone formation in vivo. This study highlights the need for optimizing in vitro bioreactor culture duration of engineered constructs to achieve the desired level of bone formation.
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Extracellular matrix-derived extracellular vesicles promote cardiomyocyte growth and electrical activity in engineered cardiac atria
Source:Biomaterials, Volume 146
Author(s): Minae An, Kihwan Kwon, Junbeom Park, Dong-Ryeol Ryu, Jung-A. Shin, Jihee Lee Kang, Ji Ha Choi, Eun-Mi Park, Kyung Eun Lee, Minna Woo, Minsuk Kim
Extracellular matrix (ECM) plays a critical role in the provision of the necessary microenvironment for the proper regeneration of the cardiac tissue. However, specific mechanisms that lead to ECM-mediated cardiac regeneration are not well understood. To elucidate the potential mechanisms, we investigated ultra-structures of the cardiac ECM using electron microscopy. Intriguingly, we observed large quantities of micro-vesicles from decellularized right atria. RNA and protein analyses revealed that these contained exosomal proteins and microRNAs (miRNAs), which we referred to herein as ECM-derived extracellular vesicles (ECM-EVs). One particular miRNA from ECM-EVs, miR-199a-3p, promoted cell growth of isolated neonatal cardiomyocytes and sinus nodal cells by repressing homeodomain-only protein (HOPX) expression and increasing GATA-binding 4 (Gata4) acetylation. To determine the mechanisms, we knocked down Gata4 and showed that miR-199a-3p actions required Gata4 for cell proliferation in isolated neonatal cardiomyocytes and sinus nodal cells. To further explore the role of this miRNA, we isolated neonatal cardiac cells and recellularized into atrial ECM, referred here has engineered atria. Remarkably, miR-199a-3p mediated the enrichment of cardiomyocyte and sinus nodal cell population, and enhanced electrocardiographic signal activity of sinus nodal cells in the engineered atria. Importantly, antisense of miRNA (antagomir) against miR-199a-3p was capable of abolishing these actions of miR-199a-3p in the engineered atria. We further showed in Ang II-infused animal model of sinus nodal dysfunction that miR-199-3p-treated cardiac cells remarkably ameliorated and restored the electrical activity as shown by normalization of the ECG, in contrast to untreated cells, which did not show electrical recovery. In conclusion, these results provide clear evidence of the critical role of ECM, in not only providing a scaffold for cardiac tissue growth, but also in promoting atrial electrical function through ECM-derived miR-199a-3p.
http://ift.tt/2wQLQZT
Engineered, axially-vascularized osteogenic grafts from human adipose-derived cells to treat avascular necrosis of bone in a rat model
Publication date: Available online 8 September 2017
Source:Acta Biomaterialia
Author(s): Tarek Ismail, Rik Osinga, Atanas Todorov Jr., Alexander Haumer, Laurent A. Tchang, Christian Epple, Nima Allafi, Nadia Menzi, René D. Largo, Alexandre Kaempfen, Ivan Martin, Dirk J. Schaefer, Arnaud Scherberich
BackgroundAvascular necrosis of bone (AVN) leads to sclerosis and collapse of bone and joints. The standard of care, vascularized bone grafts, is limited by donor site morbidity and restricted availability. The aim of this study was to generate and test engineered, axially vascularized SVF cells-based bone substitutes in a rat model of AVN.MethodsSVF cells were isolated from lipoaspirates and cultured onto porous hydroxyapatite scaffolds within a perfusion-based bioreactor system for 5 days. The resulting constructs were inserted into devitalized bone cylinders mimicking AVN-affected bone. A ligated vascular bundle was inserted upon subcutaneous implantation of constructs in nude rats. After 1 and 8 weeks in vivo, bone formation and vascularization were analyzed.ResultsNewly-formed bone was found in 80% of SVF-seeded scaffolds after 8 weeks but not in unseeded controls. Human ALU+ cells in the bone structures evidenced a direct contribution of SVF cells to bone formation. A higher density of regenerative, M2 macrophages was observed in SVF-seeded constructs. In both experimental groups, devitalized bone was revitalized by vascularized tissue after 8 weeks.ConclusionSVF cells-based osteogenic constructs revitalized fully necrotic bone in a challenging AVN rat model of clinically-relevant size. SVF cells contributed to accelerated initial vascularization, to bone formation and to recruitment of pro-regenerative endogenous cells.Statement of SignificanceAvascular necrosis (AVN) of bone often requires surgical treatment with autologous bone grafts, which is surgically demanding and restricted by significant donor site morbidity and limited availability. This paper describes a de novo engineered axially-vascularized bone graft substitute and tests the potential to revitalize dead bone and provide efficient new bone formation in a rat model.The engineering of an osteogenic/vasculogenic construct of clinically-relevant size with stromal vascular fraction of human adipose, combined to an arteriovenous bundle is described. This construct revitalized and generated new bone tissue. This successful approach proposes a novel paradigm in the treatment of AVN, in which an engineered, vascularized osteogenic graft would be used as a germ to revitalize large volumes of necrotic bone.
Graphical abstract
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SI-traceable calibration-free analysis for the active concentration of G2-EPSPS protein using surface plasmon resonance
Publication date: 1 February 2018
Source:Talanta, Volume 178
Author(s): Ping Su, Zhangjing He, Liqing Wu, Liang Li, Kangle Zheng, Yi Yang
Active proteins play important roles in the function regulation of human bodies and attract much interest for use in pharmaceuticals and clinical diagnostics. However, the lack of primary methods to analyze active proteins means there is currently no metrology standard for active protein measurement. In recent years, calibration-free concentration analysis (CFCA), which is based on surface plasmon resonance (SPR) technology, has been proposed to determine the active concentration of proteins that have specific binding activity with a binding partner without any higher order standards. The CFCA experiment observes the changes of binding rates at totally different two flow rates and uses the known diffusion coefficient of an analyte to calculate the active concentration of proteins, theoretically required, the binding process have to be under diffusion-limited conditions. Measuring the active concentration of G2-EPSPS protein by CFCA was proposed in this study. This method involves optimization of the regeneration buffer and preparation of chip surfaces for appropriate reaction conditions by immobilizing ligands (G2-EPSPS antibodies) on sensor chips (CM5) via amine coupling. The active concentration of G2-EPSPS was then determined by injection of G2-EPSPS protein samples and running buffer over immobilized and reference chip surfaces at two different flow rates (5 and 100μLmin−1). The active concentration of G2-EPSPS was obtained after analyzing these sensorgrams with the 1:1 model. Using the determined active concentration of G2-EPSPS, the association, dissociation, and equilibrium constants of G2-EPSPS and its antibody were determined to be 2.18 ± 0.03 × 106M−1s−1, 5.79 ± 0.06 ×10−3s−1, and 2.65 ± 0.06 × 10−9M, respectively. The performance of the proposed method was evaluated. The within-day precisions were from 3.26% to 4.59%, and the between-day precision was 8.36%. The recovery rate of the method was from 97.46% to 104.34% in the concentration range of 1.5–8nM. The appropriate concentration range of G2-EPSPS in the proposed method was determined to be 1.5–8nM. The active G2-EPSPS protein concentration determined by our method was only 17.82% of that obtained by isotope dilution mass spectrometry, showing the active protein was only a small part of the total G2-EPSPS protein. The measurement principle of the proposed method can be clearly described by equations and the measurement result can be expressed in SI units. Therefore, the proposed method shows promise to become a primary method for active protein concentration measurement, which can benefit the development of certified reference materials for active proteins.
Graphical abstract
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Growth of Escherichia coli on the GaAs (001) surface
Publication date: 1 February 2018
Source:Talanta, Volume 178
Author(s): Elnaz Nazemi, Walid M. Hassen, Eric H. Frost, Jan J. Dubowski
Detection of pathogenic bacteria and monitoring their susceptibility to antibiotics are of great importance in the fields of medicine, pharmaceutical research, as well as water and food industries. In order to develop a photonic biosensor for detection of bacteria by taking advantage of photoluminescence (PL) of GaAs-based devices, we have investigated the capture and growth of Escherichia coli K12 on bare and biofunctionalized surfaces of GaAs (001) – a material of interest for capping different semiconductor microstructures. The results were compared with the capture and growth of Escherichia coli K12 on Au surfaces that have commonly been applied for studying a variety of biological and biochemical reactions. We found that neither GaAs nor Au-coated glass wafers placed in Petri dishes inoculated with bacteria inhibited bacterial growth in nutrient agar, regardless of the wafers being bare or biofunctionalized. However, the capture and growth of bacteria on biofunctionalized surfaces of GaAs and Au wafers kept in a flow cell and exposed to different concentrations of bacteria and growth medium revealed that the initial surface coverage and the subsequent bacterial growth were dependent on the biofunctionalization architecture, with antibody-coated surfaces clearly being most efficient in capturing bacteria and offering better conditions for growth of bacteria. We have observed that, as long as the GaAs wafers were exposed to bacterial suspensions at concentrations of at least 105 CFU/mL, bacteria could grow on the surface of wafers, regardless of the type of biofunctionalization architecture used to capture the bacteria. These results provide important insight towards the successful development of GaAs-based devices designed for photonic monitoring of bacterial reactions to different biochemical environments.
Graphical abstract
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The prognostic value of derived neutrophil to lymphocyte ratio in oesophageal cancer treated with definitive chemoradiotherapy
Publication date: Available online 8 September 2017
Source:Radiotherapy and Oncology
Author(s): Samantha Cox, Christopher Hurt, Tal Grenader, Somnath Mukherjee, John Bridgewater, Thomas Crosby
Background and purposeThe derived neutrophil–lymphocyte ratio (dNLR) is a validated prognostic biomarker for cancer survival but has not been extensively studied in locally-advanced oesophageal cancer treated with definitive chemoradiotherapy (dCRT). We aimed to identify the prognostic value of dNLR in patients recruited to the SCOPE1 trial.Materials and methods258 patients were randomised to receive dCRT±cetuximab. Kaplan–Meier's curves and both univariable and multivariable Cox regression models were calculated for overall survival (OS), progression free survival (PFS), local PFS inside the radiation volume (LPFSi), local PFS outside the radiation volume (LPFSo), and distant PFS (DPFS).ResultsAn elevated pre-treatment dNLR≥2 was significantly associated with decreased OS in univariable (HR 1.74 [95% CI 1.29–2.35], p<0.001) and multivariable analyses (HR 1.64 [1.17–2.29], p=0.004). Median OS was 36months (95% CI 27.8–42.4) if dNLR<2 and 18.4months (95% CI 14.1–24.9) if dNLR≥2. All measures of PFS were also significantly reduced with an elevated dNLR. dNLR was prognostic for OS in cases of squamous cell carcinoma with a non-significant trend for adenocarcinoma/undifferentiated tumours.ConclusionsAn elevated pre-treatment dNLR may be an independent prognostic biomarker for OS and PFS in oesophageal cancer patients treated with definitive CRT. dNLR is a simple, inexpensive and readily available tool for risk-stratification and should be considered for use in future oesophageal cancer clinical trials.The SCOPE1 trial was an International Standard Randomised Controlled Trial [number 47718479].
http://ift.tt/2faRmgB
Transcriptional-mediated effects of radiation on the expression of immune susceptibility markers in melanoma
Publication date: Available online 8 September 2017
Source:Radiotherapy and Oncology
Author(s): Lauryn R. Werner, Jasdeep S. Kler, Monica M. Gressett, Maureen Riegert, Lindsey K. Werner, Clinton M. Heinze, Joseph G. Kern, Mahyar Abbariki, Amy K. Erbe, Ravi B. Patel, Raghava N. Sriramaneni, Paul M. Harari, Zachary S. Morris
Background and purposeWe recently reported a time-sensitive, cooperative, anti-tumor effect elicited by radiation (RT) and intra-tumoral-immunocytokine injection in vivo. We hypothesized that RT triggers transcriptional-mediated changes in tumor expression of immune susceptibility markers at delayed time points, which may explain these previously observed time-dependent effects.Materials and methodsWe examined the time course of changes in expression of immune susceptibility markers following in vitro or in vivo RT in B78 murine melanoma and A375 human melanoma using flow cytometry, immunoblotting, and qPCR.ResultsFlow cytometry and immunoblot revealed time-dependent increases in expression of death receptors and T cell co-stimulatory/co-inhibitory ligands following RT in murine and human melanoma. Using high-throughput qPCR, we observed comparable time courses of RT-induced transcriptional upregulation for multiple immune susceptibility markers. We confirmed analogous changes in B78 tumors irradiated in vivo. We observed upregulated expression of DNA damage response markers days prior to changes in immune markers, whereas phosphorylation of the STAT1 transcription factor occurred concurrently with changes following RT.ConclusionThis study highlights time-dependent, transcription-mediated changes in tumor immune susceptibility marker expression following RT. These findings may help in the design of strategies to optimize sequencing of RT and immunotherapy in translational and clinical studies.
http://ift.tt/2wP3ga7
1-Hydroxypyrido[2,3-d]pyrimidin-2(1H)-ones as Novel Selective HIV Integrase Inhibitors Obtained via Privileged Substructure-Based Compound Libraries
Publication date: Available online 8 September 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Ping Gao, Lingzi Zhang, Lin Sun, Tianguang Huang, Jing Tan, Jian Zhang, Zhongxia Zhou, Tong Zhao, Luis Menéndez-Arias, Christophe Pannecouque, Erik De Clercq, Peng Zhan, Xinyong Liu
A small library containing 3-hydroxyquinazoline-2,4(1H,3H)-dione and 1-hydroxypyrido[2,3-d]pyrimidin-2(1H)-one scaffolds was obtained via the copper(I)-catalyzed azidealkyne cycloaddition (CuAAC) reaction and evaluated for their anti-HIV activity in MT-4 cells. Among the synthesized compounds, several 1-hydroxypyrido[2,3-d]pyrimidin-2(1H)-one derivatives showed remarkable anti-HIV potency with EC50 values ranging from 0.92 to 26.85 µM. The most active one, IIA-2, also showed remarkable and selective potency against HIV type 1 integrase (IN). To the best of our knowledge, this is the first report showing that 1-hydroxypyrido[2,3-d]pyrimidin-2(1H)-ones are selective HIV IN inhibitors. Preliminary structure-activity relationship (SAR) studies suggested that the divalent metal ion chelators and the nature and position of substituents around the core are important for antiviral potency. Molecular modeling has been used to predict the binding site of the pyrido[2,3-d]pyrimidin-2(1H)-one core in HIV type 1 IN and suggestions are made for improvement of its inhibitory activity.
http://ift.tt/2gTevIf
Control of multidrug-resistant Acinetobacter baumannii in Hong Kong: Role of environmental surveillance in communal areas after a hospital outbreak
Source:American Journal of Infection Control
Author(s): Vincent C.C. Cheng, Shuk-Ching Wong, Jonathan H.K. Chen, Simon Y.C. So, Sally C.Y. Wong, Pak-Leung Ho, Kwok-Yung Yuen
BackgroundEnvironmental reservoir is an important source of multidrug-resistant Acinetobacter baumannii (MRAB) outbreaks. The role of postoutbreak environmental surveillance for guiding sustained infection control effort has not been examined.MethodsEnhanced environmental disinfection and regular environmental surveillance of ward communal areas after an outbreak were performed in a university-affiliated hospital. To assess the usefulness of environmental culture in predicting patients with MRAB, weekly surveillance of communal areas was continued for 3 months after the outbreak in intervention wards. The incidence of MRAB in intervention and nonintervention wards (control) was compared, whereas the other infection control measures remained identical.ResultsPostoutbreak weekly surveillance of communal areas showed that identification of newly diagnosed MRAB patients was significantly correlated with preceding environmental contamination with MRAB (P = .001). The incidence of nosocomial MRAB infection was significantly lower in the intervention compared with nonintervention wards (0.55 vs 2.28 per 1,000 patient days, respectively; P = .04). All MRAB isolated from the environmental and patients' samples belonged to multilocus sequence typing ST457 and were blaOXA23-like positive.ConclusionsEnvironmental surveillance may serve as a surrogate marker for the presence of MRAB carriers. Implementation of timely infection control measures should be guided by environmental culture for MRAB to minimize the risk of MRAB outbreak.
http://ift.tt/2eUE6zV
Depositional histories of faunal remains from the Neolithic cultic site of Kfar HaHoresh, Israel
Source:Journal of Anthropological Archaeology, Volume 48
Author(s): Jacqueline S. Meier, A. Nigel Goring-Morris, Natalie D. Munro
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Can predicting transfusion in cardiac surgery help patients?
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Beyond availability: the importance of routine videolaryngoscopy and institution-based rescue methods of difficult videolaryngoscopy
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Lack of benefit of near-infrared spectroscopy monitoring for improving patient outcomes. Case closed?
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Response to: Go/no-go decision in anaesthesia: wide variation in risk tolerance amongst anaesthetists
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Viscoelastometric testing, fibrinogen and transfusion during post-partum haemorrhage
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Influence of deep neuromuscular block on the surgeonś assessment of surgical conditions during laparotomy: a randomized controlled double blinded trial with rocuronium and sugammadex
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Videolaryngoscopy and obstetric anaesthesia
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Theseus, the Labyrinth, and the Minotaur of anaesthetic-induced developmental neurotoxicity
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In the September BJA…
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Anaesthesia-induced developmental neurotoxicity: reality or fiction?
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Effects of propofol and surgery on neuropathology and cognition in the 3xTgAD Alzheimer transgenic mouse model
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Perioperative goal-directed therapy with uncalibrated pulse contour methods: impact on fluid management and postoperative outcome
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Causes of sudden death of young anesthesiologists in China Response to Zhang and colleagues: Rising sudden death among anaethesiologists in China.
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Response to: Routine use of viscoelastic blood tests for diagnosis and treatment of coagulopathic bleeding in cardiac surgery: updated systematic review and meta-analysis
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Reply to Lucas and Vaughan: videolaryngoscopy and obstetric anaesthesia?
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Optimal patient blood management in cardiac surgery using viscoelastic point-of-care testing Response to: Routine use of viscoelastic blood tests for diagnosis and treatment of coagulopathic bleeding in cardiac surgery: updated systematic review and meta-analysis
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Reply to Chang: After availability, training and experience are needed
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Safety assessments in the avoidance of preoperative α-receptor blockade in phaeochromocytoma surgery: the pitfalls of a zero numerator
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Viscoelastometry guided fresh frozen plasma infusion for postpartum haemorrhage: OBS2, an observational study
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Author’s reply to Grocott: Risk of cardiac ischaemia in patients without α-receptor blockade for phaeochromocytoma surgery
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Effect of Si-rich substances on phosphorous adsorption by sandy soils
Abstract
The poor adsorption capacity of sandy soils is one of the primary reasons of a high level of phosphorus (P) leaching. Silicon (Si)-rich soil amendments have the potential to improve the low absorption capacity of sandy soils for P. The objective of this study was to evaluate the ability of different Si-rich materials to regulate P adsorption and retention by sandy soils. Amorphous fine silica (FSS), calcium silicate (CaSiO3), chemically pure CaCO3, and two types of Ca-silicate slags from metal industry (Pro-Sil) and chemical industry (TS) were used in laboratory experiments being conducted with pure quartz sand and cultivated and virgin Entisols and Spodosols collected in the South Florida. The binding energy-related constants were evaluated for soils treated by Si-rich materials and then incubated during 2 months. The following row of tested materials on the increasing level of "affinity parameter" was determined: for virgin Spodosol, Pro-Sil < CaCO3 < FSS< CaSiO3 < TS; for cultivated Spodosol, FSS < Pro-Sil < CaCO3< CaSiO3 < TS; for virgin Entisol, Pro-Sil < CaSiO3 < CaCO3 < FSS < TS; and for cultivated Entisol, FSS < Pro-Sil < CaSiO3 < CaCO3 < TS. Chemical, physical, and physical-chemical mechanisms of increasing soil adsorption capacity are hypothesized and discussed to explain the results obtained. The conducted experiments have demonstrated high prospective of Si-rich materials for reduction of P leaching from cultivated sandy soils.
http://ift.tt/2jaOBjC
Enhanced effect of HAH on citric acid-chelated Fe(II)-catalyzed percarbonate for trichloroethene degradation
Abstract
This work demonstrates the impact of hydroxylamine hydrochloride (HAH) addition on enhancing the degradation of trichloroethene (TCE) by the citric acid (CA)-chelated Fe(II)-catalyzed percarbonate (SPC) system. The results of a series of batch-reactor experiments show that TCE removal with HAH addition was increased from approximately 57 to 79% for a CA concentration of 0.1 mM and from 89 to 99.6% for a 0.5 mM concentration. Free-radical probe tests elucidated the existence of hydroxyl radical (HO•) and superoxide anion radical (O2•-) in both CA/Fe(II)/SPC and HAH/CA/Fe(II)/SPC systems. However, higher removal rates of radical probe compounds were observed in the HAH/CA/Fe(II)/SPC system, indicating that HAH addition enhanced the generation of both free radicals. In addition, increased contribution of O2•- in the HAH/CA/Fe(II)/SPC system compared to the CA/Fe(II)/SPC system was verified by free-radical scavengers tests. Complete TCE dechlorination was confirmed based on the total mass balance of the released Cl− species. Lower concentrations of formic acid were produced in the later stages of the reaction for the HAH/CA/Fe(II)/SPC system, suggesting that HAH addition favors complete TCE mineralization. Studies of the impact of selected groundwater matrix constituents indicate that TCE removal in the HAH/CA/Fe(II)/SPC system is slightly affected by initial solution pH, with higher removal rates under acidic and near neutral conditions. Although HCO3− was observed to have an adverse impact on TCE removal for the HAH/CA/Fe(II)/SPC system, the addition of HAH reduced its inhibitory effect compared to the CA/Fe(II)/SPC system. Finally, TCE removal in actual groundwater was much significant with the addition of HAH to the CA/Fe(II)/SPC system. The study results indicate that HAH amendment has potential to enhance effective remediation of TCE-contaminated groundwater.
http://ift.tt/2vVwPXO
Long-term trends in incidence and survival of penile cancer in France
Source:Cancer Epidemiology, Volume 50, Part A
Author(s): Laetitia Daubisse-Marliac, Marc Colonna, Brigitte Trétarre, Gautier Defossez, Florence Molinié, Karine Jéhannin-Ligier, Emilie Marrer, Pascale Grosclaude
BackgroundPenile cancer is rare, and few population-based studies have described changes in time trend. This study aims to determine whether there has been an evolution in incidence and survival of penile cancer over time in France.MethodsRates of age world-standardized incidence (ASRW) and net survival (NS) between 1989 and 2011 were calculated using data from 16 French cancer registries. Time trend incidence and survival analysis were confined to the eight registries operating throughout the full period. Log-linear Poisson regression analysis was used to estimate the average annual percentage change (AAPC) in incidence rates. The incidence rate for the most recent period was also calculated from all 16 cancer registries operating during 2009–2011. Human papillomavirus (HPV) exposure was deduced from the morphological code. NS was estimated using the Pohar–Perme estimator of the net cumulative rate.ResultsNo significant change in incidence was observed between 1989 and 2011 (AAPC: 0.08%; 95%CI: −1.01%; +1.17%). The incidence increased with age. The ASRW in 16 registries operating in 2009–2011 was 0.59 per 100,000 (95%CI: 0.50–0.68). The proportion of cases potentially linked to HPV was nearly 11% and did not change significantly over time. NS decreased with age but did not change over time (around 65% at 5 years).ConclusionPenile cancer remains rare in France, but survival is still low − probably because of delays in diagnosis and limited improvements in care. International clinical trials are needed to develop care recommendations based on an adequate level of evidence.
http://ift.tt/2wOLOlU
Approaches to modelling radioactive contaminations in forests – Overview and guidance
Source:Journal of Environmental Radioactivity, Volumes 178–179
Author(s): A. Diener, P. Hartmann, L. Urso, J. Vives i Batlle, M.A. Gonze, P. Calmon, M. Steiner
Modelling the radionuclide cycle in forests is important in case of contamination due to acute or chronic releases to the atmosphere and from underground waste repositories. This article describes the most important aspects to consider in forest model development. It intends to give an overview of the modelling approaches available and to provide guidance on how to address the quantification of radionuclide transport in forests. Furthermore, the most important gaps in modelling the radionuclide cycle in forests are discussed and suggestions are presented to address the variability of forest sites.
http://ift.tt/2gRRulb
Targeting dendritic cells through gold nanoparticles: A review on the cellular uptake and subsequent immunological properties
Publication date: November 2017
Source:Molecular Immunology, Volume 91
Author(s): Suhana Ahmad, Anes Ateqah Zamry, Hern-Tze Tina Tan, Kah Keng Wong, JitKang Lim, Rohimah Mohamud
Gold nanoparticles (NPs) have been proposed as a highly potential tool in immunotherapies due to its advantageous properties including customizable size and shapes, surface functionality and biocompatibility. Dendritic cells (DCs), the sentinels of immune response, have been of interest to be manipulated by using gold NPs for targeted delivery of immunotherapeutic agent. Researches done especially in human DCs showed a variation of gold NPs effects on cellular uptake and internalization, DC maturation and subsequent T cells priming as well as cytotoxicity. In this review, we describe the synthesis and physiochemical properties of gold NPs as well as the importance of gold NPs in immunotherapies through their actions on human DCs.
http://ift.tt/2f9SWiL
Calcitonin gene-related peptide exerts anti-inflammatory property through regulating murine macrophages polarization in vitro
Source:Molecular Immunology, Volume 91
Author(s): Jia-Xi Duan, Yong Zhou, Ai-Yuan Zhou, Xin-Xin Guan, Tian Liu, Hui-Hui Yang, Hui Xie, Ping Chen
Acute lung injury (ALI) is a condition resulting from direct or indirect lung injury associated with high mortality and morbidity. The phenotype of macrophages in lung contributes to the pathological progress of ALI. Calcitonin gene-related peptide (CGRP) is one of the most abundant neuropeptides in lung, and attenuates lipopolysaccharide (LPS)-induced ALI in rats. However, the exact effect of CGRP on the activation of macrophages remains unknown. Here we investigate the effect of CGRP on the macrophages activation and inflammation in murine macrophages in vitro. We found that LPS increased the expression of CGRP in a LPS-induced ALI murine model and LPS-stimulated murine macrophages. Although CGRP didn't alter the expression of tumor necrosis factor-α (a marker of pro-inflammatory phenotype of macrophages, M1 macrophages) or Arginase 1 (Arg1, a marker of M2 macrophages) in non-differentiated macrophages, CGRP significantly reduced the NLRP3 and pro-IL-1β mRNA expression induced by LPS, as well as NLRP3 protein and IL-1β secretion induced by LPS+ATP in macrophages in vitro. On the other hand, CGRP dramatically enhanced the Arg1 expression and activity induced by IL-4 in the time- and dose-dependent manners. CGRP also promoted the expression of markers of M2 macrophages (IL-10, Fizz1 and Mrc1) induced by IL-4 in murine macrophages. These effects of CGRP were also observed in primary murine peritoneal macrophages. In addition, we found that CGRP regulated macrophages polarization partially through calmodulin, PKC and PKA pathways. Specifically, CGRP could inhibit the degradation of I-κB induced by LPS, and enhance the phosphorylation of STAT6 induced by IL-4 in macrophages. In conclusion, our results indicate that CGRP regulates macrophage polarization and inhibits inflammation in murine macrophages.
http://ift.tt/2wOW7qf
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Publication date: September 2017 Source: Free Radical Biology and Medicine, Volume 110 Author(s): Lucía Fernández-del-Río, Anish Nag, Elen...
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Abstract Noise pollution is a major factor of environmental complaints in many cities, which has significant impacts on human health. As a...
