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Pearl Therapeutics

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https://www.readbyqxmd.com/read/28503985/diagnostic-and-therapeutic-management-of-a-first-unprovoked-seizure-in-children-and-adolescents-with-a-focus-on-the-revised-diagnostic-criteria-for-epilepsy
#1
Arnold J Sansevere, Jennifer Avalone, Lauren Doyle Strauss, Archana A Patel, Anna Pinto, Maya Ramachandran, Ivan Sanchez Fernandez, Ann M Bergin, Amir Kimia, Phillip L Pearl, Tobias Loddenkemper
By definition, unprovoked seizures are not precipitated by an identifiable factor, such as fever or trauma. A thorough history and physical examination are essential to caring for pediatric patients with a potential first unprovoked seizure. Differential diagnosis, EEG, neuroimaging, laboratory tests, and initiation of treatment will be reviewed. Treatment is typically initiated after 2 unprovoked seizures, or after 1 seizure in select patients with distinct epilepsy syndromes. Recent expansion of the definition of epilepsy by the ILAE allows for the diagnosis of epilepsy to be made after the first seizure if the clinical presentation and supporting diagnostic studies suggest a greater than 60% chance of a second seizure...
January 1, 2017: Journal of Child Neurology
https://www.readbyqxmd.com/read/28503347/wasting-of-extensor-digitorum-brevis-as-a-decisive-preoperative-clinical-indicator-of-lumbar-canal-stenosis-a-single-center-prospective-cohort-study
#2
S Munakomi, B M Kumar
BACKGROUND: The dilemma in managing patients with low back ache lies in differentiating radiculopathy from lumbar canal stenosis. This has a huge bearing in patients being planned for surgical intervention as underperforming leads to failed back syndrome whereas over-doing leads to instability. There still remains a loophole in clinically diagnosing lumbar canal stenosis. AIM: We opt to utilize a simple bedside clinical examination in routinely assessing patients presenting with low back ache in ruling out underlying canal stenosis...
September 2016: Annals of Medical and Health Sciences Research
https://www.readbyqxmd.com/read/28462602/-big-data-approaches-for-novel-anti-cancer-drug-discovery
#3
Graeme Benstead-Hume, Sarah K Wooller, Frances M G Pearl
The development of improved cancer therapies is frequently cited as an urgent unmet medical need. Recent advances in platform technologies and the increasing availability of biological 'big data' are providing an unparalleled opportunity to systematically identify the key genes and pathways involved in tumorigenesis. The discoveries made using these new technologies may lead to novel therapeutic interventions. Areas covered: The authors discuss the current approaches that use 'big data' to identify cancer drivers...
June 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28457677/research-pearls-the-significance-of-statistics-and-perils-of-pooling-part-3-pearls-and-pitfalls-of-meta-analyses-and-systematic-reviews
#4
Joshua D Harris, Jefferson C Brand, Mark P Cote, Aman Dhawan
Within the health care environment, there has been a recent and appropriate trend towards emphasizing the value of care provision. Reduced cost and higher quality improve the value of care. Quality is a challenging, heterogeneous, variably defined concept. At the core of quality is the patient's outcome, quantified by a vast assortment of subjective and objective outcome measures. There has been a recent evolution towards evidence-based medicine in health care, clearly elucidating the role of high-quality evidence across groups of patients and studies...
April 27, 2017: Arthroscopy: the Journal of Arthroscopic & related Surgery
https://www.readbyqxmd.com/read/28425994/modulating-the-therapeutic-response-of-tumours-to-dietary-serine-and-glycine-starvation
#5
Oliver D K Maddocks, Dimitris Athineos, Eric C Cheung, Pearl Lee, Tong Zhang, Niels J F van den Broek, Gillian M Mackay, Christiaan F Labuschagne, David Gay, Flore Kruiswijk, Julianna Blagih, David F Vincent, Kirsteen J Campbell, Fatih Ceteci, Owen J Sansom, Karen Blyth, Karen H Vousden
The non-essential amino acids serine and glycine are used in multiple anabolic processes that support cancer cell growth and proliferation (reviewed in ref. 1). While some cancer cells upregulate de novo serine synthesis, many others rely on exogenous serine for optimal growth. Restriction of dietary serine and glycine can reduce tumour growth in xenograft and allograft models. Here we show that this observation translates into more clinically relevant autochthonous tumours in genetically engineered mouse models of intestinal cancer (driven by Apc inactivation) or lymphoma (driven by Myc activation)...
April 19, 2017: Nature
https://www.readbyqxmd.com/read/28411234/phenotype-of-gaba-transaminase-deficiency
#6
Mary Kay Koenig, Ryan Hodgeman, James J Riviello, Wendy Chung, Jennifer Bain, Claudia A Chiriboga, Kazushi Ichikawa, Hitoshi Osaka, Megumi Tsuji, K Michael Gibson, Penelope E Bonnen, Phillip L Pearl
OBJECTIVE: We report a case series of 10 patients with γ-aminobutyric acid (GABA)-transaminase deficiency including a novel therapeutic trial and an expanded phenotype. METHODS: Case ascertainment, literature review, comprehensive evaluations, and long-term treatment with flumazenil. RESULTS: All patients presented with neonatal or early infantile-onset encephalopathy; other features were hypotonia, hypersomnolence, epilepsy, choreoathetosis, and accelerated linear growth...
April 14, 2017: Neurology
https://www.readbyqxmd.com/read/28323876/pim1-minicircle-as-a-therapeutic-treatment-for-myocardial-infarction
#7
Nan Liu, Bingyan J Wang, Kathleen M Broughton, Roberto Alvarez, Sailay Siddiqi, Rebeca Loaiza, Nicky Nguyen, Pearl Quijada, Natalie Gude, Mark A Sussman
PIM1, a pro-survival gene encoding a serine/ threonine kinase, influences cell proliferation and survival. Modification of cardiac progenitor cells (CPCs) or cardiomyocytes with PIM1 using a lentivirus-based delivery method showed long-term improved cardiac function after myocardial infarction (MI). However, lentivirus based delivery methods have stringent FDA regulation with respect to clinical trials. To provide an alternative and low risk PIM1 delivery method, this study examined the use of a non-viral modified plasmid-minicircle (MC) as a vehicle to deliver PIM1 into mouse CPCs (mCPCs) in vitro and the myocardium in vivo...
2017: PloS One
https://www.readbyqxmd.com/read/28323755/cyp2b6-genotype-directed-dosing-is-required-for-optimal-efavirenz-exposure-in-children-3-36-months-with-hiv-infection
#8
Carolyn Bolton Moore, Edmund V Capparelli, Pearl Samson, Mutsa Bwakura-Dangarembizi, Patrick Jean-Philippe, Carol Worrell, Barbara Heckman, Lynette Purdue, Stephen A Spector, Alex Benns, William Borkowsky, Amy Loftis, Elizabeth Hawkins, Carole Wallis, Ellen G Chadwick
OBJECTIVES: To determine safety-specific, efficacy-specific and genotypic-specific dose requirements of efavirenz (EFV) in children aged 3 to less than 36 months with HIV infection. DESIGN: IMPAACT P1070 was a 24-week prospective cohort trial of EFV (as open capsules) and two nucleoside reverse transcriptase inhibitors in children with HIV infection 3 to less than 36 months without tuberculosis (Cohort 1). METHODS: CYP2B6 G516T genotype was determined, and intensive pharmacokinetics was performed at week 2...
May 15, 2017: AIDS
https://www.readbyqxmd.com/read/28249547/clinical-presentations-of-below-knee-bone-metastases-a-case-series
#9
Matthew Choi, Linda Probyn, Leigha Rowbottom, Rachel McDonald, Adam Bobrowski, Stephanie Chan, Pearl Zaki, Angela Turner, Edward Chow
Bone metastases are a common complication of advanced malignancy; however, presentation of below-the-knee metastases, particularly affecting the fibula and tibia, are infrequently observed in both the clinical setting and the literature, and present a therapeutic challenge to patients and physicians alike. Due to the weight-bearing capacity of bones below-the-knee, the disruption of the structural and functional integrity of these bones can reduce mobility and thus quality of life. Treatment options for these patients include surgery, radiotherapy, and/or chemotherapy...
February 10, 2017: Annals of Palliative Medicine
https://www.readbyqxmd.com/read/28213850/gamma-hydroxybutyrate-ghb-content-in-hair-samples-correlates-negatively-with-age-in-succinic-semialdehyde-dehydrogenase-deficiency
#10
S S Johansen, X Wang, D Sejer Pedersen, P L Pearl, J-B Roullet, G R Ainslie, K R Vogel, K M Gibson
Gamma-hydroxybutyrate (GHB) is a drug of abuse, an approved therapeutic for narcolepsy, an agent employed for facilitation of sexual assault, as well as a biomarker of succinic semialdehyde dehydrogenase deficiency (SSADHD). Our laboratory seeks to identify surrogate biomarkers in SSADHD that can shed light on the developmental course of this neurometabolic disease. Since GHB may be quantified in hair as a potential surrogate to identify victims of drug-related assault, we have opted to examine its level in SSADHD...
February 18, 2017: JIMD Reports
https://www.readbyqxmd.com/read/28166438/supplementation-of-spirulina-arthrospira-platensis-improves-lifespan-and-locomotor-activity-in-paraquat-sensitive-dj-1%C3%AE-%C3%AE-93-flies-a-parkinson-s-disease-model-in-drosophila-melanogaster
#11
Ajay Kumar, Pearl K Christian, Komal Panchal, B R Guruprasad, Anand K Tiwari
Spirulina (Arthrospira platensis) is a cyanobacterium (blue-green alga) consumed by humans and other animals because of its nutritional values and pharmacological properties. Apart from high protein contents, it also contains high levels of antioxidant and anti-inflammatory compounds, such as carotenoids, β-carotene, phycocyanin, and phycocyanobilin, indicating its possible pharmaco-therapeutic utility. In the present study using DJ-1β(Δ93) flies, a Parkinson's disease model in Drosophila, we have demonstrated the therapeutic effect of spirulina and its active component C-phycocyanin (C-PC) in the improvement of lifespan and locomotor behavior...
September 3, 2017: Journal of Dietary Supplements
https://www.readbyqxmd.com/read/28139826/neonatal-nonepileptic-myoclonus-is-a-prominent-clinical-feature-of-kcnq2-gain-of-function-variants-r201c-and-r201h
#12
Sarah B Mulkey, Bruria Ben-Zeev, Joost Nicolai, John L Carroll, Sabine Grønborg, Yong-Hui Jiang, Nishtha Joshi, Megan Kelly, David A Koolen, Mohamad A Mikati, Kristen Park, Phillip L Pearl, Ingrid E Scheffer, Rebecca C Spillmann, Maurizio Taglialatela, Silvia Vieker, Sarah Weckhuysen, Edward C Cooper, Maria Roberta Cilio
OBJECTIVE: To analyze whether KCNQ2 R201C and R201H variants, which show atypical gain-of-function electrophysiologic properties in vitro, have a distinct clinical presentation and outcome. METHODS: Ten children with heterozygous, de novo KCNQ2 R201C or R201H variants were identified worldwide, using an institutional review board (IRB)-approved KCNQ2 patient registry and database. We reviewed medical records and, where possible, interviewed parents and treating physicians using a structured, detailed phenotype inventory focusing on the neonatal presentation and subsequent course...
March 2017: Epilepsia
https://www.readbyqxmd.com/read/28103265/rabbit-model-of-human-gliomas-implications-for-intra-arterial-drug-delivery
#13
Huamin Qin, Miroslaw Janowski, Monica S Pearl, Izabela Malysz-Cymborska, Shen Li, Charles G Eberhart, Piotr Walczak
The prognosis for malignant brain tumors remains poor despite a combination of surgery, radiotherapy, and chemotherapy. This is partly due to the blood-brain barrier, a major obstacle that prevents therapeutic agents from effectively reaching the tumor. We have recently developed a method for precise and predictable opening of the blood-brain barrier via the intra-arterial administration of mannitol, a hyperosmolar agent, in a rabbit model, whose vascular anatomy facilitates the use of standard interventional neuroradiology techniques and devices...
2017: PloS One
https://www.readbyqxmd.com/read/27992199/contribution-of-shape-and-charge-to-the-inhibition-of-a-family-gh99-endo-%C3%AE-1-2-mannanase
#14
Marija Petricevic, Lukasz F Sobala, Pearl Z Fernandes, Lluís Raich, Andrew J Thompson, Ganeko Bernardo-Seisdedos, Oscar Millet, Sha Zhu, Matthieu Sollogoub, Jesús Jiménez-Barbero, Carme Rovira, Gideon J Davies, Spencer J Williams
Inhibitor design incorporating features of the reaction coordinate and transition-state structure has emerged as a powerful approach for the development of enzyme inhibitors. Such inhibitors find use as mechanistic probes, chemical biology tools, and therapeutics. Endo-α-1,2-mannosidases and endo-α-1,2-mannanases, members of glycoside hydrolase family 99 (GH99), are interesting targets for inhibitor development as they play key roles in N-glycan maturation and microbiotal yeast mannan degradation, respectively...
January 25, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/27864823/aberrant-mtor-signaling-and-disrupted-autophagy-the-missing-link-in-potential-vigabatrin-associated-ocular-toxicity
#15
K R Vogel, G R Ainslie, P L Pearl, K M Gibson
Vigabatrin (VGB; γ-vinylGABA) is a unique antiepileptic directly elevating CNS GABA via inactivation of the GABA metabolic enzyme GABA-transaminase. VGB is effective in treating infantile spasms, a rare seizure disorder associated with significant morbidity. The potential for unexplained bilateral constriction of the visual field associated with VGB intervention can severely limit its temporal utility. Removal of this potential adverse effect with adjuvant intervention(s) would represent a significant advance in epilepsy therapeutics...
April 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27810436/different-optimal-alignment-but-equivalent-functional-outcomes-in-medial-and-lateral-unicompartmental-knee-arthroplasty
#16
Jelle P van der List, Harshvardhan Chawla, Jordan C Villa, Andrew D Pearle
INTRODUCTION: Several differences in kinematics, functional outcomes and alignment exist between medial and lateral unicompartmental knee arthroplasty (UKA). Therefore, the purpose of this study was (1) to compare functional outcomes between both procedures with the hypothesis that both have equivalent outcomes and (2) to assess the role of preoperative and postoperative alignment on functional outcomes in both procedures. METHODS: Patients who underwent UKA were included when overall function - using Western Ontario and McMaster Universities Arthritis (WOMAC) score - and joint awareness - using Forgotten Joint Score (FJS) - were available preoperatively and at minimum two-year follow-up...
December 2016: Knee
https://www.readbyqxmd.com/read/27796434/novel-encapsulation-improves-recovery-of-probiotic-strains-in-fecal-samples-of-human-volunteers
#17
Volker Mai, Sheldon Waugh, Doratha Byrd, Damion Simpson, Maria Ukhanova
Probiotic supplements can contribute to maintaining health and ameliorating various disease symptoms. Probiotics can be delivered in many forms with crucial differences in their survival during gastrointestinal (GI) passage. Previously, a novel encapsulation, Probiotic Pearls™ Acidophilus, Integrative Therapeutics, LLC, USA (Pearls), was shown to increase survival in vitro after exposure to gastric conditions. Here, we compare fecal recovery in human volunteers consuming Pearls or a conventional hard-shelled gelatin capsule...
February 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/27718775/breaking-the-cycle-of-hair-breakage-pearls-for-the-management-of-acquired-trichorrhexis-nodosa
#18
Alessandra Haskin, Shawn G Kwatra, Crystal Aguh
Acquired trichorrhexis nodosa is a common cause of hair loss for patients of all ethnicities. It is especially prevalent in black patients with tightly curled hair types and can present unique diagnostic and therapeutic challenges due to structural differences in these hair types and the combination of various hair care and styling practices that contribute to hair damage. While scalp biopsies can help rule out other etiologies of hair loss, there is a paucity of histologic findings in acquired trichorrhexis nodosa, making this primarily a clinical diagnosis...
October 10, 2016: Journal of Dermatological Treatment
https://www.readbyqxmd.com/read/27660707/into-the-clinic-talimogene-laherparepvec-t-vec-a-first-in-class-intratumoral-oncolytic-viral-therapy
#19
Hasan Rehman, Ann W Silk, Michael P Kane, Howard L Kaufman
With the recent regulatory approval of Talimogene laherparepvec (T-VEC) for the treatment of advanced of melanoma in the United States, Europe and Australia, oncolytic virus immunotherapy has earned its place in the clinic. However, the adoption of T-VEC by the U.S. oncology community has been slow, and so far has been largely limited to specialized cancer centers. Limiting factors include the intratumoral route of administration, which is unfamiliar to medical oncologists, biosafety concerns related to the use of a live virus in the clinic, and the explosion of other therapeutic strategies now available for the treatment of advanced melanoma...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27650731/transfer-of-microrna-486-5p-from-human-endothelial-colony-forming-cell-derived-exosomes-reduces-ischemic-kidney-injury
#20
Jose L Viñas, Dylan Burger, Joseph Zimpelmann, Randa Haneef, William Knoll, Pearl Campbell, Alex Gutsol, Anthony Carter, David S Allan, Kevin D Burns
Administration of human cord blood endothelial colony-forming cells (ECFCs) or their exosomes protects mice against kidney ischemia/reperfusion injury. Here we studied the microRNA (miRNA) content of ECFC exosomes and the role of miRNA transfer in kidney and endothelial cell protection. ECFC exosomes were enriched in miR-486-5p, which targets the phosphatase and tensin homolog (PTEN) and the Akt pathway. In cultured endothelial cells exposed to hypoxia, incubation with ECFC exosomes increased miR-486-5p, decreased PTEN, and stimulated Akt phosphorylation...
December 2016: Kidney International
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