bluuebunny/crossref_metadata_2025 huggingface dataset:
Gesundheitliche Themen medizinischer Online-Anfragen am UniversitätsSpital Zürich: Erfahrungen der letzten 12 Jahre
Authors: Brockes Christiane , Barresi Fabio , Schmidt Christian , Schulz Egbert , Schmidt-Weitmann Sabine
Published: October 2018

Einleitung Die Digitalisierung im Gesundheitswesen führt zu neuen Bedürfnissen und Herausforderungen in der Arzt-Patienten-Beziehung. Das UniversitätsSpital Zürich bietet seit 1999 eine webbasierte medizinische Onlineberatung für Laien an. Ziel der retrospektiven Studie war es zu analysieren, welche Anfragethemen im Vordergrund standen.

Methodik Eingeschlossen wurden Anfragen und Antworten von 2005 bis 2016. Die Berechnung der Häufigkeiten umfasste die Anfragethemen klassifiziert nach ICD-10-Kapiteln, Alter und Geschlecht der Fragesteller, Anzahl empfohlener Arztbesuche sowie Antwortbewertungen. Veränderungen in den Häufigkeiten wurden mittels Regressionsanalyse geprüft.

Ergebnis Das Durchschnittsalter der insgesamt 23 131 Anfragenden lag bei 37,9 ± 16,63 Jahren. Das Alter sowie der Anteil der männlichen Anfragenden nahm signifikant zu mit jährlich 1,22 Jahren bzw. 1,6 % Männeranteil. Die häufigsten gesundheitlichen Themen nach der ICD-10-Klassifikation beinhalteten symptomorientierte oder allgemeine Anfragen zu Beschwerden ohne Bezug auf eine bestimmte Erkrankung (Kapitel XVIII: 13,8 % und XXI: 11,6 %), gefolgt von Anfragen zur Haut (XII: 8,8 %), zum Muskel-Skelett-System (XIII: 7,5 %) und zum Urogenitalsystem (XIV: 7,4 %). Signifikant zugenommen haben die Anfragen zu den Kapiteln XVIII und II (Neubildungen). Mit „gut“ bis „sehr gut“ bewerteten 80,2 % der Anfragesteller den Nutzen und mit 96,7 % die Verständlichkeit der Online-Antworten.

Diskussion Eine webbasierte Onlineberatung kann das Patient-Empowerment und die Gesundheitskompetenz medizinischer Laien stärken durch die individuelle Bereitstellung von Gesundheitsinformationen. Dies umfasste insbesondere unklare Symptome und Befunde ohne Diagnose. Die Vorteile einer anonymen Onlineberatung wurden insbesondere bei intimen Fragestellungen und zunehmend von Männern genutzt. Die Zunahme von Anfragen zu Neubildungen sind möglicherweise auf die komplexen Behandlungsstrategien in der Onkologie zurückzuführen.
Sprunggelenksfraktur an Bord eines Frachtschiffs
Authors: Kohfahl Jens , Stuhr Markus
Published: October 2018

An einem Tag Ende August erging über das Maritime Rescue Coordination Center (MRCC) der Deutschen Gesellschaft zur Rettung Schiffbrüchiger (DGzRS) in Bremen um 15:45 Uhr folgende Meldung an einen Seenotrettungskreuzer: „Verdacht auf Unterschenkelfraktur an Bord eines Frachtschiffs“. Aufgrund der präzisen Notfallmeldung erfolgte durch den Vormann (seemännische Bezeichnung für den Kapitän eines Rettungskreuzers) vor dem Auslaufen die Anforderung eines Notarztes, sodass der Seenotrettungskreuzer um 16:00 Uhr ablegte und in Richtung des Frachtschiffs auslief. Der Einsatzort befand sich im Bereich der Elbmündung circa 16 sm (1 Seemeile/sm = 1,852 km) entfernt. Bei bedecktem Himmel wehte der Wind mit 5 Windstärken (ca. 30–40 km/h) aus einer nordwestlichen Richtung, die Seegangshöhe betrug 1–1,5 m. Durch die Gegenströmung des auflaufenden Wassers verlängerte sich die Anfahrtszeit, sodass der Seenotrettungskreuzer um 17:08 Uhr längsseits zum Frachtschiff gehen konnte (Abb. 1).

Bereits auf der Anfahrt konnte durch direkten UKW-Sprechfunkkontakt mit dem Kapitän des Schiffes in Erfahrung gebracht werden, dass der Lotse beim Übersteigen auf dem nassen Deck ausgerutscht sei und sich dabei vermutlich den Unterschenkel gebrochen habe. Aufgrund der starken Schmerzen konnte man ihn nicht bewegen. Er würde deshalb noch an Deck liegen und man habe ihn mit einer Decke zugedeckt.
Kontinuierliche nicht-invasive Blutdruckmessung mittels Pulswellen-Transit-Zeit bei Kindern und Jugendlichen
Authors: Zagrada Elena , Krickau Tobias , Rascher Wolfgang
Published: October 2018

Hintergrund Alternativ zu ambulanten 24h-Blutdruckmessgeräten wurde die kontinuierliche, nicht-invasive Blutdruckaufzeichnung mittels Pulswellenlaufzeit bzw. Puls -Transit-Zeit (PTZ) sowohl mit oszillometrischen als auch intraarteriellen Messmethoden verglichen.

Methoden An 144 pädiatrischen Patienten (9,4±5,2 Jahre) wurde der akute Blutdruck mithilfe von 3 verschiedenen Messmethoden ermittelt. An 57 Patienten (11,4±4,9 Jahre) der pädiatrischen Normalstation wurde simultan der Blutdruck kontinuierlich mittels PTZ im Vergleich zur intermittierenden oszillometrischen Langzeitmessung bestimmt. Bei 9 Patienten (9,8±6,8 Jahre) der pädiatrischen Intensivstation mit kontinuierlicher intraarterieller Blutdruckmessung wurde der Blutdruck parallel mittels PTZ gemessen.

Ergebnisse Verglichen mit dem Goldstandard der Sphygmomanometrie, waren die mittleren systolischen Blutdruckwerte mit 2 verschiedenen oszillometrischen Messgeräten vergleichbar, aber bei der diastolischen Druckmessung waren die Druckwerte signifikant niedriger bzw. höher als mit der Sphygmomanometrie und Auskultation. Die Ergebnisse der nicht-invasiven vergleichenden Langzeitmessungen zeigten insgesamt bessere Korrelationen für den systolischen als für den diastolischen Druck. Ähnliche Ergebnisse ergab der Vergleich der direkten intraarteriellen Blutdruckmessung mit dem SOMNOtouch™ NIBP -Messgerät, das den Blutdruck mittels PTZ misst.

Schlussfolgerung Die kontinuierliche, indirekte Blutdruckaufzeichnung mittels PTZ liefert im Vergleich zur Langzeitmessung des Blutdrucks bei Kindern und Jugendlichen gute Korrelationen zu den Referenzmessungen und scheint eine brauchbare Methode, v. a. in Ruhe den Blutdruck bei Kindern zu messen.
Studie zur nephroprotektiven Wirksamkeit von Paracetamol bei Erwachsenen mit schwerer Malaria tropica
Authors: Schmiedel Stefan
Published: October 2018

Plasmodium falciparum, der Erreger der Malaria tropica (englisch: falciparum malaria) ist weltweit der am häufigsten vorkommende Malariaerreger. Ein akutes Nierenversagen (ANV) ist eine häufige Komplikation einer Malaria tropica und eines der Kriterien für einen „schweren“ oder „komplizierten“ Verlauf. Ein ANV prädisponiert zu einer Reihe von weiteren Komplikationen im Verlauf einer Malaria – kardiovaskuläre Ereignisse, Entwicklung oder Progression zu einer chronischen Nierenerkrankung und erhöhte Sterblichkeit werden beobachtet.
Aktienkursentwicklung – Lohnen sich Investitionen in Unternehmen aus der Gesundheitsbranche?
Authors: Thiem Helena
Published: October 2018

Dorfleitner G et al. The financial performance of the health care industry: a global, regional and industry specific empirical investigation. Eur J Health Econ
2018; 19:585–594

Weltweit stellt der Gesundheitssektor für Investoren einen der bedeutendsten Bereiche dar. Bisher wurden nur wenige Analysen zu Prozessen in diesem Sektor
veröffentlicht. Eine empirische Untersuchung will die Entwicklung der Aktienkurse in der Gesundheitsbranche aufzeigen und Unterschiede auf globaler,
regionaler und branchenspezifischer Ebene aufdecken.
Antibiotika-Stewardship-Programme – Effektive Strategien zur Behandlung nosokomialer bakterieller Pneumonien
Authors: Thiem Helena
Published: October 2018

McKinell A et al. Effective Antimicrobial Stewardship Strategies for Cost-effective Utilization of Telavancin for the Treatment of Patients With
Hospital-acquired Bacterial Pneumonia Caused by Staphylococcus aureus. Clin Ther 2018; 40: 406–414

Bakterielle Pneumonien gelten als die häufigsten nosokomialen Infektionen in den Vereinigten Staaten. Die effektive Behandlung durch Antibiotika stellt eine
zunehmende Herausforderung dar. In einem Entscheidungsbaum-Modell sollen die finanziellen Auswirkungen zweier Therapiealternativen, einschließlich der
Kosten für Medikamente, der Gesamtbehandlungskosten und der Behandlungsergebnisse, zur Behandlung der nosokomialen Pneumonie durch Staphylococcus aureus
ermittelt werden.
Early-Onset Neonatal Sepsis with Extended Spectrum Beta-Lactamase Producing Escherichia Coli in Infants Born to South and South East Asian Immigrants: A Case Series
Authors: Dolma Kalsang , Summerlin Thanh , Wongprasert Hansa , Lal Charitharth , Philips III Joseph , Winter Lindy
Published: October 2018

Extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae represent a major worldwide threat. We present three cases of early onset ESBL Escherichia coli sepsis in infants born to families from South and Southeast Asia to inform the practitioner community about this emerging threat. Infants with suspected sepsis, whose mother is from Asia or Southeast Asia, should be suspected of having an infection with an ESBL-producing organism, and practitioners should strongly consider adding a carbapenem to their usual initial antibiotic regimen.
Antisense-Oligonukleotide II
Authors: Lehmann D. , Ludolph A. C. , Wurster C. D. , Graf H.
Published: October 2018

Antisense-Oligonukleotide (ASO) sind synthetische einzelsträngige Nukleinsäuren, die an die komplementäre Sequenz der prä- mRNA oder mRNA binden, Transkription und Translation beeinflussen und damit die Proteinsynthese modulieren. Im Jahr 2016 wurden 2 ASOs zur Behandlung neuromuskulärer Erkrankungen zugelassen. In tierexperimentellen sowie klinischen Studien zeigten sich vielversprechende Wirksamkeitsnachweise von ASOs zur Behandlung weiterer neurodegenerativer Erkrankungen. In diesem Artikel sollen die gegenwärtig zur Verfügung stehenden Ergebnisse zu ASOs bei der Behandlung der Alzheimer Demenz vorgestellt werden. Basierend auf in Tierexperimenten untersuchten ASOs sollen mögliche Zielstrukturen diskutiert werden, die zukünftig für einen Einsatz der ASO-Strategie in der Behandlung psychischer Erkrankungen sprechen könnten. Darüber hinaus sollen finanzielle und ethische Aspekte, die mit der Einführung von ASOs aufkamen, vorgestellt werden.
Rheuma und Ernährung
Authors: Michalsen A.
Published: October 2018

Viele Patienten mit rheumatischen Erkrankungen fragen nach den Möglichkeiten, ihre Erkrankung über die Ernährung zu beeinflussen. In Erhebungen und epidemiologischen Studien werden immer wieder Ernährungsfaktoren beschrieben, die mit dem Auftreten rheumatischer Erkrankungen bzw. von Schüben verbunden sind, allerdings kann kein einheitliches Ernährungsmuster beschrieben werden. Wie allgemein im nichtpharmakologischen Therapiebereich stehen nur in begrenztem Umfang Daten aus randomisierten Studien zur Evidenzbewertung zur Verfügung. Für die rheumatoide Arthritis (RA) belegen zwei randomisierte Studien die Wirksamkeit der mediterranen Ernährung. Für die vegetarischen Kostformen weisen v. a. experimentelle Daten auf grundsätzlich deutliche antientzündliche Effekte und klinische Studien auf günstige klinische Wirkungen bei kardiovaskulären Erkrankungen hin. Die Wirksamkeit glutenfreier Diäten bei RA ist fraglich und glutenfreie Diäten sollten nur bei Zöliakie oder starken Hinweisen auf eine Nicht-Zöliakie Glutensensitivität (NCGS) empfohlen werden. Mehrere Studien und eine systematische Übersicht belegen die Wirksamkeit eines sieben- bis zehntätigen Fastens auf die Symptome und Funktion bei RA. Folgt auf das Fasten eine vegane und vegetarische Ernährung, sind nachhaltige Effekte von bis zu einem Jahr dokumentiert. Der mögliche Nutzen verschiedener spezifischer Nahrungsmittel und Nahrungsergänzungen wie grüner Tee, Granatapfel, Ingwer, Leinöl, Gelbwurz ist klinisch derzeit nicht ausreichend belegt, aber v. a. für Gelbwurz (Curcuma) vielversprechend. Neuere klinisch-experimentelle Daten belegen den Einfluss des Darm-Mikrobioms auf die Entstehung der Erkrankung. Allerdings sind bislang spezifische probiotische Therapieansätze nicht ausreichend durch Daten aus klinischen Studien gestützt.
Trends in the size and age structure of marine fishes
Authors: Charbonneau Julie A , Keith David M , Hutchings Jeffrey A
Published: October 2018

Size-selective harvesting is expected to reduce the average age and weight of commercially exploited fishes. The loss of larger, older fish has been hypothesized to negatively affect metrics of population viability, such as spawning behaviour, recruitment, and adult survival. Most studies to date have focussed on individual stocks. Here, we examine trends in average age and weight at broad taxonomic and temporal scales, using subsets of data compiled on 95 marine fish stocks. Following moderate declines between 1960 and 1990, we find that the average age has generally increased since 2000, such that 71% of 69 stocks are currently above their long-term average. However, the size of the oldest individuals has generally declined over time; the average weight is currently below average in 75% of 55 stocks. A temporal decline in the mean weight of the youngest constituents within 49 stocks is most evident in the Clupeiformes. Our results indicate that recovery of age structure need not be accompanied by recovery of weights-at-age, evidenced in part by a decline in the size of the oldest individuals within populations. Further study into the drivers of these patterns, and the consequences of declining weights-at-age for population viability, is warranted.
Complex Geometry of Iwasawa Manifolds
Authors: Rogov Vasily
Published: October 2018

An Iwasawa manifold is a compact complex homogeneous manifold isomorphic to a quotient $G/\Lambda $, where $G$ is the group of complex unipotent $3 \times 3$ matrices and $\Lambda \subset G$ is a cocompact lattice. In this work, we study holomorphic submanifolds in Iwasawa manifolds. We prove that any compact complex curve in an Iwasawa manifold is contained in a holomorphic subtorus. We also prove that any complex surface in an Iwasawa manifold is either an abelian surface or a Kähler non-projective isotrivial elliptic surface of Kodaira dimension one. In the Appendix, we show that any subtorus in Iwasawa manifold carries complex multiplication.
Clinicians’ reasoning as reflected in electronic clinical note-entry and reading/retrieval: a systematic review and qualitative synthesis
Authors: Colicchio Tiago K , Cimino James J
Published: October 2018

Objective

To describe the literature exploring the use of electronic health record (EHR) systems to support creation and use of clinical documentation to guide future research.

Materials and Methods

We searched databases including MEDLINE, Scopus, and CINAHL from inception to April 20, 2018, for studies applying qualitative or mixed-methods examining EHR use to support creation and use of clinical documentation. A qualitative synthesis of included studies was undertaken.

Results

Twenty-three studies met the inclusion criteria and were reviewed in detail. We briefly reviewed 9 studies that did not meet the inclusion criteria but provided recommendations for EHR design. We identified 4 key themes: purposes of electronic clinical notes, clinicians’ reasoning for note-entry and reading/retrieval, clinicians’ strategies for note-entry, and clinicians’ strategies for note-retrieval/reading. Five studies investigated note purposes and found that although patient care is the primary note purpose, non-clinical purposes have become more common. Clinicians’ reasoning studies (n = 3) explored clinicians’ judgement about what to document and represented clinicians’ thought process in cognitive pathways. Note-entry studies (n = 6) revealed that what clinicians document is affected by EHR interfaces. Lastly, note-retrieval studies (n = 12) found that “assessment and plan” is the most read note section and what clinicians read is affected by external stimuli, care/information goals, and what they know about the patient.

Conclusion

Despite the widespread adoption of EHRs, their use to support note-entry and reading/retrieval is still understudied. Further research is needed to investigate approaches to capture and represent clinicians’ reasoning and improve note-entry and retrieval/reading.
The influence of tariff regimes on global production networks (GPNs)
Authors: Curran Louise , Nadvi Khalid , Campling Liam
Published: October 2018

Despite the recognition that trade policy—in particular, tariff regimes and rules of origin—can affect the geography of production, much GPN analyses pay scant attention to the tariff context of the sector studied. This paper proposes an analytical framework to more effectively integrate these regimes into applied GPN research. We test the framework, drawing on analysis of exports to the EU market in four sectors: textiles and apparel, floriculture, fisheries and leather goods. The analysis confirms that, in the presence of high tariffs, preferences do seem to impact on sourcing for the EU market.
Fucosyltransferase Gene Polymorphisms and Lewisb-Negative Status Are Frequent in Swedish Newborns, With Implications for Infectious Disease Susceptibility and Personalized Medicine
Authors: King Jovanka R , Varadé Jezabel , Hammarström Lennart
Published: October 2018

Background

Single-nucleotide polymorphisms (SNPs) in the fucosyltransferase genes FUT2 and FUT3 have been associated with susceptibility to various infectious and inflammatory disorders. FUT variations influence the expression of human histo-blood group antigens (HBGAs) (H-type 1 and Lewis), which are highly expressed in the gut and play an important role in microbial attachment, metabolism, colonization, and shaping of the microbiome. In particular, FUT polymorphisms confer susceptibility to specific rotavirus and norovirus genotypes, which has important global health implications.

Methods

We designed a genotyping method using a nested polymerase chain reaction approach to determine the frequency of SNPs in FUT2 and FUT3, thereby inferring the prevalence of Lewisb-positive, Lewisb-negative, secretor, and nonsecretor phenotypes in 520 Swedish newborns.

Results

There was an increased frequency of homozygotes for the minor allele for 1 SNP in FUT2 and 4 SNPs in FUT3. Overall, 37.3% of newborns were found to have Lewis b negative phenotypes (Le (a+b−) or Le (a−b−). Using our new, sensitive genotyping method, we were able to genetically define the Le (a−b−) individuals based on their secretor status and found that the frequency of Lewis b negative newborns in our cohort was 28%.

Conclusions

Given the high frequency of fucosyltransferase polymorphisms observed in our newborn cohort and the implications for disease susceptibility, FUT genotyping might play a future role in personalized health care, including recommendations for disease screening, therapy, and vaccination.
Stereotactic Brain Biopsy in Eloquent Areas Assisted by Navigated Transcranial Magnetic Stimulation: a Technical Case Report
Authors: Bartek Jiri , Cooray Gerald , Islam Mominul , Jensdottir Margret
Published: October 2018

BACKGROUND AND IMPORTANCE

Stereotactic brain biopsy (SB) is an important part of the neurosurgical armamentarium, with the possibility of achieving histopathological diagnosis in otherwise inaccessible lesions of the brain. Nevertheless, the procedure is not without the risk of morbidity, which is especially true for lesions in eloquent parts of the brain, where even a minor adverse event can result in significant deficits. Navigated transcranial magnetic stimulation (nTMS) is widely used to chart lesions in eloquent areas, successfully guiding maximal safe resection, while its potential role in aiding with the planning of a stereotactic biopsy is so far unexplored.

CLINICAL PRESENTATION

Magnetic resonance imaging of a 67-yr-old woman presenting with dysphasia revealed a noncontrast enhancing left-sided lesion in the frontal and parietal pars opercularis. Due to the location of the lesion, nTMS was used to chart both primary motor and language cortex, utilizing this information to plan a safe SB trajectory and sampling area according to the initial work-up recommendations from the multidisciplinary neuro-oncology board. The SB was uneventful, with histology revealing a ganglioglioma, WHO I. The patient was discharged the following day, having declined to proceed with tumor resection (awake surgery) due to the non-negligible risk of morbidity. Upon 1- and 3-mo follow-up, she showed no signs of any procedure-related deficits.

CONCLUSION

nTMS can be implemented to aid with the planning of a stereotactic biopsy procedure in eloquent areas of the brain, and should be considered part of the neurosurgical armamentarium.
Prediction of Spontaneous Lumbar Curve Correction After Posterior Spinal Fusion for Adolescent Idiopathic Scoliosis Lenke Type 1 Curves
Authors: Uehara Masashi , Takahashi Jun , Ikegami Shota , Kuraishi Shugo , Futatsugi Toshimasa , Oba Hiroki , Takizawa Takashi , Munakata Ryo , Koseki Michihiko , Kato Hiroyuki
Published: October 2018

Study Design:

This is a retrospective single-center and single-surgeon study.

Objective:

The present study examined for preoperative parameters having the highest correlation with compensatory thoracolumbar/lumbar (TL/L) curve correction 2 years after surgery in adolescent idiopathic scoliosis (AIS) patients with Lenke type 1 curves.

Summary of Background:

Several parameters have been considered to evaluate the flexibility of compensatory TL/L curve in AIS patients with Lenke type 1 curves. However, the imaging position with the strongest correlation with postoperative spontaneous TL/L curve correction is unknown.

Data:

In total, 37 patients with AIS Lenke type 1 curves who had undergone skip pedicle screw fixation were followed for a 2-year period were enrolled.

Materials and Methods:

TL/L Cobb angles measured at the standing posteroanterior view, supine position, supine position with maximum bending, supine position with traction, prone position, and prone-push position were determined before surgery. Using TL/L Cobb angles determined 2 years postoperatively, correlations between preoperative and postoperative Cobb angles were calculated for each position using the Spearman rank-correlation coefficient, linear regression analysis, and paired t tests.

Results:

Mean preoperative mean±SD TL/L Cobb angle was significantly improved from 31±9 to 13±8 degrees at the study end point. In analyses of correlations between postoperative TL/L Cobb angle and preoperative parameters, the supine position with traction was most strongly associated with TL/L curve correction rate at 2 years after surgery (r=0.72; P<0.01), with paired t tests revealing a significant mean difference of 3.1 degrees.

Conclusions:

Preoperative Cobb angle evaluated at the supine position with traction had the strongest correlation with spontaneously corrected TL/L curve Cobb angle after selective thoracic fusion for AIS Lenke type 1 curves. Accordingly, it may be sufficient to evaluate TL/L curve correction at this position only to reduce radiation exposure and operative time.
The association between multiple sclerosis and pain medications
Authors: Burkill Sarah , Montgomery Scott , Kockum Ingrid , Piehl Fredrik , Strid Pernilla , Hillert Jan , Alfredsson Lars , Olsson Tomas , Bahmanyar Shahram
Published: October 2018

Patients with multiple sclerosis (MS) are at greater risk of pain than people without the disease; however, the occurrence and characteristics of pain among these patients are incompletely described. We aimed to assess characteristics of pain amongst MS patients using MS patients who were recruited to participate in 3 studies in Sweden (n = 3877) and were matched with individuals without MS (n = 4548) by sex, year of birth, and region of residence. The Prescribed Drugs Register identified prescribed pain medication, overall and restricted to those given 4 or more prescriptions in 1 year to assess chronic pain. Anatomical therapeutic chemical codes classified whether pain was neuropathic, musculoskeletal, or migraine. Cox-proportional hazard models were used to estimate associations. Our findings showed patients with MS were at increased risk of pain treatment, with a hazard ratio (HR) of 2.52 (95% confidence interval 2.38-2.66). The largest magnitude HR was for neuropathic pain (5.73, 5.07-6.47) for which 34.2% (n = 1326) of the MS and 7.15% (n = 325) of the non-MS cohort were prescribed a treatment. The HR for chronic pain treatment was 3.55 (3.27-3.84), indicating an increased effect size relative to any pain treatment. Chronic neuropathic pain showed the largest HR at 7.43 (6.21-8.89). Neuropathic pain was shown to be the primary mechanism leading to increased risk of pain in patients with MS.
High-resolution Intracranial Vessel Wall Imaging in Monitoring Treatment Response in Primary CNS Angiitis
Authors: Tsivgoulis Georgios , Papadimitropoulos Georgios N. , Lachanis Stefanos , Palaiodimou Lina , Zompola Christina , Antonellou Roubina , Voumvourakis Konstantinos
Published: October 2018

Introduction:

High-resolution vessel wall imaging (HR-VWI) is emerging as a tool of notable utility in the diagnosis of intracranial vessel pathology. Its role in monitoring vessel wall disease response to treatment, however, is less well-established.

Case Report:

We report the case of a 45-year-old man with left middle and anterior cerebral artery infarcts and an National Institute of Health Stroke Scale (NIHSS) score of 2. Time-of-flight magnetic resonance angiography and digital subtraction angiography showed multifocal intracranial vessel pathology without extracranial vessel involvement. Comprehensive investigation with echocardiography and 24 hours Holter electrocardiography was unrevealing and the coagulation and routine autoimmune panel results were within normal limits. Cerebrospinal fluid showed mildly elevated protein and a diagnosis of probable primary central nervous system (PCNS) angiitis was made. The diagnosis was corroborated by intracranial HR-VWI, which showed homogenous, concentric enhancement of the left supraclinoid internal carotid artery (ICA) wall. The patient received high-dose IV methylprednisolone and cyclophosphamide. Repeat brain magnetic resonance imaging with HR-VWI at 3 and 9 months showed reduction and final resolution of vessel wall enhancement without recurrent infarcts. He has since remained clinically stable with an NIHSS score of 0 on low-dose oral glucocorticoids.

Conclusions:

Our report illustrates the utility of HR-VWI in diagnosing a case of PCNS angiitis through the demonstration of a vasculitic pattern of mural enhancement. Furthermore, it has provided evidence of disease response to treatment, assisting us in modifying treatment accordingly. Tracking disease activity and response to treatment in cases of central nervous system vasculitis can be another important use of HR-VWI in clinical practice besides assisting in establishing the diagnosis.
Disseminated High-grade Glioma in a Long-term Survivor of Medulloblastoma
Authors: Porter Alyx B. , Sio Terence T. , Nelson Kent D. , Raghunathan Aditya , Bendok Bernard R. , Mrugala Maciej M.
Published: October 2018

We describe a gentleman diagnosed with a posterior fossa medulloblastoma in 1998, successfully treated with craniospinal radiation therapy (RT) and posterior fossa RT boost, followed by 12 months of adjuvant chemotherapy. Nineteen years later, at the age of 28, the patient presented with multiple cranial neuropathies and was found to have disseminated high-grade glioma with leptomeningeal dissemination. In addition to the salient features of this case, we provide a brief review of RT-induced malignancies and the need for further research regarding surveillance and prevention strategies.
Characteristics and Outcomes of Liver Transplantation for Primary Biliary Cholangitis in Young Patients: Analysis of the United Network for Organ Sharing Database
Authors: Singh Amandeep , Fritze Danielle , Mansouri Mahsa , Lopez Rocio , Poordad Fred , Lawitz Eric , Cigarroa Francisco , Halff Glen , Alkhouri Naim
Published: October 2018

Background.

Primary biliary cholangitis (PBC) in younger patients has been suggested to require liver transplantation (LT) in early adulthood, but data is limited on its outcomes. We aimed to evaluate the characteristics and outcome of LT in young patients with PBC in comparison with older adults.

Methods.

The United Network for Organ Sharing database was analyzed for all patients with PBC who underwent LT between 2000 and 2012. Based on age at the time of LT, subjects were divided into 2 groups: young patients (≤40 y) and older adults (≥41 y). Baseline demographics, clinical parameters, and outcomes of LT were then compared between the 2 groups. Univariable and multivariable analyses were performed to assess the factors associated with outcomes of LT.

Results.

A total of 2084 patients with PBC were included in the analysis with 158 young patients. Compared with older adults, younger patients were more likely to be male (27.2% versus 15.4%) and nonwhite (43.7% versus 21.5%), but they were less likely to have obesity, diabetes, or hypertension (P < 0.05) and had a lower mortality (8.2% versus 15.1%) but higher retransplantation rate (14.6% versus 4.7%) (P < 0.001). On multivariable analysis, older age, dialysis or ventilator use, and lower albumin were associated with high post-LT mortality.

Conclusions.

Compared with older adults, early-onset PBC in younger patients requiring LT had higher percentage of males and nonwhites and had a lower prevalence of metabolic comorbidities but higher retransplantation rates. Further studies are warranted to confirm these findings.
Heritability and genetic variance of dementia with Lewy bodies
Authors: Guerreiro Rita , Escott-Price Valentina , Hernandez Dena G. , Kun-Rodrigues Celia , Ross Owen A. , Orme Tatiana , Luis Neto Joao , Carmona Susana , Dehghani Nadia , Eicher John D. , Shepherd Claire , Parkkinen Laura , Darwent Lee , Heckman Michael G. , Scholz Sonja W. , Troncoso Juan C. , Pletnikova Olga , Dawson Ted , Rosenthal Liana , Ansorge Olaf , Clarimon Jordi , Lleo Alberto , Morenas-Rodriguez Estrella , Clark Lorraine , Honig Lawrence S , Marder Karen , Lemstra Afina , Rogaeva Ekaterina , George-Hyslop Peter St. , Londos Elisabet , Zetterberg Henrik , Barber Imelda , Braae Anne , Brown Kristelle , Morgan Kevin , Troakes Claire , Al-Sarraj Safa , Lashley Tammaryn , Holton Janice , Compta Yaroslau , Van Deerlin Vivianna , Serrano Geidy E , Beach Thomas G , Lesage Suzanne , Galasko Douglas , Masliah Eliezer , Santana Isabel , Pastor Pau , Diez-Fairen Monica , Aguilar Miquel , Tienari Pentti J. , Myllykangas Liisa , Oinas Minna , Revesz Tamas , Lees Andrew , Boeve Brad F , Petersen Ronald C. , Ferman Tanis J , Graff-Radford Neill , Cairns Nigel J. , Morris John C. , Pickering-Brown Stuart , Mann David , Halliday Glenda M. , Hardy John , Trojanowski John Q. , Dickson Dennis W. , Singleton Andrew ,   for the International Parkinson’s Disease Genomics Consortium, Stone David J. , Bras Jose
Published: October 2018

Recent large-scale genetic studies have allowed for the first glimpse of the effects of common genetic variability in dementia with Lewy bodies (DLB), identifying risk variants with appreciable effect sizes. However, it is currently well established that a substantial portion of the genetic heritable component of complex traits is not captured by genome-wide significant SNPs. To overcome this issue, we have estimated the proportion of phenotypic variance explained by genetic variability (SNP heritability) in DLB using a method that is unbiased by allele frequency or linkage disequilibrium properties of the underlying variants. This shows that the heritability of DLB is nearly twice as high as previous estimates based on common variants only (31% vs 59.9%). We also determine the amount of phenotypic variance in DLB that can be explained by recent polygenic risk scores from either Parkinson’s disease (PD) or Alzheimer’s disease (AD), and show that, despite being highly significant, they explain a low amount of variance. Additionally, to identify pleiotropic events that might improve our understanding of the disease, we performed genetic correlation analyses of DLB with over 200 diseases and biomedically relevant traits. Our data shows that DLB has a positive correlation with education phenotypes, which is opposite to what occurs in AD. Overall, our data suggests that novel genetic risk factors for DLB should be identified by larger GWAS and these are likely to be independent from known AD and PD risk variants.
Genomic evidence supports a clonal diaspora model for metastases of esophageal adenocarcinoma
Authors: Noorani Ayesha , Goddard Martin , Crawte Jason , Alexandrov Ludmil B. , Li Xiaodun , Secrier Maria , Eldridge Matthew D. , Bower Lawrence , Weaver Jamie , Lao-Sirieix Pierre , Martincorena Inigo , Debiram-Beecham Irene , Grehan Nicola , MacRae Shona , Malhotra Shalini , Miremadi Ahmad , Thomas Tabitha , Galbraith Sarah , Petersen Lorraine , Preston Stephen D. , Gilligan David , Hindmarsh Andrew , Hardwick Richard H. ,   OCCAMS Consortium, Stratton Michael R. , Wedge David C. , Fitzgerald Rebecca C.
Published: October 2018

Continual evolution of cancer makes it challenging to predict clinical outcomes. Highly varied and unpredictable patient outcomes in esophageal adenocarcinoma (EAC) prompted us to question the pattern and timing of metastatic spread. Whole genome sequencing and phylogenetic analysis of 396 samples across 18 EAC cases demonstrated a stellate pattern on the phylogenetic trees in 90% cases. The age-dependent trinucleotide signature, which can serve as a molecular clock, was absent or reduced in the stellate branches beyond the trunk in most cases (p<0.0001). Clustering of lymph nodes and distant metastases (n=250) demonstrated samples sharing a common clonal origin were widely dispersed anatomically. Metastatic subclones at autopsy were present in tissue and blood samples from earlier time-points. We infer that metastasis occurs rapidly across multiple sites, constituting a model of metastatic spread we term clonal diaspora. This has implications for understanding metastatic progression, clinical staging and patient management.
The rat medial prefrontal cortex exhibits flexible neural activity states during the performance of an odor span task
Authors: De Falco E , An L , Sun N , Roebuck AJ , Greba Q , Lapish CC , Howland JG
Published: October 2018

Medial prefrontal cortex (mPFC) activity is fundamental for working memory (WM), attention, and behavioral inhibition; however, a comprehensive understanding of the neural computations underlying these processes is still forthcoming. Towards this goal, neural recordings were obtained from the mPFC of awake, behaving rats performing an odor span task of WM capacity. Neural populations were observed to encode distinct task epochs and the transitions between epochs were accompanied by abrupt shifts in neural activity patterns. Putative pyramidal neuron activity increased significantly earlier in the delay for sessions where rats achieved higher spans. Furthermore, increased putative interneuron activity was only observed at the termination of the delay thus indicating that local processing in inhibitory networks was a unique feature to initiate foraging. During foraging, changes in neural activity patterns associated with the approach to a novel odor, but not familiar odors, were robust. Collectively, these data suggest that distinct mPFC activity states underlie the delay, foraging, and reward epochs of the odor span task. Transitions between these states enable successful performance in dynamic environments placing strong demands on the substrates of working memory.
Characterization of α3 Glycine Receptors with Ginkgolide B and Picrotoxin
Authors: Chakrabarti Sampurna , Neelakantan Anil , Slaughter Malcolm M.
Published: October 2018

Ginkgolide B (GB) and picrotoxin (PTX) are antagonists of the major inhibitory receptors of the central nervous system: GABA and glycine receptors (GlyRs). GlyRs contain one or more of the four alpha subunit isoforms of which α1 and α2 have been extensively studied. This report compares GB and PTX block of α3 GlyRs expressed in HEK 293 cells, using whole-cell patch clamp techniques. In CNS, α3 exists as a heteropentamer in conjunction with beta subunits in a 2α:3β ratio. Thus, the nature of block was also tested in α3β heteromeric glycine receptors. GB and PTX blocked α3 GlyRs both in the presence (liganded state) and absence of glycine (unliganded state). This property is unique to α3 subunits; α1 and α2 subunits are only blocked in the liganded state. The GB block of α3 GlyRs is voltage-dependent (more effective when the cell is depolarized) and non-competitive, while the PTX block is competitive and not voltage-dependent. The heteromeric and homomeric α3 GlyRs recovered significantly faster from unliganded GB block compared to liganded GB block, but no such distinction was found for PTX block suggesting more than one binding site for GB. This study sheds light on features of the α3 GlyR that distinguish it from the more widely studied α1 and α2 subunits. Understanding these properties can help decipher the physiological functioning of GlyRs in the CNS and may permit development of subunit specific drugs.
Resource misallocation as a mediator of fitness costs in antibiotic resistance
Authors: Trauner Andrej , Banaei-Esfahani Amir , Gygli Sebastian M. , Warmer Philipp , Feldmann Julia , Shafieechashmi Seyedehsara , Eschbach Katja , Zampieri Mattia , Borrell Sonia , Collins Ben C. , Beisel Christian , Aebersold Ruedi , Gagneux Sebastien
Published: October 2018

Antimicrobial resistance poses a threat to global health and the economy. It is widely accepted that, in the absence of antibiotics, drug resistance mutations carry a fitness cost. In the case of rifampicin resistance in fast-growing bacteria, this cost stems from a reduced transcription rate of the RNA polymerase resulting in slower ribosome biosynthesis. However, this relationship does not apply in the slow-growingMycobacterium tuberculosis, where the true mechanism of fitness cost of rifampicin resistance as well as the impact of compensatory evolution remain unknown. Here we show, using global transcriptomic and proteomic profiling of selectedM. tuberculosismutants and clinical strains, that the fitness cost of rifampicin resistance inM. tuberculosisis the result of the physiological burden caused by aberrant gene expression. We further show that the perceived burden can be increased, effectively suppressing the emergence of drug resistance.
Complementary networks of cortical somatostatin interneurons enforce layer specific control
Authors: Naka Alexander , Veit Julia , Shababo Ben , Chance Rebecca K. , Risso Davide , Stafford David , Snyder Benjamin , Egladyous Andrew Y. , Chu Desi , Sridharan Savitha , Paninski Liam , Ngai John , Adesnik Hillel
Published: October 2018

The neocortex is organized into discrete layers of excitatory neurons: layer 4 receives the densest ‘bottom up’ projection carrying external sensory data, while layers 2/3 and 5 receive ‘top down’ inputs from higher cortical areas that may convey sensory expectations and behavioral goals. A subset of cortical somatostatin (SST) neurons gate top down input and control sensory computation by inhibiting the apical dendrites of pyramidal cells in layers 2/3 and 5. However, it is unknown whether an analogous inhibitory mechanism separately and specifically controls activity in layer 4. We hypothesized that distinct SST circuits might exist to inhibit specific cortical layers. By enforcing layer-specific inhibition, distinct SST subnetworks could mediate pathway-specific gain control, such as regulating the balance between bottom up and top down input. Employing a combination of high precision circuit mapping, in vivo optogenetic perturbations, and single cell transcriptional profiling, we reveal distinct and complementary SST circuits that specifically and reciprocally interconnect with excitatory cells in either layer 4 or layers 2/3 and 5. Our data further define a transcriptionally distinct SST neuronal sub-class that powerfully gates bottom up sensory activity during active sensation by regulating layer 4 activity. This integrated paradigm further represents a potentially generalizable approach to identify and characterize neuronal cell types and reveal their in vivo function.
Pregnancy-associated plasma protein-aa promotes neuron survival by regulating mitochondrial function
Authors: Alassaf Mroj , Daykin Emily , Wolman Marc
Published: October 2018

A neuron’s longevity is regulated by both extracellular molecular factors and the regulation of its intracellular functions, including mitochondrial activity. It remains poorly understood which extracellular factors promote neuron survival by influencing mitochondrial function. Through zebrafish mutant analysis, we reveal a novel extracellular neuronal survival factor: Pregnancy-associated plasma protein-aa (Pappaa). Neurons inpappaamutant larvae die precociously and exhibit multiple mitochondrial defects, including elevated mitochondrial calcium, membrane potential, and reactive oxygen species production (ROS). Inpappaamutants, neuron loss is exacerbated by stimulation of mitochondrial calcium load or ROS production and suppressed by exposure to a mitochondrial ROS scavenger. As a secreted metalloprotease, Pappaa stimulates local insulin-like growth factor 1 (IGF1) signaling; a known regulator of mitochondrial function and neuron survival. Inpappaamutants, neurons show reduced IGF1-receptor activity and neuron loss is attenuated by stimulation of IGF1 signaling. These results suggest Pappaa-IGF1 signaling promotes neuron survival by regulating mitochondrial function.
Identification of transcription factors regulating senescence in wheat through gene regulatory network modelling
Authors: Borrill Philippa , Harrington Sophie A. , Simmonds James , Uauy Cristobal
Published: October 2018

Senescence is a tightly regulated developmental programme which is coordinated by transcription factors. Identifying these transcription factors in crops will provide opportunities to tailor the senescence process to different environmental conditions and regulate the balance between yield and grain nutrient content. Here we use ten time points of gene expression data alongside gene network modelling to identify transcription factors regulating senescence in polyploid wheat. We observe two main phases of transcription changes during senescence: early downregulation of housekeeping and metabolic processes followed by upregulation of transport and hormone related genes. We have identified transcription factor families associated with these early and later waves of differential expression. Using gene regulatory network modelling alongside complementary publicly available datasets we identified candidate transcription factors for controlling senescence. We validated the function of one of these candidate transcription factors in senescence using wheat chemically-induced mutants. This study lays the ground work to understand the transcription factors which regulate senescence in polyploid wheat and exemplifies the integration of time-series data with publicly available expression atlases and networks to identify candidate regulatory genes.
Genome wide association study of hippocampal subfield volume in PTSD cases and trauma-exposed controls
Authors: Morey Rajendra A. , Garrett Melanie E. , Stevens Jennifer S. , Clarke Emily , Haswell Courtney C. , van Rooij Sanne J.H. , Fani Negar , Lori Adriana ,   VA Mid-Atlantic MIRECC Workgroup, Marx Christine E. , Beckham Jean C. , McCarthy Gregory , Hauser Michael A. , Ashley-Koch Allison E.
Published: October 2018

Behavioral, structural, and functional neuroimaging have implicated the hippocampus as a critical brain region in PTSD pathogenesis. We conducted a GWAS of hippocampal subfield volumes in a sample of recent military veteran trauma survivors (n=157), including some with PTSD (n=66). Covariates in our analysis included lifetime PTSD diagnosis, sex, intracranial volume, genomic estimates of ancestry, and childhood trauma. Interactions between genetic variants and lifetime PTSD or childhood trauma were interrogated for SNPs with significant main effects. Several genetic associations surpassed correction for multiple testing for several hippocampal subfields, including fimbria, subiculum, cornu ammonis-1(CA1), and hippocampal amygdala transition area (HATA). One association replicated in an independent cohort of civilians with PTSD (rs12880795 inTUNARwith L-HATA volume,p=3.43 × 10-7in the discovery andp=0.0004 in the replication cohort). However, the most significant association in the discovery data set was between rs6906714 inLINC02571and R-fimbria volume (p=5.99 ×10-8,q=0.0056). Interestingly, the effect of rs6906714 on R-fimbria volume increased with childhood trauma (G*E interactionp=0.022). In addition to variants in long intergenic non-coding RNAs (lincRNAs), we identified SNPs associated with hippocampal subfield volume, which are also quantitative trait loci (QTLs) for genes involved in RNA editing of glutamate receptor subunits (GluRs), oxidative stress, and autoimmune disorders. Genomic regions, some with putative regulatory roles, influence the volume of hippocampal subfields. Neuroimaging phenotypes may offer important insight into the genetic architecture and neurobiological pathways relevant to PTSD, as well as in the identification of potential biomarkers and drug targets for PTSD.
Accurate prediction of cell composition, age, smoking consumption and infection serostatus based on blood DNA methylation profiles
Authors: Bergstedt Jacob , Urrutia Alejandra , Duffy Darragh , Albert Matthew L. , Quintana-Murci Lluís , Patin Etienne
Published: October 2018

DNA methylation is a stable epigenetic alteration that plays a key role in cellular differentiation and gene regulation, and that has been proposed to mediate environmental effects on disease risk. Epigenome-wide association studies have identified and replicated associations between methylation sites and several disease conditions, which could serve as biomarkers in predictive medicine and forensics. Nevertheless, heterogeneity in cellular proportions between the compared groups could complicate interpretation. Reference-based cell-type deconvolution methods have proven useful in correcting epigenomic studies for cellular heterogeneity, but they rely on reference libraries of sorted cells and only predict a limited number of cell populations. Here we leverage >850,000 methylation sites included in the MethylationEPIC array and use elastic net regularized and stability selected regression models to predict the circulating levels of 70 blood cell subsets, measured by standardized flow cytometry in 962 healthy donors of western European descent. We show that our predictions, based on a hundred of methylation sites or lower, are less error-prone than other existing methods, and extend the number of cell types that can be accurately predicted. Application of the same methods to age, smoking consumption and several serological responses to pathogen antigens also provide accurate estimations. Together, our study substantially improves predictions of blood cell composition based on methylation profiles, which will be critical in the emerging field of medical epigenomics.