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Laura J Mosher, Sean C Godar, Marc Morissette, Kenneth M McFarlin, Simona Scheggi, Carla Gambarana, Stephen C Fowler, Thérèse Di Paolo, Marco Bortolato
The enzyme steroid 5α-reductase 2 (5αR2) catalyzes the conversion of testosterone into the potent androgen 5α-dihydrotestosterone. Previous investigations showed that 5αR2 is expressed in key brain areas for emotional and socio-affective reactivity, yet the role of this enzyme in behavioral regulation remains mostly unknown. Here, we profiled the behavioral characteristics of 5αR2 heterozygous (HZ) and knockout (KO) mice, as compared with their wild-type (WT) littermates. While male 5αR2 KO mice displayed no overt alterations in motoric, sensory, information-processing and anxiety-related behaviors, they exhibited deficits in neurobehavioral correlates of dominance (including aggression against intruders, mating, and tube dominance) as well as novelty-seeking and risk-taking responses...
February 16, 2018: Psychoneuroendocrinology
Jemma Haines, James H Hull, Stephen J Fowler
PURPOSE OF REVIEW: Many aspects of inducible laryngeal obstruction (ILO) are still poorly understood. However, in recent years there have been advances made and an international consensus has achieved a standardized taxonomy. This review will synthesize recent research; specifically, relating to clinical presentation, assessment, and therapeutic interventions. RECENT FINDINGS: The evidence base is growing but still limited for ILO and mostly comprises retrospective reviews, case studies, and anecdotal reports...
March 6, 2018: Current Opinion in Otolaryngology & Head and Neck Surgery
A Schröder, F A Campbell, W A Farhat, J L Pippi Salle, D J Bägli, A J Lorenzo, M A Koyle
INTRODUCTION: There are limited data about pain patterns, analgesic requirements and factors predicting opioid requirements of children undergoing outpatient urologic surgery. This prospective study aimed to assess recovery profiles and pain medication requirements. METHODS: Patients between 6 months and 12 years of age were recruited prospectively between December 2013 and June 2014. Demographic and operative characteristics were collected. Following discharge home, the parents were asked to administer both acetaminophen and ibuprofen Q6H at a weight-adjusted dose, based on a schedule, until the end of postoperative day 2, and to administer the medication as required on postoperative day 3...
January 31, 2018: Journal of Pediatric Urology
Nicole A Kratochwil, Miriam Triyatni, Martina B Mueller, Florian Klammers, Brian Leonard, Dan Turley, Josephine Schmaler, Aynur Ekiciler, Birgit Molitor, Isabelle Walter, Pierre-Alexis Gonsard, Charles A Tournillac, Alexandre Durrwell, Michaela Marschmann, Russell Jones, Mohammed Ullah, Franziska Boess, Giorgio Ottaviani, Yuyan Yin, Neil J Parrott, Stephen Fowler
Long-term in vitro liver models are now widely explored for human hepatic metabolic clearance prediction, enzyme phenotyping, cross species metabolism, comparison of low clearance drugs as well as induction studies. Here, we present studies using a long-term liver model which show how metabolism and active transport, drug-drug interactions and enzyme induction in healthy and diseased states, e.g. hepatitis B virus (HBV) infection, may be assessed in a single test system to enable effective data integration for PBPK modeling...
February 16, 2018: Journal of Pharmacology and Experimental Therapeutics
Man Yan Wong, Changliang Liu, Shan Shan H Wang, Aram C F Roquas, Stephen C Fowler, Pascal S Kaeser
The presynaptic active zone provides sites for vesicle docking and release at central nervous synapses and is essential for speed and accuracy of synaptic transmission. Liprin-α binds to several active zone proteins, and loss-of-function studies in invertebrates established important roles for Liprin-α in neurodevelopment and active zone assembly. However, Liprin-α localization and functions in vertebrates have remained unclear. We used stimulated emission depletion superresolution microscopy to systematically determine the localization of Liprin-α2 and Liprin-α3, the two predominant Liprin-α proteins in the vertebrate brain, relative to other active-zone proteins...
February 8, 2018: Proceedings of the National Academy of Sciences of the United States of America
Stephen J Fowler
No abstract text is available yet for this article.
January 2018: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
Catherine E Hanratty, John G Matthews, Joseph R Arron, David F Choy, Ian D Pavord, P Bradding, Christopher E Brightling, Rekha Chaudhuri, Douglas C Cowan, Ratko Djukanovic, Nicola Gallagher, Stephen J Fowler, Tim C Hardman, Tim Harrison, Cécile T Holweg, Peter H Howarth, James Lordan, Adel H Mansur, Andrew Menzies-Gow, Sofia Mosesova, Robert M Niven, Douglas S Robinson, Dominick E Shaw, Samantha Walker, Ashley Woodcock, Liam G Heaney
BACKGROUND: Patients with difficult-to-control asthma consume 50-60% of healthcare costs attributed to asthma and cost approximately five-times more than patients with mild stable disease. Recent evidence demonstrates that not all patients with asthma have a typical type 2 (T2)-driven eosinophilic inflammation. These asthmatics have been called 'T2-low asthma' and have a minimal response to corticosteroid therapy. Adjustment of corticosteroid treatment using sputum eosinophil counts from induced sputum has demonstrated reduced severe exacerbation rates and optimized corticosteroid dose...
January 4, 2018: Trials
Yumi Cleary, Michael Gertz, Peter N Morcos, Li Yu, Kuresh Youdim, Alex Phipps, Stephen Fowler, Neil Parrott
Alectinib is a selective anaplastic lymphoma kinase (ALK) inhibitor approved for the treatment of ALK-positive non-small cell lung cancer. Alectinib and its major active metabolite M4 exhibited drug-drug interaction (DDI) potential through cytochrome P450 (CYP) enzymes CYP3A4 and CYP2C8 in vitro. Clinical relevance of the DDI risk was investigated as part of a rapid development program to fulfill the breakthrough therapy designation. Therefore, a strategy with a combination of physiologically based pharmacokinetic (PBPK) modeling and limited clinical trials focused on generating informative data for modeling was made to ensure extrapolation ability of DDI risk...
December 11, 2017: Clinical Pharmacology and Therapeutics
Akihiro Igarashi, Kenta Kikuchi, Kenjiro Ogushi, Mariko Hasegawa, Masahiro Hatanaka, Junko Fujino, Yoko Kishi, Hitoshi Ikeda
PURPOSE: To discuss an optimal surgical approach for impalpable testis in children, our own treatment results and those reported in the literature were reviewed. MATERIALS AND METHODS: Seventy-two impalpable testes were diagnosed in 68 patients: unilateral in 64 patients and bilateral in 4 patients. All patients underwent surgical exploration at the ages of 6 to 140months (median, 15months). The inguinal canal was initially explored, and abdominal exploration was performed with laparoscopy when an extra-abdominal testis was not identified...
October 16, 2017: Journal of Pediatric Surgery
Xinyue Zhang, Chengyuan Li, Stephen C Fowler, Zheng Zhang, Brian S J Blagg, Rick T Dobrowsky
Increased expression of the c-jun transcription factor occurs in a variety of human neuropathies and is critical in promoting Schwann cell (SC) dedifferentiation and loss of the myelinated phenotype. Using cell culture models, we previously identified KU-32 as a novobiocin-based C-terminal heat shock protein 90 (Hsp90) inhibitor that decreased c-jun expression and the extent of demyelination. Additional chemical optimization has yielded KU-596 as a neuroprotective novologue whose mechanistic efficacy to improve a metabolic neuropathy requires the expression of Hsp70...
November 9, 2017: ACS Chemical Neuroscience
Maurizio Pacilli, Yves Heloury, Mike O'Brien, Tess Lionti, Margaret Rowell, John Hutson
INTRODUCTION: Prader-Willi syndrome (PWS) is a rare (1:20.000) genetic condition affecting both males and females. Among other features, in boys, the syndrome is characterized by cryptorchidism in 86-100% of cases, hypogonadism, delayed puberty and infertility. The aim of the present study is to appraise the results of orchidopexy in this selected population of children. STUDY DESIGN: A follow-up study of children with PWS treated for undescended testes at a single institution over a 20-year period was performed...
October 16, 2017: Journal of Pediatric Urology
Okechukwu Hyginus Ekwunife, Victor Ifeanyichukwu Modekwe, Jideofor Okechukwu Ugwu, Chuka Abunike Ugwunne
BACKGROUND: Nonpalpable undescended testes (NPT) constitute 20%-30% of undescended testes, and its management has been a challenge both in diagnosis and treatment. Worldwide, laparoscopy is the current gold standard of management. In Nigeria, the management of NPT has largely been by open surgery with consequent high morbidity. In Nigeria, the trend is changing from a largely open management with its attendant high morbidity, to laparoscopic management which is the current worldwide gold standard of care...
July 2017: Nigerian Journal of Surgery: Official Publication of the Nigerian Surgical Research Society
Deepak Bagga, Ashish Prasad, Shabnam Bhandari Grover, Nidhi Sugandhi, Narender Tekchandani, Samir Kant Acharya, Amat Samie
INTRODUCTION: The best operative intervention for intrabdominal testis (IAT) has not been standardized as yet. The question of whether to bring down an IAT with a single-staged vessel-intact laparoscopic orchidopexy (VILO) or a two-staged laparoscopic Fowler-Stephens orchidopexy (FSLO) is still undergoing debate, with both the procedures being popular. The present study has been designed to evaluate the factors predicting the success or failure of two-staged FSLO for (IAT). METHODS: 43 boys with 49 non-palpable testes underwent diagnostic laparoscopy out of which 35 underwent two-staged FSLO...
January 2018: Pediatric Surgery International
Rajarshi Kumar, Kartik Chandra Mandal, Pankaj Halder, Md Hadiuzzaman, Madhumita Mukhopadhyay, Biswanath Mukhopadhyay
AIMS: The aim of this study is to report and analyze results of laparoscopy in impalpable testes performed between 2009 and 2016 and its short-term outcomes. MATERIALS AND METHODS: Demographic data, laterality, laparoscopic findings, operative time, procedure, hospital stay, complications, and follow-up data of 76 patients with 79 impalpable testes from 2009 to 2016 were retrospectively collected and analyzed. Successful outcome was defined as maintenance of intrascrotal position with no atrophy at a follow-up of at least 6 months...
October 2017: Journal of Indian Association of Pediatric Surgeons
Pieter-Paul Hekking, Matthew J Loza, Stelios Pavlidis, Bertrand De Meulder, Diane Lefaudeux, Frederic Baribaud, Charles Auffray, Ariane H Wagener, Paul Brinkman, René Lutter, Aruna T Bansal, Ana R Sousa, Stewart A Bates, Ioannis Pandis, Louise J Fleming, Dominick E Shaw, Stephen J Fowler, Yike Guo, Andrea Meiser, Kai Sun, Julie Corfield, Peter Howarth, Elisabeth H Bel, Ian M Adcock, Kian Fan Chung, Ratko Djukanovic, Peter J Sterk
A proportion of severe asthma patients suffers from persistent airflow limitation (PAL), often associated with more symptoms and exacerbations. Little is known about the underlying mechanisms. Here, our aim was to discover unexplored potential mechanisms using Gene Set Variation Analysis (GSVA), a sensitive technique that can detect underlying pathways in heterogeneous samples.Severe asthma patients from the U-BIOPRED cohort with PAL (post-bronchodilator forced expiratory volume in 1 s/forced vital capacity ratio below the lower limit of normal) were compared with those without PAL...
September 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
Oluwasola Lawal, Howbeer Muhamadali, Waqar Ahmed, Iain R White, Tamara M E Nijsen, Royston Goodacre, Stephen J Fowler
Ventilator-associated pneumonia (VAP) is a healthcare-acquired infection arising from the invasion of the lower respiratory tract by opportunistic pathogens in critically ill ventilated patients. The current method of diagnosis requires the culture of an airway sample such as bronchoalveolar lavage, which is invasive to obtain and may take up to seven days to identify a causal pathogen, or indeed rule out infection. While awaiting results, patients are administered empirical antibiotics; risks of this approach include lack of effect on the causal pathogen, contribution to the development of antibiotic resistance and downstream effects such as increased length of intensive care stay, cost, morbidity and mortality...
September 26, 2017: Journal of Breath Research
David P Jarmolowicz, Jennifer L Hudnall, Luanne Hale, Stephen C Fowler, Marco Bortolato, Shea M Lemley, Michael J Sofis
Obesity is a major public health problem, which, like many forms of addiction, is associated with an elevated tendency to choose smaller immediate rather than larger delayed rewards, a response pattern often referred to as excessive delay discounting. Although some accounts of delay discounting conceptualize this process as impulsivity (placing the emphasis on overvaluing the smaller immediate reward), others have conceptualized delay discounting as an executive function (placing the emphasis on delayed rewards failing to retain their value)...
September 2017: Journal of the Experimental Analysis of Behavior
Nicholas Denny, Usman Maqsood, Stephen Fowler, Mohammed Munavvar
Tracheobronchial foreign body (TFB) aspiration is a common occurrence in children compared with adults. Long-standing cases of TFB aspiration during childhood presenting in an adult have rarely been reported. We report the unique case of an endobronchial Playmobil traffic cone that went undetected for 40 years and presented as a suspected bronchogenic carcinoma. This was subsequently removed successfully with flexible bronchoscopy. To our knowledge this is the first case of a TFB that was overlooked this length of time...
September 21, 2017: BMJ Case Reports
Waqar M Ahmed, Oluwasola Lawal, Tamara M Nijsen, Royston Goodacre, Stephen J Fowler
With heightened global concern of microbial drug resistance, advanced methods for early and accurate diagnosis of infection are urgently needed. Analysis of exhaled breath volatile organic compounds (VOCs) toward detecting microbial infection potentially allows a highly informative and noninvasive alternative to current genomics and culture-based methods. We performed a systematic review of research literature reporting human and animal exhaled breath VOCs related to microbial infections. In this Review, we find that a wide range of breath sampling and analysis methods are used by researchers, which significantly affects interstudy method comparability...
October 13, 2017: ACS Infectious Diseases
Oluwasola Lawal, Waqar M Ahmed, Tamara M E Nijsen, Royston Goodacre, Stephen J Fowler
BACKGROUND: The potential of exhaled breath sampling and analysis has long attracted interest in the areas of medical diagnosis and disease monitoring. This interest is attributed to its non-invasive nature, access to an unlimited sample supply (i.e., breath), and the potential to facilitate a rapid at patient diagnosis. However, progress from laboratory setting to routine clinical practice has been slow. Different methodologies of breath sampling, and the consequent difficulty in comparing and combining data, are considered to be a major contributor to this...
2017: Metabolomics: Official Journal of the Metabolomic Society
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