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https://www.readbyqxmd.com/read/28334487/growing-up-with-perinatal-human-immunodeficiency-virus-a-life-not-expected
#1
Elaine Fay Williams
AIM AND OBJECTIVES: To describe the lived experience of young adults with perinatally acquired HIV (PaHIV). BACKGROUND: The advancement of the highly active antiretroviral treatment, PaHIV-infection has transformed into a chronic lifelong illness that is faced by young adults who grew up with HIV. The known challenges that are associated with HIV are poverty, stigma and social and emotional isolation. DESIGN: This was a qualitative single interview study of a convenience sample of PaHIV-infected young adults receiving care at a large metropolitan pediatric hospital...
March 23, 2017: Journal of Clinical Nursing
https://www.readbyqxmd.com/read/28332183/retinoic-acid-receptor-related-orphan-receptor-ror%C3%AE-regulates-differentiation-and-survival-of-keratinocytes-during-hypoxia
#2
Hongyu Li, Longjian Zhou, Jun Dai
Low O2 pressures present in the microenvironment of epidermis control keratinocyte differentiation and epidermal barrier function through hypoxia inducible factors (HIFs) dependent gene expression. This study focuses on investigating relations of the retinoic acid receptor-related orphan receptor alpha (RORα) to HIF-1α in keratinocytes under hypoxic conditions. The expression level of RORα is significantly elevated under hypoxia in both human and murine keratinocytes. Gene silencing of RORA attenuates hypoxia-stimulated expression of genes related to late differentiation and epidermal barrier function, and leads to an enhanced apoptotic response...
March 23, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28330384/federal-procurement-of-unlicensed-medicines-in-brazil-findings-and-implications
#3
Cristiane Roberta Dos Santos Teodoro, André Luís Almeida Dos Reis, Brian Godman, Rosângela Caetano, Claudia Garcia Serpa Osorio-de-Castro
BACKGROUND: There are safety concerns with using unlicensed medicines across countries including Brazil. Consequently this needs to be evaluated and concerns address if pertinent. AIM: Investigate such purchases by the Brazilian Federal Government from 2004 to 2013. METHODS: Procurement data from a public-access databank that contains procurement information of the Brazilian Federal Government. Each procured item was cross-referenced to its active drug approval status in the Brazilian National Register (DOU)...
March 23, 2017: Expert Review of Pharmacoeconomics & Outcomes Research
https://www.readbyqxmd.com/read/28328317/antiproliferative-and-apoptotic-effects-of-novel-anti-ror1-single-chain-antibodies-in-hematological-malignancies
#4
Leili Aghebati-Maleki, Vahid Younesi, Behzad Baradaran, Jalal Abdolalizadeh, Morteza Motallebnezhad, Hamid Nickho, Dariush Shanehbandi, Jafar Majidi, Mehdi Yousefi
Receptor tyrosine kinase-like orphan receptor (ROR) proteins are a conserved family of tyrosine kinase receptors that function in developmental processes including cell survival, differentiation, cell migration, cell communication, cell polarity, proliferation, metabolism, and angiogenesis. ROR1 has recently been shown to be expressed in various types of cancer cells but not normal cells. Pharmacokinetics and pharmacodynamics of single-chain Fragment variable (scFv) antibodies provide potential therapeutic advantages over whole antibody molecules...
April 2017: SLAS Discov
https://www.readbyqxmd.com/read/28327641/sequential-displacement-of-type-vi-secretion-system-effector-genes-leads-to-evolution-of-diverse-immunity-gene-arrays-in-vibrio-cholerae
#5
Paul C Kirchberger, Daniel Unterweger, Daniele Provenzano, Stefan Pukatzki, Yan Boucher
Type VI secretion systems (T6SS) enable bacteria to engage neighboring cells in contact-dependent competition. In Vibrio cholerae, three chromosomal clusters each encode a pair of effector and immunity genes downstream of those encoding the T6SS structural machinery for effector delivery. Different combinations of effector-immunity proteins lead to competition between strains of V. cholerae, which are thought to be protected only from the toxicity of their own effectors. Screening of all publically available V...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28326681/population-pharmacokinetics-of-selumetinib-and-its-metabolite-n-desmethyl-selumetinib-in-adult-patients-with-advanced-solid-tumors-and-children-with-low-grade-gliomas
#6
Y T Patel, V M Daryani, P Patel, D Zhou, J Fangusaro, D J Carlile, P D Martin, L Aarons, C F Stewart
Selumetinib (AZD6244, ARRY-142886), a mitogen activated protein kinases (MEK1 and 2) inhibitor, has been granted orphan drug designation for differentiated thyroid cancer. The primary aim of this analysis was to characterize the population pharmacokinetics of selumetinib and its active metabolite N-desmethyl-selumetinib in patients with cancer. Concentration-time data from adult and pediatric clinical trials were pooled to develop a population pharmacokinetic model using a sequential approach where selumetinib and N-desmethyl-selumetinib data were modeled separately...
March 22, 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/28326223/clinical-cellular-microscopic-and-ultrastructural-studies-of-a-case-of-fibrogenesis-imperfecta-ossium
#7
Melissa L Barron, Mark S Rybchyn, Sutharshani Ramesh, Rebecca S Mason, S Fiona Bonar, Paul Stalley, Sundeep Khosla, Bernie Hudson, Christopher Arthur, Edward Kim, Roderick J Clifton-Bligh, Phillip B Clifton-Bligh
Fibrogenesis imperfecta ossium is a rare disorder of bone usually characterized by marked osteopenia and associated with variable osteoporosis and osteosclerosis, changing over time. Histological examination shows that newly formed collagen is abnormal, lacking birefringence when examined by polarized light. The case presented demonstrates these features and, in addition, a previously undocumented finding of a persistent marked reduction of the serum C3 and C4. Osteoblasts established in culture from a bone biopsy showed abnormal morphology on electron microscopy and increased proliferation when cultured with benzoylbenzoyl-ATP and 1,25-dihydroxyvitamin D, contrasting with findings in normal osteoblasts in culture...
2017: Bone Research
https://www.readbyqxmd.com/read/28325781/hete-signals-through-g-protein-coupled-receptor-gpr75-gq-to-affect-vascular-function-and-trigger-hypertension
#8
Victor Garcia, Ankit Gilani, Brian Shkolnik, Varunkumar Pandey, Frank F Zhang, Rambabu Dakarapu, Shyam K Gandham, N R Reddy, Joan P Graves, Artiom Gruzdev, Darryl C Zeldin, Jorge H Capdevila, John R Falck, Michal L Schwartzman
Rationale: 20-Hydroxyeicosatetraenoic acid (20-HETE), one of the principle cytochrome P450 (CYP) eicosanoids, is a potent vasoactive lipid whose vascular effects include stimulation of smooth muscle contractility, migration and proliferation, as well as endothelial cell dysfunction and inflammation. Increased levels of 20-HETE in experimental animals and in humans are associated with hypertension, stroke, myocardial infarction and vascular diseases. Objective: To date, a receptor/binding site for 20-HETE has been implicated based on the use of specific agonists and antagonists...
March 21, 2017: Circulation Research
https://www.readbyqxmd.com/read/28324017/a-novel-selective-bombesin-receptor-subtype-3-agonist-promotes-weight-loss-in-male-diet-induced-obese-rats-with-circadian-rhythm-change
#9
Yasunori Nio, Natsu Hotta, Minoru Maruyama, Kenichi Hamagami, Toshimi Nagi, Masaaki Funata, Junichi Sakamoto, Masanori Nakakariya, Nobuyuki Amano, Tomohiro Okawa, Yasuyoshi Arikawa, Shinobu Sasaki, Shoki Okuda, Shizuo Kasai, Yugo Habata, Yasutaka Nagisa
Bombesin receptor subtype 3 (BRS-3) is an orphan G-protein-coupled receptor. Based on the obese phenotype of male BRS-3-deficient mice, BRS-3 has been considered an attractive target for obesity treatment. Here, we developed a novel selective BRS-3 agonist (Compound-A) and evaluated its anti-obesity effects. Compound-A showed anorectic effects and enhanced energy expenditure in diet-induced obese (DIO)-F344 rats. Moreover, repeated oral administration of Compound-A for 7 days resulted in a significant body weight reduction in DIO-F344 rats...
March 16, 2017: Endocrinology
https://www.readbyqxmd.com/read/28322790/short-chain-fatty-acids-gpr41-and-gpr43-ligands-inhibit-tnf-%C3%AE-induced-mcp-1-expression-by-modulating-p38-and-jnk-signaling-pathways-in-human-renal-cortical-epithelial-cells
#10
Mamiko Kobayashi, Daisuke Mikami, Hideki Kimura, Kazuko Kamiyama, Yukie Morikawa, Seiji Yokoi, Kenji Kasuno, Naoki Takahashi, Takanobu Taniguchi, Masayuki Iwano
Short-chain fatty acids (SCFAs), such as acetate, propionate, and butyrate, are produced predominantly by gut microbiota fermentation of dietary fiber. SCFAs are newly identified as endogenous ligands of two orphan G protein-coupled receptors, GPR41 and GPR43, which have the potential to modulate inflammation. Therefore, GPR41 and GPR43 may mediate the link between the gut microbiome status and various disease conditions including renal inflammation. This study aimed at investigating whether SCFAs activate GPR41 and GPR43, and thereby exert anti-inflammatory effects in human renal cortical epithelial cells (HRCEs) as a main component of kidney tissue...
March 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28319268/developmental-changes-in-feeding-behaviors-of-infant-chimpanzees-at-mahale-tanzania-implications-for-nutritional-independence-long-before-cessation-of-nipple-contact
#11
Takuya Matsumoto
OBJECTIVES: Weaning of chimpanzees is considered to occur at 4-5-years-old with complete cessation of nipple contact and timing of reconception calculated by inter-birth interval minus gestation length. This is also the basis of "early weaning" in humans (i.e., approximately 2.5-years-old). However, recent studies of the survival of orphans and the first molar (M1) eruption in wild chimpanzees have predicted that infants move toward nutritional independence at 3-years-old. Therefore, this study aimed to investigate ontogeny of feeding behavior at around 3-years-old in wild infant chimpanzees...
March 20, 2017: American Journal of Physical Anthropology
https://www.readbyqxmd.com/read/28318945/identification-and-structure-activity-relationships-of-quinoline-tertiary-alcohol-modulators-of-ror%C3%AE-t
#12
David A Kummer, Maxwell D Cummings, Marta Abad, Joseph Barbay, Glenda Castro, Ronald Wolin, Kevin D Kreutter, Umar Maharoof, Cynthia Milligan, Rachel Nishimura, Joan Pierce, Celine Schalk-Hihi, John Spurlino, Maud Urbanski, Hariharan Venkatesan, Aihua Wang, Craig Woods, Xiaohua Xue, James P Edwards, Anne M Fourie, Kristi Leonard
A high-throughput screen of the ligand binding domain of the nuclear receptor retinoic acid-related orphan receptor gamma t (RORγt) employing a thermal shift assay yielded a quinoline tertiary alcohol hit. Optimization of the 2-, 3- and 4-positions of the quinoline core using structure-activity relationships and structure-based drug design methods led to the discovery of a series of modulators with improved RORγt inhibitory potency and inverse agonism properties.
February 21, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28317799/a-first-insight-into-the-genetic-diversity-of-mycobacterium-tuberculosis-in-veracruz-mexico
#13
Raquel Almaraz-Velasco, Daniela Munro-Rojas, Javier Fuentes-Domínguez, Raquel Muñiz-Salazar, Maria Angélica Ibarra-Estela, Alma Delia Guevara-Méndez, Rosa Icela Chaparro-Martinez, Monserrat Perez-Navarro, Roberto Zenteno-Cuevas
OBJECTIVE/BACKGROUND: Tuberculosis (TB) remains one of the most important infectious diseases. Although Mexico is one of the Latin American countries with the largest contribution to these statistics, there are few reports that describe the genotypic characteristics of TB. The aim of this study was to use the MIRU-VNTR-24 loci to analyze the genetic diversity of M. tuberculosis circulating in the state of Veracruz, Mexico. METHODS: Here, we analyze by MIRU-VNTR-24 loci 80 clinical isolates from individuals with confirmed TB from Veracruz México, also clinical and epidemiological variables were recovered and analyzed...
January 2017: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/28317348/-expression-and-significance-of-wingless-type-mmtv-integration-site-family-member-5a-receptor-tyrosine-kinase-like-orphan-receptor-2-in-the-rat-dental-follicle
#14
Wang Liping, Li Boqi, Wang Qi, Tie Xiaomin, Liu Yishan
OBJECTIVE: To observe the expression of wingless-type MMTV integration site family, member 5A (Wnt5A)/receptor tyrosine kinase-like orphan receptor 2 (Ror2) signal in the dental follicle cells during the normal eruption of the teeth as well as to explore the relationship between the expression of dental follicle cells and the formation of mature osteoclasts and eruption of the teeth. METHODS: The mandibulars of 1-13 d old SD rats were separated to observe the growth and develop-ment of the teeth and alveolar bone through hematoxylin-eosin(HE) staining...
August 1, 2016: Hua Xi Kou Qiang Yi Xue za Zhi, Huaxi Kouqiang Yixue Zazhi, West China Journal of Stomatology
https://www.readbyqxmd.com/read/28315972/emotional-health-and-self-esteem-among-adolescents-in-malaysian-orphanages
#15
Marjan Mohammadzadeh, Hamidin Awang, Hayati Kadir Shahar, Suriani Ismail
This study aimed to assess the prevalence and risk factors of depression, anxiety, stress and low self-esteem among institutional Malaysian adolescents. This cross-sectional descriptive study included 287 adolescents aged 12-18 years living in six selected orphan homes. Study's instruments included Socio-demographic questionnaire, validated Malay version of Depression Anxiety Stress Scale-21 and Rosenberg Self-Esteem Scale. The findings revealed that 85.2, 80.1 and 84.7% of participants had depression, anxiety and stress respectively...
March 18, 2017: Community Mental Health Journal
https://www.readbyqxmd.com/read/28314976/enzyme-replacement-therapy-and-beyond-in-memoriam-roscoe-o-brady-m-d-1923-2016
#16
REVIEW
Markus Ries
Lysosomal storage disorders are strong candidates for the development of specific innovative therapies. The discovery of enzyme deficiencies is an important milestone in understanding the underlying cause of disease. Being able to replace the first missing enzyme in a lysosomal storage required three decades of dedicated research. Successful drug development for lysosomal storage disorders was fostered by the U.S. Orphan Drug Act. Various optimization strategies have the potential to overcome the current limitations of enzyme replacement therapies...
March 17, 2017: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/28314853/activation-of-the-orphan-g-protein-coupled-receptor-gpr27-by-surrogate-ligands-promotes-%C3%AE-arrestin-2-recruitment
#17
Nadine Dupuis, Celine Laschet, Delphine Franssen, Martyna Szpakowska, Julie Gilissen, Pierre Geubelle, Arvind Soni, Anne-Simone Parent, Bernard Pirotte, Andy Chevigne, Jean-Claude Twizere, Julien Hanson
G protein-coupled receptors are the most important drug targets for human diseases. An important number of them remain devoid of confirmed ligands. GPR27 is one of these orphan receptors, characterized by a high level of conservation among vertebrates and a predominant expression in the central nervous system. In addition, it has recently been linked to insulin secretion. However, the absence of endogenous or surrogate ligands for GPR27 complicates the examination of its biological function. Our aim was to validate GPR27 signaling pathways and therefore we sought to screen a diversity oriented synthesis library to identify GPR27-specific surrogate agonists...
March 17, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28303834/trends-in-spoligotype-patterns-of-mycobacterium-tuberculosis-strains-in-central-india
#18
Prabha Desikan, Devendra S Chauhan, Nikita Panwalkar, Pragya Sharma, Priyanka Yadav
This study aims to understand trends in spoligotype patterns of Mycobacterium tuberculosis (MTB) in Central India. Elucidation of these trends may provide baseline information to understand the transmission dynamics of strains of MTB in the region. Spoligotyping was carried out on 340 MTB strains isolated from clinical samples received from 2007 to 2011. The prevalence of ST26/CAS1_Del, ST11/EAI3_IND, ST288/CAS2, ST25/CAS1_Del and Beijing lineages showed waxing and waning trends. ST26/CAS1_Del and ST11/EAI3_IND lineages were consistently present and were predominant...
January 2017: Indian Journal of Medical Microbiology
https://www.readbyqxmd.com/read/28301168/deletion-of-a-histone-acetyltransferase-leads-to-the-pleiotropic-activation-of-natural-products-in-metarhizium-robertsii
#19
Aili Fan, Wubin Mi, Zhiguo Liu, Guohong Zeng, Peng Zhang, Youcai Hu, Weiguo Fang, Wen-Bing Yin
Histone deacetylation normally decreases the gene expression in organisms. By genome-wide deletions of epigenetic regulators in entomopathogenic fungus Metarhizium robertsii, unexpected activations of orphan secondary metabolite genes have been found upon the disruption of a histone acetyltransferase (HAT) gene Hat1. This led to the characterization of 11 new natural products, including eight isocoumarin derivatives meromusides A-H and two nonribosomal peptides meromutides A and B. Therefore, disruption of HAT represents a new approach to mine chemical diversity from fungi...
March 16, 2017: Organic Letters
https://www.readbyqxmd.com/read/28300844/il-27-triggers-il-10-production-in-th17-cells-via-a-c-maf-ror%C3%AE-t-blimp-1-signal-to-promote-the-progression-of-endometriosis
#20
Kai-Kai Chang, Li-Bing Liu, Li-Ping Jin, Bing Zhang, Jie Mei, Hui Li, Chun-Yan Wei, Wen-Jie Zhou, Xiao-Yong Zhu, Jun Shao, Da-Jin Li, Ming-Qing Li
Endometriosis is an estrogen-dependent inflammatory disease. The anti-inflammatory cytokine IL-10 is also increased in endometriosis. IL-10 production by Th17 cells is critical for limiting autoimmunity and inflammatory responses. However, the mechanism of inducing IL-10-producing Th17 cells is still largely unknown. The present study investigated the differentiation mechanism and role of IL-10-producing Th17 cells in endometriosis. Here, we report that IL-10(+)Th17 cells are significantly increased in the peritoneal fluid of women with endometriosis, along with an elevation of IL-27, IL-6 and TGF-β...
March 16, 2017: Cell Death & Disease
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