Τετάρτη 10 Ιανουαρίου 2018

Muscle cooling: too much of a good thing?

Abstract

It is well documented that strenuous exercise elicits stress on the body, which may lead to physiological impairments and associated reductions in muscle function and fatigue, in the hours and days post-exercise.

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Kompetenzbasierte Ausbildung im „geschützten Umfeld“: vom Schonraum zum Realraum

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 12-19
DOI: 10.1055/s-0043-105257

„Lernen im geschützten Umfeld" ist ein häufig gebrauchter, aber unklarer Begriff im Rahmen der anästhesiologischen postgradualen Weiterbildung. Dieser Artikel beleuchtet seine Bedeutung in der Anästhesiologie – einschließlich Lehr- und Lernstrategien, wie kompetenzorientierte und simulationsbasierte Ausbildung. Ein Versuch der Klassifikation von Simulatoren und Unterrichtsmethoden sowie deren Probleme bei der Umsetzung runden den Beitrag ab.
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Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
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Behandlung im Voraus planen – Bedeutung für die Intensiv- und Notfallmedizin

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 62-70
DOI: 10.1055/s-0042-118690

Behandlung im Voraus planen (BVP) – im Englischen Advance Care Planning (ACP) – etabliert sich auch in Deutschland als ein neues Konzept zur Realisierung wirksamer Patientenverfügungen. Das Konzept beinhaltet Prozesse zur Ermittlung, Dokumentation und Umsetzung von Behandlungswünschen für den Fall, dass die Betroffenen nicht (mehr) selbst entscheiden können.
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Georg Thieme Verlag KG Stuttgart · New York

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Begünstigt Kaudalanästhesie postoperative Komplikationen nach Hypospadie-OP?

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 6-7
DOI: 10.1055/s-0043-123122



Georg Thieme Verlag KG Stuttgart · New York

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„Lernen im geschützten Umfeld“: Implementierung in die Fort- und Weiterbildung

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 35-46
DOI: 10.1055/s-0043-105259

Aktuelle Aus- und Fortbildungskonzepte in der Akut- oder Notfallmedizin beinhalten Simulations- und Skill-Trainings unter Berücksichtigung von Methoden und Mechanismen der Fehler- und Zwischenfallprävention wie Human Factors, Shared mental Models und Closed-Loop-Communication. Immer noch ungeklärt ist die Frage nach der optimalen Kombination der einzelnen Methoden und Inhalte eines Fortbildungsprogramms in Abhängigkeit von individuellen Abteilungen eines Krankenhauses und dem einzelnen Mitarbeiter bzw. seinem individuellen Ausbildungsstand. Ein von uns angebotenes Konzept ist das „Lernen im geschützten Umfeld": Hier werden Teilnehmer und Patient vor den negativen Auswirkungen einer konventionellen klinisch-praktischen Ausbildungssituation beschützt. Gleichzeitig profitieren die Teilnehmer in unserem Fortbildungsprogramm von standardisierten Kursmodellen. Das Ziel der optimalen Vorbereitung auf die klinische Tätigkeit und einer möglichst praktischen bzw. wirklichkeitsnahen Aus- und Fortbildung wird durch eine ständige Re-Evaluation der Inhalte und Methoden komplettiert. Die Implementierung eines solchen multimodalen Teamtrainings ist für jede Institution individuell anzupassen. Die Methoden zur Implementierung sollten standardisiert angewendet werden. Wir empfehlen eine Curriculumsentwicklung auf Grundlage des „Kern-Zyklus". Auf dieser Basis gelingt die Kombination aus „Lernen im geschützten Umfeld" und Zwischenfalltraining zur optimalen Vorbereitung auf eine akutmedizinische, klinische Tätigkeit mit dem Ziel einer höchstmöglichen Patientensicherheit.
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Georg Thieme Verlag KG Stuttgart · New York

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Hyperchlorämie ist mit akutem Nierenversagen nach SAB verbunden

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 7-8
DOI: 10.1055/s-0043-123121



Georg Thieme Verlag KG Stuttgart · New York

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Lernen im geschützten Umfeld

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 10-11
DOI: 10.1055/s-0043-122170



Georg Thieme Verlag KG Stuttgart · New York

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Etomidat-Analogon mit verringerter Nebennierensuppression

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 8-8
DOI: 10.1055/s-0043-117029



Georg Thieme Verlag KG Stuttgart · New York

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Simulation als Fortbildungsmethode zur Professionalisierung von Teams

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 20-33
DOI: 10.1055/s-0043-105261

Simulation ist eine Methode, virtuelle Lernumgebungen zu erzeugen. Mittels Simulation können Technical Skills, aber auch Soft Skills wie die Funktionsfähigkeit von Teams sehr gut vermittelt werden. Dieser Team-Aspekt wird nachfolgend vor dem Hintergrund spezifischer Trainingsmethoden näher beleuchtet. Der Artikel bezieht sich dabei auf „Zwischenfalltrainings", die in den Zentren der Autoren einen großen Anteil des Kursangebotes einnehmen.
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Georg Thieme Verlag KG Stuttgart · New York

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The Same Procedure As Last Year?

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 9-9
DOI: 10.1055/s-0043-123165



Georg Thieme Verlag KG Stuttgart · New York

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„Das Kind hat einen Fremdkörper verschluckt“ – was tun?

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 48-60
DOI: 10.1055/s-0042-120991

Sowohl Ingestions- als auch Aspirationsunfälle sind häufige Ereignisse bei Kindern. Sie können unmittelbar lebensbedrohlich sein oder bei fehlender direkter Bedrohung dennoch erhebliche langfristige Beeinträchtigungen für die Kinder verursachen. Der Beitrag zeigt die diagnostischen und therapeutischen Möglichkeiten und Notwendigkeiten auf, durch die eine bestmögliche Sicherheit und möglichst geringe Folgeschäden zu gewährleisten sind.
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Georg Thieme Verlag KG Stuttgart · New York

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Neurologischer Schaden nach Wirbelsäulen-OP

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 71-75
DOI: 10.1055/s-0043-122628

Schlichtungsstellen für Arzthaftpflichtfragen bieten Patienten, Ärzten und Versicherern eine Möglichkeit, Arzthaftungsstreitigkeiten außergerichtlich zu klären. In der Rubrik „Fälle der Schlichtungsstelle" stellen wir abgeschlossene Fälle aus der Schlichtungsstelle für Arzthaftpflichtfragen der norddeutschen Ärztekammern vor.
[...]

Georg Thieme Verlag KG Stuttgart · New York

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Entwicklung neuer Antibiotika: Endpunkte klinischer Studien teils ungeeignet

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 5-6
DOI: 10.1055/s-0043-117062



Georg Thieme Verlag KG Stuttgart · New York

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Atemübungen schützen ältere Patienten vor gefährlichen Lungenentzündungen

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 753-753
DOI: 10.1055/s-0043-121213



Georg Thieme Verlag KG Stuttgart · New York

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Interventionen zur präoperativen Unterstützung geriatrischer Patienten mit Frailty

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 777-783
DOI: 10.1055/s-0043-104684

Der stetig zu beobachtende demografische Wandel geht mit veränderten Anforderungen an die Patientenbetreuung einher. Ältere Patienten weisen häufig einen erhöhten Behandlungsbedarf und eine höhere Komplexität des klinischen Gesamtbildes auf. Dieser Umstand ist – abgesehen von der Routineversorgung – besonders dann zu beachten, wenn eine angedachte Intervention zu schweren und potenziell lebensbedrohlichen Komplikationen führen kann.
[...]

Georg Thieme Verlag KG Stuttgart · New York

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Therapiebegrenzung: DIVI empfiehlt neuen Dokumentationsbogen

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 752-753
DOI: 10.1055/s-0043-119947



Georg Thieme Verlag KG Stuttgart · New York

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Zervikale Plexusblockaden

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 806-813
DOI: 10.1055/s-0043-115204

Eine vollständige Blockade des Plexus cervicalis ist weder erwünscht noch ausreichend für eine chirurgische Anästhesie in der vorderen Halsregion. Supplementierungen durch Opioide oder topische Lokalanästhetika sind daher häufig. Die Blockade beteiligter Hirnnerven und des Truncus sympathicus verbessert möglicherweise die Anästhesiequalität, führt aber auch zu typischen Nebenwirkungen. Dieser Beitrag liefert anatomisches Hintergrundwissen und stellt Indikationen vor – auch außerhalb der Karotischirurgie.
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Georg Thieme Verlag KG Stuttgart · New York

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Warum und wie sollte ich Frailty erfassen? – ein Ansatz für die Anästhesieambulanz

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 765-776
DOI: 10.1055/s-0043-104682

Frailty (Gebrechlichkeit) ist eine Einschränkung der physiologischen Reserve bei älteren Patienten mit schwerwiegenden individuellen und sozioökonomischen Folgen. Multiple Aspekte der Patientenbehandlung sowie das Outcome werden durch Frailty nachhaltig beeinflusst. Obwohl mehr als 60 Messinstrumente existieren, sind die Erfassung und Berücksichtigung funktioneller Assessments in der klinischen Routine unzureichend umgesetzt. Das interdisziplinäre und interprofessionelle Verständnis, warum und wie Frailty beurteilt werden sollte, ist die Grundlage für die dauerhafte Implementierung. Der Artikel zeigt die Auswirkungen von Frailty und Vorteile einer Früherkennung auf und gibt einen Überblick über die wichtigsten Instrumente, die in der Frailty-Erkennung und -Bewertung verwendet werden können. Die frühe präoperative Detektion bietet ein vielfältiges Optimierungspotenzial für die peri- und intraoperative Versorgung. Verschiedene Frailty-Assessment-Tools körperlicher, kognitiver und psychosozialer Domänen werden vorgestellt und diskutiert. Frailty-Assessments variieren immens in Bezug auf die erforderliche Zeit, die Ausrüstung und das Fachwissen zur Durchführung. Wir empfehlen mindestens einen Test für die einzelnen Dimensionen von Frailty, um ein holistisches Bild der geriatrischen Patienten zu erhalten. Die Bewertung von Frailty sollte übergreifend in die interdisziplinären Strukturen der klinischen Routine implementiert werden, um die Patientensicherheit sowie das kurz- und langfristige Outcome zu verbessern.
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Georg Thieme Verlag KG Stuttgart · New York

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Vielen Dank!

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 754-754
DOI: 10.1055/s-0043-121256



Georg Thieme Verlag KG Stuttgart · New York

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Die meisten Todesbescheinigungen weisen Fehler auf

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 752-752
DOI: 10.1055/s-0043-121621



Georg Thieme Verlag KG Stuttgart · New York

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Patienten mit Frailty: Anästhesiologie in der Verantwortung

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 756-757
DOI: 10.1055/s-0043-117836



Georg Thieme Verlag KG Stuttgart · New York

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Tools Allowing Independent Visualization and Genetic Manipulation of Drosophila melanogaster Macrophages and Surrounding Tissues

Drosophila melanogaster plasmatocytes, the phagocytic cells among hemocytes, are essential for immune responses, but also play key roles from early development to death through their interactions with other cell types. They regulate homeostasis and signaling during development, stem cell proliferation, metabolism, cancer, wound responses and aging, displaying intriguing molecular and functional conservation with vertebrate macrophages. Given the relative ease of genetics in Drosophila compared to vertebrates, tools permitting visualization and genetic manipulation of plasmatocytes and surrounding tissues independently at all stages would greatly aid in fully understanding these processes, but are lacking. Here we describe a comprehensive set of transgenic lines that allow this. These include extremely brightly fluorescing mCherry-based lines that allow GAL4-independent visualization of plasmatocyte nuclei, cytoplasm or actin cytoskeleton from embryonic Stage 8 through adulthood in both live and fixed samples even as heterozygotes, greatly facilitating screening. These lines allow live visualization and tracking of embryonic plasmatocytes, as well as larval plasmatocytes residing at the body wall or flowing with the surrounding hemolymph. With confocal imaging, interactions of plasmatocytes and inner tissues can be seen in live or fixed embryos, larvae and adults. They permit efficient GAL4-independent FACS analysis/sorting of plasmatocytes throughout life. To facilitate genetic analysis of reciprocal signaling, we have also made a plasmatocyte-expressing QF2 line that in combination with extant GAL4 drivers allows independent genetic manipulation of both plasmatocytes and surrounding tissues, and a GAL80 line that blocks GAL4 drivers from affecting plasmatocytes, both of which function from the early embryo to the adult.



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Construction of Designer Selectable Marker Deletions with CRISPR-Cas9 Toolbox in Schizosaccharomyces pombe and Optimized Design of Common Entry Vectors

Vectors encoding selectable markers have been widely used in yeast to maintain or express exogenous DNA fragments. In the fission yeast Schizosaccharomyces pombe, several engineered markers have been reported and widely used, such as ura4+ and ScLEU2 from Saccharomyces cerevisiae, which complement ura4 and leu1 mutations, respectively. These two auxotrophic markers share no homology with the Sch. pombe genome, however most others can recombine with the genomic due to sequence homology shared between the genomic and plasmid-born copies of the markers. Here, we describe a CRISPR-Cas9 toolbox that can be used to quickly introduce into host strains "designer" auxotrophic marker deletions, including leu1-0, his3-0 and lys9-0. Together with ura4-D18, this brings the total number of available designer deletion auxotrophic markers to four. The toolbox consists of a Cas9-gRNA expression vector and a donor DNA plasmid pair for each designer deletion. Using this toolbox, a set of auxotrophic Sch. pombe strains was constructed. Further, we reorganized essential components in the commonly used pREP series of plasmids and assembled the corresponding auxotrophic marker gene onto these plasmids. This toolbox for producing designer deletions, together with the newly developed strains and plasmids will benefit the whole yeast community.



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Re: Characteristics of a Mild Traumatic Brain Injury Sample Recruited Using Amazon’s Mechanical Turk

As Mr Bernstein and Dr Calamia note in their recent article, "Characteristics of a Mild Traumatic Brain Injury Sample Recruited Using Amazon's Mechanical Turk," Amazon's Mechanical Turk (MTurk) is an increasingly popular platform for recruiting research participants in the behavioral and health sciences [1]. We agree that MTurk provides efficient and low-cost access to high-quality data. However, researchers must also navigate important drawbacks to effectively use this platform. We use Bernstein and Calamia's study to highlight some of these drawbacks and offer strategies to address them.

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Response to Shapiro and Chandler Letter to the Editor

We thank Drs Shapiro and Chandler for their helpful comments [1] on our manuscript [2] and their larger discussion of the potential pitfalls when using MTurk to assess clinical populations. In the space below, as a response to some of the concerns noted, we provide additional details not included in our manuscript on a few aspects of our study.

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Successful Endoscopic Transmural Drainage of Septate Walled off Necrosis by Fracturing the Septum under EUS guidance



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Reply to “Movement-related neural processing in people with congenital mirror movements beyond the (cortical) surface”

Thank you for the invitation to respond, and for bringing to our attention the interesting research of Manara and colleagues on Kallmann syndrome (KS). We would first like to point out that our published research involving people with mirror movements has focused only on those with isolated congenital mirror movements, that is non-syndromic (referred to as 'CMM' in our papers and in this response). CMM involves mirroring of the hands/fingers in the homologous motor system(s) of intended unimanual movements, although a minority of cases also show evidence of mirroring in the upper arms or feet (Franz, 2003; Franz et al., 2015; Franz and Fu, 2017).

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Successful Endoscopic Transmural Drainage of Septate Walled off Necrosis by Fracturing the Septum under EUS guidance



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High intraoperative inspiratory oxygen fraction and risk of major respiratory complications

British Journal of Anaesthesia, 2017; 119(1): 140–9, DOI 10.1093/bja/aex128

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Ohio ambulance manufacturer, Braun Industries, awarded contract for Detroit Fire Department

Braun Industries will deliver 49 new ambulances to the city of Detroit over the next 5 years. VAN WERT, Ohio — Braun Industries is pleased to announce that they will be manufacturing the new ambulance units for the Detroit Fire Department. The city of Detroit placed an order for 49 new Chief XL ambulances. Under the five-year contract, Braun Industries delivered 14 new units by the end of 2017 ...

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ESO Solutions predicts key hospital trends to watch in 2018

Focus on Acute Care, Healthcare Financing, and Interoperability will be essential. You can download the free white paper here. AUSTIN — ESO Solutions, the leading data and software company serving emergency medical services, fire departments, and hospitals, today shared the trends it predicts will have the biggest impact on hospitals in 2018: A greater emphasis on evidence-based approaches to ...

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The European Society of Regional Anaesthesia and Pain Therapy/American Society of Regional Anesthesia and Pain Medicine Recommendations on Local Anesthetics and Adjuvants Dosage in Pediatric Regional Anesthesia

Background and Objectives Dosage of local anesthetics (LAs) used for regional anesthesia in children is not well determined. In order to evaluate and come to a consensus regarding some of these controversial topics, The European Society of Regional Anaesthesia and Pain Therapy (ESRA) and the American Society of Regional Anesthesia and Pain Medicine (ASRA) developed a Joint Committee Practice Advisory on Local Anesthetics and Adjuvants Dosage in Pediatric Regional Anesthesia. Methods Representatives from both ASRA and ESRA composed the joint committee practice advisory. Evidence-based recommendations were based on a systematic search of the literature. In cases where no literature was available, expert opinion was elicited. Results Spinal anesthesia with bupivacaine can be performed with a dose of 1 mg/kg for newborn and/or infant and a dose of 0.5 mg/kg in older children (>1 year of age). Tetracaine 0.5% is recommended for spinal anesthesia (dose, 0.07–0.13 mL/kg). Ultrasound-guided upper-extremity peripheral nerve blocks (eg, axillary, infraclavicular, interscalene, supraclavicular) in children can be performed successfully and safely using a recommended LA dose of bupivacaine or ropivacaine of 0.5 to 1.5 mg/kg. Dexmedetomidine can be used as an adjunct to prolong the duration of peripheral nerve blocks in children. Conclusions High-level evidence is not yet available to guide dosage of LA used in regional blocks in children. The ASRA/ESRA recommendations intend to provide guidance in order to reduce the large variability of LA dosage currently observed in clinical practice. Accepted for publication August 20, 2017. Address correspondence to: Santhanam Suresh, MD, Ann & Robert H. Lurie Children's Hospital of Chicago, 225 E Chicago Ave, Chicago, IL 60611 (e-mail: ssuresh@luriechildrens.org). Identification of institution(s) where work is attributed: Ann & Robert H. Lurie Children's Hospital of Chicago Northwestern University, Chicago, IL; and Department of Anesthesiology at Rhode Island Hospital, Alpert School of Medicine, Brown University, Providence, RI. The authors declare no conflict of interest. Copyright © 2018 by American Society of Regional Anesthesia and Pain Medicine.

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Epidural Hematoma Following Interlaminar Epidural Injection in Patient Taking Aspirin

Objective We present a case report of a patient who developed an epidural hematoma following an interlaminar epidural steroid injection with no risk factors aside from old age and aspirin use for secondary prevention. Case Report A 79-year-old man developed an epidural hematoma requiring surgical treatment following an uncomplicated interlaminar epidural steroid injection performed for neurogenic claudication. In the periprocedural period, he continued aspirin for secondary prophylaxis following a myocardial infarction. Conclusions For patients taking aspirin for primary or secondary prophylaxis, the American Society of Regional Anesthesia and Pain Medicine antiplatelet and anticoagulation guidelines for spine and pain procedures recommend a shared assessment and risk stratification when deciding to hold the medication for intermediate-risk neuraxial procedures. Cases such as this serve to highlight the importance of giving careful consideration to medical optimization of a patient even when a low- or intermediate-risk procedure is planned. Accepted for publication September 2, 2017. Address correspondence to: Rebecca A. Sanders, MD, 200 First Street SW, Rochester, MN 55901 (e-mail: Sanders.rebecca@mayo.edu). The authors declare no conflict of interest. A case abstract was presented at the 2016 Annual Meeting of the American Academy of Pain Medicine; February 18 to 21, 2016; Palm Springs, CA. Copyright © 2018 by American Society of Regional Anesthesia and Pain Medicine.

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Physiological Responses to Overdressing and Exercise-Heat Stress in Trained Runners

AbstractHeat acclimation is the best strategy to improve performance in a hot environment. Many athletes seeking the benefits of heat acclimation lack access to a hot environment for exercise, and thus rely on over-dressing to simulate environmental heat stress. It is currently unknown whether this approach produces the requisite thermoregulatory strain necessary for heat acclimation in trained men and women.PURPOSETo compare physiological and cellular responses to exercise in a hot environment (HOT; 40°C, 30%rh) with minimal clothing (clo= 0.87) and in a temperate environment (CLO; 15°C, 50%rh) with overdressing (clo=1.89) in both men and women.METHODSHeart rate (HR), rectal temperature (Tre), mean skin temperature (Tsk), sweating rate (SR), and extracellular heat shock protein (eHSP)72 were measured in 13 (7M, 6F) well-trained runners (VO2max: 58.7±10.7 ml·kg-1·min-1) in response to ~60 minutes of treadmill running at 50-60% VO2max in HOT and CLO.RESULTSTre increased in both conditions, but the increase was greater in HOT ([INCREMENT]Tre HOT: 2.6 ± 0.1°C; CLO 2.0 ± 0.1°C; p=0.0003). SR was also higher in HOT (1.41± 0.1L·hr-1; CLO: 1.16 ± 0.1L·hr-1; p=0.0001). eHSP72 increased in HOT (% change: 59±11%; p=0.03) but not in CLO (6±2%; p=0.31). Mean Tsk and HR were not different between HOT and CLO in men, but were higher in HOT for women.CONCLUSIONSThese data support the idea that over-dressing during exercise in a temperate environment may produce the high Tre, Tsk, HR, and SR necessary for adaptation, but these responses do not match those in hot, dry environments. It is possible that a greater exercise stimulus, warmer environment, or more clothing may be required to allow for a similar level of acclimation. Heat acclimation is the best strategy to improve performance in a hot environment. Many athletes seeking the benefits of heat acclimation lack access to a hot environment for exercise, and thus rely on over-dressing to simulate environmental heat stress. It is currently unknown whether this approach produces the requisite thermoregulatory strain necessary for heat acclimation in trained men and women. PURPOSE To compare physiological and cellular responses to exercise in a hot environment (HOT; 40°C, 30%rh) with minimal clothing (clo= 0.87) and in a temperate environment (CLO; 15°C, 50%rh) with overdressing (clo=1.89) in both men and women. METHODS Heart rate (HR), rectal temperature (Tre), mean skin temperature (Tsk), sweating rate (SR), and extracellular heat shock protein (eHSP)72 were measured in 13 (7M, 6F) well-trained runners (VO2max: 58.7±10.7 ml·kg-1·min-1) in response to ~60 minutes of treadmill running at 50-60% VO2max in HOT and CLO. RESULTS Tre increased in both conditions, but the increase was greater in HOT ([INCREMENT]Tre HOT: 2.6 ± 0.1°C; CLO 2.0 ± 0.1°C; p=0.0003). SR was also higher in HOT (1.41± 0.1L·hr-1; CLO: 1.16 ± 0.1L·hr-1; p=0.0001). eHSP72 increased in HOT (% change: 59±11%; p=0.03) but not in CLO (6±2%; p=0.31). Mean Tsk and HR were not different between HOT and CLO in men, but were higher in HOT for women. CONCLUSIONS These data support the idea that over-dressing during exercise in a temperate environment may produce the high Tre, Tsk, HR, and SR necessary for adaptation, but these responses do not match those in hot, dry environments. It is possible that a greater exercise stimulus, warmer environment, or more clothing may be required to allow for a similar level of acclimation. Corresponding Author: Christopher T. Minson, PhD, Department of Human Physiology, 1240 University of Oregon, 122C Esslinger Hall, Eugene, OR 97403, Email: minson@uoregon.edu Funding was provided by the Kenneth and Kenda Singer Endowment. We do not have any conflicts of interest, and all results are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. The results of the present study do not constitute endorsement by the ACSM. Accepted for Publication: 1 December 2017 © 2018 American College of Sports Medicine

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BMP3 promoter hypermethylation in plasma-derived cell-free DNA in colorectal cancer patients

Abstract

Detecting cfDNA in plasma or serum could serve as a 'liquid biopsy', for circulating tumor DNA with aberrant methylation patterns offer a possible method for early detection of several cancers which could avoid the need for tumor tissue biopsies. Bone Morphogenetic Protein 3 (BMP3) was identified as a candidate tumor suppressor gene putatively down-regulated in colorectal cancer (CRC). In this study, we aimed to assess the potential role of BMP3 promoter methylation changes in plasma DNA for detection of colorectal cancerous and precancerous lesions. Plasma DNA samples were extracted from 50 patients with histologically diagnosed polyps or tumor and 50 patients reported negative for polyps or tumors. The procedure consists of bisulfite conversion of the extracted DNA, purification of bis-DNA, and BMP3 methylation status analysis by using the bisulfite specific high resolution melting analysis. This study demonstrated that there was a significantly higher frequency of BMP3 methylated DNA in plasma in patients with polyps versus healthy controls with a sensitivity and specificity of 40 and 94%, respectively. In conclusion, our results demonstrated that BMP3 DNA methylation in plasma had not have sufficient sensitivity and it should be used in combination with other biomarkers for the detection of CRC.



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Prone Position, Cerebral Oximetry, and Delirium

No abstract available

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Ill. foundation to help with more AEDs in schools

Operation Revive aims to add or replace AEDs in schools, and will start with rural schools farthest away from first responders

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ZICO launches line of brackets for improved tool mounting

YARDLEY, Pa. — Ziamatic Corp. (Zico) introduces Slotted Variable Mounts, a new line of brackets for the mounting of handheld tools, designed to provide improved flexibility and customization when laying out and mounting to 1"x1" tool board grids. With their easy-to-use slotted bases, Slotted Variable Mounts eliminate the positioning restrictions of pre-drilled holes and increase total ...

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New app could provide vital patient information to EMS providers

Vital ICE is an application that stores important information like contact numbers, lists of prescription medications, blood type and healthcare conditions

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Fire department increases survival rate with pit crew CPR

Each team member has a job, including one to do compressions, one to ventilate and another to medicate

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What's on the EMS radar screen for 2018?

By Ed Racht, MD I'm betting that we would all agree that never in our careers has there been so much change and disruption (both good and not-so-good) in both the art and science of emergency medical services. There's so much going on in clinical medicine, operational delivery, cultural expectations of EMS, healthcare system changes at the macro level, system design and the technology that ...

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The large-conductance voltage- and Ca2+-activated K+ channel and its γ1 subunit modulate mouse uterine artery function during pregnancy

Abstract

Insufficient vasodilation of the uterine artery (UA) during pregnancy leads to poor utero-placental perfusion, contributing to intrauterine growth restriction and fetal loss. Activity of the large conductance Ca2+-activated K+ (BKCa) channel increases in the UA during pregnancy, and its inhibition reduces uterine blood flow, highlighting a role of this channel in UA adaptation to pregnancy. The auxiliary γ1-subunit increases BKCa activation in vascular smooth muscle, but its role in pregnancy-associated UA remodelling is unknown. We explored whether the BKCa and its γ1-subunit contribute to UA remodelling during pregnancy. Doppler imaging revealed that, compared to UAs from wild-type (WT) mice, UAs from BKCa knockout (BKCa−/−) mice had lower resistance at pregnancy day 14 (P14) but not at P18. Lumen diameters were two-fold larger in pressurized UAs from P18 WT mice than in those from non-pregnant mice, but this difference was not seen in UAs from BKCa−/− mice. UAs from pregnant WT mice constricted 20–50% in response to the BKCa blocker iberiotoxin (IbTX), whereas UAs from non-pregnant WT mice only constricted 15%. Patch-clamp analysis of WT UA smooth muscle cells confirmed that BKCa activity increased over pregnancy, showing three distinct voltage-sensitivities. The γ1-subunit transcript increased 7-10-fold during pregnancy. Furthermore, γ1-subunit knockdown reduced IbTX-sensitivity in UAs from pregnant mice, whereas γ1-subunit overexpression increased IbTX-sensitivity in UAs from non-pregnant mice. Finally, at P18, γ1-knockout (γ1−/−) mice had smaller UA diameters than WT mice, and IbTX-mediated vasoconstriction was prevented in UAs from γ1−/− mice. Our results suggest that the γ1-subunit increases BKCa activation in UAs during pregnancy.

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Aging of the carotid body

Abstract

The aging process is characterized by a decline in several physiological functions resulting in a reduced capability to maintain homeostasis. The lowered homeostatic capacity seems to involve the carotid body (CB), whose role is to modulate ventilation and tissue oxygen supply, thus playing a prime role in all aging processes. Aging causes marked changes in CB morphology. Indeed, it is enlarged and shows a concomitant decrease in the percentage of chemoreceptor tissue, as well as a proliferation of Type II cells. The carotid glomitis is present with aggregates of lymphocytes and fibrosis of the lobules. Type I cells are dehydrated, with a profound vacuolization, a shrinking nucleus, and lipofuscin accumulation. With increased age human CB shows a reduction in the number and volume of mitochondria, fewer synaptic junctions between glomi, along with a reduction in CB content of neurotransmitters, leading to a sort of 'physiological denervation'. Aging could be interpreted as a cumulative result of oxidative damage to cells, which derives from aerobic metabolism. Moreover, metabolism rate is tightly correlated with life duration, thus a loss in mitochondrial function is one of the prime factors affecting CB aging processes. The age-related reduction in synaptic junctions might be a self-protective mechanism through which cells buffer themselves against accumulation of reactive oxygen species. The correlation between hypoxia and life duration of CB cells remains open until the question of how and why cells sense oxygen is solved.

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Pharmacological modulation of mitochondrial calcium homeostasis

Abstract

Mitochondria are pivotal organelles in calcium (Ca2+) handling and signalling, constituting intracellular checkpoints for numerous processes that are vital for cell life. Alterations in mitochondrial Ca2+ homeostasis have been linked to a variety of pathological conditions and are critical in the etiology of several human diseases. Efforts have been taken to harness mitochondrial Ca2+ transport mechanisms for therapeutic intervention but pharmacological compounds that direct and selectively modulate mitochondrial Ca2+ homeostasis are currently lacking. New avenues have however emerged with the breakthrough discoveries on the genetic identification of the main players involved in mitochondrial Ca2+ influx and efflux pathways and with recent hints towards a deep understanding of the function of these molecular systems. Here, we review the current advances in the understanding of the mechanisms and regulation of mitochondrial Ca2+ homeostasis and its contribution to physiology and human disease. We also introduce and comment on the recent progresses towards a systems-level pharmacological targeting of mitochondrial Ca2+ homeostasis.

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Identification of a single MPV17 nonsense-associated altered splice variant in 24 South African infants with mitochondrial neurohepatopathy

Abstract

MPV17-related mitochondrial neurohepatopathy is a rare genetic disorder worldwide. We report on a novel pathogenic variant in the MPV17 gene in 24 unrelated neurohepatopathic infants of non-consanguineous Black South African heritage.

Exome sequencing identified homozygosity for a c.106C>T nonsense variant in exon 3 of the human MPV17 gene in two unrelated index patients. mRNA analysis revealed transcripts both with and without exon 3, indicating both reduced splice efficiency and premature termination as mechanisms for disease. Carrier frequency in this population was found to be 1 in 68 (95% CI; 1/122 – 1/38) with an estimated newborn incidence of 1 in 18496 (95% CI; 1/59536 – 1/5776). Affected infants all presented with infantile onset neurohepatopathy with none surviving beyond infancy. This description of a relatively common pathogenic variant underlying a previously uncharacterised severe neurohepatopathy in South Africa will engender increased awareness, earlier diagnosis and possibly improve outcome if preventative or specific therapeutic options can be found.

Thumbnail image of graphical abstract

Exome sequencing reveals homozygous nonsense mutation (c.106C>T) in MPV17 in 24 Black South African patients with mitochondrial neurohepatopathy. The variant is shown to result in 2 nonsense transcripts: One caused by the introduction of a premature stop codon (p.Gln36Ter) and the second due to nonsense-associated alternative splicing caused by a reduction in exonic splice enhancer efficiency (p.Ser25Profs*49).



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Lactate metabolism: historical context, prior misinterpretations, and current understanding

Abstract

Lactate (La) has long been at the center of controversy in research, clinical, and athletic settings. Since its discovery in 1780, La has often been erroneously viewed as simply a hypoxic waste product with multiple deleterious effects. Not until the 1980s, with the introduction of the cell-to-cell lactate shuttle did a paradigm shift in our understanding of the role of La in metabolism begin. The evidence for La as a major player in the coordination of whole-body metabolism has since grown rapidly. La is a readily combusted fuel that is shuttled throughout the body, and it is a potent signal for angiogenesis irrespective of oxygen tension. Despite this, many fundamental discoveries about La are still working their way into mainstream research, clinical care, and practice. The purpose of this review is to synthesize current understanding of La metabolism via an appraisal of its robust experimental history, particularly in exercise physiology. That La production increases during dysoxia is beyond debate, but this condition is the exception rather than the rule. Fluctuations in blood [La] in health and disease are not typically due to low oxygen tension, a principle first demonstrated with exercise and now understood to varying degrees across disciplines. From its role in coordinating whole-body metabolism as a fuel to its role as a signaling molecule in tumors, the study of La metabolism continues to expand and holds potential for multiple clinical applications. This review highlights La's central role in metabolism and amplifies our understanding of past research.



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De novo variants in SETD1B are associated with intellectual disability, epilepsy and autism

Abstract

SETD1B (SET domain containing 1B) is a component of SET1 histone methyltransferase complex, which mediates the methylation of histone H3 on lysine 4 (H3K4). Here, we describe two unrelated individuals with de novo variants in SETD1B identified by trio-based whole exome sequencing: c.5524C>T, p.(Arg1842Trp) and c.5575C>T, p.(Arg1859Cy). The two missense variants occurred at evolutionarily conserved amino acids and are located within the SET domain, which plays a pivotal role in catalyzing histone methylation. Previous studies have suggested that de novo microdeletions in the 12q24.3 region encompassing SETD1B were associated with developmental delays, intellectual disabilities, autism/autistic behavior, large stature and craniofacial anomalies. Comparative mapping of 12q24.3 deletions refined the candidate locus, indicating KDM2B and SETD1B to be the most plausible candidate genes for the pathogenicity of 12q24.3 deletion syndrome. Our cases showed epilepsy, developmental delay, intellectual disabilities, autistic behavior and craniofacial dysmorphic features, which are consistent with those of individuals with de novo 12q24.31 deletions. Therefore, our study suggests that SETD1B aberration is likely to be the core defect in 12q24.3 deletion syndrome.



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UK Families with Children with Rare Chromosome Disorders: Changing Experiences of Diagnosis and Counseling (2003 to 2013)

ABSTRACT

The latest United Kingdom (UK) strategy for rare diseases emphasises the need to empower affected populations to improve diagnosis, intervention, and coordination of care. Families who have a child with a rare chromosome disorder (RCD) are a challenging group to include. We report the findings of two large-scale surveys, undertaken by the UK RCD Support Group Unique, of these families' experiences over a ten year period. Seven stages of the patient journey were examined. From pre-testing, through diagnosis, genetics consultation, clinical follow-up and peer support. Overall, 1,158 families replied; 36.4% response rate (2003) and 53.6% (2013). Analysis of responses identifies significant differences (p<0.001) over time with a decrease in results reported face-to-face (76-62%), doubling by telephone (12-22%), improved explanation of chromosome disorder (57-75%), and increased signposting to peer support group (34-62%). However, conduct of the consultation raises a number of important questions. Overall, 28 aspects of the patient journey are recognised as requiring improvement; only 12/28 are currently incorporated in UK service specifications. Involvement of RCD families has identified key service improvements. This approach can empower those affected by such extremely rare disorders, and also enable professionals to design improved services in partnership with 'expert families'. Further surveys are planned.

Thumbnail image of graphical abstract

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Associations Between Peer Counseling and Breastfeeding Initiation and Duration: An Analysis of Minnesota Participants in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC)

Abstract

Background Peer counseling (PC) has been associated with increased breastfeeding initiation and duration, but few analyses have examined the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) model for peer counseling or the continuation of breastfeeding from birth through 12 months postpartum. Objectives Identify associations between Minnesota WIC Peer Breastfeeding Support Program services and breastfeeding initiation and continuation. Methods Retrospective analysis of observational data from the Minnesota WIC program's administrative database of women who gave birth in 2012 and accepted a PC program referral prenatally (n = 2219). Multivariate logistic regression and Cox regression models examined associations between peer services and breastfeeding initiation and continuation of any breastfeeding. Results Among women who accepted referral into a PC program, odds of initiation were significantly higher among those who received peer services (Odds Ratio (OR): 1.66; 95% CI 1.19–2.32), after adjusting for confounders. Women who received peer services had a significantly lower hazard of breastfeeding discontinuation from birth through 12 months postpartum than women who did not receive services. (Hazard Ratio (HR) month one: 0.45; 95% CI 0.33–0.61; months two through twelve: 0.33; 95% CI 0.18–0.60). The effect of peer counseling did not differ significantly by race and ethnicity, taking into account mother's country of origin. Conclusion for practice Receipt of peer services was positively associated with breastfeeding initiation and continued breastfeeding from birth through 12 months postpartum. Making peer services available to more women, especially in communities with low initiation and duration, could improve maternal and child health in Minnesota.



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