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https://www.readbyqxmd.com/read/27900261/targeting-the-endocannabinoid-cb1-receptor-system-for-treating-obesity-in-prader-willi-syndrome
#1
Ibrahim Knani, Brian J Earley, Shiran Udi, Alina Nemirovski, Rivka Hadar, Asaad Gammal, Resat Cinar, Harry J Hirsch, Yehuda Pollak, Itai Gross, Talia Eldar-Geva, Daniela P Reyes-Capo, Joan C Han, Andrea M Haqq, Varda Gross-Tsur, Rachel Wevrick, Joseph Tam
OBJECTIVE: Extreme obesity is a core phenotypic feature of Prader-Willi syndrome (PWS). Among numerous metabolic regulators, the endocannabinoid (eCB) system is critically involved in controlling feeding, body weight, and energy metabolism, and a globally acting cannabinoid-1 receptor (CB1R) blockade reverses obesity both in animals and humans. The first-in-class CB1R antagonist rimonabant proved effective in inducing weight loss in adults with PWS. However, it is no longer available for clinical use because of its centrally mediated, neuropsychiatric, adverse effects...
December 2016: Molecular Metabolism
https://www.readbyqxmd.com/read/27896684/use-of-spray-dried-dispersions-in-early-pharmaceutical-development-theoretical-and-practical-challenges
#2
Jinjiang Li, Dhaval Patel, George Wang
Spray-dried dispersions (SDDs) have become an important formulation technology for the pharmaceutical product development of poorly water-soluble (PWS) compounds. Although this technology is now widely used in the industry, especially in the early-phase development, the lack of mechanistic understanding still causes difficulty in selecting excipients and predicting stability of SDD-based drug products. In this review, the authors aim to discuss several principles of polymer science pertaining to the development of SDDs, in terms of selecting polymers and solvents, optimizing drug loading, as well as assessing physical stability on storage and supersaturation maintenance after dissolution, from both thermodynamic and kinetic considerations...
November 28, 2016: AAPS Journal
https://www.readbyqxmd.com/read/27894106/prader-willi-syndrome-due-to-an-unbalanced-de-novo-translocation-t-15-19-q12-p13-3
#3
Vy Dang, Abhilasha Surampalli, Ann M Manzardo, Stephanie Youn, Merlin G Butler, June-Anne Gold, Virginia E Kimonis
Prader-Willi syndrome (PWS) is a complex, multisystem genetic disorder characterized by endocrine, neurologic, and behavioral abnormalities. We report the first case of an unbalanced de novo reciprocal translocation of chromosomes 15 and 19, 45,XY,-15,der(19)t(15;19)(q12;p13.3), resulting in monosomy for the PWS critical chromosome region. Our patient had several typical features of PWS including infantile hypotonia, a poor suck and feeding difficulties, tantrums, skin picking, compulsions, small hands and feet, and food seeking, but not hypopigmentation, a micropenis, cryptorchidism or obesity as common findings seen in PWS at the time of examination at 6 years of age...
November 29, 2016: Cytogenetic and Genome Research
https://www.readbyqxmd.com/read/27876116/could-field-cancerization-be-interpreted-as-a-biochemical-anomaly-amplification-due-to-transformed-cells
#4
Janeth Fernández P, Stelia C Méndez-Sánchez, C A Gonzalez-Correa, David A Miranda
Field cancerization is a concept used to explain cellular and molecular alterations in tissue associated to neoplasia and cancer. This effect was proposed by Slaughter in order to explain the development of multiple primary tumors and locally recurrent cancer. The particular changes associated with this effect, in each type of cancer, have been detected even at distances greater than 10cm off the tumor, in areas classified as normal by histopathological studies. Early detection of lung, colon, and ovary cancer has been reported by the use of Partial Wave Microscopy Spectroscopy (PWS) and has been explained in terms of the field cancerization effect...
December 2016: Medical Hypotheses
https://www.readbyqxmd.com/read/27872318/biomechanical-indices-for-rupture-risk-estimation-in-abdominal-aortic-aneurysms
#5
Eva L Leemans, Tineke P Willems, Maarten J van der Laan, Cornelis H Slump, Clark J Zeebregts
PURPOSE: To review the use of biomechanical indices for the estimation of abdominal aortic aneurysm (AAA) rupture risk, emphasizing their potential use in a clinical setting. METHODS: A search of the PubMed, Embase, Scopus, and Compendex databases was made up to June 2015 to identify articles involving biomechanical analysis of AAA rupture risk. Outcome variables [aneurysm diameter, peak wall stress (PWS), peak wall shear stress (PWSS), wall strain, peak wall rupture index (PWRI), and wall stiffness] were compared for asymptomatic intact AAAs vs symptomatic or ruptured AAAs...
November 21, 2016: Journal of Endovascular Therapy
https://www.readbyqxmd.com/read/27871485/unusual-processing-generates-spa-lncrnas-that-sequester-multiple-rna-binding-proteins
#6
Huang Wu, Qing-Fei Yin, Zheng Luo, Run-Wen Yao, Chuan-Chuan Zheng, Jun Zhang, Jian-Feng Xiang, Li Yang, Ling-Ling Chen
We identify a type of polycistronic transcript-derived long noncoding RNAs (lncRNAs) that are 5' small nucleolar RNA (snoRNA) capped and 3' polyadenylated (SPAs). SPA processing is associated with nascent mRNA 3' processing and kinetic competition between XRN2 trimming and Pol II elongation. Following cleavage/polyadenylation of its upstream gene, the downstream uncapped pre-SPA is trimmed by XRN2 until this exonuclease reaches the co-transcriptionally assembled snoRNP. This snoRNP complex prevents further degradation, generates a snoRNA 5' end, and allows continuous Pol II elongation...
November 3, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27870064/the-effect-of-plant-water-storage-on-water-fluxes-within-the-coupled-soil-plant-system
#7
Cheng-Wei Huang, Jean-Christophe Domec, Eric J Ward, Tomer Duman, Gabriele Manoli, Anthony J Parolari, Gabriel G Katul
In addition to buffering plants from water stress during severe droughts, plant water storage (PWS) alters many features of the spatio-temporal dynamics of water movement in the soil-plant system. How PWS impacts water dynamics and drought resilience is explored using a multi-layer porous media model. The model numerically resolves soil-plant hydrodynamics by coupling them to leaf-level gas exchange and soil-root interfacial layers. Novel features of the model are the considerations of a coordinated relationship between stomatal aperture variation and whole-system hydraulics and of the effects of PWS and nocturnal transpiration (Fe,night) on hydraulic redistribution (HR) in the soil...
November 21, 2016: New Phytologist
https://www.readbyqxmd.com/read/27865225/reactions-of-protective-service-workers-towards-people-who-stutter
#8
Jian Li, Hayley S Arnold, Ann Beste-Guldborg
PURPOSE: This study sought to assess whether protective service workers differ from people in non-protective services occupations in their intended reactions towards people who stutter (PWS). METHODS: Analyses were based on questionnaire responses regarding intended reactions toward PWS from 171 protective services workers and 2595 non-protective services workers in the United States. A propensity score matching procedure was used to identify a comparison group of non-protective services workers for the protective services workers...
December 2016: Journal of Fluency Disorders
https://www.readbyqxmd.com/read/27863129/mechanisms-of-obesity-in-prader-willi-syndrome
#9
REVIEW
M J Khan, K Gerasimidis, C A Edwards, M G Shaikh
Obesity is the most common cause of metabolic complications and poor quality of life in Prader-Willi syndrome (PWS). Hyperphagia and obesity develop after an initial phase of poor feeding and failure to thrive. Several mechanisms for the aetiology of obesity in PWS are proposed, which include disruption in hypothalamic pathways of satiety control resulting in hyperphagia, aberration in hormones regulating food intake, reduced energy expenditure because of hypotonia and altered behaviour with features of autism spectrum disorder...
November 10, 2016: Pediatric Obesity
https://www.readbyqxmd.com/read/27857842/zebrafish-models-of-prader-willi-syndrome-fast-track-to-pharmacotherapeutics
#10
Emma D Spikol, Caroline E Laverriere, Maya Robnett, Gabriela Carter, Erin Wolfe, Eric Glasgow
Prader-Willi syndrome (PWS) is a rare genetic neurodevelopmental disorder characterized by an insatiable appetite, leading to chronic overeating and obesity. Additional features include short stature, intellectual disability, behavioral problems and incomplete sexual development. Although significant progress has been made in understanding the genetic basis of PWS, the mechanisms underlying the pathogenesis of the disorder remain poorly understood. Treatment for PWS consists mainly of palliative therapies; curative therapies are sorely needed...
March 2016: Diseases (Basel)
https://www.readbyqxmd.com/read/27854358/causes-of-death-in-prader-willi-syndrome-prader-willi-syndrome-association-usa-40-year-mortality-survey
#11
Merlin G Butler, Ann M Manzardo, Janalee Heinemann, Carolyn Loker, James Loker
BACKGROUND: Prader-Willi syndrome (PWS) is a rare, complex, neurodevelopmental genetic disorder that is associated with hyperphagia and morbid obesity in humans and leads to a shortened life expectancy. This report summarizes the primary causes of death and evaluates mortality trends in a large cohort of individuals with PWS. METHODS: The US Prader-Willi Syndrome Association (PWSA (USA)) syndrome-specific database of death reports was collected through a cursory bereavement program for PWSA (USA) families using a brief survey created in 1999...
November 17, 2016: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/27853446/when-the-eyes-no-longer-lead-familiarity-and-length-effects-on-eye-voice-span
#12
Susana Silva, Alexandra Reis, Luís Casaca, Karl M Petersson, Luís Faísca
During oral reading, the eyes tend to be ahead of the voice (eye-voice span, EVS). It has been hypothesized that the extent to which this happens depends on the automaticity of reading processes, namely on the speed of print-to-sound conversion. We tested whether EVS is affected by another automaticity component - immunity from interference. To that end, we manipulated word familiarity (high-frequency, low-frequency, and pseudowords, PW) and word length as proxies of immunity from interference, and we used linear mixed effects models to measure the effects of both variables on the time interval at which readers do parallel processing by gazing at word N + 1 while not having articulated word N yet (offset EVS)...
2016: Frontiers in Psychology
https://www.readbyqxmd.com/read/27852283/effect-of-cessation-of-gh-treatment-on-cognition-during-transition-phase-in-prader-willi-syndrome-results-of-a-2-year-crossover-gh-trial
#13
R J Kuppens, E F Mahabier, N E Bakker, E P C Siemensma, S H Donze, A C S Hokken-Koelega
BACKGROUND: Patients with Prader-Willi syndrome (PWS) have a cognitive impairment. Growth hormone (GH) treatment during childhood improves cognitive functioning, while cognition deteriorates in GH-untreated children with PWS. Cessation of GH treatment at attainment of adult height (AH) might deteriorate their GH-induced improved cognition, while continuation might benefit them. We, therefore, investigated the effects of placebo versus GH administration on cognition in young adults with PWS who were GH-treated for many years during childhood and had attained AH...
November 16, 2016: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/27849534/random-walk-graph-laplacian-based-smoothness-prior-for-soft-decoding-of-jpeg-images
#14
Xianming Liu, Gene Cheung, Xiaolin Wu, Debin Zhao
Given the prevalence of JPEG compressed images, optimizing image reconstruction from the compressed format remains an important problem. Instead of simply reconstructing a pixel block from the centers of indexed DCT coefficient quantization bins (hard decoding), soft decoding reconstructs a block by selecting appropriate coefficient values within the indexed bins with the help of signal priors. The challenge thus lies in how to define suitable priors and apply them effectively. In this paper, we combine three image priors-Laplacian prior for DCT coefficients, sparsity prior and graph-signal smoothness prior for image patches-to construct an efficient JPEG soft decoding algorithm...
November 10, 2016: IEEE Transactions on Image Processing: a Publication of the IEEE Signal Processing Society
https://www.readbyqxmd.com/read/27836461/cognition-in-people-with-prader-willi-syndrome-insights-into-genetic-influences-on-cognitive-and-social-development
#15
REVIEW
Joyce Whittington, Anthony Holland
We present a mini-review of cognition in Prader-Willi syndrome. Studies cited include findings on general ability (IQ), IQ correlates with family members, strengths and weaknesses in cognitive profiles in genetic subtypes, attainment in literacy and numeracy, language, comprehension, modality preferences, executive functions, and social cognition. The latter includes investigations of theory of mind, emotion recognition, face processing and knowledge of social norms. Results from research on mouse models and brain imaging studies relevant to cognition are briefly discussed...
November 8, 2016: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/27825021/abnormal-auditory-synchronization-in-stuttering-a-magnetoencephalographic-study
#16
Yoshikazu Kikuchi, Tsuyoshi Okamoto, Katsuya Ogata, Koichi Hagiwara, Toshiro Umezaki, Masamutsu Kenjo, Takashi Nakagawa, Shozo Tobimatsu
In a previous magnetoencephalographic study, we showed both functional and structural reorganization of the right auditory cortex and impaired left auditory cortex function in people who stutter (PWS). In the present work, we reevaluated the same dataset to further investigate how the right and left auditory cortices interact to compensate for stuttering. We evaluated bilateral N100m latencies as well as indices of local and inter-hemispheric phase synchronization of the auditory cortices. The left N100m latency was significantly prolonged relative to the right N100m latency in PWS, while healthy control participants did not show any inter-hemispheric differences in latency...
November 5, 2016: Hearing Research
https://www.readbyqxmd.com/read/27823858/ambient-temperature-modulates-the-effects-of-the-prader-willi-syndrome-candidate-gene-snord116-on-energy-homeostasis
#17
Y Qi, L Purtell, M Fu, K Sengmany, K Loh, L Zhang, S Zolotukhin, A Sainsbury, L Campbell, H Herzog
Germline deletion of the Prader-Willi syndrome (PWS) candidate gene Snord116 in mice leads to some classical symptoms of human PWS, notably reductions in body weight, linear growth and bone mass. However, Snord116 deficient mice (Snord116(-/-)) do not develop an obese phenotype despite their increased food intake and the underlying mechanism for that is unknown. We tested the phenotypes of germline Snord116(-/-) as well as neuropeptide Y (NPY) neuron specific Snord116(lox/lox)/NPY(cre/+) mice at 30°C, the thermoneutral temperature of mice, and compared these to previous reports studies conducted at normal room temperature...
October 27, 2016: Neuropeptides
https://www.readbyqxmd.com/read/27823848/association-of-clinical-and-radiographic-signs-of-femoroacetabular-impingement-in-the-general-population
#18
Ryota Yamauchi, Ryo Inoue, Daisuke Chiba, Yuji Yamamoto, Yoshifumi Harada, Ippei Takahashi, Shigeyuki Nakaji, Yasuyuki Ishibashi
BACKGROUND: The relationships between the clinical and radiographic signs of femoroacetabular impingement (FAI) are unknown. The purpose of this study was to assess the relationship between hip pain, a positive anterior impingement sign (AIS), and radiographic signs of FAI in a general Japanese population. METHODS: A total of 616 individuals participated in this study. Hip pain was assessed using the Japanese Orthopaedic Association Hip-Disease Evaluation Questionnaire (JHEQ) pain category score and the AIS was used as a provocation test...
November 4, 2016: Journal of Orthopaedic Science: Official Journal of the Japanese Orthopaedic Association
https://www.readbyqxmd.com/read/27812680/critical-analysis-of-the-quality-readability-and-technical-aspects-of-online-information-provided-for-neck-lifts
#19
Hani Rayess, Giancarlo F Zuliani, Amar Gupta, Peter F Svider, Adam J Folbe, Jean Anderson Eloy, Michael A Carron
Importance: The number of patients using the internet to obtain health information is growing. This material is unregulated and heterogeneous and can influence patient decisions. Objective: To compare the quality, readability, and technical aspects of online information about neck-lifts provided by private practice websites vs academic medical centers and reference sources. Design, Setting, and Participants: In this cross-sectional analysis conducted between November 2015 and January 2016, a Google search of the term neck-lift was performed, and the first 45 websites were evaluated...
November 3, 2016: JAMA Facial Plastic Surgery
https://www.readbyqxmd.com/read/27810647/investigating-the-feasibility-of-using-transcranial-direct-current-stimulation-to-enhance-fluency-in-people-who-stutter
#20
Jennifer Chesters, Kate E Watkins, Riikka Möttönen
Developmental stuttering is a disorder of speech fluency affecting 1% of the adult population. Long-term reductions in stuttering are difficult for adults to achieve with behavioural therapies. We investigated whether a single session of transcranial direct current stimulation (TDCS) could improve fluency in people who stutter (PWS). In separate sessions, either anodal TDCS (1mA for 20min) or sham stimulation was applied over the left inferior frontal cortex while PWS read sentences aloud. Fluency was induced during the stimulation period by using choral speech, that is, participants read in unison with another speaker...
October 31, 2016: Brain and Language
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