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https://www.readbyqxmd.com/read/27925688/rare-deleterious-pard3-variants-in-the-apkc-binding-region-are-implicated-in-the-pathogenesis-of-human-cranial-neural-tube-defects-via-disrupting-apical-tight-junction-formation
#1
Xiaoli Chen, Yu An, Yonghui Gao, Liu Guo, Lei Rui, Hua Xie, Mei Sun, Siv Lam Hung, Xiaoming Sheng, Jizhen Zou, Yihua Bao, Hongyan Guan, Bo Niu, Zandong Li, Richard H Finnell, James F Gusella, Bai-Lin Wu, Ting Zhang
Increasing evidence that mutation of planar cell polarity (PCP) genes contributes to human cranial NTD susceptibility prompted us to hypothesize that rare variants of genes in the core apical-basal polarity (ABP) pathway are risk factors for cranial NTDs. In this study, we screened for rare genomic variation of PARD3 in 138 cranial NTD cases and 274 controls. Overall, the rare deleterious variants of PARD3 were significantly associated with increased risk for cranial NTDs (11/138 vs.7/274, p<0.05, OR = 3...
December 7, 2016: Human Mutation
https://www.readbyqxmd.com/read/27922695/effects-of-five-candidate-laxatives-derived-from-liriope-platyphylla-on-the-5-ht-receptor-signaling-pathway-in-three-cell-types-present-in-the-transverse-colon
#2
Ji Eun Kim, Eun Kyoung Koh, Sung Hwa Song, Ji Eun Sung, Hyun Ah Lee, Hong Gu Lee, Young Whan Choi, Dae Youn Hwang
The laxative effects of aqueous extract of Liriope platyphylla (AEtLP) on loperamide (Lop)‑induced constipation have been reported; however, the key compounds and the mechanism underlying these effects remain unclear. Therefore, the laxative effects of five candidates derived from L. platyphylla: Diosgenin (DG), 5-hydroxymethylfurfural (5-HMF), adenosine (AD), hydroxypropyl cellulose (HPC) and uridine (UD) were investigated by examining the alteration of G protein α (Gα) expression, protein kinase C (PKC) phosphorylation and inositol triphosphate (IP3) concentration levels in the 5-hydroxytryptamine (5‑HT; serotonin) receptor signaling pathway...
December 5, 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27916716/effects-of-a-non-competitive-n-methyl-d-aspartate-nmda-antagonist-tiletamine-in-adult-zebrafish
#3
Tatiana O Kolesnikova, Sergey L Khatsko, Vadim A Shevyrin, Yuri Yu Morzherin, Allan V Kalueff
Tiletamine is a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist chemically related to ketamine and phencyclidine. A common veterinary anesthetic drug, tiletamine is currently a Schedule III controlled substance. This compound exerts sedative effects in humans and animals, also having an abuse potential, toxicity and dissociative hallucinogenic properties clinically. However, the neurotropic profile of tiletamine remains poorly understood, necessitating novel models and in-vivo screens, including non-mammalian species...
December 1, 2016: Neurotoxicology and Teratology
https://www.readbyqxmd.com/read/27916424/caring-for-children-with-medical-complexity-perspectives-of-primary-care-providers
#4
Carolyn C Foster, Rita Mangione-Smith, Tamara D Simon
OBJECTIVE: To describe typical care experiences and key barriers and facilitators to caring for children with medical complexity (CMC) from the perspective of community primary care providers (PCPs). STUDY DESIGN: PCPs participating in a randomized controlled trial of a care-coordination intervention for CMC were sent a 1-time cross-sectional survey that asked PCPs to (1) describe their experiences with caring for CMC; (2) identify key barriers affecting their ability to care for CMC; and (3) prioritize facilitators enhancing their ability to provide care coordination for CMC...
December 2, 2016: Journal of Pediatrics
https://www.readbyqxmd.com/read/27914948/triazolopyridine-ethers-as-potent-orally-active-mglu2-positive-allosteric-modulators-for-treating-schizophrenia
#5
Mendi A Higgins, Lawrence R Marcin, F Christopher Zusi, Robert Gentles, Min Ding, Bradley C Pearce, Amy Easton, Walter A Kostich, Matthew A Seager, Clotilde Bourin, Linda J Bristow, Kim A Johnson, Regina Miller, John Hogan, Valerie Whiterock, Michael Gulianello, Meredith Ferrante, Yanling Huang, Adam Hendricson, Andrew Alt, John E Macor, Joanne J Bronson
Triazolopyridine ethers with mGlu2 positive allosteric modulator (PAM) activity are disclosed. The synthesis, in vitro activity, and metabolic stability data for a series of analogs is provided. The effort resulted in the discovery of a potent, selective, and brain penetrant lead molecule BMT-133218 ((+)-7m). After oral administration at 10mg/kg, BMT-133218 demonstrated full reversal of PCP-stimulated locomotor activity and prevented MK-801-induced working memory deficits in separate mouse models. Also, reversal of impairments in executive function were observed in rat set-shifting studies at 3 and 10mg/kg (p...
November 14, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27913685/novel-biomarkers-in-kidney-disease-roles-for-cilia-wnt-signalling-and-atmin-in-polycystic-kidney-disease
#6
REVIEW
Paraskevi Goggolidou, Patricia D Wilson
Biomarkers, the measurable indicators of biological conditions, are fast becoming a popular approach in providing information to track disease processes that could lead to novel therapeutic interventions for chronic conditions. Inherited, chronic kidney disease affects millions of people worldwide and although pharmacological treatments exist for some conditions, there are still patients whose only option is kidney dialysis and kidney transplantation. In the past 10 years, certain chronic kidney diseases have been reclassified as ciliopathies...
December 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27911818/planar-cell-polarity-signaling-in-the-uterus-directs-appropriate-positioning-of-the-crypt-for-embryo-implantation
#7
Jia Yuan, Jeeyeon Cha, Wenbo Deng, Amanda Bartos, Xiaofei Sun, Hsin-Yi Henry Ho, Jean-Paul Borg, Terry P Yamaguchi, Yingzi Yang, Sudhansu K Dey
Blastocyst implantation is a complex process requiring coordination of a dynamic sequence of embryo-uterine interactions. Blood vessels enter the uterus from the mesometrium, demarcating the uterus into mesometrial (M) and antimesometrial (AM) domains. Implantation occurs along the uterine longitudinal axis within specialized implantation chambers (crypts) that originate within the evaginations directed from the primary lumen toward the AM domain. The morphological orientation of crypts in rodent uteri was recognized more than a century ago, but the mechanism remained unknown...
November 28, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27904052/recent-advances-in-the-diagnosis-of-pneumocystis-pneumonia
#8
Yinggai Song, Yi Ren, Xiaowen Wang, Ruoyu Li
Pneumocystis jirovecii is a prototypical opportunistic pathogen, causing an asymptomatic or mild infection in normal hosts and fulminating pneumonia (Pneumocystis pneumonia, PCP) in immunocompromised hosts. PCP is a leading cause of morbidity and mortality in immunocompromised patients such as AIDS patients. Microscopic detection of cysts and trophic forms of P. jirovecii in respiratory secretions is simple and useful but may underestimate the P. jirovecii infection. Conventional polymerase chain reaction (PCR) and nested PCR increase the sensitivity and specificity to identify PCP and provide an approach to discriminate PCP from pulmonary P...
2016: Medical Mycology Journal
https://www.readbyqxmd.com/read/27903126/potential-evolution-of-neurosurgical-treatment-paradigms-for-craniopharyngioma-based-on-genomic-and-transcriptomic-characteristics
#9
Leslie C Robinson, Sandro Santagata, Todd C Hankinson
The recent genomic and transcriptomic characterization of human craniopharyngiomas has provided important insights into the pathogenesis of these tumors and supports that these tumor types are distinct entities. Critically, the insights provided by these data offer the potential for the introduction of novel therapies and surgical treatment paradigms for these tumors, which are associated with high morbidity rates and morbid conditions. Mutations in the CTNNB1 gene are primary drivers of adamantinomatous craniopharyngioma (ACP) and lead to the accumulation of β-catenin protein in a subset of the nuclei within the neoplastic epithelium of these tumors...
December 2016: Neurosurgical Focus
https://www.readbyqxmd.com/read/27903124/diagnosis-and-management-of-craniopharyngiomas-in-the-era-of-genomics-and-targeted-therapy
#10
Juan Carlos Martinez-Gutierrez, Megan R D'Andrea, Daniel P Cahill, Sandro Santagata, Fred G Barker, Priscilla K Brastianos
Craniopharyngiomas are rare intracranial neoplasms that pose clinical challenges due to their location adjacent to vital structures. The authors have previously shown high mutation rates of BRAF V600E in papillary craniopharyngioma and of CTNNB1 in adamantinomatous craniopharyngioma. These activating driver mutations are potential therapeutic targets, and the authors have recently reported a significant response to BRAF/MEK inhibition in a patient with multiply recurrent PCP. As these targetable mutations warrant prospective research, the authors will be conducting a national National Cancer Institute-sponsored multicenter clinical trial to investigate BRAF/MEK inhibition in the treatment of craniopharyngioma...
December 2016: Neurosurgical Focus
https://www.readbyqxmd.com/read/27900010/a-novel-mutation-of-the-fat2-gene-in-spinal-meningioma
#11
Genshu Tate, Koji Kishimoto, Toshiyuki Mitsuya
Meningiomas may be classified as neurofibromin 2 (NF2)-associated and non-NF2 meningiomas depending on the presence or absence of molecular alterations in the NF2 gene. One of the characteristic histological features of meningiomas is the whorl formation of neoplastic arachnoid cells. NF2 is a human homolog of the Drosophila gene, Merlin (Mer). In humans, NF2 is the gene responsible for the disease neurofibromatosis type II, which results in the development of brain tumors, including acoustic neurinoma and meningioma...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27896618/loss-of-liver-kinase-b1-causes-planar-polarity-defects-in-cochlear-hair-cells-in-mice
#12
Yuqin Men, Aizhen Zhang, Liwen Zhang, Yecheng Jin, Zhishuo Wang, Jing Zhao, Xiaolin Yu, Jian Zhang, Jiangang Gao
The tumor suppressor gene liver kinase B1 (LKB1), also called STK11, encodes a serine/threonine kinase. LKB1 plays crucial roles in cell differentiation, proliferation, and polarity. In this study, LKB1 conditional knockout mice (LKB1(Pax2) CKO mice) were generated using Pax2-Cre mice to investigate the function of LKB1 in inner ear hair cells during early embryonic period. LKB1(Pax2) CKO mice died perinatally. Immunofluorescence and scanning electron microscopy revealed that stereociliary bundles in LKB1(Pax2) CKO mice were clustered and misoriented, respectively...
November 28, 2016: Frontiers of Medicine
https://www.readbyqxmd.com/read/27896552/primary-care-physicians-willingness-to-prescribe-hiv-pre-exposure-prophylaxis-for-people-who-inject-drugs
#13
E Jennifer Edelman, Brent A Moore, Sarah K Calabrese, Gail Berkenblit, Chinazo Cunningham, Viraj Patel, Karran Phillips, Jeanette M Tetrault, Minesh Shah, David A Fiellin, Oni Blackstock
Pre-exposure prophylaxis for HIV (PrEP) is recommended for people who inject drugs (PWID). Despite their central role in disease prevention, willingness to prescribe PrEP to PWID among primary care physicians (PCPs) is largely understudied. We conducted an online survey (April-May 2015) of members of a society for academic general internists regarding PrEP. Among 250 respondents, 74% (n = 185) of PCPs reported high willingness to prescribe PrEP to PWID. PCPs were more likely to report high willingness to prescribe PrEP to all other HIV risk groups (p's < 0...
November 28, 2016: AIDS and Behavior
https://www.readbyqxmd.com/read/27893293/prevelence-of-primary-aldosteronism-in-an-urban-hypertensive-population
#14
Sandi-Jo Galati, Khadeen C Cheesman, Ryan Springer-Miller, Sarah M Hopkins, Lawrence Krakoff, Emilia Bagiella, Rachel A Zhuk, Tiffany K Ying, Chelsey Amer, Michael K Boyajian, W B Inabnet, Alice C Levine
OBJECTIVE: To determine the prevalence of primary aldosteronism (PA) in hypertensive patients presenting to the primary care clinic at The Mount Sinai Hospital, regardless of the degree of hypertension and to identify clinical criteria that should prompt screening for PA. METHODS: An aldosterone:renin ratio (ARR, cutoff ≥20, with plasma aldosterone concentration [PAC] ≥10 and suppressed renin) was used to prospectively screen 296 hypertensive patients (blood pressure [BP] ≥140/90) over the age of 18 from August 2012 through May 2013...
November 2016: Endocrine Practice
https://www.readbyqxmd.com/read/27890947/profile-of-pneumocystis-infection-in-a-tertiary-care-institute-in-north-india
#15
Ravinder Kaur, Pragyan Swagatika Panda, Richa Dewan
CONTEXT: Pneumocystis jirovecii pneumonia (PcP) is still remains a common opportunistic disease in human immunodeficiency virus (HIV) infected individuals. Study on PcP in developing countries are scarce. AIMS: To study the occurrence of P. jirovecii infection in clinically suspected individuals in a tertiary care institute. SETTINGS AND DESIGN: Retrospective study conducted in a tertiary care hospital. MATERIALS AND METHODS: Two years data regarding respiratory sample analysis, HIV status, and cluster of differentiation 4 (CD4) cell count of clinically suspected pneumocystis infection patients with known/unknown HIV status were analyzed...
July 2016: Indian Journal of Sexually Transmitted Diseases
https://www.readbyqxmd.com/read/27890517/correlates-of-receiving-a-recommendation-for-more-physical-activity-from-a-primary-care-provider
#16
Samuel N Forjuoh, Chanam Lee, Jaewoong Won, Samuel D Towne, Suojin Wang, Marcia G Ory
INTRODUCTION: Primary care providers (PCPs) are strategically positioned to communicate with their overweight/obese patients about positive behavioral changes to improve health and functioning. Demographic and behavioral correlates of receiving a recommendation for more physical activity (PA) from a PCP by overweight/obese patients were assessed. METHODS: Community-dwelling adults aged ≥50 years from four Texas cities who were seen by a family physician in a primary care clinic were surveyed from October 2013 to June 2014...
November 24, 2016: American Journal of Preventive Medicine
https://www.readbyqxmd.com/read/27887664/translating-sickle-cell-guidelines-into-practice-for-primary-care-providers-with-project-echo
#17
Lisa M Shook, Christina B Farrell, Karen A Kalinyak, Stephen C Nelson, Brandon M Hardesty, Angeli G Rampersad, Kay L Saving, Wanda J Whitten-Shurney, Julie A Panepinto, Russell E Ware, Lori E Crosby
BACKGROUND: Approximately 100,000 persons with sickle cell disease (SCD) live in the United States, including 15,000 in the Midwest. Unfortunately, many patients experience poor health outcomes due to limited access to primary care providers (PCPs) who are prepared to deliver evidence-based SCD care. Sickle Treatment and Outcomes Research in the Midwest (STORM) is a regional network established to improve care and outcomes for individuals with SCD living in Indiana, Illinois, Michigan, Minnesota, Ohio, and Wisconsin...
2016: Medical Education Online
https://www.readbyqxmd.com/read/27884458/risk-of-carotid-stroke-after-chiropractic-care-a-population-based-case-crossover-study
#18
J David Cassidy, Eleanor Boyle, Pierre Côté, Sheilah Hogg-Johnson, Susan J Bondy, Scott Haldeman
BACKGROUND: Chiropractic manipulation is a popular treatment for neck pain and headache, but may increase the risk of cervical artery dissection and stroke. Patients with carotid artery dissection can present with neck pain and/or headache before experiencing a stroke. These are common symptoms seen by both chiropractors and primary care physicians (PCPs). We aimed to assess the risk of carotid artery stroke after chiropractic care by comparing association between chiropractic and PCP visits and subsequent stroke...
November 21, 2016: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
https://www.readbyqxmd.com/read/27882775/association-between-availability-of-care-providers-and-healthcare-utilizations-among-adults-with-asthma
#19
Minchul Kim, Carl V Asche, William Tillis, Jinma Ren
BACKGROUND: Limited accessibility to providers may delay appropriate control of asthma exacerbations. The objective of our study is to estimate the contributors to the hospital/emergency department (ED) visits among adults with asthma focusing on the availability of healthcare providers. METHODS: We conducted a pooled cross-sectional analysis using the 2011-2013 Asthma Call-Back Survey linked with 2012-2016 Area Health Resource Files. We employed multivariable logistic regression with dichotomous outcomes of hospitalization and ED visits...
December 2, 2016: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/27875771/nemo-like-kinase-1-nlk1-and-paraxial-protocadherin-papc-cooperatively-control-xenopus-gastrulation-through-regulation-of-wnt-planar-cell-polarity-pcp-signaling
#20
Rahul Kumar, Anja Ciprianidis, Susanne Theiß, Herbert Steinbeißer, Lilian T Kaufmann
The Wnt/planar cell polarity (PCP) pathway directs cell migration during vertebrate gastrulation and is essential for proper embryonic development. Paraxial protocadherin (PAPC, Gene Symbol pcdh8.2) is an important activator of Wnt/PCP signaling during Xenopus gastrulation, but how PAPC activity is controlled is incompletely understood. Here we show that Nemo-like kinase 1 (Nlk1), an atypical mitogen-activated protein (MAP) kinase, physically associates with the C-terminus of PAPC. This interaction mutually stabilizes both proteins by inhibiting polyubiquitination...
October 28, 2016: Differentiation; Research in Biological Diversity
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