Πέμπτη 1 Μαρτίου 2018
Sectioned images and 3D models of a cadaver head with reference to dermal filler injection
Publication date: Available online 2 March 2018
Source:Annals of Anatomy - Anatomischer Anzeiger
Author(s): Dong Sun Shin, YoungJoo Shim, Bong Chul Kim
The purpose of this study was to describe anatomical consideration with reference to dermal filler injection on sectioned images and three dimensional (3D) models using Visible Korean for medical education and clinical training purposes in the field of facial surgery. Serially sectioned images of the head were acquired from a cadaver. Anatomic structures related to dermal filler injection were 3D-reconstructed based on sectioned images, and additional structures were built on the basis of the established ones using a semi-automatic method. The anatomical 3D models were assembled and converted to a PDF file (66MB), which can be downloaded and used for free. In the PDF file, noticeable anatomical structures related with dermal filler injection can be identified on the 3D models as well as on the sectioned anatomical images. The 3D models in PDF were optimized and displayed in real time. These state-of-the-art sectioned images, outlined images, and 3D models will aid students and trainees to acquire a better understanding of the anatomy related to dermal filler injection, and will also improve medical understanding of patients and the general public. The 3D models in PDF files also can be used on dermal filler injection simulations.
http://ift.tt/2oNOzhx
Editorial Board
Publication date: March 2018
Source:Annals of Anatomy - Anatomischer Anzeiger, Volume 216
http://ift.tt/2HTl32l
Living Up to the Hype: Protein Synthesis Promotes Hypertranscription in Embryonic Stem Cells
Publication date: 1 March 2018
Source:Cell Stem Cell, Volume 22, Issue 3
Author(s): Miriama Kruta, Robert A.J. Signer
The rapid proliferation and unlimited self-renewal of embryonic stem cells depends upon a permissive chromatin landscape that enables hypertranscription. In this issue of Cell Stem Cell, Bulut-Karslioglu et al. report that euchromatin and transcriptional output are enhanced by protein synthesis in embryonic stem cells (Bulut-Karslioglu et al., 2018).
Teaser
The rapid proliferation and unlimited self-renewal of embryonic stem cells depends upon a permissive chromatin landscape that enables hypertranscription. In this issue of Cell Stem Cell, Bulut-Karslioglu et al. report that euchromatin and transcriptional output are enhanced by protein synthesis in embryonic stem cells (Bulut-Karslioglu et al., 2018).http://ift.tt/2oNNoyD
Sensors of Succinate: Neural Stem Cell Grafts Fight Neuroinflammation
Publication date: 1 March 2018
Source:Cell Stem Cell, Volume 22, Issue 3
Author(s): Zaal Kokaia, Olle Lindvall
In this issue of Cell Stem Cell, Peruzzotti-Jametti et al. (2018) demonstrate how neural stem cells, transplanted in a mouse model of multiple sclerosis, respond to extracellular succinate and modulate neuroinflammation by releasing anti-inflammatory prostaglandin E2 and scavenging succinate. This mechanism reduces CNS damage and ameliorates motor impairment.
Teaser
In this issue of Cell Stem Cell, Peruzzotti-Jametti et al. (2018) demonstrate how neural stem cells, transplanted in a mouse model of multiple sclerosis, respond to extracellular succinate and modulate neuroinflammation by releasing anti-inflammatory prostaglandin E2 and scavenging succinate. This mechanism reduces CNS damage and ameliorates motor impairment.http://ift.tt/2HXQbhk
Reversing Time: Ezh1 Deficiency Hastens Definitive Hematopoiesis
Publication date: 1 March 2018
Source:Cell Stem Cell, Volume 22, Issue 3
Author(s): April C. Apostol, Anna E. Beaudin
The inability to derive multipotent hematopoietic stem cells in vitro stems in part from a limited understanding of how multipotency is acquired during development. Recently in Nature,Vo et al. (2018) reveal the epigenetic enzyme Ezh1 as a master regulator of multipotency during hematopoietic stem cell development.
Teaser
The inability to derive multipotent hematopoietic stem cells in vitro stems in part from a limited understanding of how multipotency is acquired during development. Recently in Nature, Vo et al. (2018) reveal the epigenetic enzyme Ezh1 as a master regulator of multipotency during hematopoietic stem cell development.http://ift.tt/2oJFNB1
Who Defends the Stem Cell’s Citadel?
Publication date: 1 March 2018
Source:Cell Stem Cell, Volume 22, Issue 3
Author(s): Hélène Strick-Marchand, David Durantel
Recently in Cell, Wu et al. (2018) demonstrated that intrinsic expression of a subset of interferon stimulated genes confers resistance to viral infections in stem cells both in vitro and in vivo, while differentiated cells lose this intrinsic gatekeeper expression pattern in favor of inducible interferon responses.
Teaser
Recently in Cell, Wu et al. (2018) demonstrated that intrinsic expression of a subset of interferon stimulated genes confers resistance to viral infections in stem cells both in vitro and in vivo, while differentiated cells lose this intrinsic gatekeeper expression pattern in favor of inducible interferon responses.http://ift.tt/2HVTXrD
Organoid Models of Cancer Explode with Possibilities
Publication date: 1 March 2018
Source:Cell Stem Cell, Volume 22, Issue 3
Author(s): Senthil K. Muthuswamy
Organoids have tremendous promise for modeling human cancers and revealing new biological insights. Sachs et al. (2018), Seino et al. (2018) (in this issue of Cell Stem Cell), and Broutier et al. (2017) derive cancer organoids from breast, pancreas, and liver, respectively, not only reporting new methodologies but also showing their utility for translational and clinical cancer research.
Teaser
Organoids have tremendous promise for modeling human cancers and revealing new biological insights. Sachs et al. (2018), Seino et al. (2018) (in this issue of Cell Stem Cell), and Broutier et al. (2017) derive cancer organoids from breast, pancreas, and liver, respectively, not only reporting new methodologies but also showing their utility for translational and clinical cancer research.http://ift.tt/2oMwjES
Engineering a Strong Bond between Stem Cells and Biotechnology
Publication date: 1 March 2018
Source:Cell Stem Cell, Volume 22, Issue 3
Author(s): Anh Nguyen, Matt Pavlovich
http://ift.tt/2HVTTbn
Mentoring the Next Generation: Robert Langer
Publication date: 1 March 2018
Source:Cell Stem Cell, Volume 22, Issue 3
Mentor-mentee relationships are essential for professional development, but developing these interpersonal skills is not often highlighted as a priority in scientific endeavors. In a yearlong series, Cell Stem Cell interviews prominent scientists who have prioritized mentorship over the years. Here, we chat with Dr. Robert Langer about his views.
Teaser
Mentor-mentee relationships are essential for professional development, but developing these interpersonal skills is not often highlighted as a priority in scientific endeavors. In a yearlong series, Cell Stem Cell interviews prominent scientists who have prioritized mentorship over the years. Here, we chat with Dr. Robert Langer about his views.http://ift.tt/2oJNI19
Human Pluripotent Stem Cell-Derived Engineered Tissues: Clinical Considerations
Publication date: 1 March 2018
Source:Cell Stem Cell, Volume 22, Issue 3
Author(s): Kelly R. Stevens, Charles E. Murry
The combined power of human pluripotent stem cells and tissue engineering promises to revolutionize medicine by building tissue patches and artificial replacement organs for patients battling diverse diseases. Here, we articulate some big questions that need to be addressed before such engineered tissues become mainstream in the clinic.
Teaser
The combined power of human pluripotent stem cells and tissue engineering promises to revolutionize medicine by building tissue patches and artificial replacement organs for patients battling diverse diseases. Here, we articulate some big questions that need to be addressed before such engineered tissues become mainstream in the clinic.http://ift.tt/2HWIasN
Engineering Human Bone Marrow Proxies
Publication date: 1 March 2018
Source:Cell Stem Cell, Volume 22, Issue 3
Author(s): Paul E. Bourgine, Ivan Martin, Timm Schroeder
Recent advances in engineering complex organs in vitro inspire the development of human bone marrow equivalents to foster scientific discovery and innovative therapeutics. Here, we discuss challenges in generating relevant human bone marrow proxies, potential design principles, and future directions.
Teaser
Recent advances in engineering complex organs in vitro inspire the development of human bone marrow equivalents to foster scientific discovery and innovative therapeutics. Here, we discuss challenges in generating relevant human bone marrow proxies, potential design principles, and future directions.http://ift.tt/2oK86PC
Understanding the Extracellular Matrix to Enhance Stem Cell-Based Tissue Regeneration
Publication date: 1 March 2018
Source:Cell Stem Cell, Volume 22, Issue 3
Author(s): Laura E. Niklason
The extracellular matrix is a biologically critical entity that has historically been poorly understood. Here we discuss how new tools for characterizing matrix composition and function enable us to design and deliver advanced matrices in vitro, to optimize regeneration, and in vivo, within a variety of tissues and organs.
Teaser
The extracellular matrix is a biologically critical entity that has historically been poorly understood. Here we discuss how new tools for characterizing matrix composition and function enable us to design and deliver advanced matrices in vitro, to optimize regeneration, and in vivo, within a variety of tissues and organs.http://ift.tt/2HVTs0J
Regenerative Rehabilitation: Applied Biophysics Meets Stem Cell Therapeutics
Publication date: 1 March 2018
Source:Cell Stem Cell, Volume 22, Issue 3
Author(s): Thomas A. Rando, Fabrisia Ambrosio
The emerging field of regenerative rehabilitation integrates biological and bioengineering advances in regenerative medicine with rehabilitative sciences. Here we highlight recent stem cell-based examples of the regenerative rehabilitation paradigm to promote tissue repair and regeneration, and we discuss remaining challenges and future directions for the field.
Teaser
The emerging field of regenerative rehabilitation integrates biological and bioengineering advances in regenerative medicine with rehabilitative sciences. Here we highlight recent stem cell-based examples of the regenerative rehabilitation paradigm to promote tissue repair and regeneration, and we discuss remaining challenges and future directions for the field.http://ift.tt/2oJFN3Z
Organs-on-a-Chip: A Fast Track for Engineered Human Tissues in Drug Development
Publication date: 1 March 2018
Source:Cell Stem Cell, Volume 22, Issue 3
Author(s): Kacey Ronaldson-Bouchard, Gordana Vunjak-Novakovic
Organs-on-a-chip (OOCs) are miniature tissues and organs grown in vitro that enable modeling of human physiology and disease. The technology has emerged from converging advances in tissue engineering, semiconductor fabrication, and human cell sourcing. Encompassing innovations in human stem cell technology, OOCs offer a promising approach to emulate human patho/physiology in vitro, and address limitations of current cell and animal models. Here, we review the design considerations for single and multi-organ OOCs, discuss remaining challenges, and highlight the potential impact of OOCs as a fast-track opportunity for tissue engineering to advance drug development and precision medicine.
Teaser
Ronaldson-Bouchard and Vunjak-Novakovic discuss the design considerations for single and multi-organ organs-on-a-chip (OOCs) and highlight the potential impact of OOCs as a fast-track opportunity for tissue engineering to advance drug development and precision medicine.http://ift.tt/2HX6wTe
Engineering Stem and Stromal Cell Therapies for Musculoskeletal Tissue Repair
Publication date: 1 March 2018
Source:Cell Stem Cell, Volume 22, Issue 3
Author(s): Claudia Loebel, Jason A. Burdick
Stem cells and tissue-derived stromal cells stimulate the repair of degenerated and injured tissues, motivating a growing number of cell-based interventions in the musculoskeletal field. Recent investigations have indicated that these cells are critical for their trophic and immunomodulatory role in controlling endogenous cells. This Review presents recent clinical advances where stem cells and stromal cells have been used to stimulate musculoskeletal tissue repair, including delivery strategies to improve cell viability and retention. Emerging bioengineering strategies are highlighted, particularly toward the development of biomaterials for capturing aspects of the native tissue environment, altering the healing niche, and recruiting endogenous cells.
Teaser
Loebel and Burdick highlight emerging bioengineering strategies using stem and stromal cells for musculoskeletal tissue repair, particularly focusing on the development of biomaterials for capturing aspects of the native tissue environment, altering the healing niche, and recruiting endogenous cells.http://ift.tt/2oKxl4l
Vascular Tissue Engineering: Progress, Challenges, and Clinical Promise
Publication date: 1 March 2018
Source:Cell Stem Cell, Volume 22, Issue 3
Author(s): H.-H. Greco Song, Rowza T. Rumma, C. Keith Ozaki, Elazer R. Edelman, Christopher S. Chen
Although the clinical demand for bioengineered blood vessels continues to rise, current options for vascular conduits remain limited. The synergistic combination of emerging advances in tissue fabrication and stem cell engineering promises new strategies for engineering autologous blood vessels that recapitulate not only the mechanical properties of native vessels but also their biological function. Here we explore recent bioengineering advances in creating functional blood macro and microvessels, particularly featuring stem cells as a seed source. We also highlight progress in integrating engineered vascular tissues with the host after implantation as well as the exciting pre-clinical and clinical applications of this technology.
Teaser
Song et al. explore recent bioengineering advances in creating functional blood macro- and microvessels, particularly featuring stem cells as a seed source. They highlight progress in integrating engineered vascular tissues with the host after implantation as well as the exciting pre-clinical and clinical applications of this technology.http://ift.tt/2HX5M0x
The Transcriptionally Permissive Chromatin State of Embryonic Stem Cells Is Acutely Tuned to Translational Output
Publication date: 1 March 2018
Source:Cell Stem Cell, Volume 22, Issue 3
Author(s): Aydan Bulut-Karslioglu, Trisha A. Macrae, Juan A. Oses-Prieto, Sergio Covarrubias, Michelle Percharde, Gregory Ku, Aaron Diaz, Michael T. McManus, Alma L. Burlingame, Miguel Ramalho-Santos
A permissive chromatin environment coupled to hypertranscription drives the rapid proliferation of embryonic stem cells (ESCs) and peri-implantation embryos. We carried out a genome-wide screen to systematically dissect the regulation of the euchromatic state of ESCs. The results revealed that cellular growth pathways, most prominently translation, perpetuate the euchromatic state and hypertranscription of ESCs. Acute inhibition of translation rapidly depletes euchromatic marks in mouse ESCs and blastocysts, concurrent with delocalization of RNA polymerase II and reduction in nascent transcription. Translation inhibition promotes rewiring of chromatin accessibility, which decreases at a subset of active developmental enhancers and increases at histone genes and transposable elements. Proteome-scale analyses revealed that several euchromatin regulators are unstable proteins and continuously depend on a high translational output. We propose that this mechanistic interdependence of euchromatin, transcription, and translation sets the pace of proliferation at peri-implantation and may be employed by other stem/progenitor cells.
Graphical abstract
Teaser
Bulut-Karslioglu et al. show that the transcriptionally permissive chromatin landscapes in mouse embryonic stem cells and blastocysts are acutely sensitive to variations in translational output. This positive feedback loop between permissive chromatin and translation, in turn, may set the rapid pace of growth during early embryonic development.http://ift.tt/2oIwm4T
CD157 Marks Tissue-Resident Endothelial Stem Cells with Homeostatic and Regenerative Properties
Publication date: 1 March 2018
Source:Cell Stem Cell, Volume 22, Issue 3
Author(s): Taku Wakabayashi, Hisamichi Naito, Jun-ichi Suehiro, Yang Lin, Hideya Kawaji, Tomohiro Iba, Tsukasa Kouno, Sachi Ishikawa-Kato, Masaaki Furuno, Kazuhiro Takara, Fumitaka Muramatsu, Jia Weizhen, Hiroyasu Kidoya, Katsuhiko Ishihara, Yoshihide Hayashizaki, Kohji Nishida, Mervin C. Yoder, Nobuyuki Takakura
The generation of new blood vessels via angiogenesis is critical for meeting tissue oxygen demands. A role for adult stem cells in this process remains unclear. Here, we identified CD157 (bst1, bone marrow stromal antigen 1) as a marker of tissue-resident vascular endothelial stem cells (VESCs) in large arteries and veins of numerous mouse organs. Single CD157+ VESCs form colonies in vitro and generate donor-derived portal vein, sinusoids, and central vein endothelial cells upon transplantation in the liver. In response to injury, VESCs expand and regenerate entire vasculature structures, supporting the existence of an endothelial hierarchy within blood vessels. Genetic lineage tracing revealed that VESCs maintain large vessels and sinusoids in the normal liver for more than a year, and transplantation of VESCs rescued bleeding phenotypes in a mouse model of hemophilia. Our findings show that tissue-resident VESCs display self-renewal capacity and that vascular regeneration potential exists in peripheral blood vessels.
Graphical abstract
Teaser
Whether tissue-resident vascular endothelial stem cells (VESCs) exist has remained unclear. The present study demonstrates that CD157 marks vessel-resident VESCs in mouse organs that are capable of clonal expansion, angiogenesis initiation, and blood vessel maintenance. These findings represent a paradigm shift in understanding endothelial cell hierarchy within the blood vessels.http://ift.tt/2HX5Ygv
Vangl2/RhoA Signaling Pathway Regulates Stem Cell Self-Renewal Programs and Growth in Rhabdomyosarcoma
Publication date: 1 March 2018
Source:Cell Stem Cell, Volume 22, Issue 3
Author(s): Madeline N. Hayes, Karin McCarthy, Alexander Jin, Mariana L. Oliveira, Sowmya Iyer, Sara P. Garcia, Sivasish Sindiri, Berkley Gryder, Zainab Motala, G. Petur Nielsen, Jean-Paul Borg, Matt van de Rijn, David Malkin, Javed Khan, Myron S. Ignatius, David M. Langenau
Tumor growth and relapse are driven by tumor propagating cells (TPCs). However, mechanisms regulating TPC fate choices, maintenance, and self-renewal are not fully understood. Here, we show that Van Gogh-like 2 (Vangl2), a core regulator of the non-canonical Wnt/planar cell polarity (Wnt/PCP) pathway, affects TPC self-renewal in rhabdomyosarcoma (RMS)—a pediatric cancer of muscle. VANGL2 is expressed in a majority of human RMS and within early mononuclear progenitor cells. VANGL2 depletion inhibited cell proliferation, reduced TPC numbers, and induced differentiation of human RMS in vitro and in mouse xenografts. Using a zebrafish model of embryonal rhabdomyosarcoma (ERMS), we determined that Vangl2 expression enriches for TPCs and promotes their self-renewal. Expression of constitutively active and dominant-negative isoforms of RHOA revealed that it acts downstream of VANGL2 to regulate proliferation and maintenance of TPCs in human RMS. Our studies offer insights into pathways that control TPCs and identify new potential therapeutic targets.
Graphical abstract
Teaser
Hayes et al. find that Vangl2 specifically labels progenitors that sustain growth and self-renewal in both zebrafish and human rhabdomyosarcoma and is required for their maintenance. This work reveals direct regulation of stem cell programs and tumor growth by Vangl2/RhoA signaling, offering opportunities for direct assessment and therapeutic targeting.http://ift.tt/2oHVPLu
SETD7 Drives Cardiac Lineage Commitment through Stage-Specific Transcriptional Activation
Publication date: 1 March 2018
Source:Cell Stem Cell, Volume 22, Issue 3
Author(s): Jaecheol Lee, Ning-Yi Shao, David T. Paik, Haodi Wu, Hongchao Guo, Vittavat Termglinchan, Jared M. Churko, Youngkyun Kim, Tomoya Kitani, Ming-Tao Zhao, Yue Zhang, Kitchener D. Wilson, Ioannis Karakikes, Michael P. Snyder, Joseph C. Wu
Cardiac development requires coordinated and large-scale rearrangements of the epigenome. The roles and precise mechanisms through which specific epigenetic modifying enzymes control cardiac lineage specification, however, remain unclear. Here we show that the H3K4 methyltransferase SETD7 controls cardiac differentiation by reading H3K36 marks independently of its enzymatic activity. Through chromatin immunoprecipitation sequencing (ChIP-seq), we found that SETD7 targets distinct sets of genes to drive their stage-specific expression during cardiomyocyte differentiation. SETD7 associates with different co-factors at these stages, including SWI/SNF chromatin-remodeling factors during mesodermal formation and the transcription factor NKX2.5 in cardiac progenitors to drive their differentiation. Further analyses revealed that SETD7 binds methylated H3K36 in the bodies of its target genes to facilitate RNA polymerase II (Pol II)-dependent transcription. Moreover, abnormal SETD7 expression impairs functional attributes of terminally differentiated cardiomyocytes. Together, these results reveal how SETD7 acts at sequential steps in cardiac lineage commitment, and they provide insights into crosstalk between dynamic epigenetic marks and chromatin-modifying enzymes.
Graphical abstract
Teaser
Wu and colleagues define SETD7 as a key regulator of cardiac lineage commitment. SETD7 regulates the expression of lineage-specific target genes and interacts with various co-factors during cardiomyocyte differentiation. SETD7 associates with H3K36me3 histone modification, which is required for the transcriptional activation.http://ift.tt/2HWEnvL
A new technique for evaluating heel xerosis grade and the effects of moisturizer on heel skin dryness
Abstract
Background
Dryness-related heel skin problems are common; however, there are very few studies about heel skin dryness. The objective of this study was to develop new assessment methods for evaluating heel skin dryness, to clarify the characteristics associated with heal skin dryness, and assess the effectiveness of moisturizer use according to dryness severity.
Materials and methods
We investigated the heel skin of 150 Korean women (aged 20-78 years). Heel skin images were taken using a DSLR camera and the distribution or severity of flakes, scaling, cracking, and fissures were visually assessed. Skin properties such as hydration, transepidermal water loss (TEWL), amount of dead skin cells, and efficacy of moisturizer were evaluated according to heel xerosis grade. Furthermore, as conventional evaluation methods for desquamation are not appropriate for heel skin, we developed new techniques using binarization of magnified images.
Results
Skin hydration tended to decrease and TEWL tended to increase as heel dryness grade increased. The amount of dead skin cells increased with increasing dryness grade using the new technique. Subjects in the severe dryness group achieved similar hydration levels as normal subjects at baseline after 3 hours of moisturizer application.
Conclusion
Our new methods of visually classifying heel dryness and quantifying dead skin cells using magnified images effectively evaluated heel skin properties. As heel skin is prone to dryness, daily repetitive application of moisturizer might be helpful for hydrating dry heel skin, and ultimately preventing complications.
http://ift.tt/2t9oxKN
Poor inter-rater reliability of hidradenitis suppurativa phenotypes
Publication date: Available online 2 March 2018
Source:Journal of the American Academy of Dermatology
Author(s): K.R. van Straalen, T. Verhagen, B. Horváth, C. Ardon, A.R.J.V. Vossen, R. Driessen, J. Boer, A. Rondags, E.P. Prens, H.H. van der Zee
http://ift.tt/2tahyBq
T-cell–mediated immune response to pneumococcal conjugate vaccine (PCV-13) and tetanus toxoid vaccine in patients with moderate-to-severe psoriasis during tofacitinib treatment
Publication date: Available online 2 March 2018
Source:Journal of the American Academy of Dermatology
Author(s): Kevin L. Winthrop, Neil Korman, William Abramovits, Scott T. Rottinghaus, Huaming Tan, Annie Gardner, Geoffrey Mukwaya, Mandeep Kaur, Hernan Valdez
BackgroundPsoriasis is often treated with immunomodulatory therapies that can affect the immune response to common antigens. Tofacitinib is an oral Janus kinase inhibitor.ObjectiveTo characterize the effect of long-term exposure to tofacitinib 10 mg twice daily on T-cell function in psoriasis patients.MethodsPatients completing at least 3 months' continuous treatment with tofacitinib 10 mg twice daily were vaccinated with T-cell–dependent vaccines (monovalent tetanus toxoid and 13-valent pneumococcal conjugate [PCV-13]). Patients were assessed at baseline (before vaccination) and then again 4 weeks after vaccination. For PCV-13, we evaluated serotype-specific, opsonophagocytic antibody responses, and for tetanus toxoid, we evaluated humoral responses.ResultsAmong 60 patients who completed the study, the geometric mean fold rise from baseline for the 13 PCV serotypes at 4 weeks postvaccination varied from 8.3 (serotype 3) to 101.9 (serotype 6A). Similar results were observed for patients with and without lymphopenia at baseline. For tetanus toxoid, 51 (88%) patients had ≥2-fold and 35 (60%) patients had ≥4-fold rise in antibody concentration.LimitationsThere was no placebo control.ConclusionMost psoriasis patients who receive tofacitinib can mount satisfactory T-cell–dependent responses to PCV-13 and tetanus vaccines.
http://ift.tt/2FK6xcI
Book Review: Dermatology: Visual Recognition and Case Reviews by Christine J. Ko
Publication date: Available online 2 March 2018
Source:Journal of the American Academy of Dermatology
Author(s): Dirk M. Elston
http://ift.tt/2F6yJW9
Interleukin-17, Inflammation, and Cardiovascular Risk in Patients With Psoriasis
Publication date: Available online 2 March 2018
Source:Journal of the American Academy of Dermatology
Author(s): Benjamin Lockshin, Yevgeniy Balagula, Joseph F. Merola
In addition to being recognized as a chronic inflammatory disease that manifests in the skin, psoriasis is increasingly understood to be a systemic disease that causes immune dysregulation throughout the body. The systemic nature of psoriasis is evidenced by the higher burden of comorbidities and shorter life expectancies of patients with psoriasis, particularly those with early onset and severe disease. Notably, psoriasis is associated with an increased risk for cardiovascular disease, which is the most common cause of morbidity and mortality in patients with psoriasis. In this review, we examine the association between psoriasis and cardiovascular disease and specifically focus on the role of interleukin-17–mediated inflammation as a potential mechanistic link between psoriasis and cardiovascular disease. Moreover, we describe potential treatment approaches to reduce the burden of cardiovascular disease in patients with psoriasis, and discuss the clinical importance of the association of these 2 diseases with respect to patient management and education.
http://ift.tt/2FNLx4Z
The SS18-SSX Oncoprotein Hijacks KDM2B-PRC1.1 to Drive Synovial Sarcoma
Publication date: Available online 1 March 2018
Source:Cancer Cell
Author(s): Ana Banito, Xiang Li, Aimée N. Laporte, Jae-Seok Roe, Francisco Sanchez-Vega, Chun-Hao Huang, Amanda R. Dancsok, Katerina Hatzi, Chi-Chao Chen, Darjus F. Tschaharganeh, Rohit Chandwani, Nilgun Tasdemir, Kevin B. Jones, Mario R. Capecchi, Christopher R. Vakoc, Nikolaus Schultz, Marc Ladanyi, Torsten O. Nielsen, Scott W. Lowe
Synovial sarcoma is an aggressive cancer invariably associated with a chromosomal translocation involving genes encoding the SWI-SNF complex component SS18 and an SSX (SSX1 or SSX2) transcriptional repressor. Using functional genomics, we identify KDM2B, a histone demethylase and component of a non-canonical polycomb repressive complex 1 (PRC1.1), as selectively required for sustaining synovial sarcoma cell transformation. SS18-SSX1 physically interacts with PRC1.1 and co-associates with SWI/SNF and KDM2B complexes on unmethylated CpG islands. Via KDM2B, SS18-SSX1 binds and aberrantly activates expression of developmentally regulated genes otherwise targets of polycomb-mediated repression, which is restored upon KDM2B depletion, leading to irreversible mesenchymal differentiation. Thus, SS18-SSX1 deregulates developmental programs to drive transformation by hijacking a transcriptional repressive complex to aberrantly activate gene expression.
Graphical abstract
Teaser
Banito et al. show that SS18-SSX fusions characteristic of synovial sarcoma associate with KDM2B-PRC1.1, a non-canonical polycomb repressive complex 1, to aberrantly activate the expression of developmentally regulated transcription factors that are normally targets of polycomb-mediated gene repression.http://ift.tt/2t8sEH1
ORY-1001, a Potent and Selective Covalent KDM1A Inhibitor, for the Treatment of Acute Leukemia
Publication date: Available online 1 March 2018
Source:Cancer Cell
Author(s): Tamara Maes, Cristina Mascaró, Iñigo Tirapu, Angels Estiarte, Filippo Ciceri, Serena Lunardi, Nathalie Guibourt, Alvaro Perdones, Michele M.P. Lufino, Tim C.P. Somervaille, Dan H. Wiseman, Cihangir Duy, Ari Melnick, Christophe Willekens, Alberto Ortega, Marc Martinell, Nuria Valls, Guido Kurz, Matthew Fyfe, Julio Cesar Castro-Palomino, Carlos Buesa
The lysine-specific demethylase KDM1A is a key regulator of stem cell potential in acute myeloid leukemia (AML). ORY-1001 is a highly potent and selective KDM1A inhibitor that induces H3K4me2 accumulation on KDM1A target genes, blast differentiation, and reduction of leukemic stem cell capacity in AML. ORY-1001 exhibits potent synergy with standard-of-care drugs and selective epigenetic inhibitors, reduces growth of an AML xenograft model, and extends survival in a mouse PDX (patient-derived xenograft) model of T cell acute leukemia. Surrogate pharmacodynamic biomarkers developed based on expression changes in leukemia cell lines were translated to samples from patients treated with ORY-1001. ORY-1001 is a selective KDM1A inhibitor in clinical trials and is currently being evaluated in patients with leukemia and solid tumors.
Teaser
Maes et al. develop ORY-1001, a highly potent and selective inhibitor of KDM1A/LSD1. ORY-1001 induces differentiation of leukemic cells in cell lines, primary AML samples, and AML patients. ORY-1001 is able to decrease leukemic growth and prolong survival of mouse models of acute leukemia.http://ift.tt/2FKyMIm
Comparative Heterochromatin Profiling Reveals Conserved and Unique Epigenome Signatures Linked to Adaptation and Development of Malaria Parasites
Publication date: Available online 1 March 2018
Source:Cell Host & Microbe
Author(s): Sabine A. Fraschka, Michael Filarsky, Regina Hoo, Igor Niederwieser, Xue Yan Yam, Nicolas M.B. Brancucci, Franziska Mohring, Annals T. Mushunje, Ximei Huang, Peter R. Christensen, Francois Nosten, Zbynek Bozdech, Bruce Russell, Robert W. Moon, Matthias Marti, Peter R. Preiser, Richárd Bártfai, Till S. Voss
Heterochromatin-dependent gene silencing is central to the adaptation and survival of Plasmodium falciparum malaria parasites, allowing clonally variant gene expression during blood infection in humans. By assessing genome-wide heterochromatin protein 1 (HP1) occupancy, we present a comprehensive analysis of heterochromatin landscapes across different Plasmodium species, strains, and life cycle stages. Common targets of epigenetic silencing include fast-evolving multi-gene families encoding surface antigens and a small set of conserved HP1-associated genes with regulatory potential. Many P. falciparum heterochromatic genes are marked in a strain-specific manner, increasing the parasite's adaptive capacity. Whereas heterochromatin is strictly maintained during mitotic proliferation of asexual blood stage parasites, substantial heterochromatin reorganization occurs in differentiating gametocytes and appears crucial for the activation of key gametocyte-specific genes and adaptation of erythrocyte remodeling machinery. Collectively, these findings provide a catalog of heterochromatic genes and reveal conserved and specialized features of epigenetic control across the genus Plasmodium.
Graphical abstract
Teaser
Fraschka, Filarsky et al. performed a genome-wide characterization of heterochromatin organization across multiple species, strains, and life cycle stages of malaria parasites. This revealed that heterochromatic gene silencing is a conserved strategy to drive clonal variation of surface antigens and to control life cycle stage transitions and cell differentiation.http://ift.tt/2FIOnYM
Inflammation-Modulated Metabolic Reprogramming Is Required for DUOX-Dependent Gut Immunity in Drosophila
Publication date: Available online 1 March 2018
Source:Cell Host & Microbe
Author(s): Kyung-Ah Lee, Kyu-Chan Cho, Boram Kim, In-Hwan Jang, Kibum Nam, Young Eun Kwon, Myungjin Kim, Do Young Hyeon, Daehee Hwang, Jae-Hong Seol, Won-Jae Lee
DUOX, a member of the NADPH oxidase family, acts as the first line of defense against enteric pathogens by producing microbicidal reactive oxygen species. DUOX is activated upon enteric infection, but the mechanisms regulating DUOX activity remain incompletely understood. Using Drosophila genetic tools, we show that enteric infection results in "pro-catabolic" signaling that initiates metabolic reprogramming of enterocytes toward lipid catabolism, which ultimately governs DUOX homeostasis. Infection induces signaling cascades involving TRAF3 and kinases AMPK and WTS, which regulate TOR kinase to control the balance of lipogenesis versus lipolysis. Enhancing lipogenesis blocks DUOX activity, whereas stimulating lipolysis via ATG1-dependent lipophagy is required for DUOX activation. Drosophila with altered activity in TRAF3-AMPK/WTS-ATG1 pathway components exhibit abolished infection-induced lipolysis, reduced DUOX activation, and enhanced susceptibility to enteric infection. Thus, this work uncovers signaling cascades governing inflammation-induced metabolic reprogramming and provides insight into the pathophysiology of immune-metabolic interactions in the microbe-laden gut epithelia.
Graphical abstract
Teaser
DUOX, a member of the NADPH oxidase family, acts as the first line of host defense in the Drosophila intestine. Lee et al. show that pathogen infection stimulates pro-catabolic signaling that initiates metabolic reprogramming toward lipid catabolism, which is required for DUOX activation and host resistance to enteric infection.http://ift.tt/2FLHsOI
Dual Antithrombotic Plus Adjunctive Antiinflammatory Therapy to Improve Cardiovascular Outcome in Atrial Fibrillation Patients with Concurrent Acute Coronary Syndrome: A Triple-Pathway Strategy
Source:Medical Hypotheses
Author(s): Gerald Chi, Adeel Jamil, Miroslav Radulovic, Umer Jamil, Muhammad A. Balouch, Jolanta Marszalek, Zahra Karimi, Seyedmahdi Pahlavani, Mehrian Jafarizade, Husnain Shaukat, Sunny Kumar, Arzu Kalayci
The concurrence of atrial fibrillation and acute coronary syndrome poses a conundrum in the antithrombotic management as intensification of anticoagulation or antiplatelet therapy inevitably comes at the price of an increased bleeding risk. Various antithrombotic combinations have been attempted to prevent the recurrent cardiovascular events, however, there has been limited success in effective risk reduction for this high risk population. Given the overarching effect of interleukin 1β-driven inflammation on the arrhythmogenesis, thrombogenesis, and hypercoagulability, we hypothesize that the triple-pathway strategy (i.e., incorporating antiinflammatory therapy into anticoagulant and antiplatelet therapy) would grant incremental cardiovascular benefits for atrial fibrillation patients with coexisting acute coronary syndrome and stent placement.
http://ift.tt/2oJzrBE
Collagen type III and elastin genes polymorphism and the risk of nonsyndromic striae
Summary
Background
Striae have been reported to be one of the most common skin lesions and a commonly encountered esthetic problem.
Objectives
The aim of this research was to examine elastin gene polymorphism (rs7787362, ELN) and collagen type III alpha 1 polymorphism (rs1800255, COL3A1) among polish woman population with SD in comparison with women without the lesions and to verify these polymorphisms as risk factors for SD.
Methods
Seventy female students (35 with striae (the mean age 23.9 years, SD 1.2 years) and 35 without these lesions (22.9 years, SD 1.7 years)) were included in the study. The subjects were asked to fill out a questionnaire including questions concerning risk factors for SD and had a cheek swabbed for cells for DNA isolation.
Results
Analysis of polymorphisms of elastin gene (rs7787362) and COL3A1 gene (rs1800255) showed that women with SD and without these lesions did not differ in these aspects. Polymorphism rs7787362 was also analyzed in relation to SD in different locations, and showed no differences.
Conclusion
In conclusion, we found that there are some clinical factors that reduced the risk of SD: history of intended weight loss, negative family history of SD, and lower BMI. Gene polymorphisms analysis in patients with SD may help to establish the etiology of these lesions and to target the therapy. Analysis of polymorphisms of elastin gene (rs7787362) did not show differences in allele distribution between women with and without SD. Polymorphisms of COL3A1 gene (rs1800255) also did not differ between the examined groups.
http://ift.tt/2FdVQ4b
IL1A (-889) gene polymorphism is associated with the effect of diet as a risk factor in Acne Vulgaris
Summary
Background
Despite the several studies suggesting the genetic basis of acne vulgaris, the exact genetic architecture of this very common condition is not yet clear.
Aim of the work
This study aimed to investigate the association between IL-1A (−889) gene polymorphism and acne vulgaris in a sample of patients.
Subjects and Method
Blood samples from 100 patients with acne vulgaris and 100 healthy age, sex, and BMI matched controls were obtained. DNA samples were isolated from blood cells, and the PCR-RFLP method was used for genotyping.
Results
The genotype distributions of IL-1A (−889) polymorphism were as expected under Hardy-Weinberg equilibrium. T allele was predominant in the patients, while C allele predominated in the control subjects (P value < .001). The frequency of TT genotype in patients was significantly higher than in the control subjects (P value < .001). CT genotype was significantly more frequent in the control subjects compared to patients (P value < .001). Among the 47 patients who reported diet as a risk factor for triggering or exacerbating their lesions, 62.5% had TT genotype (P value = .038).
Conclusion
IL-1A (−889) gene polymorphism has a role in the pathogenesis of acne vulgaris. We suggest that the triggering or exacerbating effect of diet on acne may be related to IL-1A (−889) gene polymorphism.
http://ift.tt/2CSFuZP
A Novel Transcranial Magnetic Stimulator for Focal Stimulation of Rodent Brain
Source:Brain Stimulation
Author(s): Qinglei Meng, Li Jing, Jean Paul Badjo, Xiaoming Du, Elliot Hong, Yihong Yang, Hanbing Lu, Fow-Sen Choa
http://ift.tt/2F7k1hm
Low maternal melatonin level increases autism spectrum disorder risk in children
Source:Research in Developmental Disabilities
Author(s): Wiebe Braam, Friederike Ehrhart, Anneke P.H.M. Maas, Marcel G. Smits, Leopold Curfs
BackgroundIt is assumed that autism spectrum disorder (ASD) is caused by a combination of de novo inherited variation and common variation as well as environmental factors. It often co-occurs with intellectual disability (ID). Almost eight hundred potential causative genetic variations have been found in ASD patients. However, not one of them is responsible for more than 1% of ASD cases. Low melatonin levels are a frequent finding in ASD patients. Melatonin levels are negatively correlated with severity of autistic impairments, it is important for normal neurodevelopment and is highly effective in protecting DNA from oxidative damage. Melatonin deficiency could be a major factor, and well a common heritable variation, that increases the susceptibility to environmental risk factors for ASD. ASD is already present at birth. As the fetus does not produce melatonin, low maternal melatonin levels may be involved.MethodsWe measured 6-sulfatoxymelatonin in urine of 60 mothers of a child with ASD and controls.Results6-sulfatoxymelatonin levels were significantly lower in mothers with an ASD child than in controls (p = 0.012).ConclusionsLow parental melatonin levels could be one of the contributors to ASD and possibly ID etiology. Our findings need to be duplicated on a larger scale. If our hypothesis is correct, this could lead to policies to detect future parents who are at risk and to treatment strategies to ASD and intellectual disability risk.
http://ift.tt/2FdHT6y
Hemophagocytic lymphohistiocytosis (HLH) secondary to disseminated histoplasmosis in the setting of Acquired Immunodeficiency Syndrome (AIDS)
Publication date: June 2018
Source:Medical Mycology Case Reports, Volume 20
Author(s): Samuel Asanad, Brendan Cerk, Veronica Ramirez
Hemophagocytic lymphohistiocytosis (HLH) is a rare and aggressive disease involving immune system over-activation leading to hemophagocytosis. HLH requires early diagnosis and prompt treatment initiation, especially in patients with Acquired Immunodeficiency Syndrome (AIDS). We present a case of a middle-aged male with AIDS and renal failure, who developed HLH secondary to disseminated histoplasmosis. Etoposide chemotherapy as recommended by the HLH 2004 Guidelines was deferred and treatment focused instead on anti-fungal therapy. Anti-retroviral therapy followed thereafter.
http://ift.tt/2FNzJ2F
Mould meningitis associated with intravenous drug use
Publication date: June 2018
Source:Medical Mycology Case Reports, Volume 20
Author(s): Hassan Shah, Stephen Honeybul, Stephanie Tang, Ian Arthur, Sally McLaren, Peter Boan
Fungal meningitis is most commonly causes by Cryptococcus species and dimorphic fungi. We present a rare case of mould meningitis, ventriculitis and subependymal nodules in an immunocompetent patient, having likely seeded the meninges and ventricular system through intravenous drug use. The causative mould remains undetermined. The case highlights the poor sensitivity of CSF culture and the need to consider surgical biopsy where there is diagnostic difficulty and fungal infection is being considered.
http://ift.tt/2t5NGGl
Acute paracoccidioidomycosis with duodenal and cutaneous involvement and obstructive jaundice
Publication date: June 2018
Source:Medical Mycology Case Reports, Volume 20
Author(s): Fred Bernardes Filho, Isabela Sgarbi, Santos Flávia da Silva Domingos, Rafael Cruz Rios Sampaio, Rodolfo Mendes Queiroz, Sílvia Nunes Szente Fonseca, Roderick James Hay, Loan Towersey
Paracoccidioidomycosis (PCM) is the most widespread endemic mycosis in LatinAmerica. If PCM is not diagnosed and treated early and adequately, the endemic fungal infection could result in serious sequelae. We report a case of PCM with duodenal and cutaneous involvement simulating cholangitis that was initially misdiagnosed as a lymphoproliferative disease. Clinicians should consider acute paracoccidioidomycosis in the differential diagnosis of jaundice and/or signs/symptoms of cholangitis developing in young patients from paracoccidioidomycosis endemic regions.
http://ift.tt/2FIxiyb
Case of Scedosporium aurantiacum infection detected in a subcutaneous abscess
Publication date: June 2018
Source:Medical Mycology Case Reports, Volume 20
Author(s): Makoto Kondo, Hiroyuki Goto, Keiichi Yamanaka
This is the case report of a Scedosporium aurantiacum infection in a subcutaneous abscess. The patient had underlying diabetes and malignant lymphoma. Scedosporium species occur widely in nature and are increasingly recognized as pathologies under specific conditions, such as in immunocompromised hosts.
http://ift.tt/2t4xRQ6
Tracheal, laryngeal and pulmonary mucormycosis followed by organizing pneumonia in a patient with Adult Onset Still's Disease
Publication date: June 2018
Source:Medical Mycology Case Reports, Volume 20
Author(s): Fabian Leo, Michael Zeh, Annegret Prothmann, Oliver Kurzai, Sylke Kurz, Christian Grohé
We report a case of tracheal, laryngeal and pulmonary mucormycosis in a patient receiving immunosuppressive medication for an autoinflammatory fever syndrome. Mucormycosis was confirmed by histopathology from tracheal specimens and molecular evidence of Lichtheimia.A surgical approach was not possible because of the multifocal disease pattern and the extent of tracheal involvement. The patient was successfully treated with liposomal amphotericin B followed by posaconazole maintenance therapy. After 9 months, recurrent pulmonary mucormycosis was suspected but emerged as organizing pneumonia without evidence of active fungal infection.
http://ift.tt/2FIHlDm
Assessment of Systemic Adenosine Effect Using Color Doppler Ultrasound of the Splenic Artery—Feasibility and Potential Clinical Utility for Coronary Interventions
Source:Ultrasound in Medicine & Biology
Author(s): Oliver Klein-Wiele, Walied Sherifa, Marietta Garmer, Kaffer Kara, Dietrich Grönemeyer, Birgit Hailer
Adenosine induces coronary vasodilation and simultaneously reduces splanchnic perfusion. This effect can be absent in adenosine non-responders. Imaging of splanchnic arteries under adenosine assessing this effect has not been performed in humans previously. In 26 patients, splenic artery color Doppler was performed during an infusion of adenosine. Peak velocity in the splenic artery was measured before the infusion and at 2 min. Results were compared qualitatively with perfusion imaging in magnetic resonance. A total of 24 patients showed a drop of splenic artery peak velocity from 62.3 ± 18.1 to 40.4 ± 15.7 cm/s (p < 0.001), which corresponded to perfusion restriction in magnetic resonance. Two patients with constant splenic artery velocity did not show perfusion restriction. We showed feasibility of assessing changes in splenic artery velocity under adenosine for the first time in humans. Further studies are needed to investigate whether this novel application is a robust tool to rule out inadequate adenosine effect during measurement of fractional flow reserve in coronary catheterization.
http://ift.tt/2FJ9om2
Newer advances in lesional surgery for movement disorders
Neurology India 2018 66(7):113-121
An analysis of the existing literature on lesioning for movement disorders was undertaken to review lesion therapy and its advances. Advances in imaging technology and electrophysiological techniques used for localization of brain structures and its functions, such as microelectrode recordings and macrostimulation, have greatly improved the ability to accurately identify the target nuclei such as the ventrointermediate nucleus (Vim), globus pallidus interna (GPi) and subthalamic nucleus (STN). Many important changes are happening in the understanding of lesion making. Its application as a cheaper modality of treatment; being less cumbersome; having a wider geographical appeal; and more options to create a lesion, appeals to the clinician. The procedure is undergoing a revival.
http://ift.tt/2CSQSVc
Expanding the phenotypic spectrum of type III GM1 gangliosidosis: Progressive dystonia with auditory startle
Neurology India 2018 66(7):149-150
http://ift.tt/2FgAB1y
Interleaving pallidal deep brain stimulation improves the degree of benefit obtained in a patient with dystonia
Neurology India 2018 66(7):138-141
http://ift.tt/2F5Qk4v
Neurosurgery for movement disorders in India: Balloons to Electrodes
Neurology India 2018 66(7):5-9
http://ift.tt/2CS1B2v
Lateralized hyperkinetic motor behavior
Neurology India 2018 66(7):131-134
Seizures are followed by a post-ictal period, which is characterized by usual slowing of brain activity. This case report describes a 68-year old woman who presented with right-sided rhythmic, non-voluntary, semi-purposeful motor behavior that started 2 days after an episode of generalized seizure. Her initial electroencephalogram (EEG) showed beta activity with no evidence of epileptiform discharges. Computed tomography scan showed hypodensity in the left parieto-occipital region. Magnetic resonance imaging (MRI) showed restricted diffusion/fluid-attenuated inversion recovery hyperintensities in the left precentral and post-central gyrus. Unilateral compulsive motor behavior during the post-ictal state should be considered, and not confused with partial status epilepticus to avoid unnecessary treatment. Abnormal magnetic resonance imaging (MRI) findings, which are reversible, can help with the diagnostic and therapeutic approach.
http://ift.tt/2FgFHew
Classification of movement disorders: The problem of terminology
Neurology India 2018 66(7):12-14
http://ift.tt/2CRJIRm
Hemimyoclonus: A rare presentation of hemimegalencephaly
Neurology India 2018 66(7):142-145
http://ift.tt/2Fi20Ag
Parkinsonian syndromes: A review
Neurology India 2018 66(7):15-25
Since James Parkinson published his remarkable clinical observations in the "An Essay On The Shaking Palsy" in 1817, the number of diseases included in the spectrum of parkinsonian syndromes (a group of diseases that have some part of their clinical features resembling those seen in Parkinson's disease), are growing. Careful history taking, comprehensive neurological examination, and utilization of proper investigations will lead the physicians to make an accurate diagnosis of the specific disease entity present. In this recent review, we cover the issue of classification of parkinsonian syndromes, and comprehensively review the characteristic features of the commonly encountered diseases that present with this syndrome. The salient aspects of the epidemiology, key clinical features, proper investigations, and possible treatment options of these diseases have also been addressed.
http://ift.tt/2CTuhYJ
Does cerebral infarction ameliorate essential tremor? A mini-review
Neurology India 2018 66(7):152-154
http://ift.tt/2Fe6LuF
Chemical Shift Magnetic Resonance Imaging Could Predict Subclinical Cortisol Production from an Incidentally Discovered Adrenal Mass
Abstract
Context
To investigate whether any association between chemical shift magnetic resonance (MRI) findings, cortisol secretion and pathological findings exist that could predict subclinical hypercortisolism (SCH) in patients with adrenal incidentalomas (AI).
Design
Retrospective, cross sectional study in a tertiary centre.
Patients
Sixty-eight subjects with AIs and 13 patients with Cushing's syndrome (CS). Patients with AIs were categorized according to cortisol levels post 1mg dexamethasone (post-DST).
Measurements
Visual inspection of the lipid content of the adrenal tumour and calculation of adrenal-to-spleen ratio (ASR), the signal intensity index (SII), volume and the assessment of the association between pathological, radiological and hormonal findings in surgically treated patients.
Results
Percentage of clear cells was correlated with ASR (r= -.525, p=0.01), SII (r=.465, p=0.025), post-DST cortisol (r= -.711, p<0.001) and ACTH (r=.475, p=0.046). By ANOVA and post hoc analysis patients with CS and five subjects with a post-DST cortisol greater than 137nmol/l differed significantly in ASR and SII from those with a post-DST cortisol less than 50nmol/l. An ASR level higher than 0.245 (OR 19.7, 95% CI 1.5–257.5; P=.023) and a SII level lower than 78.37 (OR 15.6, 95% CI 1.2–20; P=.034) remained as the independent predictors for SCH while age, presence of arterial hypertension or tumour volume did not make significant contribution to the models.
Conclusions
Cortisol hypersecretion by adrenal adenomas is associated with distinctive MRI characteristics. The quantitative assessment of intracellular lipid in an AI could help distinguish patients with a clear phenotype of SCH.
This article is protected by copyright. All rights reserved.
http://ift.tt/2t6GBoV
Associations of insulin-like growth factor-I and insulin-like growth factor binding protein-3 with bone quality in the general adult population
Summary
Objective
Growth hormone (GH) and its main mediator, insulin-like growth factor-I (IGF-I) play a significant role in bone metabolism. The relations between IGF-I and bone mineral density (BMD) or osteoporosis have been assessed in previous studies but whether the associations are sex-specific remains uncertain. Moreover, only few studies examined bone quality assessed by quantitative ultrasound (QUS). We aimed to investigate these associations in the general population of northeast Germany.
Design and Measurements
Data from 1759 men and 1784 women who participated in the baseline examination of the Study of Health in Pomerania (SHIP)-Trend were used. IGF-I and IGF-binding protein-3 (IGFBP-3) concentrations were measured on the IDS-iSYS multidiscipline automated analyzer (Immunodiagnostic Systems Limited). QUS measurements were performed at the heel (Achilles InSight, GE Healthcare). Sex-specific linear and multinomial logistic regression models adjusted for potential confounders were calculated.
Results
Linear regression analyses revealed significant positive associations between IGF-I and IGF-I/IGFBP-3 ratio, a marker for free IGF-I, with all QUS parameters in men. Among women, we found an inverse association between IGF-I and the QUS-based fracture risk but no association with any other QUS parameter. There was no association between IGFBP-3 and the QUS-based fracture risk.
Conclusions
Our data suggest an important role of IGF-I on bone quality in men. The observed association of IGF-I with the QUS-based stiffness index and QUS-based fracture risk in the present study might animate clinicians to refer patients with low IGF-I levels, particularly men, to a further evaluation of risk factors for osteoporosis and a detailed examination of the skeletal system.
This article is protected by copyright. All rights reserved.
http://ift.tt/2FJol7L
Copyright
Source:Anesthesiology Clinics, Volume 36, Issue 1
http://ift.tt/2oNiDd8
Contributors
Source:Anesthesiology Clinics, Volume 36, Issue 1
http://ift.tt/2HUXMx0
Contents
Source:Anesthesiology Clinics, Volume 36, Issue 1
http://ift.tt/2oHExOM
Forthcoming Issues
Source:Anesthesiology Clinics, Volume 36, Issue 1
http://ift.tt/2HXzIK7
Improving Perioperative Care: What Are the Tools That Lead to Sustainable Change?
Source:Anesthesiology Clinics, Volume 36, Issue 1
Author(s): Lee A. Fleisher
http://ift.tt/2oIT9O0
Quality Improvement and Implementation Science
Source:Anesthesiology Clinics, Volume 36, Issue 1
Author(s): Meghan B. Lane-Fall, Lee A. Fleisher
http://ift.tt/2HVJnkf
Quality Improvement and Implementation Science: Different Fields with Aligned Goals
Source:Anesthesiology Clinics, Volume 36, Issue 1
Author(s): Meghan B. Lane-Fall, Lee A. Fleisher
http://ift.tt/2oJeWVL
Implementation Science in Perioperative Care
Publication date: March 2018
Source:Anesthesiology Clinics, Volume 36, Issue 1
Author(s): Meghan B. Lane-Fall, Benjamin T. Cobb, Crystal Wiley Cené, Rinad S. Beidas
Teaser
There is a 17-year gap between the initial publication of scientific evidence and its uptake into widespread practice in health care. The field of implementation science (IS) emerged in the 1990s as an answer to this "evidence-to-practice gap." In this article, we present an overview of implementation science, focusing on the application of IS principles to perioperative care. We describe opportunities for additional training and discuss strategies for funding and publishing IS work. The objective is to demonstrate how IS can improve perioperative patient care, while highlighting perioperative IS studies and identifying areas in need of additional investigation.http://ift.tt/2HWFCLB
Human Factors Applied to Perioperative Process Improvement
Publication date: March 2018
Source:Anesthesiology Clinics, Volume 36, Issue 1
Author(s): Joseph R. Keebler, Elizabeth H. Lazzara, Elizabeth Blickensderfer, Thomas D. Looke
Teaser
This article discusses some of the major theories of the science of human factors/ergonomics (HF/E) in relation to perioperative medicine, with a focus on safety and errors within these systems. The discussion begins with human limitations based in cognition, decision making, stress, and fatigue. Given these limitations, the importance of measuring human performance is discussed. Finally, using the HF/E perspective on safety, high-level recommendations are provided for increasing safety within the perioperative environment.http://ift.tt/2oJeRkV
Quality Improvement in Anesthesiology — Leveraging Data and Analytics to Optimize Outcomes
Publication date: March 2018
Source:Anesthesiology Clinics, Volume 36, Issue 1
Author(s): Elizabeth A. Valentine, Scott A. Falk
Teaser
Quality improvement is at the heart of practice of anesthesiology. Objective data are critical for any quality improvement initiative; when possible, a combination of process, outcome, and balancing metrics should be evaluated to gauge the value of an intervention. Quality improvement is an ongoing process; iterative reevaluation of data is required to maintain interventions, ensure continued effectiveness, and continually improve. Dashboards can facilitate rapid analysis of data and drive decision making. Large data sets can be useful to establish benchmarks and compare performance against other providers, practices, or institutions. Audit and feedback strategies are effective in facilitating positive change.http://ift.tt/2HZ0u4D
Emergency Manuals
Publication date: March 2018
Source:Anesthesiology Clinics, Volume 36, Issue 1
Author(s): Sara N. Goldhaber-Fiebert, Carl Macrae
Teaser
How can teams manage critical events more effectively? There are commonly gaps in performance during perioperative crises, and emergency manuals are recently available tools that can improve team performance under stress, via multiple mechanisms. This article examines how the principles of implementation science and quality improvement were applied by multiple teams in the development, testing, and systematic implementations of emergency manuals in perioperative care. The core principles of implementation have relevance for future patient safety innovations perioperatively and beyond, and the concepts of emergency manuals and interprofessional teamwork are applicable for diverse fields throughout health care.http://ift.tt/2oI6DcP
Use of Simulation in Performance Improvement
Publication date: March 2018
Source:Anesthesiology Clinics, Volume 36, Issue 1
Author(s): Amanda Burden, Erin White Pukenas
Teaser
Human error and system failures continue to play a substantial role in preventable errors that lead to adverse patient outcomes or death. Many of these deaths are not the result of inadequate medical knowledge and skill, but occur because of problems involving communication and team management. Anesthesiologists pioneered the use of simulation for medical education in an effort to improve physician performance and patient safety. This article explores the use of simulation for performance improvement. Educational theories that underlie effective simulation programs are described as driving forces behind the advancement of simulation in performance improvement.http://ift.tt/2HTh7ih
Developing Multicenter Registries to Advance Quality Science
Publication date: March 2018
Source:Anesthesiology Clinics, Volume 36, Issue 1
Author(s): Laura E. Schleelein, Kathleen A. Harris, Elizabeth M. Elliott
Teaser
There are several benefits to clinical registries as an information repository tool, ultimately lending itself to the acquisition of new knowledge. Registries have the unique advantage of garnering much data quickly and are, therefore, especially helpful for niche populations or low-prevalence diseases. They can be used to inform on the ideal structure, process, or outcome involving an identified population. The data can be used in many ways, for example, as an observational tool to reveal associations or as a basis for framing future research studies or quality improvement projects.http://ift.tt/2oJeXsN
Handovers in Perioperative Care
Publication date: March 2018
Source:Anesthesiology Clinics, Volume 36, Issue 1
Author(s): Atilio Barbeito, Aalok V. Agarwala, Amanda Lorinc
Teaser
Handovers around the time of surgery are common, yet complex and error prone. Interventions aimed at improving handovers have shown increased provider satisfaction and teamwork, improved efficiency, and improved communication and have been shown to reduce errors and improve clinical outcomes in some studies. Common recommendations in the literature include a standardized institutional process that allows flexibility among different units and settings, the completion of urgent tasks before information transfer, the presence of all members of the team for the duration of the handover, a structured conversation that uses a cognitive aid, and education in team skills and communication.http://ift.tt/2HUXKoS
Rethinking Clinical Workflow
Publication date: March 2018
Source:Anesthesiology Clinics, Volume 36, Issue 1
Author(s): Joseph J. Schlesinger, Kendall Burdick, Sarah Baum, Melissa Bellomy, Dorothee Mueller, Alistair MacDonald, Alex Chern, Kristin Chrouser, Christie Burger
Teaser
The concept of clinical workflow borrows from management and leadership principles outside of medicine. The only way to rethink clinical workflow is to understand the neuroscience principles that underlie attention and vigilance. With any implementation to improve practice, there are human factors that can promote or impede progress. Modulating the environment and working as a team to take care of patients is paramount. Clinicians must continually rethink clinical workflow, evaluate progress, and understand that other industries have something to offer. Then, novel approaches can be implemented to take the best care of patients.http://ift.tt/2oHvz3S
Developing Capacity to Do Improvement Science Work
Publication date: March 2018
Source:Anesthesiology Clinics, Volume 36, Issue 1
Author(s): Irene McGhee, Yehoshua Gleicher
Teaser
Developing capacity to do improvement science starts with prioritizing quality improvement training in all health professions curricula so that a common knowledge base and understanding are created. Educational programs should include opportunities for colearning with patients, health professionals, and leaders. In this way, knowledge translation (also called implementation) is more effective and better coordinated when applied across organizations. Key factors that enable and drive behavior change are reviewed, as is the importance of influence and leadership. A comprehensive approach that accounts for these factors hardwires quality improvement into the health care systems and creates a culture that enables its ongoing development.http://ift.tt/2HVsfLq
Diffusing Innovation and Best Practice in Health Care
Publication date: March 2018
Source:Anesthesiology Clinics, Volume 36, Issue 1
Author(s): Philip E. Greilich, Mary Eleanor Phelps, William Daniel
Teaser
Diffusing innovation and best practices in healthcare are among the most challenging aspects of advancing patient safety and quality improvement. Recommendations from the Baldrige Foundation, Institute for Healthcare Improvement, and The Joint Commission provide guidance on the principles for successful diffusion. Perioperative leaders are encouraged to applying these principles to high priority areas such as handovers, enhanced recovery and patient blood management. Completing a successful pilot project can be exciting, however, effective diffusion is essential to achieving meaningful and lasting impact on the service line and health system.http://ift.tt/2oJeDKB
The role of efflux pumps in Bacteroides fragilis resistance to antibiotics
Source:Microbiological Research
Author(s): Reza Ghotaslou, Mina Yekani, Mohammad Yousef Memar
The resistance of Bacteroides fragilis to the most antimicrobial agents has been reported in the world. Identification of the microbial resistance mechanisms can play an important role in controlling these resistances. Currently, B. fragilis is resistant to most antibiotics. The multi-drug efflux pumps have been shown to underlie the antimicrobial resistance in B. fragilis strains. Two types of these efflux pumps including RND and MATE can be regarded as main structures responsible for antibiotic resistance. Therefore, the strategy for suppressing of this efflux system may be useful in the treatment and control of the multidrug-resistant B. fragilis. The purpose of this study is to review the B. fragilis efflux pumps and their functions in the resistance to antibiotics.
http://ift.tt/2F736vm
Control of hyperglycemia in male mice by leflunomide: mechanisms of action
p70 S6 kinase (S6K1) is a serine/threonine kinase that phosphorylates the insulin receptor substrate-1 (IRS-1) at serine 1101 and desensitizes insulin receptor signaling. S6K1 hyperactivation due to overnutrition leads to hyperglycemia and type 2 diabetes. Our recent study showed that A77 1726, the active metabolite of the anti-rheumatoid arthritis (RA) drug leflunomide, is an inhibitor of S6K1. Whether leflunomide can control hyperglycemia and sensitize the insulin receptor has not been tested. Here we report that A77 1726 increased AKTS473/T308 and S6K1T389 phosphorylation but decreased S6S235/236 and IRS-1S1101 phosphorylation in 3T3-L1 adipocytes, C2C12 and L6 myotubes. A77 1726 increased insulin receptor tyrosine phosphorylation and binding of the p85 subunit of the PI-3 kinase to IRS-1. A77 1726 enhanced insulin-stimulated glucose uptake in L6 myotubes and 3T3-L1 adipocytes, and enhanced insulin-stimulated glucose transporter type 4 (GLUT4) translocation to the plasma membrane of L6 cells. Finally, we investigated the anti-hyperglycemic effect of leflunomide on ob/ob and high-fat diet (HFD)-induced diabetes mouse models. Leflunomide treatment normalized blood glucose levels and overcame insulin resistance in glucose and insulin tolerance tests in ob/ob and HFD-fed mice but had no effect on mice fed a normal chow diet (NCD). Leflunomide treatment increased AKTS473/T308 phosphorylation in the fat and muscle of ob/ob mice but not in normal mice. Our results suggest that leflunomide sensitizes the insulin receptor by inhibiting S6K1 activity in vitro, and that leflunomide could be potentially useful for treating patients with both RA and diabetes.
http://ift.tt/2HVnKk0
Do we choose control diets wisely?
Publication date: Available online 1 March 2018
Source:Trends in Endocrinology & Metabolism
Author(s): Ana D. Mandić, Michael Blaut
In a recent article in Cell Reports, Dalby and colleagues convincingly demonstrate that choosing an inadequate control diet in animal experiments that investigate the interaction of nutrition, gut microbiota, and obesity development may lead to the wrong conclusions. The authors systematically compared the effects of refined high- and low-fat diets (rHFD and rLFD) with those of a standard chow diet on mouse physiology, microbiota composition, cecal fermentation, and intestinal morphology. The results obtained in this study question the conclusions drawn from animal studies that compared the effects of HFDs with those of chow diets.
http://ift.tt/2CQzd0B
PARP1 interacts with STAT3 and retains active phosphorylated-STAT3 in nucleus during pathological myocardial hypertrophy
Publication date: Available online 1 March 2018
Source:Molecular and Cellular Endocrinology
Author(s): Luping Wang, Zhuoming Li, Yinzi Tan, Qian Li, Hanwei Yang, Panxia Wang, Jing Lu, Peiqing Liu
The activation of signal transducer and activator of transcription 3 (STAT3) positively regulates myocardial hypertrophy, and its transcriptional activity is finely conditioned by diverse extracellular growth factors and cytokines. Here, we introduce novel evidence that poly(ADP-ribose) polymerase 1 (PARP1) interacts with STAT3 and promotes its activation in cardiomyocytes and rat heart tissues. PARP1 activity and phosphorylated STAT3 were augmented by hypertrophic stimuli both in vitro and in vivo. Infection of PARP1 adenovirus induced cardiomyocyte hypertrophy, which could be prevented by STAT3 knockdown or inhibition. Additionally, PARP1 enhanced STAT3 phosphorylation level, nuclear accumulation and transcriptional activity. Mechanistically, PARP1 interacts with STAT3 and retains active phosphorylated-STAT3 in nucleus. In conclusion, our findings provide the first evidence that PARP1 exacerbates cardiac hypertrophy by stabilizing active phosphorylated-STAT3, which suggests that multi-target therapeutic strategies counteracting PARP1 activity and STAT3 activation would be potential for treating cardiovascular diseases.
http://ift.tt/2t9AXCn
New transcriptomic tools to understand testis development and functions
Publication date: Available online 1 March 2018
Source:Molecular and Cellular Endocrinology
Author(s): Estelle Lecluze, Bernard Jégou, Antoine D. Rolland, Frédéric Chalmel
The testis plays a central role in the male reproductive system - secreting several hormones including male steroids and producing male gametes. A complex and coordinated molecular program is required for the proper differentiation of testicular cell types and maintenance of their functions in adulthood. The testicular transcriptome displays the highest levels of complexity and specificity across all tissues in a wide range of species. Many studies have used high-throughput sequencing technologies to define the molecular dynamics and regulatory networks in the testis as well as to identify novel genes or gene isoforms expressed in this organ. This review intends to highlight the complementarity of these transcriptomic studies and to show how the use of different sequencing protocols contribute to improve our global understanding of testicular biology.
http://ift.tt/2oA6U2i
Editorial Board
Publication date: 15 March 2018
Source:Acta Biomaterialia, Volume 69
http://ift.tt/2FKsrwz
Assessment of focal laser photocoagulations’ early effect on polypoidal choroidal vasculopathy with optical coherence tomography angiography
Abstract
Polypoidal choroidal vasculopathy (PCV) is seen with polypoidal lesions and branching vascular networks (BVNs) (Spaide et al. in Retina 15(2):100–110, 1995; Yannuzzi et al. in Retina 10(1):1–8, 1990). There are reports about laser photocoagulation for PCV (Yuzawa et al. in Japan J Ophthalmol 47(4):379–384, 2003; Lee et al. in Eye 23(1):145–148, 2009); however, all these reports are about final vision and frequent relapses. Therefore, this treatment merits rigorous scrutiny using optical coherence tomography angiography (OCTA).
http://ift.tt/2t8NyWt
Native RNA-Sequencing Throws its Hat into the Transcriptomics Ring
Publication date: Available online 1 March 2018
Source:Trends in Biochemical Sciences
Author(s): Shobbir Hussain
De novo sequence-level surveys of transcriptomes have previously relied on sequencing via a DNA intermediate. While such methods can yield massive data sets, various problems mean that these do not always accurately reflect the true innate composition of transcriptomes. Enter Garalde et al., who present for the first time highly parallel native RNA-Sequencing (RNA-seq), with potentially disruptive future-implications for the transcriptomics field.
http://ift.tt/2oAIqpA
Identification and Screening of Potent Antimicrobial Peptides in Arthropod Genomes
Source:Peptides
Author(s): Deepesh Duwadi, Anishma Shrestha, Binyam Yilma, Itamar Kozlovski, Munaya Sa-eed, Nikesh Dahal, James Jukosky
Using tBLASTn and BLASTp searches, we queried recently sequenced arthropod genomes and expressed sequence tags (ESTs) using a database of known arthropod cecropins, defensins, and attacins. We identified and synthesized 6 potential AMPs and screened them for antimicrobial activity. Using radial diffusion assays and microtiter antimicrobial assays, we assessed the in vitro antimicrobial effects of these peptides against several human pathogens including Gram-positive and Gram-negative bacteria and fungi. We also conducted hemolysis assays to examine the cytotoxicity of these peptides to mammalian cells. Four of the six peptides identified showed antimicrobial effects in these assays. We also created truncated versions of these four peptides to assay their antimicrobial activity. Two cecropins derived from the monarch butterfly genome (Danaus plexippus), DAN1 and DAN2, showed minimum inhibitory concentrations (MICs) in the range of 2–16 μg/ml when screened against Gram-negative bacteria. HOLO1 and LOUDEF1, two defensin-like peptides derived from red flour beetle (Tribolium castaneum) and human body louse (Pediculus humanus humanus), respectively, exhibited MICs in the range of 13–25 μg/mL against Gram-positive bacteria. Furthermore, HOLO1 showed an MIC less than 5 μg/mL against the fungal species Candida albicans. These peptides exhibited no hemolytic activity at concentrations up to 200 μg/ml. The truncated peptides derived from DAN2 and HOLO1 showed very little antimicrobial activity. Our experiments show that the peptides DAN1, DAN2, HOLO1, and LOUDEF1 showed potent antimicrobial activity in vitro against common human pathogens, did not lyse mammalian red blood cells, and indicates their potential as templates for novel therapeutic agents against microbial infection.
http://ift.tt/2F6XVLW
Thyroid hormone receptor localization in target tissues
The thyroid hormone receptors, TRα1, TRβ1 and other subtypes, are members of the nuclear receptor superfamily that mediate the action of thyroid hormone signaling in numerous tissues to regulate important physiological and developmental processes. Their most well-characterized role is as ligand-dependent transcription factors; TRs bind thyroid hormone response elements in the presence or absence of thyroid hormone to facilitate the expression of target genes. Although primarily residing in the nucleus, TRα1 and TRβ1 shuttle rapidly between the nucleus and cytoplasm. We have identified multiple nuclear localization signals and nuclear export signals within TRα1 and TRβ1 that interact with importins and exportins, respectively, to mediate translocation across the nuclear envelope. More recently, enigmatic cytoplasmic functions have been ascribed to other TR subtypes, expanding the diversity of the cellular response to thyroid hormone. By integrating data on localization signal motifs, this review provides an overview of the complex interplay between TR's dynamic transport pathways and thyroid hormone signaling activities. We examine the variation in TR subtype response to thyroid hormone signaling, and what is currently known about regulation of the variety of tissue-specific localization patterns, including targeting to the nucleus, the mitochondria and the inner surface of the plasma membrane.
http://ift.tt/2t5rkF1
Metabolic effects of short-term caloric restriction in mice with reduced insulin gene dosage
Caloric restriction (CR) is the only environmental intervention with robust evidence that it extends lifespan and delays the symptoms of aging, but its mechanisms are incompletely understood. Based on the prolonged longevity of knockout models, it was hypothesized that the insulin-IGF pathway could be a target for developing a CR mimic. This study aimed to test whether CR has additive effects on glucose homeostasis and beta-cell function in mice with reduced insulin gene dosage. To study models with a range of basal insulin levels, wild-type C57BL/6J and mice on an Ins2 – / – background, were put on 8 weeks of 40% CR at various ages. Both male and female mice rapidly lost weight due to a reduced WAT mass. Glucose tolerance was improved and fasting glucose levels were reduced by CR in both wild type and 45- and 70-week-old Ins2 – / – mice. The effects of CR and reduced insulin on glucose tolerance were non-additive in 20-week-old mice. Interestingly, mice on CR generally exhibited an inability to further depress blood glucose after insulin injection, pointing to possible alterations in insulin sensitivity. In conclusion, our results demonstrate that CR can cause weight loss in the context of reduced insulin production, but that CR-improved glucose homeostasis does not occur near the 'insulin floor' in young mice. Collectively, these data shed further light on the relationships between CR, insulin and glucose homeostasis.
http://ift.tt/2oBDsZt
Importin-β Directly Regulates the Motor Activity and Turnover of a Kinesin-4
Publication date: Available online 1 March 2018
Source:Developmental Cell
Author(s): Anindya Ganguly, Logan DeMott, Chuanmei Zhu, Daniel D. McClosky, Charles T. Anderson, Ram Dixit
Spatiotemporal regulation of kinesins is essential for microtubule-dependent intracellular transport. In plants, cell wall deposition depends on the FRA1 kinesin, whose abundance and motility are tightly controlled to match cellular growth rate. Here, we show that an importin-β, IMB4, regulates FRA1 activity in a developmental manner. IMB4 physically interacts with a PY motif in the FRA1 motor domain and inhibits its motility by preventing microtubule binding, while also protecting FRA1 against proteasome-mediated degradation, thus providing a mechanism to couple the motility and stability of FRA1. This regulatory mechanism is likely to be broadly applicable, based on the conservation of the PY motif in the motor domains of plant and animal kinesins and the direct interaction of multiple plant kinesins with IMB4. Together, our data establish IMB4 as a multi-functional regulator of FRA1 and reveal a mechanism for how plants control the magnitude of cargo transport needed for cell wall assembly.
Graphical abstract
Teaser
How the activity of kinesins is regulated to meet cellular needs remains poorly understood. Ganguly et al. show that the motility and proteasome-mediated degradation of a kinesin-4 is regulated in a developmental manner by the binding of an importin-β to a conserved PY motif in the kinesin motor domain.http://ift.tt/2CQD6CI
Chaperone-Independent Peripheral Quality Control of CFTR by RFFL E3 Ligase
Publication date: Available online 1 March 2018
Source:Developmental Cell
Author(s): Tsukasa Okiyoneda, Guido Veit, Ryohei Sakai, Misaki Aki, Takeshi Fujihara, Momoko Higashi, Seiko Susuki-Miyata, Masanori Miyata, Norihito Fukuda, Akihiko Yoshida, Haijin Xu, Pirjo M. Apaja, Gergely L. Lukacs
The peripheral protein quality control (QC) system removes non-native membrane proteins, including ΔF508-CFTR, the most common CFTR mutant in cystic fibrosis (CF), from the plasma membrane (PM) for lysosomal degradation by ubiquitination. It remains unclear how unfolded membrane proteins are recognized and targeted for ubiquitination and how they are removed from the apical PM. Using comprehensive siRNA screens, we identified RFFL, an E3 ubiquitin (Ub) ligase that directly and selectively recognizes unfolded ΔF508-CFTR through its disordered regions. RFFL retrieves the unfolded CFTR from the PM for lysosomal degradation by chaperone-independent K63-linked poly-ubiquitination. RFFL ablation enhanced the functional expression of cell-surface ΔF508-CFTR in the presence of folding corrector molecules, and this effect was further improved by inhibiting the Hsc70-dependent ubiquitination machinery. We propose that multiple peripheral QC mechanisms evolved to dispose of non-native PM proteins and to preserve cellular proteostasis, even at the cost of eliminating partially functional polypeptides.
Graphical abstract
Teaser
Okiyoneda et al. investigate how ubiquitination targets ΔF508-CFTR, the most common CFTR mutant found in cystic fibrosis, at the cell surface. The authors show that RFFL, a ubiquitin ligase that directly and selectively recognizes unfolded ΔF508-CFTR through its disordered regions, promotes K63-linked poly-ubiquitination of CFTR to stimulate lysosomal degradation.http://ift.tt/2F42HxW
Enteroid Monolayers Reveal an Autonomous WNT and BMP Circuit Controlling Intestinal Epithelial Growth and Organization
Publication date: Available online 1 March 2018
Source:Developmental Cell
Author(s): Curtis A. Thorne, Ina W. Chen, Laura E. Sanman, Melanie H. Cobb, Lani F. Wu, Steven J. Altschuler
The intestinal epithelium maintains a remarkable balance between proliferation and differentiation despite rapid cellular turnover. A central challenge is to elucidate mechanisms required for robust control of tissue renewal. Opposing WNT and BMP signaling is essential in establishing epithelial homeostasis. However, it has been difficult to disentangle contributions from multiple sources of morphogen signals in the tissue. Here, to dissect epithelial-autonomous morphogenic signaling circuits, we developed an enteroid monolayer culture system that recapitulates four key properties of the intestinal epithelium, namely the ability to maintain proliferative and differentiated zones, self-renew, polarize, and generate major intestinal cell types. We systematically perturb intrinsic and extrinsic sources of WNT and BMP signals to reveal a core morphogenic circuit that controls proliferation, tissue organization, and cell fate. Our work demonstrates the ability of intestinal epithelium, even in the absence of 3D tissue architecture, to control its own growth and organization through morphogen-mediated feedback.
Graphical abstract
Teaser
Thorne, Chen et al. develop an enteroid monolayer culture system that recapitulates cell-type composition, crypt organization, and turnover kinetics of the intestinal epithelium. The authors use the enteroid monolayer to uncover an epithelium-intrinsic Wnt and BMP morphogenic circuit that regulates proliferation and tissue organization in the intestinal epithelium.http://ift.tt/2CT5Avv
Assessment of quality of life in patients who underwent breast reduction using BREAST-Q
Dear Sir,
http://ift.tt/2Fd7WuC
The effect of template-based sequential (TBS) coding on an NHS plastic surgical practice
Clinical coding is often a mystery to us surgeons but in actuality, it has a huge bearing on the financial sustainability of our services. Given the rapid innovations in plastic surgical procedures, clinical coders often struggle to decipher the extent of surgery. Meeting midway is the way forward here.
http://ift.tt/2GXw3dF
A supermicrosurgery training model using the chicken mid and lower wing
Supermicrosurgery is considered the pinnacle of microsurgery with its challenging nature of dissection and anastomosis of very small diameter vessels in the 0.3 to 0.8 mm range.
http://ift.tt/2oxElm4
On the electrode positioning for bipolar EMG recording of forearm extensor and flexor muscle activity after transcranial magnetic stimulation
Publication date: Available online 1 March 2018
Source:Journal of Electromyography and Kinesiology
Author(s): Moniek A.M. Munneke, Chantal D. Bakker, Eline A. Goverde, Jaco W. Pasman, Dick F. Stegeman
After stroke, motor pathways are often affected, leading to paresis. It remains difficult to reliably predict motor recovery of the upper extremity, for which transcranial magnetic stimulation (TMS) may add to clinical examination. Placement of the surface electromyography (sEMG) electrodes in TMS is essential for information about specific muscle groups and corticospinal pathways. This study primarily aimed to determine the optimal sEMG electrode positions for recording activity of forearm flexor and extensor muscles. The first goal was to optimize sensitivity in measuring any motor evoked potentials (MEP), because they may be reduced or absent in stroke patients. The second goal was adequate distinction between forearm flexor and extensor muscle groups. For optimal flexibility in choosing montages, a multichannel sEMG set-up with 37 electrodes encircled the forearm. The determination of optimal pairs was based upon electrical peripheral nerve stimulation. We found pairs with the highest compound nerve action potential (CMAP) amplitudes and pairs that optimally distinguished between the flexor and extensor muscles. Large interelectrode distances lead to responses with larger amplitudes and therefore sensitively measure any remaining corticomuscular connections. As a follow-up, specific muscle group responses can be targeted with smaller interelectrode distances. In conclusion, this study helps to identify better electrode locations for the use of clinical TMS studies.
http://ift.tt/2F5ETtE
Telangiectatic Matting is Associated with Hypersensitivity and a Bleeding Tendency
Publication date: Available online 1 March 2018
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Pooja Kadam, Jerrick Lim, Ian Paver, David E. Connor, Kurosh Parsi
ObjectiveThe aim was to investigate the pathogenesis of telangiectatic matting (TM) and identify possible risk factors.MethodsThis study had two parts. The clinical records of consecutive patients were retrospectively analysed to identify risk factors for TM. In the second part, the haemostatic and coagulation profile of the subset of patients with TM were analysed and compared with controls using standard coagulation tests, platelet function and a global assay of coagulation (rotational thromboelastometry, ROTEM).ResultsIn 352 consecutive patients presenting to a phlebology practice, 25 patients had TM (7.1%). All 25 patients were female with the median age of 45 (27–57) years. A comprehensive medical history was taken. Among 27 possible risk factors assessed, statistically significant associations included recurrent epistaxis, easy bruising, hypersensitivity (eczema, hives, hay fever, and rhinitis), previous treatment with sclerotherapy or endovenous laser for lower limb veins, and a family history of telangiectasias. Variables not associated with TM included oral contraceptive intake, hormone replacement therapy, and age. The haemostatic and coagulation profile of 12 patients (6 male and 6 female) with TM did not differ significantly from those without TM.ConclusionTM is associated with both hypersensitivity and a bleeding tendency. This study revealed no significant increase in the incidence of haemostatic abnormalities in patients with TM compared with the control group. Given the significant association with hypersensitivity disorders, the underlying mast cell hyper-reactivity may contribute to both hypersensitivity and a bleeding tendency and predispose patients to TM.
http://ift.tt/2t7AEYP
Re-interventions After Repair of Ruptured Abdominal Aortic Aneurysm: A Report From the IMPROVE Randomised Trial
Publication date: Available online 1 March 2018
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Janet T. Powell, Michael J. Sweeting, Pinar Ulug, Matthew M. Thompson, Robert J. Hinchliffe
Objective/BackgroundThe aim was to describe the re-interventions after endovascular and open repair of rupture, and investigate whether these were associated with aortic morphology.MethodsIn total, 502 patients from the IMPROVE randomised trial (ISRCTN48334791) with repair of rupture were followed-up for re-interventions for at least 3 years. Pre-operative aortic morphology was assessed in a core laboratory. Re-interventions were described by time (0–90 days, 3 months–3 years) as arterial or laparotomy related, respectively, and ranked for severity by surgeons and patients separately. Rare re-interventions to 1 year, were summarised across three ruptured abdominal aortic aneurysm trials (IMPROVE, AJAX, and ECAR) and odds ratios (OR) describing differences were pooled via meta-analysis.ResultsRe-interventions were most common in the first 90 days. Overall rates were 186 and 226 per 100 person years for the endovascular strategy and open repair groups, respectively (p = .20) but between 3 months and 3 years (mid-term) the rates had slowed to 9.5 and 6.0 re-interventions per 100 person years, respectively (p = .090) and about one third of these were for a life threatening condition. In this latter, mid-term period, 42 of 313 remaining patients (13%) required at least one re-intervention, most commonly for endoleak or other endograft complication after treatment by endovascular aneurysm repair (EVAR) (21 of 38 re-interventions), whereas distal aneurysms were the commonest reason (four of 23) for re-interventions after treatment by open repair. Arterial re-interventions within 3 years were associated with increasing common iliac artery diameter (OR 1.48, 95% confidence interval [CI] 0.13–0.93; p = .004). Amputation, rare but ranked as the worst re-intervention by patients, was less common in the first year after treatment with EVAR (OR 0.2, 95% CI 0.05–0.88) from meta-analysis of three trials.ConclusionThe rate of mid-term re-interventions after rupture is high, more than double that after elective EVAR and open repair, suggesting the need for bespoke surveillance protocols. Amputations are much less common in patients treated by EVAR than in those treated by open repair.
http://ift.tt/2FJ8vdo
One Year Outcomes of 101 BeGraft Stent Grafts used as Bridging Stents in Fenestrated Endovascular Repairs
Publication date: Available online 1 March 2018
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Rafaelle Spear, Jonathan Sobocinski, Adrien Hertault, Matthieu Delloye, Richard Azzauiu, Dominique Fabre, Stéphan Haulon
ObjectivesTo evaluate the outcomes of the second generation BeGraft balloon expandable covered stent Graft System (Bentley InnoMed, Hechingen, Germany) implanted as bridging stent grafts during fenestrated endovascular aortic repair (FEVAR) of complex aneurysms.DesignThis was a single centre prospective study including all consecutive patients treated by FEVAR performed with second generation BeGraft stent grafts as bridging stents.MethodsDemographics of patients, diameter and length of the bridging stent grafts, technical success, re-interventions, occlusions, post-operative events, and imaging (Cone Beam CT and/or CT scan, and contrast enhanced ultrasound) were prospectively collected in an electronic database. Duplex ultrasound was performed before discharge and at 6 month follow-up. At 1 year, patients were evaluated clinically and by imaging (CT and ultrasound).ResultsBetween November 2015 and September 2016, 39 consecutive patients (one woman) were treated with custom made fenestrated endografts (2–5 fenestrations) for complex aneurysms or type 1 endoleak after EVAR, using a variety of bridging stents including the BeGraft. All 101 BeGraft stent grafts were successfully delivered and deployed. There was no in hospital mortality. Early fenestration patency rate was 99% (96/97); the sole target vessel post-operative occlusion was secondary to a dissection of the renal artery distal to the stent. Complementary stenting was unsuccessful in recovering renal artery patency; bilateral renal stent occlusion was observed in the same patient on a CT scan performed 2 months after the procedure. He required post-operative dialysis. No additional renal impairment was observed. During follow-up (median 13 months [11–15]), all fenestrations stented with BeGraft stent grafts remained patent (95/97, 98%). One type 1b endoleak was detected and treated (2.6%).ConclusionsBeGraft stent grafts used as bridging stents during FEVAR are associated with favourable outcomes at 1 year follow-up. Long-term follow-up is required to confirm these promising results.
http://ift.tt/2F4Ezas
Why Should Vascular Surgeons be More Involved in Kidney Transplantation?
Publication date: Available online 1 March 2018
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Anne Lejay, Sophie Caillard, Fabien Thaveau, Nabil Chakfé
http://ift.tt/2FIbcM8
Commentary on “An Updated Systematic Review and Meta-analysis of Outcomes Following Eversion vs. Conventional Carotid Endarterectomy in Randomised Controlled Trials and Observational Studies”
Publication date: Available online 1 March 2018
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Jean-Baptiste Ricco, Nabil Chakfe
http://ift.tt/2t6PeQe
Hidradenitis Suppurativa: Disease Burden and Etiology in Skin of Color
Hidradenitis suppurativa (HS) is a chronic, debilitating skin disease. Although most studies on HS are conducted in largely Caucasian populations, evidence demonstrates a higher prevalence in patients with skin of color, including African and Hispanic populations. These racial subgroups are likely at risk for greater disease burden due to a higher prevalence of components of the metabolic syndrome, comorbid depression, and low socioeconomic status; however, there is a paucity of research in these populations. Additionally, studies examining the genetic and anatomical basis for HS, as well as the response to HS therapies, are lacking for patients with skin of color. Complicating this issue is the limited access to effective medical care, including dermatologists, for African and Hispanic populations as well as other minority groups. In this review, we identify gaps in the knowledge base, highlight the association between HS and patients with skin of color, and provide direction for much needed research into this condition.
Dermatology
http://ift.tt/2oIu7yg
Origins and specificity of auto-antibodies in Sm+ SLE patients
Source:Journal of Autoimmunity
Author(s): Olga Kalinina, Yoram Louzoun, Yue Wang, Tammy Utset, Martin Weigert
Systemic lupus erythematosus (SLE) is a complex autoimmune disease accompanied by production of autoantibodies directed to a variety of self-proteins and nucleic acids. The genetic basis of SLE is also complex with at least 40 susceptibility loci identified. This complexity suggests that there are a variety of SLE manifestations; nevertheless, SLE is treated as a single disease clinically. One unique SLE target is the Smith antigen (Sm), a nuclear ribonucleoprotein complex. Sm response occurs in 25% of patients with SLE. To simplify analysis of the disease and its associated autoantibody repertoire, we focused on this subset [referred to here as "Sm positive", Sm+]. We analyzed the memory B cell repertoire and identified a V region, Vκ4-1, which was significantly overrepresented in the Sm+ SLE subset. Antibodies that express Vκ4-1 are enriched in antinuclear (ANA) positive specificities and often associated with speckled ANA pattern that is a characteristic of Sm binding. In healthy individuals Vκ4-1 B cells are enriched in the unswitched memory population. Unswitched memory B cells resemble mouse marginal zone B cells and this population is decreased in all SLE patients. Moreover, we found a similar decrease in healthy African American donors. African Americans have a significantly higher prevalence of SLE compared to Caucasians. Thus, reduced unswitched memory B cell compartment may represent a new susceptibility marker for SLE.
http://ift.tt/2oMQJOr
Εγγραφή σε:
Αναρτήσεις (Atom)
-
Summary Insulinomas are rare neuroendocrine tumours that classically present with fasting hypoglycaemia. This case report discusses an un...
-
The online platform for Taylor & Francis Online content New for Canadian Journal of Remote Sen...
