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Nadia Mohd Effendy, Mohd Fadhli Khamis, Ahmad Nazrun Shuid
BACKGOUND: Labisia pumila (LP) is a popular herb used by women over the past few decades. This herb has shown potentials as an alternative agent for treatment and prevention of postmenopausal osteoporosis. It was observed in previous studies that supplementation to ovariectomized rats were associated with increased bone antioxidative enzymes and reduced lipid peroxidation activity. It had also improved bone formation markers in ovariectomized rats. This study aimed to evaluate the effects of giving different forms of LP extracts on the trabecular bone microarchitecture of ovariectomised rats...
October 21, 2016: Journal of X-ray Science and Technology
Samuel B Pattle, Natasa Utjesanovic, Athena Togo, Lucy Wells, Brendan Conn, Hannah Monaghan, Elizabeth Junor, Ingolfur Johannessen, Kate Cuschieri, Simon Talbot
Squamous cell carcinomas of the hypopharynx (HPSCC) and oropharynx (OPSCC) have markedly different patient outcomes. Differences in HPV prevalence between these two patient groups may account for some of this difference, but other molecular markers of prognosis or pathological phenotype have not been established. Copy number gain of oncogenes is a well-established molecular change contributing to HNSCC development. Quantitative PCR was used to explore copy number gains of specific genes (3q - PIK3CA, TP63; 11q13...
October 17, 2016: Genes, Chromosomes & Cancer
Andrew Wood, Fiona Young, James Morrison, Brendon I Conn
We present a case of sclerosing odontogenic carcinoma (SOC) occurring on the hard palate of a 43-year-old female. The tumor presented as an asymptomatic firm swelling and histopathologically was characterized by widely dispersed nests and cords of bland cells infiltrating between hyalinized collagen fibers. Prominent perineural and intraneural invasion and erosion of bone was noted. The tumor cells showed staining with antibodies to pan-cytokeratin (PanCK), cytokeratin 19 (CK19), cytokeratin 5/6 (CK5/6), cytokeratin 14 (CK14), p63 and E-cadherin, but no staining with antibodies to carcinoembryonic antigen (CEA), cytokeratin 7 (CK7), cytokeratin 20 (CK20), estrogen receptor (ER), progesterone receptor (PR) or S100...
July 25, 2016: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Bryan P Fitzgerald, Kelly M Conn, Joanne Smith, Andrew Walker, Amy L Parkhill, James E Hilbert, Elizabeth A Luebbe, Richard T Moxley Iii
Myotonic dystrophy (DM) and facioscapulohumeral muscular dystrophy (FSHD) are the two most common adult muscular dystrophies and have progressive and often disabling manifestations. Higher levels of medication adherence lead to better health outcomes, especially important to patients with DM and FSHD because of their multisystem manifestations and complexity of care. However, medication adherence has not previously been studied in a large cohort of DM type 1 (DM1), DM type 2 (DM2), and FSHD patients. The purpose of our study was to survey medication adherence and disease manifestations in patients enrolled in the NIH-supported National DM and FSHD Registry...
October 12, 2016: Journal of Neurology
Lorraine J Phillips, Gregory F Petroski, Vicki S Conn, Marybeth Brown, Emily Leary, Linda Teri, Sheryl Zimmerman
This study examined the relationships between individual and environmental factors and physical activity, and between physical activity and functional limitations and disability in residential care/assisted living (RC/AL) residents. Participants completed questionnaires and physical performance tests, and wore the Fitbit Motion Tracker® to capture physical activity. Model fit was analyzed using two-level path models with residents nested within RC/AL settings. Model parameters were estimated using the MPlus robust maximum likelihood method...
October 4, 2016: Journal of Applied Gerontology: the Official Journal of the Southern Gerontological Society
Amanda B Longo, Wendy E Ward
Higher intakes of polyunsaturated fatty acids (PUFA) are associated with benefits at several skeletal sites in postmenopausal women and in rodent models, but the effect of PUFA-containing oils on tooth-supporting alveolar bone of the mandible has not been studied. Moreover, direct comparison of the effect of flaxseed oil (a source of alpha-linolenic acid (ALA)) and menhaden oil (a source of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) is unknown. One-month old female Sprague-Dawley rats (n = 48) were randomized to and fed a diet containing flaxseed oil or menhaden oil from one to six months of age...
2016: Nutrients
Daniel J Foster, Jermaine M Wilson, Daniel H Remke, M Suhaib Mahmood, M Jashim Uddin, Jürgen Wess, Sachin Patel, Lawrence J Marnett, Colleen M Niswender, Carrie K Jones, Zixiu Xiang, Craig W Lindsley, Jerri M Rook, P Jeffrey Conn
Muscarinic receptors represent a promising therapeutic target for schizophrenia, but the mechanisms underlying the antipsychotic efficacy of muscarinic modulators are not well understood. Here, we report that activation of M4 receptors on striatal spiny projection neurons results in a novel form of dopaminergic regulation resulting in a sustained depression of striatal dopamine release that is observed more than 30 min after removal of the muscarinic receptor agonist. Furthermore, both the M4-mediated sustained inhibition of dopamine release and the antipsychotic-like efficacy of M4 activators were found to require intact signaling through CB2 cannabinoid receptors...
September 21, 2016: Neuron
Michael D Grannan, Catharine A Mielnik, Sean P Moran, Robert W Gould, Jacob Ball, Zhuoyan Lu, Michael Bubser, Amy J Ramsey, Masahito Abe, Hyekyung P Cho, Kellie D Nance, Anna L Blobaum, Colleen M Niswender, P Jeffrey Conn, Craig W Lindsley, Carrie K Jones
Abnormalities in the signaling of the N-methyl-d-aspartate subtype of the glutamate receptor (NMDAR) within cortical and limbic brain regions are thought to underlie many of the complex cognitive and affective symptoms observed in individuals with schizophrenia. The M1 muscarinic acetylcholine receptor (mAChR) subtype is a closely coupled signaling partner of the NMDAR. Accumulating evidence suggests that development of selective positive allosteric modulators (PAMs) of the M1 receptor represent an important treatment strategy for the potential normalization of disruptions in NMDAR signaling in patients with schizophrenia...
October 5, 2016: ACS Chemical Neuroscience
Mary-Anne Aarts, Nardhana Sivapalan, Seyed-Ehsan Nikzad, Kristin Serodio, Sanjeev Sockalingam, Lesley Gotlib Conn
BACKGROUND: Failure to follow-up post-bariatric surgery has been associated with higher postoperative complications, lower percentage weight loss and poorer nutrition. OBJECTIVE: This study aimed to understand the patient follow-up experience in order to optimize follow-up care within a comprehensive bariatric surgery program. METHODS: Qualitative telephone interviews were conducted in patients who underwent surgery through a publically funded multidisciplinary bariatric surgery program in 2011, in Ontario, Canada...
September 7, 2016: Obesity Surgery
Rebecca L Gibeault, Kristen L Conn, Michael D Bildersheim, Luis M Schang
Although ICP4 is the only essential transcription activator of herpes simplex virus 1 (HSV-1), its mechanisms of action are still only partially understood. We and others propose a model in which HSV-1 genomes are chromatinized as a cellular defense to inhibit HSV-1 transcription. To counteract silencing, HSV-1 would have evolved proteins that prevent or destabilize chromatinization to activate transcription. These proteins should act as HSV-1 transcription activators. We have shown that HSV-1 genomes are organized in highly dynamic nucleosomes and that histone dynamics increase in cells infected with wild type HSV-1...
August 2016: PLoS Pathogens
C Bazley, P Vink
This paper discusses the importance of including time in environmental design and the challenges facing environmental design now and in the future. Research shows that important factors for studying the effects of environments are time, body movement, control and sensory variability. There are many ways to incorporate time into the design and it is dependent on the type of environmental design. Research also suggests that discomfort in restrictive environments, e.g., in an airplane or automobile are strongly related long periods of inactivity and lack of sensory stimulation...
August 12, 2016: Work: a Journal of Prevention, Assessment, and Rehabilitation
Nihad Abdallah, Rory Conn, Abdel Latif Marini
Physical health monitoring is an integral part of caring for patients with mental health problems. It is proven that serious physical health problems are more common among patients with severe mental health illness (SMI), this monitoring can be challenging and there is a need for improvement. The project aimed at improving the physical health monitoring among patients with SMI who are receiving antipsychotic medications. The improvement process focused on ensuring there is a good communication with general practitioners (GPs) as well as patient's education and education of care home staff...
2016: BMJ Quality Improvement Reports
Vicki S Conn, Janet S Carpenter, Carol Estwing Ferrans, Janet L Larson, Ann Marie McCarthy
No abstract text is available yet for this article.
September 2016: Western Journal of Nursing Research
Alexander R Geanes, Hykeyung P Cho, Kellie D Nance, Kevin M McGowan, P Jeffrey Conn, Carrie K Jones, Jens Meiler, Craig W Lindsley
This Letter describes a ligand-based virtual screening campaign utilizing SAR data around the M5 NAMs, ML375 and VU6000181. Both QSAR and shape scores were employed to virtually screen a 98,000-member compound library. Neither approach alone proved productive, but a consensus score of the two models identified a novel scaffold which proved to be a modestly selective, but weak inhibitor (VU0549108) of the M5 mAChR (M5 IC50=6.2μM, M1-4 IC50s>10μM) based on an unusual 8-((1,3,5-trimethyl-1H-pyrazol-4-yl)sulfonyl)-1-oxa-4-thia-8-azaspiro[4,5]decane scaffold...
September 15, 2016: Bioorganic & Medicinal Chemistry Letters
Kimberly O Cameron, Daniel W Kung, Amit S Kalgutkar, Ravi G Kurumbail, Russell Miller, Christopher T Salatto, Jessica Ward, Jane M Withka, Samit K Bhattacharya, Markus Boehm, Kris A Borzilleri, Janice A Brown, Matthew Calabrese, Nicole L Caspers, Emily Cokorinos, Edward L Conn, Matthew S Dowling, David J Edmonds, Heather Eng, Dilinie P Fernando, Richard Frisbie, David Hepworth, James Landro, Yuxia Mao, Francis Rajamohan, Allan R Reyes, Colin R Rose, Tim Ryder, Andre Shavnya, Aaron C Smith, Meihua Tu, Angela C Wolford, Jun Xiao
Adenosine monophosphate-activated protein kinase (AMPK) is a protein kinase involved in maintaining energy homeostasis within cells. On the basis of human genetic association data, AMPK activators were pursued for the treatment of diabetic nephropathy. Identification of an indazole amide high throughput screening (HTS) hit followed by truncation to its minimal pharmacophore provided an indazole acid lead compound. Optimization of the core and aryl appendage improved oral absorption and culminated in the identification of indole acid, PF-06409577 (7)...
September 8, 2016: Journal of Medicinal Chemistry
Lisa M Zychowski, Amy Logan, Mary Ann Augustin, Alan L Kelly, Alexandru Zabara, James A O'Mahony, Charlotte E Conn, Mark A E Auty
Milk has been used commercially as a carrier for phytosterols, but there is limited knowledge on the effect of added plant sterols on the properties of the system. In this study, phytosterols dispersed in milk fat at a level of 0.3 or 0.6% were homogenized with an aqueous dispersion of whey protein isolate (WPI). The particle size, morphology, ζ-potential, and stability of the emulsions were investigated. Emulsion crystallization properties were examined through the use of differential scanning calorimetry (DSC) and Synchrotron X-ray scattering at both small and wide angles...
August 31, 2016: Journal of Agricultural and Food Chemistry
Michael R Wood, Meredith J Noetzel, James C Tarr, Alice L Rodriguez, Atin Lamsal, Sichen Chang, Jarrett J Foster, Emery Smith, Peter Chase, Peter S Hodder, Darren W Engers, Colleen M Niswender, Nicholas J Brandon, Michael W Wood, Mark E Duggan, P Jeffrey Conn, Thomas M Bridges, Craig W Lindsley
This Letter describes the chemical optimization of a novel series of M4 PAMs based on a non-enolizable ketone core, identified from an MLPCN functional high-throughput screen. The HTS hit was potent, selective and CNS penetrant; however, the compound was highly cleared in vitro and in vivo. SAR provided analogs for which M4 PAM potency and CNS exposure were maintained; yet, clearance remained high. Metabolite identification studies demonstrated that this series was subject to rapid, and near quantitative, reductive metabolism to the corresponding secondary alcohol metabolite that was devoid of M4 PAM activity...
September 1, 2016: Bioorganic & Medicinal Chemistry Letters
Felicia Leccia, Marie Batisse-Lignier, Isabelle Sahut-Barnola, Pierre Val, A-Marie Lefrançois-Martinez, Antoine Martinez
Adrenal cortex tumors are divided into benign forms, such as primary hyperplasias and adrenocortical adenomas (ACAs), and malignant forms or adrenocortical carcinomas (ACCs). Primary hyperplasias are rare causes of adrenocorticotropin hormone-independent hypercortisolism. ACAs are the most common type of adrenal gland tumors and they are rarely "functional," i.e., producing steroids. When functional, adenomas result in endocrine disorders, such as Cushing's syndrome (hypercortisolism) or Conn's syndrome (hyperaldosteronism)...
2016: Frontiers in Endocrinology
Hanna Remde, Anna Dietz, Rebecca Emeny, Anna Riester, Annette Peters, Tonia de Las Heras Gala, Cornelia Then, Jochen Seissler, Felix Beuschlein, Martin Reincke, Marcus Quinkler
CONTEXT: Copeptin and high-sensitive C-reactive protein (hsCRP) are biomarkers associated with increased mortality in patients with cardiovascular and cerebrovascular disease as well as in the general population. No data exist regarding these markers in patients with primary aldosteronism. OBJECTIVE: To evaluate copeptin and hsCRP levels as cardiovascular risk markers in primary aldosteronism patients. METHODS: A total of 113 primary aldosteronism patients (64% male) from two centers of the prospective German Conn's Registry were identified, for whom a full data set and blood samples at baseline and follow-up (14 ± 3...
October 2016: Journal of Hypertension
Colleen M Niswender, Carrie K Jones, Xin Lin, Michael Bubser, Analisa Thompson Gray, Anna L Blobaum, Darren W Engers, Alice L Rodriguez, Matthew T Loch, J Scott Daniels, Craig W Lindsley, Corey R Hopkins, Jonathan A Javitch, P Jeffrey Conn
Metabotropic glutamate receptor 4 (mGlu4) is emerging as a potential therapeutic target for numerous central nervous system indications, including Parkinson's disease (PD). As the glutamate binding sites among the eight mGlu receptors are highly conserved, modulation of receptor activity via allosteric sites within the receptor transmembrane domains using positive and negative allosteric modulators (PAMs and NAMs, respectively) has become a common strategy. We and others have used PAMs targeting mGlu4 to show that potentiation of receptor signaling induces antiparkinsonian activity in a variety of PD animal models, including haloperidol-induced catalepsy and 6-hydroxydopamine-induced lesion...
September 21, 2016: ACS Chemical Neuroscience
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