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https://www.readbyqxmd.com/read/28541457/bumped-kinase-inhibitor-gastrointestinal-exposure-is-necessary-to-treat-cryptosporidium-infection
#1
Samuel L M Arnold, Ryan Choi, Matthew A Hulverson, Deborah A Schaefer, Sumiti Vinayak, Rama S R Vidadala, Molly C McCloskey, Grant R Whitman, Wenlin Huang, Lynn K Barrett, Kayode K Ojo, Erkang Fan, Dustin J Maly, Michael W Riggs, Boris Striepen, Wesley C Van Voorhis
There is a substantial need for novel therapeutics to combat the widespread impact caused by Crytosporidium infection. However, there is a lack of knowledge on which drug pharmacokinetic characteristics are key to generate an in vivo response specifically if systemic drug exposure is crucial for in vivo efficacy. To identify which pharmacokinetic properties are correlated with in vivo efficacy, we generated physiologically based pharmacokinetic (PBPK) models to simulate systemic and gastrointestinal (GI) drug concentrations for a series of bumped kinase inhibitors (BKI) that have nearly identical in vitro potency against Cryptosporidium but display divergent pharmacokinetic properties...
May 24, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28541267/choroidal-melanoma-sector-melanocytosis-and-retinal-pigment-epithelial-microdetachments-in-birt-hogg-dub%C3%A3-syndrome
#2
Charlotte L Marous, Molly R Marous, R Joel Welch, Jerry A Shields, Carol L Shields
PURPOSE: Birt-Hogg-Dubé Syndrome (BHDS) is a rare autosomal dominant condition that can predispose patients to numerous cutaneous fibrofolliculomas and other cutaneous lesions, pulmonary cysts with spontaneous pneumothorax, and multifocal renal tumors and cancer. The genetic mutations responsible for BHDS are related to tumor suppression and the mammalian target of rapamycin (mTOR) pathway. Previous reports of the ocular findings in BHDS include eyelid fibrofolliculomas, "flecked chorioretinopathy," and one report of choroidal melanoma...
May 22, 2017: Retinal Cases & Brief Reports
https://www.readbyqxmd.com/read/28541155/characterization-of-aminoaciduria-and-hypoaminoacidemia-in-dogs-with-hepatocutaneous-syndrome
#3
John P Loftus, Sharon A Center, John M Lucy, Julie A Stanton, Sean P McDonough, Jeanine Peters-Kennedy, Kenneth A Arceneaux, Molly A Bechtold, Courtney L Bennett, Christina A Bradbury, Martha G Cline, Deborah L Hall-Fonte, Julie F Hammer-Landrum, Janice L Huntingford, Jennifer Marshall, Kristopher S Sharpe, Jessica L Redin, Samuel T Selva, Tomasina A Lucia
OBJECTIVE To characterize aminoaciduria and plasma amino acid concentrations in dogs with hepatocutaneous syndrome (HCS). ANIMALS 20 client-owned dogs of various breeds and ages. PROCEDURES HCS was definitively diagnosed on the basis of liver biopsy specimens (n = 12), gross and histologic appearance of skin lesions (4), and examination of skin and liver biopsy specimens (2) and presumptively diagnosed on the basis of cutaneous lesions with compatible clinicopathologic and hepatic ultrasonographic (honeycomb or Swiss cheese pattern) findings (2)...
June 2017: American Journal of Veterinary Research
https://www.readbyqxmd.com/read/28540527/alignment-of-inducible-vascular-progenitor-cells-on-a-micro-bundle-scaffold-improves-cardiac-repair-following-myocardial-infarction
#4
Anurag Jamaiyar, Weiguo Wan, Vahagn Ohanyan, Molly Enrick, Danielle Janota, Devan Cumpston, Hokyung Song, Kelly Stevanov, Christopher L Kolz, Tatev Hakobyan, Feng Dong, Bi-Min Zhang Newby, William M Chilian, Liya Yin
Ischemic heart disease is still the leading cause of death even with the advancement of pharmaceutical therapies and surgical procedures. Early vascularization in the ischemic heart is critical for a better outcome. Although stem cell therapy has great potential for cardiovascular regeneration, the ideal cell type and delivery method of cells have not been resolved. We tested a new approach of stem cell therapy by delivery of induced vascular progenitor cells (iVPCs) grown on polymer micro-bundle scaffolds in a rat model of myocardial infarction...
July 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28537726/hot-spotting-with-thermal-scanning-a-ligand-and-structure-independent-assessment-of-target-ligandability
#5
Molly Chilton, Ben Clennell, Fredrik Edfeldt, Stefan Geschwindner
Evaluating the ligandability of a protein target is a key component when defining hit-finding strategies or to prioritize amongst drug targets. Computational as well as biophysical approaches based on nuclear magnetic resonance (NMR) fragment screening are powerful approaches, but suffer from specific constraints that limit their usage. Here, we demonstrate the applicability of high-throughput thermal scanning (HTTS) as a simple and generic biophysical fragment screening method to reproduce assessments from NMR-based screening...
May 24, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28535804/housing-first-and-harm-reduction-a-rapid-review-and-document-analysis-of-the-us-and-canadian-open-access-literature
#6
REVIEW
Dennis P Watson, Valery Shuman, James Kowalsky, Elizabeth Golembiewski, Molly Brown
BACKGROUND: Housing First is an evidence-based practice intended to serve chronically homeless individuals with co-occurring serious mental illness and substance use disorders. Despite housing active substance users, harm reduction is an often-overlooked element during the Housing First implementation process in real-world settings. In this paper, we explore the representation of the Housing First model within the open-access scholarly literature as a potential contributing factor for this oversight...
May 23, 2017: Harm Reduction Journal
https://www.readbyqxmd.com/read/28534406/relationships-between-exciton-dissociation-and-slow-recombination-within-znse-cds-and-cdse-cds-dot-in-rod-heterostructures
#7
Amanda N Grennell, James K Utterback, Orion M Pearce, Molly B Wilker, Gordana Dukovic
Type-II and quasi type-II heterostructure nanocrystals are known to exhibit extended excited-state lifetimes compared to their single material counterparts because of reduced wavefunction overlap between the electron and hole. However, due to fast and efficient hole trapping and non-uniform morphologies, the photophysics of dot-in-rod heterostructures are more rich and complex than this simple picture. Using transient absorption spectroscopy, we observe that the behavior of electrons in the CdS "rod" or "bulb" regions of non-uniform ZnSe/CdS and CdSe/CdS dot-in-rods is similar regardless of the "dot" material, which supports previous work demonstrating that hole trapping and particle morphology drive electron dynamics...
May 23, 2017: Nano Letters
https://www.readbyqxmd.com/read/28533246/5-aminopyrazole-4-carboxamide-based-compounds-prevent-the-growth-of-cryptosporidium-parvum
#8
Wenlin Huang, Ryan Choi, Matthew A Hulverson, Zhongsheng Zhang, Molly C McCloskey, Deborah A Schaefer, Grant R Whitman, Lynn K Barrett, Rama Subba Rao Vidadala, Michael W Riggs, Dustin J Maly, Wesley C Van Voorhis, Kayode K Ojo, Erkang Fan
Cryptosporidium parvum calcium-dependent protein kinase 1 (CpCDPK1) is a promising target for drug development against cryptosporidiosis. We report a series of low nanomolar CpCDPK1 5-aminopyrazole-4-carboxamide (AC) scaffold inhibitors that also potently inhibit C. parvum growth in vitro Correlation between anti-CpCDPK1 and C. parvum growth inhibition, as previously reported for pyrazolopyrimidines, was not apparent. Nonetheless, lead AC-compounds exhibited a substantial reduction of parasite burden in the neonatal mouse cryptosporidiosis model when dosed at 25 mg/kg...
May 22, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28533056/white-matter-damage-after-traumatic-brain-injury-a-role-for-damage-associated-molecular-patterns
#9
REVIEW
Molly Braun, Kumar Vaibhav, Nancy M Saad, Sumbul Fatima, John R Vender, Babak Baban, Md Nasrul Hoda, Krishnan M Dhandapani
Traumatic brain injury (TBI) is a leading cause of mortality and long-term morbidity worldwide. Despite decades of pre-clinical investigation, therapeutic strategies focused on acute neuroprotection failed to improve TBI outcomes. This lack of translational success has necessitated a reassessment of the optimal targets for intervention, including a heightened focus on secondary injury mechanisms. Chronic immune activation correlates with progressive neurodegeneration for decades after TBI; however, significant challenges remain in functionally and mechanistically defining immune activation after TBI...
May 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28531276/impact-of-vitamin-a-and-carotenoids-on-the-risk-of-tuberculosis-progression
#10
Omowunmi Aibana, Molly F Franke, Chuan-Chin Huang, Jerome T Galea, Roger Calderon, Zibiao Zhang, Mercedes C Becerra, Emily R Smith, Alayne G Ronnenberg, Carmen Contreras, Rosa Yataco, Leonid Lecca, Megan B Murray
Background: Low and deficient levels of vitamin A are common in low and middle income countries where tuberculosis (TB) burden is high. We assessed the impact of baseline levels of vitamins A and carotenoids on TB disease risk. Methods: We conducted a case-control study nested within a longitudinal cohort of household contacts of pulmonary TB cases in Lima, Peru. We defined cases as HIV-negative household contacts with blood samples who developed TB disease at least 15 days after enrollment of index patient...
May 20, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28530678/the-complex-genetics-of-hypoplastic-left-heart-syndrome
#11
Xiaoqin Liu, Hisato Yagi, Shazina Saeed, Abha S Bais, George C Gabriel, Zhaohan Chen, Kevin A Peterson, You Li, Molly C Schwartz, William T Reynolds, Manush Saydmohammed, Brian Gibbs, Yijen Wu, William Devine, Bishwanath Chatterjee, Nikolai T Klena, Dennis Kostka, Karen L de Mesy Bentley, Madhavi K Ganapathiraju, Phillip Dexheimer, Linda Leatherbury, Omar Khalifa, Anchit Bhagat, Maliha Zahid, William Pu, Simon Watkins, Paul Grossfeld, Stephen A Murray, George A Porter, Michael Tsang, Lisa J Martin, D Woodrow Benson, Bruce J Aronow, Cecilia W Lo
Congenital heart disease (CHD) affects up to 1% of live births. Although a genetic etiology is indicated by an increased recurrence risk, sporadic occurrence suggests that CHD genetics is complex. Here, we show that hypoplastic left heart syndrome (HLHS), a severe CHD, is multigenic and genetically heterogeneous. Using mouse forward genetics, we report what is, to our knowledge, the first isolation of HLHS mutant mice and identification of genes causing HLHS. Mutations from seven HLHS mouse lines showed multigenic enrichment in ten human chromosome regions linked to HLHS...
May 22, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28530427/a-meta-analytic-review-of-the-association-between-pubertal-timing-and-psychopathology-in-adolescence-are-there-sex-differences-in-risk
#12
Josie M Ullsperger, Molly A Nikolas
Research examining pubertal timing effects on psychopathology has emphasized that a subset of adolescents, particularly females, who experience early pubertal maturation relative to their peers appear to be at increased risk for psychopathology. The aims of the current meta-analysis were (a) to quantify the magnitude of early pubertal timing effects on psychopathology, (b) to examine potential moderators of pubertal timing effects (sex, psychopathology domain, sample composition, measurement method, and mean sample age), and (c) to examine findings in relation to hypotheses in the extant literature explicating differential pubertal timing effects for early versus late youth and males versus females...
May 22, 2017: Psychological Bulletin
https://www.readbyqxmd.com/read/28529162/cirrhosis-presenting-as-cutaneous-calciphylaxis
#13
Connie R Shi, Molly Plovanich, Susan Burgin
No abstract text is available yet for this article.
May 18, 2017: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28528414/tissue-contaminant-burdens-in-san-francisco-estuary-white-sturgeon-acipenser-transmontanus-implications-for-population-recovery
#14
Deke T Gundersen, Steven C Zeug, Robert B Bringolf, Joseph Merz, Zachary Jackson, Molly A H Webb
The San Francisco Estuary (SFE) is heavily influenced by anthropogenic activities, including historic and chronic contaminant inputs. These contaminants can adversely affect SFE fish populations, particularly white sturgeon, because they are a benthic dwelling, long-lived species. We measured a suite of metals and organic contaminants in liver and gonad tissues of 25 male and 32 female white sturgeon as well as several physiological indicators of sturgeon health. Most sturgeon (68% of males and 83% of females) were estimated to be between 13 and 17 years of age...
May 20, 2017: Archives of Environmental Contamination and Toxicology
https://www.readbyqxmd.com/read/28527671/inferences-about-moral-character-moderate-the-impact-of-consequences-on-blame-and-praise
#15
Jenifer Z Siegel, Molly J Crockett, Raymond J Dolan
Moral psychology research has highlighted several factors critical for evaluating the morality of another's choice, including the detection of norm-violating outcomes, the extent to which an agent caused an outcome, and the extent to which the agent intended good or bad consequences, as inferred from observing their decisions. However, person-centered accounts of moral judgment suggest that a motivation to infer the moral character of others can itself impact on an evaluation of their choices. Building on this person-centered account, we examine whether inferences about agents' moral character shape the sensitivity of moral judgments to the consequences of agents' choices, and agents' role in the causation of those consequences...
May 17, 2017: Cognition
https://www.readbyqxmd.com/read/28526814/kras-and-gnas-co-mutation-in-metastatic-low-grade-appendiceal-mucinous-neoplasm-lamn-to-the-ovaries-a-practical-role-for-next-generation-sequencing
#16
Daniel R Matson, Jin Xu, Laura Huffman, Lisa Barroilhet, Molly Accola, William M Rehrauer, Paul Weisman
BACKGROUND Low-grade appendiceal mucinous neoplasms (LAMNs) are cytologically low-grade tumors of the appendix and are a frequent cause of pseudomyxoma peritonei. They can become a diagnostic challenge when they metastasize to the ovaries, where they may mimic primary ovarian mucinous tumors. CASE REPORT We report the case of a patient with very large bilateral ovarian mucinous tumors and a concurrent minute LAMN incidentally discovered in a grossly normal appendix. A primary ovarian tumor was suspected, but histological analysis of the ovaries suggested an appendiceal origin...
May 20, 2017: American Journal of Case Reports
https://www.readbyqxmd.com/read/28526733/discovery-and-optimization-of-hkt288-a-cadherin-6-targeting-adc-for-the-treatment-of-ovarian-and-renal-cancer
#17
Carl U Bialucha, Scott D Collins, Xiao Li, Parmita Saxena, Xiamei Zhang, Clemens Dürr, Bruno LaFont, Pierric Prieur, Yeonju Shim, Rebecca Mosher, David Lee, Lance Ostrom, Tiancen Hu, Sanela Bilic, Ivana Liric Rajlic, Vladimir Capka, Wei Jiang, Joel P Wagner, GiNell Elliott, Artur Veloso, Jessica C Piel, Meghan M Flaherty, Keith G Mansfield, Emily K Meseck, Tina Rubic-Schneider, Anne Serdakowski London, William R Tschantz, Markus Kurz, Duc Nguyen, Aaron Bourret, Matthew J Meyer, Jason E Faris, Mary J Janatpour, Vivien W Chan, Nicholas C Yoder, Kalli C Catcott, Molly A McShea, Xiuxia Sun, Hui Gao, Juliet Williams, Francesco Hofmann, Jeffrey A Engelman, Seth A Ettenberg, William R Sellers, Emma Lees
Despite an improving therapeutic landscape, significant challenges remain in treating the majority of advanced ovarian and renal cancer patients. We identified the cell-cell adhesion molecule cadherin-6 (CDH6) as a lineage gene having significant differential expression in ovarian and kidney cancer. HKT288 is an optimized CDH6-targeting DM4-based antibody drug conjugate (ADC) developed for the treatment of these diseases. Our study provides mechanistic evidence supporting the importance of linker choice for optimal anti-tumor activity and highlights CDH6 as a novel antigen for biotherapeutic development...
May 19, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28526485/improving-the-sexual-health-of-young-people-with-mobility-impairments-challenges-and-recommendations
#18
Molly Secor-Turner, Barbara J McMorris, Peter Scal
INTRODUCTION: This mixed-method study (a) describes challenges to providing sexual health services to youth with mobility impairments from the perspective of health care providers and experts and (b) describes and compares sexual health-related experiences of youth with mobility impairments. METHOD: Secondary data analysis of My Path, a study focused on the transition to adulthood for youth with mobility impairments. Using an exploratory sequential design, qualitative data (n = 10) were analyzed using systematic content analysis followed by quantitative analysis of survey data (N = 337)...
May 16, 2017: Journal of Pediatric Health Care
https://www.readbyqxmd.com/read/28526242/factors-predicting-complications-after-sacral-neuromodulation-in-children
#19
Molly E Fuchs, Peter L Lu, Stephanie J Vyrostek, Steven Teich, Seth A Alpert
OBJECTIVES: To identify if any pre-operative variable are associated with post-operative complications after pediatric sacral neuromodulation (SNM). METHODS: A review of all patients undergoing SNM with an implantable pulse generator at our institution was performed. Post-operative infection, lead migration, lead breakage and need for reoperation were recorded in a prospective database. We collected demographic information and indication for the procedure. We defined indication for procedure as either primarily bowel, or primarily bladder symptoms...
May 16, 2017: Urology
https://www.readbyqxmd.com/read/28526088/assessment-of-parasitological-findings-in-heartworm-infected-beagles-treated-with-advantage-multi%C3%A2-for-dogs-10-imidacloprid%C3%A2-%C3%A2-2-5-moxidectin-and-doxycycline
#20
Molly D Savadelis, Cameon M Ohmes, Joe A Hostetler, Terry L Settje, Robert Zolynas, Michael T Dzimianski, Andrew R Moorhead
BACKGROUND: Anecdotal reports support the position that the adulticidal heartworm treatment utilizing doxycycline and Advantage Multi®/Advocate® for Dogs (10% imidacloprid + 2.5% moxidectin) has successfully converted antigen-positive dogs to antigen-negative. To date, no controlled experimental studies have demonstrated the adulticidal efficacy of this treatment regimen. The aim of this study was to evaluate the parasitological and clinical efficacy of Advantage Multi® for Dogs (IMD + MOX) and doxycycline in heartworm-infected beagles...
May 19, 2017: Parasites & Vectors
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