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https://www.readbyqxmd.com/read/29232712/bioinformatic-analysis-reveals-new-determinants-of-antigenic-14-3-3-proteins-and-a-novel-antifungal-strategy
#1
Jenna E McGowan, Jacqueline Kratch, Saurabh Chattopadhyay, Bina Joe, Heather R Conti, Ritu Chakravarti
The ubiquitously expressed 14-3-3 family of proteins is evolutionarily conserved from yeast to mammals. Their involvement in humoral and cellular immune responses is emerging through studies in drosophila and humans. In humans, a select group of 14-3-3 isoforms are antigenic; however the determinants of their antigenicity are not known. Here, we show that although mammalian 14-3-3 proteins are mostly conserved, subtle differences between their isoforms may give rise to their antigenicity. We observed syntenic relations among all the isoforms of 14-3-3 for mammals, but not with that of birds or amphibians...
2017: PloS One
https://www.readbyqxmd.com/read/29232584/natural-product-inspired-library-synthesis-identification-of-2-3-diarylbenzofuran-and-2-3-dihydrobenzofuran-based-inhibitors-of-chlamydia-trachomatis
#2
Michael Saleeb, Sergio Mojica, Anna U Eriksson, C David Andersson, Åsa Gylfe, Mikael Elofsson
A natural product inspired library was synthesized based on 2,3-diarylbenzofuran and 2,3-diaryl-2,3-dihydrobenzofuran scaffolds. The library of forty-eight compounds was prepared by utilizing Pd-catalyzed one-pot multicomponent reactions and ruthenium-catalyzed intramolecular carbenoid C-H insertions. The compounds were evaluated for antibacterial activity in a panel of test systems including phenotypic, biochemical and image-based screening assays. We identified several potent inhibitors that block intracellular replication of pathogenic Chlamydia trachomatis with IC50 ≤ 3 μM...
December 5, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29232436/cellular-versus-acellular-grafts-for-diabetic-foot-ulcers-altering-the-protocol-to-improve-recruitment-to-a-comparative-efficacy-trial
#3
Catherine N Tchanque-Fossuo, Sara E Dahle, Hadar Lev-Tov, Chin-Shang Li, R Rivkah Isseroff
Diabetic foot ulcers (DFUs) have a substantial impact on public health. The standard of care (SOC) for DFUs consists of a multidisciplinary approach involving glycemic control, wound care with debridement of necrotic tissue, application of a moist dressing, infection control, use of off-loading devices, and patient education. New therapeutic devices aim to target the extracellular matrix (ECM) that is impaired in DFU; however, there is insufficient data on the effectiveness of such therapies along with lack of evidence on their long-term effectiveness...
November 2017: Cutis; Cutaneous Medicine for the Practitioner
https://www.readbyqxmd.com/read/29232209/recent-progress-in-understanding-hiv-reservoirs
#4
Hsiao-Hsuan Kuo, Mathias Lichterfeld
PURPOSE OF REVIEW: Reservoirs of HIV-1-infected cells persist long-term despite highly effective antiretroviral suppression therapy and represent the main barrier against a cure for HIV-1. This review summarizes recent advances in understanding the complexity and diversity of viral reservoir cells. RECENT FINDINGS: Latently infected memory CD4 T cells are the predominant cell compartment responsible for viral persistence, but some studies suggest that myeloid cells, and possibly hematopoietic progenitors, can also serve as long-term viral reservoirs...
December 11, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/29232103/game-changers-new-%C3%AE-lactamase-inhibitor-combinations-targeting-antibiotic-resistance-in-gram-negative-bacteria
#5
Karen Bush
Recent regulatory approvals for the β-lactam inhibitor combinations of ceftazidime-avibactam and meropenem-vaborbactam have provided two novel therapeutic options for the treatment of multidrug-resistant infections caused by Gram-negative bacteria. Most importantly, these combination agents have satisfied an important medical need related to antibiotic-resistant Klebsiella pneumoniae that produce serine carbapenemases, especially the Klebsiella pneumoniae carbapenemase (KPC) enzymes. Both combinations contain non-β-lactam β-lactamase inhibitors of novel chemical classes not previously developed as antibacterial agents, the diazabicyclooctanes and cyclic boronic acid derivatives...
December 12, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/29231806/a-picorna-like-virus-suppresses-the-n-end-rule-pathway-to-inhibit-apoptosis
#6
Zhaowei Wang, Xiaoling Xia, Xueli Yang, Xueyi Zhang, Yongxiang Liu, Di Wu, Yuan Fang, Yujie Liu, Jiuyue Xu, Yang Qiu, Xi Zhou
The N-end rule pathway is an evolutionarily conserved proteolytic system that degrades proteins containing N-terminal degradation signals called N-degrons, and has emerged as a key regulator of various processes. Viruses manipulate diverse host pathways to facilitate viral replication and evade antiviral defenses. However, it remains unclear if viral infection has any impact on the N-end rule pathway. Here, using a picorna-like virus as a model, we found that viral infection promoted the accumulation of caspase-cleaved Drosophila Inhibitor of Apoptosis 1 (DIAP1) by inducing the degradation of N-terminal amidohydrolase 1 (NTAN1), a key N-end rule component that identifies N-degron to initiate the process...
December 12, 2017: ELife
https://www.readbyqxmd.com/read/29231283/new-potent-inhibitors-against-newcastle-disease-virus-haemagglutinin-neuraminidase
#7
Paola Rota, Paolo La Rocca, Marco Piccoli, Marco Montefiori, Federica Cirillo, Lars Olsen, Marica Orioli, Pietro Allevi, Luigi Anastasia
Neuraminidase activity is essential for the infection and propagation of Paramyxoviruses, including human parainfluenza viruses (hPIVs) and the Newcastle Disease Virus (NDV). Thus, many inhibitors have been developed based on the 2-deoxy-2,3-didehydro-D-N-acetylneuraminic acid inhibitor (DANA) backbone. Along this line, we report here a series of neuraminidase inhibitors, having C-4 (ptoluensulfonamide and azido substituents) and C-5 (N-perfluorinated chains) modifications to the DANA backbone, that resulted 5- to 15-folds more potent than the current most active compound, the Ntrifluoroacetyl derivative of DANA (FANA), on the NDV haemagglutinin-neuraminidase (NDV-HN)...
December 12, 2017: ChemMedChem
https://www.readbyqxmd.com/read/29231258/retrospective-review-of-immunocompromised-children-undergoing-skin-biopsy-for-suspected-invasive-infection-analysis-of-factors-predictive-of-invasive-mold
#8
Robert J Smith, Sarah B Klieger, Salwa E Sulieman, Emily Berger, James R Treat, Brian T Fisher
OBJECTIVES: Cutaneous lesions are often the first marker of invasive mold infection, which can cause substantial morbidity in immunocompromised children. The purpose of this study was to describe the evaluation and outcomes of immunocompromised children who presented with findings requiring skin biopsy because of concern about invasive infection. In children who were biopsied, we sought to determine the factors predictive of invasive mold infection. METHODS: A retrospective review was conducted at the Children's Hospital of Philadelphia...
December 12, 2017: Pediatric Dermatology
https://www.readbyqxmd.com/read/29230580/in-vivo-studies-of-the-effectiveness-of-novel-n-halomethylated-and-non-halomethylated-quaternary-ammonium-salts-in-the-topical-treatment-of-cutaneous-leishmaniasis
#9
Maritza Fernandez, Javier Murillo, Luz Amalia Ríos-Vásquez, Rogelio Ocampo-Cardona, David L Cedeño, Marjorie A Jones, Iván D Velez, Sara M Robledo
The physicochemical properties of four N-halomethylated and one non-halomethylated ammonium salts, with proven in vitro antileishmanial activity, were determined according to pharmaceutical standard procedures. The effectiveness and toxicity of these compounds were assessed in hamsters infected with Leishmania (Viannia) braziliensis and compared to that showed by meglumine antimoniate. Animals were followed during 90 days after the completion of treatment. Therapeutic response was determined according to the reduction of size of skin lesions...
December 11, 2017: Parasitology Research
https://www.readbyqxmd.com/read/29230542/secondary-intracranial-hypertension-pseudotumor-cerebri-presenting-as-post-traumatic-headache-in-mild-traumatic-brain-injury-a-case-series
#10
Tonia Sabo, Charlene Supnet, Sushmita Purkayastha
BACKGROUND: Cerebral edema peaks 36-72 h after moderate traumatic brain injury but thought to be uncommon after mild traumatic brain injury. Post-traumatic headache can develop 48-72 h post-injury, perhaps reflecting the developing cerebral edema. Pseudotumor cerebri can result from various causes, including cerebral edema, and is characterized by increased intracranial pressure, headache, visual, and other common symptoms. Our objective was to report a phenotypically identifiable post-traumatic headache subtype...
December 11, 2017: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://www.readbyqxmd.com/read/29230203/ibalizumab-targeting-cd4-receptors-an-emerging-molecule-in-hiv-therapy
#11
REVIEW
Simona A Iacob, Diana G Iacob
The HIV infection is responsible for the most devastating global pandemic of the last century. More than 39 million people have died of HIV/AIDS since 1981. The development of the antiretroviral (ARV) treatment begins with the discovery of zidovudine a nucleoside reverse transcriptase inhibitor. This breakthrough was followed by other ARV drug classes and representatives. Presently, HIV treatment employs 27 ARV representatives belonging to five different classes. Despite the proven benefits of ARV treatment and its long-term control of the HIV infection, there is an increasing concern about the numerous adverse effects and resistance to current ARV drugs...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29230047/three-dimensional-3d-culture-of-adult-murine-colon-as-an-in-vitro-model-of-cryptosporidiosis-proof-of-concept
#12
Martha Baydoun, Sadia Benamrouz Vanneste, Colette Creusy, Karine Guyot, Nausicaa Gantois, Magali Chabe, Baptiste Delaire, Anthony Mouray, Atallah Baydoun, Gerard Forzy, Vincent Chieux, Pierre Gosset, Vincent Senez, Eric Viscogliosi, Jérôme Follet, Gabriela Certad
Cryptosporidium parvum is a major cause of diarrheal illness and was recently potentially associated with digestive carcinogenesis. Despite its impact on human health, Cryptosporidium pathogenesis remains poorly known, mainly due to the lack of a long-term culture method for this parasite. Thus, the aim of the present study was to develop a three-dimensional (3D) culture model from adult murine colon allowing biological investigations of the host-parasite interactions in an in vivo-like environment and, in particular, the development of parasite-induced neoplasia...
December 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29229643/cystatin-9-and-c-a-novel-immunotherapy-that-protects-against-multi-drug-resistant-new-delhi-metallo-beta-lactamase-1-producing-klebsiella-pneumoniae
#13
Alex J Holloway, JiehJuen Yu, Bernard P Arulanandam, Sarah M Hoskinson, Tonyia Eaves-Pyles
Multidrug-resistant (MDR) bacterial pneumonia can induce dysregulated pulmonary and systemic inflammation leading to morbidity and mortality. Antibiotics to treat MDR pathogens do not function to modulate the extent and intensity of inflammation and can have serious side effects. Herein, we evaluate the efficacy of two human cysteine proteinase inhibitors, cystatin 9 and cystatin C, as a novel immunotherapeutic treatment to combat MDR New Delhi metallo-beta-lactamase-1 (NDM-1) producing Klebsiella pneumoniae (Kp)...
December 11, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29229641/hyperbaric-oxygen-reduces-aspergillus-fumigatus-proliferation-in-vitro-and-influences-in-vivo-disease-outcomes
#14
Sourabh Dhingra, Jay C Buckey, Robert A Cramer
Recent estimates suggest that more than 3 million people have chronic or invasive fungal infections, causing more than 600,000 deaths every year. Aspergillus fumigatus causes invasive pulmonary aspergillosis (IPA) in patients with compromised immune systems and is a primary contributor to increases in human fungal infections. Thus, developing new clinical modalities as standalone or adjunctive therapy for improving IPA patient outcomes is critically needed. Here we test the in vitro and in vivo impact of hyperbaric oxygen (100% oxygen, >1 ATA) (HBO) on A...
December 11, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29229636/topical-antibiotic-use-co-selects-for-the-carriage-of-mobile-genetic-elements-conferring-resistance-to-unrelated-antimicrobials-in-staphylococcus-aureus
#15
Glen P Carter, Mark B Schultz, Sarah L Baines, Anders Goncalves da Silva, Helen Heffernan, Audrey Tiong, Peter H Pham, Ian R Monk, Timothy P Stinear, Benjamin P Howden, Deborah A Williamson
Topical antibiotics such as mupirocin and fusidic acid are commonly used in the prevention and treatment of skin infections, particularly those caused by staphylococci. However, widespread use of these agents is associated with increased resistance to these agents, potentially limiting their efficacy. Of particular concern is the observation that resistance to topical antibiotics is often associated with multidrug resistance, suggesting that topical antibiotics may play a role in the emergence of multidrug-resistant (MDR) strains...
December 11, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29229592/a-human-centered-platform-for-hiv-infection-reduction-in-new-york-development-and-usage-analysis-of-the-ending-the-epidemic-ete-dashboard
#16
Ashish Joshi, Chioma Amadi, Benjamin Katz, Sarah Kulkarni, Denis Nash
BACKGROUND: Dashboards have been increasingly used in clinic-based interventions, such as clinical performance improvement and monitoring risk of hospital readmissions, and are now gaining traction in population-based interventions, especially in disease assessment. OBJECTIVE: We describe the design, development, and usage analysis of a geovisualization dashboard, the Ending the Epidemic (ETE) Dashboard. The ETE dashboard is a tool developed to track New York's progress towards achieving the goal of its ETE Initiative, to reduce new HIV infections from 3000 per year to 750 per year by the end of 2020...
December 11, 2017: JMIR Public Health and Surveillance
https://www.readbyqxmd.com/read/29229573/merkel-cell-carcinoma-an-update-and-review-part-ii-current-and-future-therapy
#17
REVIEW
Tiffany L Tello, Kathleen Coggshall, Sue S Yom, Siegrid S Yu
Merkel cell carcinoma (MCC) is a rare neuroendocrine tumor of the skin associated with a high risk of local recurrence and distant metastases. It most commonly occurs on sun-exposed areas of Caucasian patients over the age of 65.1,2 The Merkel cell polyomavirus (MCV) is thought to be responsible for malignant transformation in approximately 80% of cases in the northern hemisphere,3 while ultraviolet radiation induced DNA damage is implicated in MCV-negative tumors.4 The overall incidence of MCC is low, with approximately 1600 cases diagnosed annually in the United States...
December 8, 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/29229552/caspase-6-is-a-dispensable-enabler-of-adult-mammalian-axonal-degeneration
#18
V Woo, C Cheng, A Duraikannu, A Chandrasekhar, K Purdy, J A Martinez, D W Zochodne
The progress of axonal degeneration (AxD) following injury or insult impacts both recovery from axonal transection and protection of axons from diverse insults, or axonopathy. Here we provide evidence that increases in capase-6 (Casp6) expression and action contribute to the progression of AxD. The expression of Casp6 protein and mRNA in distal branches of sensory axons undergoing AxD was confirmed. We developed and utilized a new model of axonopathy in live mice by serially visualizing the viability of cutaneous axons in the ear pinna that expressed an axonal YFP transgene, in response to capasaicin-induced AxD...
December 8, 2017: Neuroscience
https://www.readbyqxmd.com/read/29229544/a-new-textured-polyphosphazene-biomaterial-with-improved-blood-coagulation-and-microbial-infection-responses
#19
Li-Chong Xu, Zhongjing Li, Zhicheng Tian, Chen Chen, Harry R Allcock, Christopher A Siedlecki
A new poly[bis(octafluoropentoxy) phosphazene] (OFP) was synthesized for the purpose of blood contacting medical devices. OFP was further either developed into crosslinkable polyphosphazene (X-OFP) or blended with polyurethane (PU) as the mixture (OFP/PU) for improvement of mechanical property of polyphosphazene polymers. All the materials were fabricated as smooth films or further textured with submicron pillars for the assay of antimicrobial and antithrombotic properties. Results showed that crosslinkable OFP (X-OFP) and blends of OFP/PU successfully improved the mechanical strength of OFP and fewer defects of pillars were found on the textured polyphosphazene surfaces...
December 8, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/29229442/quantitative-analysis-of-tnf-%C3%AE-il-4-and-il-10-expression-nitric-oxide-response-and-apoptosis-in-encephalitozoon-cuniculi-infected-rabbits
#20
Alicia M Nevárez-Garza, Uziel Castillo-Velázquez, Adolfo Soto-Domínguez, R Montes-de-Oca-Luna, Diana E Zamora-Ávila, Alfredo Wong-González, Luis E Rodríguez-Tovar
The expression of tumor necrosis factor (TNF) -α, interleukin (IL) -4 and IL-10, as well as apoptosis and nitric oxide (NO) levels were measured in the brain and kidneys of immunocompetent and immunosuppressed New Zealand White rabbits infected with Encephalitozoon cuniculi. All of the animals had clinical signs histopathological lesions compatible with encephalitozoonosis and were E. cuniculi-positive by using a carbon immunoassay test. Encephalitozoon cuniculi infection promoted the expression of TNF-α and NO production in the kidneys of infected rabbits, and a synergic effect was observed in animal treated with dexamethasone...
December 8, 2017: Developmental and Comparative Immunology
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