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Ryan C Johnson, Michael W Ellis, Carey D Schlett, Eugene V Millar, Patrick T LaBreck, Deepika Mor, Emad M Elassal, Jeffrey B Lanier, Cassie L Redden, Tianyuan Cui, Nimfa Teneza-Mora, Danett K Bishop, Eric R Hall, Kimberly A Bishop-Lilly, D Scott Merrell
: Military trainees are at high risk for skin and soft-tissue infections (SSTIs). Although Staphylococcus aureus is associated with purulent SSTI, it is unclear to what degree this pathogen causes nonpurulent cellulitis. To inform effective prevention strategies and to provide novel insights into SSTI pathogenesis, we aimed to determine the etiology of SSTI in this population. We conducted a prospective observational study in US Army Infantry trainees with SSTI (cutaneous abscesses and cellulitis) from July 2012 through December 2014...
2016: PloS One
Sebastian Schneider, Davide Provasi, Marta Filizola
Substantial attention has recently been devoted to G protein-biased agonism of the µ-opioid receptor (MOR) as an ideal new mechanism for the design of analgesics devoid of serious side effects. However, designing opioids with appropriate efficacy and bias is challenging because it requires an understanding of the ligand binding process and of the allosteric modulation of the receptor. Here, we investigated these phenomena for TRV-130, a G protein-biased MOR small-molecule agonist that has been shown to exert analgesia with less respiratory depression and constipation than morphine, and that it is currently being evaluated in human clinical trials for acute pain management...
October 25, 2016: Biochemistry
Sheng-Ren Chen, Yi-Yu Ke, Teng-Kuang Yeh, Shu-Yu Lin, Li-Chin Ou, Shu-Chun Chen, Wan-Ting Chang, Hsiao-Fu Chang, Zih-Huei Wu, Chih-Chien Hsieh, Ping-Yee Law, Horace H Loh, Chuan Shih, Yiu-Kay Lai, Shiu-Hwa Yeh, Shau-Hua Ueng
μ-Opioid receptor (MOR) agonists are analgesics used clinically for the treatment of moderate to severe pain, but their use is associated with severe adverse effects such as respiratory depression, constipation, tolerance, dependence, and rewarding effects. In this study, we identified N-({2-[(4-bromo-2-trifluoromethoxyphenyl)sulfonyl]-1,2,3,4-tetrahydro-1-isoquinolinyl}methyl)cyclohexanecarboxamide (1) as a novel opioid receptor agonist by high-throughput screening. Structural modifications made to 1 to improve potency and blood-brain-barrier (BBB) penetration resulted in compounds 45 and 46...
September 20, 2016: European Journal of Medicinal Chemistry
Mor Shlezinger, Yael Houri-Haddad, Shunit Coppenhagen-Glazer, Grégory Resch, Yok-Ai Que, Shaul Beyth, Elisheva Dorfman, Ronen Hazan, Nurit Beyth
Dental diseases are perhaps the most prevalent infection-related diseases in humans. Biofilm is involved in almost every infectious disease compromising oral health, notably caries, periodontal disease, gingivitis, endodontic infections and peri-implantitis. Current therapies of biofilm-derived oral infections lack sensitivity; they are not species-specific and kill pathogenic species as well as commensal species, which are protective against the formation of pathogenic biofilms. Moreover, antibiotics have a limited effect on biofilm and are almost unused in oral diseases...
September 30, 2016: Current Topics in Medicinal Chemistry
Lei Zhou, Shenhui Li, Guodong Qi, Yongchao Su, Jing Li, Anmin Zheng, Xianfeng Yi, Qiang Wang, Feng Deng
The carbonylation of methanol with carbon monoxide to generate methyl acetate over Cu-H-MOR and H-MOR zeolites is studied using solid-state NMR spectroscopy. It is found that the catalytic activity of Cu-H-MOR zeolite is much higher than that of H-MOR zeolite. The presence of Cu(+) species enables the stabilization of dimethyl ether, which efficiently suppresses the hydrocarbon formation during carbonylation process over Cu-H-MOR zeolite. In addition, the carbon monoxide adsorbed on Cu(+) site is not an active species to produce either methyl acetate or acetic acid...
October 6, 2016: Solid State Nuclear Magnetic Resonance
Ron Bochner, Liat Samuelov, Ofer Sarig, Qiaoli Li, Christopher A Adase, Ofer Isakov, Natalia Malchin, Dan Vodo, Ronna Shayevitch, Alon Peled, Benjamin D Yu, Gilad Fainberg, Emily Warshauer, Noam Adir, Noam Erez, Andrea Gat, Yehonatan Gottlieb, Tova Rogers, Mor Pavlovsky, Ilan Goldberg, Noam Shomron, Aileen Sandilands, Linda E Campbell, Stephanie MacCallum, W H Irwin McLean, Gil Ast, Richard L Gallo, Jouni Uitto, Eli Sprecher
Congenital erythroderma is a rare and often life-threatening condition, which has been shown to result from mutations in several genes encoding important components of the epidermal differentiation program. Using whole exome sequencing, we identified in a child with congenital exfoliative erythroderma, hypotrichosis, severe nail dystrophy and failure to thrive, two heterozygous mutations in ABCA12 (c.2956C>T, p.R986W; c.5778+2T>C, p. G1900Mfs*16), a gene known to be associated with 2 forms of ichthyosis, autosomal recessive congenital ichthyosis and harlequin ichthyosis...
October 18, 2016: Journal of Investigative Dermatology
Nitzan Krinsky, Maya Kaduri, Janna Shainsky-Roitman, Mor Goldfeder, Eran Ivanir, Itai Benhar, Yuval Shoham, Avi Schroeder
Cell-free protein synthesis (CFPS) systems are important laboratory tools that are used for various synthetic biology applications. Here, we present a simple and inexpensive laboratory-scale method for preparing a CFPS system from E. coli. The procedure uses basic lab equipment, a minimal set of reagents, and requires less than one hour to process the bacterial cell mass into a functional S30-T7 extract. BL21(DE3) and MRE600 E. coli strains were used to prepare the S30-T7 extract. The CFPS system was used to produce a set of fluorescent and therapeutic proteins of different molecular weights (up to 66 kDa)...
2016: PloS One
N P Soumya, D N Das, S Jeyakumar, S Mondal, A Mor, U T Mundhe
Embryonic mortality is found to be the main source of reproductive wastage in domestic ruminants. Many genes are involved in the growth and development of the embryo, and the interferon-stimulated gene 15 (ISG 15) is one of the major gene stimulated by interferon tau, the maternal recognition of pregnancy signal in ruminants. In this study, both genomic and cDNA sequences of ISG 15 from Bos indicus (Deoni breed) were amplified and characterized. The genomic sequence of Deoni ISG 15 exhibited 99% identity with Bos taurus and 97% identity with that of Bos mutus and Bubalus bubalis...
October 21, 2016: Reproduction in Domestic Animals, Zuchthygiene
Momotazur Rahman, David C Grabowski, Vincent Mor, Edward C Norton
OBJECTIVE: To determine whether the observed differences in the risk-adjusted rehospitalization rates across skilled nursing facilities (SNFs) reflect true differences or merely differences in patient severity. SETTINGS: Elderly Medicare beneficiaries newly admitted to an SNF following hospitalization. STUDY DESIGN: We used 2009-2012 Medicare data to calculate SNFs' risk-adjusted rehospitalization rate. We then estimated the effect of these rehospitalization rates on the rehospitalization of incident patients in 2013, using an instrumental variable (IV) method and controlling for patient's demographic and clinical characteristics and residential zip code fixed effects...
October 21, 2016: Health Services Research
D Reiss, R A Ceredig, T Secher, J Boué, F Barreau, G Dietrich, C Gavériaux-Ruff
BACKGROUND: Opiates act through opioid receptors to diminish pain. Here, we investigated whether mu (MOR) and delta (DOR) receptor endogenous activity assessed in the whole mouse body or in particular at peripheral receptors on primary nociceptive neurons, control colonic pain. METHODS: We compared global MOR and DOR receptor knockout (KO) mice, mice with a conditional deletion of MOR and DOR in Nav1.8-positive nociceptive primary afferent neurons (cKO), and control floxed mice of both genders for visceral sensitivity...
October 17, 2016: European Journal of Pain: EJP
Jatinder Singh, Ryan C Johnson, Carey D Schlett, Emad M Elassal, Katrina B Crawford, Deepika Mor, Jeffrey B Lanier, Natasha N Law, William A Walters, Nimfa Teneza-Mora, Jason W Bennett, Eric R Hall, Eugene V Millar, Michael W Ellis, D Scott Merrell
Skin and soft tissue infections (SSTIs) are common in the general population, with increased prevalence among military trainees. Previous research has revealed numerous nasal microbial signatures that correlate with SSTI development and Staphylococcus aureus colonization. Thus, we hypothesized that the ecology of the inguinal, oropharynx, and perianal regions may also be altered in response to SSTI and/or S. aureus colonization. We collected body site samples from 46 military trainees with purulent abscess (SSTI group) as well as from 66 asymptomatic controls (non-SSTI group)...
September 2016: MSphere
Ramona Sturm, David Heftrig, Katharina Mörs, Nils Wagner, Kerstin Kontradowitz, Katrin Jurida, Ingo Marzi, Borna Relja
OBJECTIVE: Phagocytizing leukocytes (granulocytes and monocytes) play a fundamental role in immunological defense against pathogens and clearance of cellular debris after tissue injury due to trauma. According to the "two-hit hypothesis", phagocytes become primed due to/after trauma. Subsequently, a secondary stimulus may lead to their exaggerated response. This immune dysfunction can result in serious infectious complications, also depending on trauma injury pattern. Here, we investigated the phagocytizing capacity of leukocytes, and its correlation to trauma injury pattern...
September 29, 2016: Immunobiology
Jianguo Zhuang, Xiuping Gao, Franklin Gao, Fadi Xu
We tested the hypothesis that mu-opioid receptors (MORs) in the caudomedial nucleus tractus solitarius (cmNTS) are important for the ventilatory responses to stimulation of bronchopulmonary C-fibers (PCFs), the carotid body-mediated hypoxia, and hypercapnia independent of the carotid body. First, we used immunohistochemistry to map MORs distribution in the caudal medulla. Then we compared the effects of intra-cmNTS microinjection of DAMGO (a MOR agonist) with or without a combination of CTAP (a MOR antagonist) on the ventilatory responses to: 1) right atrial injection of capsaicin (to stimulation of PCFs) and 2) acute hypoxia (HVR, to stimulate the carotid body) in awake intact rats; and 3) hypercapnia (HCVR) in the carotid body ablated rats...
October 12, 2016: Respiratory Physiology & Neurobiology
Orly Sarid, Richard Isralowitz, Mor Yehudai, Alexander Reznik
BACKGROUND: There is a dearth of information about mothers in methadone maintenance treatment (MMT), their parental stress, and suicidal ideation. AIM: To evaluate parenting stress and suicidal ideation among heroin-dependent mothers in MMT. METHOD: The study was conducted at an MMT center. Inclusion criteria were mothers with at least one child between 6-12 years of age. Mothers (n = 41) were interviewed about their background characteristics, drug use, parenting stress, and suicide ideation...
October 12, 2016: Crisis
Jalees Fatima, Ritu Karoli, Ruchita Sharma, Saumya Gupta, Aman Mor
No abstract text is available yet for this article.
January 2016: Journal of the Association of Physicians of India
Sumita Chakrabarti, Andrew Chang, Nai-Jiang Liu, Alan R Gintzler
Caveolin-1 is the predominant structural protein of caveolae, a subset of (lipid) membrane rafts that compartmentalize cell signaling. Caveolin-1 binds most to G protein-coupled receptors and their signaling partners, thereby enhancing interactions among signaling cascade components and the relative activation of specific G protein-coupled pathways. This study reveals that chronic opioid exposure of μ-opioid receptor (MOR) expressing Chinese hamster ovary cells (MOR-CHO) and chronic in vivo morphine exposure of rat spinal cord augmented recruitment of multiple components of MOR-adenylyl cyclase (AC) stimulatory signaling by caveolin-1...
October 10, 2016: Journal of Neurochemistry
Batel Deri, Margarita Kanteev, Mor Goldfeder, Daniel Lecina, Victor Guallar, Noam Adir, Ayelet Fishman
Tyrosinases are responsible for melanin formation in all life domains. Tyrosinase inhibitors are used for the prevention of severe skin diseases, in skin-whitening creams and to avoid fruit browning, however continued use of many such inhibitors is considered unsafe. In this study we provide conclusive evidence of the inhibition mechanism of two well studied tyrosinase inhibitors, KA (kojic acid) and HQ (hydroquinone), which are extensively used in hyperpigmentation treatment. KA is reported in the literature with contradicting inhibition mechanisms, while HQ is described as both a tyrosinase inhibitor and a substrate...
October 11, 2016: Scientific Reports
Eiko Yokota, Yuko Koyanagi, Kiyofumi Yamamoto, Yoshiyuki Oi, Noriaki Koshikawa, Masayuki Kobayashi
The insular cortex (IC) plays a principal role in the regulation of pain processing. Although opioidergic agonists depress cortical excitatory synaptic transmission, little is known about opioidergic roles in inhibitory synaptic transmission. In the IC, the opioid receptors differentially regulate the excitatory propagation: agonists of the mu (MOR), delta (DOR), and kappa (KOR) exhibit suppressive, facilitative, and little effects, respectively. Thus, we aimed to examine the effects of opioid receptor agonists on unitary inhibitory postsynaptic currents (uIPSCs) in the IC...
October 7, 2016: Neuroscience
Joan M Teno, Pedro Gozalo, Nita Khandelwal, J Randall Curtis, David Meltzer, Ruth Engelberg, Vincent Mor
Importance: Mechanical ventilation may be lifesaving, but in certain persons, such as those with advanced dementia, it may prolong patient suffering without a clear survival benefit. Objective: To describe the use and outcomes of mechanical ventilation and its association with the increasing numbers of intensive care unit (ICU) beds in the United States for patients with advanced dementia residing in a nursing home 120 days before that hospital admission. Design, Setting, and Participants: This retrospective cohort study evaluated Medicare beneficiaries with advanced dementia hospitalized from January 1, 2000, to December 31, 2013, using the Minimum Data Set assessments linked with Medicare part A claims...
October 10, 2016: JAMA Internal Medicine
Christopher K Arnatt, Bethany A Falls, Yunyun Yuan, Thomas J Raborg, Ruturaj R Masvekar, Nazira El-Hage, Dana E Selley, Anthony V Nicola, Pamela E Knapp, Kurt F Hauser, Yan Zhang
Modern antiretroviral therapies have provided HIV-1 infected patients longer lifespans and better quality of life. However, several neurological complications are now being seen in these patients due to HIV-1 associated injury of neurons by infected microglia and astrocytes. In addition, these effects can be further exacerbated with opiate use and abuse. One possible mechanism for such potentiation effects of opiates is the interaction of the mu opioid receptor (MOR) with the chemokine receptor CCR5 (CCR5), a known HIV-1 co-receptor, to form MOR-CCR5 heterodimer...
September 26, 2016: Bioorganic & Medicinal Chemistry
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