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Author (up) Burnett, L.C.; LeDuc, C.A.; Sulsona, C.R.; Paull, D.; Rausch, R.; Eddiry, S.; Carli, J.F.M.; Morabito, M.V.; Skowronski, A.A.; Hubner, G.; Zimmer, M.; Wang, L.; Day, R.; Levy, B.; Fennoy, I.; Dubern, B.; Poitou, C.; Clement, K.; Butler, M.G.; Rosenbaum, M.; Salles, J.P.; Tauber, M.; Driscoll, D.J.; Egli, D.; Leibel, R.L. url  doi
openurl 
  Title Deficiency in prohormone convertase PC1 impairs prohormone processing in Prader-Willi syndrome Type Journal Article
  Year 2017 Publication The Journal of Clinical Investigation Abbreviated Journal J Clin Invest  
  Volume 127 Issue 1 Pages 293-305  
  Keywords  
  Abstract Prader-Willi syndrome (PWS) is caused by a loss of paternally expressed genes in an imprinted region of chromosome 15q. Among the canonical PWS phenotypes are hyperphagic obesity, central hypogonadism, and low growth hormone (GH). Rare microdeletions in PWS patients define a 91-kb minimum critical deletion region encompassing 3 genes, including the noncoding RNA gene SNORD116. Here, we found that protein and transcript levels of nescient helix loop helix 2 (NHLH2) and the prohormone convertase PC1 (encoded by PCSK1) were reduced in PWS patient induced pluripotent stem cell-derived (iPSC-derived) neurons. Moreover, Nhlh2 and Pcsk1 expression were reduced in hypothalami of fasted Snord116 paternal knockout (Snord116p-/m+) mice. Hypothalamic Agrp and Npy remained elevated following refeeding in association with relative hyperphagia in Snord116p-/m+ mice. Nhlh2-deficient mice display growth deficiencies as adolescents and hypogonadism, hyperphagia, and obesity as adults. Nhlh2 has also been shown to promote Pcsk1 expression. Humans and mice deficient in PC1 display hyperphagic obesity, hypogonadism, decreased GH, and hypoinsulinemic diabetes due to impaired prohormone processing. Here, we found that Snord116p-/m+ mice displayed in vivo functional defects in prohormone processing of proinsulin, pro-GH-releasing hormone, and proghrelin in association with reductions in islet, hypothalamic, and stomach PC1 content. Our findings suggest that the major neuroendocrine features of PWS are due to PC1 deficiency.  
  Address  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0021-9738 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:27941249; PMCID:PMC5199710 Approved no  
  Call Number refbase @ user @ Serial 16636  
Permanent link to this record
 

 
Author (up) Chu J.; Bruyninckx F.; Neuhauser D.V. url  openurl
  Title Autonomic components of complex regional pain syndrome (CRPS) are favourably affected by electrical twitch-obtaining intramuscular stimulation (ETOIMS): Effects on blood pressure and heart rate Type Journal Article
  Year 2017 Publication BMJ Innov. Abbreviated Journal  
  Volume 3 Issue 3 Pages 176-187  
  Keywords analgesia; article; autonomic neuropathy; backache; blood pressure; clinical article; complex regional pain syndrome; controlled study; diastolic blood pressure; electrical twitch obtaining intramuscular stimulation; electromagnetism; electrostimulation; fatigue; health insurance; heart rate; human; male; muscle hypertonia; muscle twitch; nuclear magnetic resonance imaging; outcome assessment; priority journal; pulse pressure; pulse rate; range of motion; supersensitivity; systolic blood pressure; transcranial magnetic stimulation  
  Abstract Introduction Favourable pain relief results on evoking autonomous twitches at myofascial trigger points with Electrical Twitch Obtaining Intramuscular Stimulation (ETOIMS). Aim To document autonomic nervous system (ANS) dysfunction in Complex Regional Pain Syndrome (CRPS) from blood pressure (BP) and pulse/heart rate changes with ETOIMS. Methods and materials A patient with persistent pain regularly received serial ETOIMS sessions of 60, 90, 120 or >=150 min over 24 months. Outcome measures include BP: systolic, diastolic, pulse pressure and pulse/heart rate, pre-session/immediate-post-session summed differences (SDPPP index), and pain reduction. His results were compared with that of two other patients and one normal control. Each individual represented the following maximal elicitable twitch forces (TWF) graded 1-5: maximum TWF2: control subject; maximum TWF3: CRPS patient with suspected ANS dysfunction; and maximum TWF4 and TWF5: two patients with respective slow-fatigue and fast-fatigue twitches who during ETOIMS had autonomous twitching at local and remote myotomes simultaneously from denervation supersensitivity. ETOIMS results between TWFs were compared using one-way analysis of variance test. Results The patients showed immediate significant pain reduction, BP and pulse/heart rate changes/reduction(s) except for diastolic BP in the TWF5 patient. TWF2 control subject had diastolic BP reduction with ETOIMS but not with rest. Linear regression showed TWF grade to be the most significant variable in pain reduction, more so than the number of treatments, session duration and treatment interval. TWF grade was the most important variable in significantly reducing outcome measures, especially pulse/heart rate. Unlike others, the TWF3 patient had distinctive reductions in SDPPP index. Conclusions Measuring BP and pulse/heart rate is clinically practical for alerting ANS dysfunction maintained CRPS. SDPPP index (>=26) and pulse/heart rate (>=8) reductions with almost every ETOIMS treatment, plus inability to evoke autonomous twitches due to pain-induced muscle hypertonicity, are pathognomonic of this problem.  
  Address J. Chu, Department of Physical Medicine and Rehabilitation, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 2055-642x ISBN Medium  
  Area Expedition Conference  
  Notes Approved no  
  Call Number refbase @ admin @ Serial 17126  
Permanent link to this record
 

 
Author (up) Chu J.; Bruyninckx F.; Neuhauser D.V. url  openurl
  Title Autonomic components of complex regional pain syndrome (CRPS) are favourably affected by electrical twitch-obtaining intramuscular stimulation (ETOIMS): Effects on blood pressure and heart rate Type Journal Article
  Year 2017 Publication BMJ Innov. Abbreviated Journal  
  Volume 3 Issue 3 Pages 176-187  
  Keywords analgesia; article; autonomic neuropathy; backache; blood pressure; clinical article; complex regional pain syndrome; controlled study; diastolic blood pressure; electrical twitch obtaining intramuscular stimulation; electromagnetism; electrostimulation; fatigue; health insurance; heart rate; human; male; muscle hypertonia; muscle twitch; nuclear magnetic resonance imaging; outcome assessment; priority journal; pulse pressure; pulse rate; range of motion; supersensitivity; systolic blood pressure; transcranial magnetic stimulation  
  Abstract Introduction Favourable pain relief results on evoking autonomous twitches at myofascial trigger points with Electrical Twitch Obtaining Intramuscular Stimulation (ETOIMS). Aim To document autonomic nervous system (ANS) dysfunction in Complex Regional Pain Syndrome (CRPS) from blood pressure (BP) and pulse/heart rate changes with ETOIMS. Methods and materials A patient with persistent pain regularly received serial ETOIMS sessions of 60, 90, 120 or >=150 min over 24 months. Outcome measures include BP: systolic, diastolic, pulse pressure and pulse/heart rate, pre-session/immediate-post-session summed differences (SDPPP index), and pain reduction. His results were compared with that of two other patients and one normal control. Each individual represented the following maximal elicitable twitch forces (TWF) graded 1-5: maximum TWF2: control subject; maximum TWF3: CRPS patient with suspected ANS dysfunction; and maximum TWF4 and TWF5: two patients with respective slow-fatigue and fast-fatigue twitches who during ETOIMS had autonomous twitching at local and remote myotomes simultaneously from denervation supersensitivity. ETOIMS results between TWFs were compared using one-way analysis of variance test. Results The patients showed immediate significant pain reduction, BP and pulse/heart rate changes/reduction(s) except for diastolic BP in the TWF5 patient. TWF2 control subject had diastolic BP reduction with ETOIMS but not with rest. Linear regression showed TWF grade to be the most significant variable in pain reduction, more so than the number of treatments, session duration and treatment interval. TWF grade was the most important variable in significantly reducing outcome measures, especially pulse/heart rate. Unlike others, the TWF3 patient had distinctive reductions in SDPPP index. Conclusions Measuring BP and pulse/heart rate is clinically practical for alerting ANS dysfunction maintained CRPS. SDPPP index (>=26) and pulse/heart rate (>=8) reductions with almost every ETOIMS treatment, plus inability to evoke autonomous twitches due to pain-induced muscle hypertonicity, are pathognomonic of this problem.  
  Address J. Chu, Department of Physical Medicine and Rehabilitation, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 2055-642x ISBN Medium  
  Area Expedition Conference  
  Notes Approved no  
  Call Number refbase @ admin @ Serial 17128  
Permanent link to this record
 

 
Author (up) Etzioni, A.; Etzioni, O. openurl 
  Title Incorporating Ethics into Artificial Intelligence Type Journal Article
  Year 2017 Publication The Journal of Ethics Abbreviated Journal  
  Volume 21 Issue 4 Pages 403-418  
  Keywords artificial intelligence, AI, autonomy, ethics, self-driving cars, trolley problem  
  Abstract This article reviews the reasons scholars hold that driverless cars and many other AI equipped machines must be able to make ethical decisions, and the difficulties this approach faces. It then shows that cars have no moral agency, and that the term autonomous, commonly applied to these machines, is misleading, and leads to invalid conclusions about the ways these machines can be kept ethical. The articles most important claim is that a significant part of the challenge posed by AI-equipped machines can be addressed by the kind of ethical choices made by human beings for millennia. Ergo, there is little need to teach machines ethics even if this could be done in the first place. Finally, the article points out that it is a grievous error to draw on extreme outlier scenarios–such as the Trolley narratives–as a basis for conceptualizing the ethical issues at hand.  
  Address  
  Corporate Author Thesis  
  Publisher Springer Nature Place of Publication Editor  
  Language Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN ISBN Medium  
  Area Expedition Conference  
  Notes Approved no  
  Call Number refbase @ admin @ etzioni_incorporating_2017 Serial 17420  
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Author (up) Kueppers, F.; Sanders, C. url  doi
openurl 
  Title State-of-the-art testing for alpha-1 antitrypsin deficiency Type Journal Article
  Year 2017 Publication Allergy and Asthma Proceedings Abbreviated Journal Allergy Asthma Proc  
  Volume 38 Issue 2 Pages 108-114  
  Keywords Asthma/diagnosis; Diagnosis, Differential; Genetic Testing/economics/*methods; Genotype; Genotyping Techniques; High-Throughput Nucleotide Sequencing/economics/*methods; Humans; Sequence Analysis, DNA/economics/methods; alpha 1-Antitrypsin/blood/*genetics; alpha 1-Antitrypsin Deficiency/blood/*diagnosis/genetics  
  Abstract BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) is a genetic condition characterized by low serum levels of the protein alpha-1 antitrypsin. Because there are no unique clinical symptoms that point to a definitive diagnosis of AATD, laboratory testing is crucial to differentiate this disease from others. OBJECTIVE: To summarize advances in laboratory techniques used to test for AATD. METHODS: Data were sourced from a nonsystematic literature review of MEDLINE and the author's personal literature collection, and by checking reference lists of sourced articles. RESULTS: Since the original description of AATD by Laurell and Eriksson in 1963, testing methods have undergone major changes. Currently, alpha-1 antitrypsin protein is quantified by immunologic measurement in serum, and the phenotype is characterized by isoelectric focusing and/or targeted genotyping of predefined mutations. In addition, whole-gene sequencing of the gene SERPINA1 can be undertaken. However, this is costly and generally used only if targeted genotyping cannot conclusively identify the variant. The introduction of next-generation sequencing (NGS), which enables rapid and accurate sequencing of large quantities of DNA fragments in a single reaction, may help reduce costs. With its increasing availability, NGS may begin to appear in testing protocols. Clinical guidelines recommend that patients are tested for AATD if they have chronic irreversible airflow obstruction, especially those with early onset disease or a positive family history of AATD. Despite this, AATD is still underrecognized, and significant delays exist between symptom onset and diagnosis. CONCLUSION: Traditional testing practices have limitations. Screening programs that incorporate NGS are the most comprehensive methods available for accurate diagnosis of AATD.  
  Address  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1088-5412 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28120746 Approved no  
  Call Number refbase @ user @ Serial 17101  
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