bluuebunny/crossref_metadata_2025 huggingface dataset:
Fecal microbiota transplantation prevents Candida albicans from colonizing the gastrointestinal tract
Authors: Matsuo Kenzo , Haku Akira , Bi Beibei , Takahashi Hiroki , Kamada Nobuhiko , Yaguchi Takashi , Saijo Shinobu , Yoneyama Mitsutoshi , Goto Yoshiyuki
Published: March 2019

Gut microbes symbiotically colonize the gastrointestinal (GI) tract, interacting with each other and their host to maintain GI tract homeostasis. Recent reports have shown that gut microbes help protect the gut from colonization by pathogenic microbes. Here, we report that commensal microbes prevent colonization of the GI tract by the pathogenic fungus, Candida albicans. Wild‐type specific pathogen‐free (SPF) mice are resistant to C. albicans colonization of the GI tract. However, administering certain antibiotics to SPF mice enables C. albicans colonization. Quantitative kinetics of commensal bacteria are inversely correlated with the number of C. albicans in the gut. Here, we provide further evidence that transplantation of fecal microbiota is effective in preventing Candida colonization of the GI tract. These data demonstrate the importance of commensal bacteria as a barrier for the GI tract surface and highlight the potential clinical applications of commensal bacteria in preventing pathogenic fungal infections.
Effect of pretreatment with intracerebroventricular injection of minocycline on morphine‐induced memory impairment in passive avoidance test: Role of P‐CREB and c‐Fos expression in the dorsal hippocampus and basolateral amygdala regions
Authors: Hamidkhaniha Shokouh , Bashiri Hamideh , Omidi Ameneh , Hosseini‐Chegeni Ali , Tavangar Seyed Mohammad , Sabouri Salehe , Montazeri Hamed , Sahebgharani Mousa
Published: March 2019

Minocycline as a member of the tetracycline family is a lipophilic broad‐spectrum antibiotic, which can display some non‐antibiotic properties such as antioxidant, antiapoptosis, neuroprotection and modulation of pharmacological traits of drugs of abuse (ie, reward, sensitization and/or analgesia). Thus, the aim of the present study was to investigate the effect of intracerebroventricular (ICV) injection of minocycline on morphine‐induced memory impairment and motor function in male Wistar rats. The behavioural responses were measured by a passive avoidance test for evaluating memory, and in the open field for studying motor function. Furthermore, the expression of Phospho‐cAMP response element‐binding protein (P‐CREB) and c‐Fos were assessed using immunohistochemistry in the dorsal hippocampus and basolateral amygdala (BLA). Our results showed that morphine dose‐dependently impairs memory consolidation, but not motor function. Maximum effect was achieved with morphine at dose of 5 mg/kg. Pretreatment with ICV injection of minocycline (50 μg/rat) prevented morphine‐induced memory impairment, but there was no effect on motor function. The results of immunohistochemistry analysis demonstrated that morphine decreased expression of P‐CREB positive cells compared to saline control group in the BLA, but not in the dorsal hippocampus. On the other hand, pretreatment of animals with ICV injection of minocycline increased the expression of P‐CREB in both brain areas. Moreover, there was no significant change in the expression of c‐Fos positive cells in above‐mentioned regions. In summary, our results indicated that pretreatment with ICV injection of minocycline prevented morphine‐induced memory impairment and increased P‐CREB expression in the dorsal hippocampus and BLA, which may explain its memory improvement property.
In Praise of Heresy: Hus, Luther, and the Ethos of Reformation
Authors: Fudge Thomas A.
Published: March 2019

Reformation is confined neither chronologically nor geographically but is best understood as a series of efforts to recover particular visions of Christian faith and practice. These endeavours always have potential for religious and social change. The martyred Bohemian priest Jan Hus (1372–1415) has often been characterised as a forerunner of the European Reformations and Martin Luther frequently referred to him. Past scholarship has evaluated the relation between Hussite history and the Reformation, Hus and Luther, in a variety of ways arguing either for organic connections or dismissing the possibility of causal connections. I argue that what Hus and Luther shared was not theology, common principles of reform, or visions of religious practice as much as a particular ethos. That ethos can best be understood within the idea of heresy. This article examines what Hus and Luther were striving to achieve, assesses the assumptions about Hus current in the sixteenth century, evaluates the Hus myth, and argues for a reconsideration and rehabilitation of heresy, a concept that epitomises the shared ethos that made Hus relevant to sixteenth‐century reformers.
The academic and social profiles of pupils with attention deficit hyperactivity disorder and mild general learning disability in mainstream education in the Republic of Ireland
Authors: Scanlon Geraldine , McEnteggart Ciara , Barnes‐Holmes Yvonne
Published: March 2019

Several gaps exist in the standardised assessment of pupils with Special Educational Needs and Disabilities (SEND) in the Irish mainstream education context at the point of transition from primary to post‐primary school. These gaps may lead to a lack of adequate focus on the continuity of resources at this timepoint. The current study examined academic and social attainment in three cohorts of pupils in Ireland (Attention Deficit Hyperactivity Disorder, ADHD, N = 12; Mild General Learning Difficulties, MGLD, N = 12; and typically developing individuals, N = 11). Four standardised measures were used in a non‐experimental design to assess cognitive attainment (Wide Range Achievements Test 4, WRAT‐4), learning competency and self‐concept (Myself as a Learner Scale, MALS; the Burnett Self Scale, BSS), and perceived control (Multidimensional Measure of Children's Perception of Control scale, MMCPC) across the three groups prior to transition to post‐primary school. Results indicated that the typically developing pupils performed strongest on attainment followed by those with ADHD and MGLD. While the latter two groups were weaker on attainment, neither group perceived of themselves as weaker. The results are discussed within the context of formal assessment for pupils with SEND in mainstream education and how these diverse outcomes may have implications for policy.
Gout and the risk of Alzheimer′s disease: A Mendelian randomization study
Authors: Lee Young Ho
Published: March 2019

Objective

This study aimed to examine whether gout is causally associated with Alzheimer's disease.

Methods

I used the publicly available summary statistics datasets of three genome‐wide association studies (GWASs) on gout as the exposure dataset and meta‐analysis results of four GWAS datasets consisting of 17 008 cases with Alzheimer's disease and 37 154 controls of European descent as the outcome dataset. The data were subjected to 2‐sample Mendelian randomization (MR) analysis using the inverse‐variance weighted (IVW), weighted median, and MR‐Egger regression methods.

Results

I selected seven independent single nucleotide polymorphisms (SNPs) from gout GWASs as instrumental variables (IVs) to improve inference. These SNPs were located at MAP3K11 (rs10791821), SLC2A9 (rs11722228, rs734553), GCKR (rs1260326), ABCG2 (rs2231142, rs2728125), and CNIH‐2 (rs4073582). The IVW data did not support a causal association between gout and Alzheimer's disease (β = 0.013, standard error [SE] = 0.017, P = 0.445). The MR‐Egger regression indicated that directional pleiotropy did not bias the result (intercept = 0.002, P = 0.654); it also revealed no causal association between gout and Alzheimer's disease (β = −0.013, SE = 0.076, P = 0.870). The weighted median approach yielded similar results (β = 0.004, SE = 0.022, P = 0.846). Cochran's Q test indicated no evidence of heterogeneity between IV estimates based on individual variants, and the results of “leave‐one‐out” analysis demonstrated that no single SNP drove the IVW estimate.

Conclusions

The MR analysis results did not support a causal association between gout and Alzheimer's disease.
Medication adherence and cost‐related medication non‐adherence in patients with rheumatoid arthritis: A cross‐sectional study
Authors: Heidari Parvaneh , Cross Wendy , Weller Carolina , Nazarinia Mohammadali , Crawford Kimberley
Published: March 2019

Aim

First, to assess the clinical characteristics and medication adherence to oral rheumatoid arthritis (RA) medications in patients with RA. Second, to examine adherence determinants with a focus on the effect of medication out‐of‐pocket (OOP) costs on medication adherence to oral RA medications. Lastly, to examine cost‐related medication non‐adherence (CRN) in patients with RA.

Methods

A cross‐sectional study of patients with RA was conducted at rheumatology outpatient clinics in Shiraz, Iran. The data collection survey consisted of 5 sections including demographic questions, disease‐related questions, Compliance Questionnaire Rheumatology (CQR), CRN questions and an open‐ended question. SPSS version 24 was used for analysis.

Results

A total of 308 completed surveys were collected. Adherence to oral RA medications was 40.3%. Just under 20% of participants were biologic disease‐modifying antirheumatic drugs (bDMARDs) users and these bDMARDs users were 0.82 times less likely to be adherent to their oral RA medications compared to non‐bDMARDs users (P < 0.05). There was no statistically significant association between OOP costs and adherence to oral RA medications (P > 0.05). However, 28.7% of participants reported not refilling, delaying to refill, skipping doses or taking smaller doses due to cost. In findings of the open‐ended question, medication costs and affordability were the most commonly mentioned barriers to medication adherence.

Conclusion

Non‐adherence to oral RA medications was prevalent among Iranian patients with RA and OOP costs were a barrier to medication adherence.
Investor Overreaction to Earnings Surprises and Post‐Earnings‐Announcement Reversals
Authors: Bathke Allen W. , Mason Terry W. , Morton Richard M.
Published: March 2019

Prior literature suggests that the market underreacts to the positive correlation in a typical firm's seasonal earnings changes, which leads to a post‐earnings‐announcement drift (PEAD) in prices. We examine the market reaction for a distinct set of firms whose seasonal earnings changes are uncorrelated and show that the market incorrectly assumes that the earnings changes of these firms are positively correlated. We also document that positive (negative) seasonal earnings changes in the current quarter are associated with negative (positive) abnormal returns in the next quarter. Thus, we observe a reversal of abnormal returns, consistent with a systematic overreaction to earnings, rather than the previously documented PEAD. Additional analysis indicates that financial analysts similarly overestimate the autocorrelation of these firms, although to a lesser extent. We also find that the magnitude of overestimation and the subsequent price reversal are inversely related to the richness of the information environment. Our results challenge the notion that investors recognize but consistently underestimate earnings correlation and provide a new perspective on the inability of prices to fully reflect the implications of current earnings for future earnings. That is, we show that investors predictably overestimate correlation when it is lacking, but underestimate it when it is present.
Glucocorticosteroids for sepsis in children. A protocol for a systematic review
Authors: Korang Steven Kwasi , Gluud Christian , Jakobsen Janus C.
Published: March 2019

Background

Sepsis is the primary diagnosis in more than 8% of all critically ill children and sepsis is among the ten leading causes of death in children <10 years. Glucocorticosteroids are currently recommended in septic children with fluid or catecholamine resistant refractory shock. Glucocorticosteroids are widely used for severe sepsis in paediatric intensive care units worldwide. However, the evidence on the clinical effects of glucocorticosteroids for sepsis in children is unclear.

Methods

We will perform a systematic review with meta‐analysis and Trial Sequential Analysis of randomised clinical trials. We will include randomised clinical trials assessing the effects of glucocorticosteroids vs placebo or no intervention as an add‐on therapy to standard care for sepsis in children. For the assessment of harms, we will also include quasi‐randomised studies and observational studies identified during our searches for randomised clinical trials.

Discussion

This review will seek to assess whether glucocorticosteroids indeed have their therapeutic place in the standard treatment for sepsis in children.
Myofunctional therapy and prefabricated functional appliances: an overview of the history and evidence
Authors: Wishney M , Darendeliler MA , Dalci O
Published: March 2019

Malocclusion represents the clinically observable endpoint of numerous genetic and environmental influences. Oral Myofunctional Therapy (OMT) aims to treat malocclusions by improving the oral environment through re‐education of musculature and respiratory patterns. Although the concept of OMT has existed since the early part of the 20th Century, many of its purported benefits for the treatment of malocclusion remain undemonstrated in the scientific literature. However, a more recent application of OMT for the treatment of Obstructive Sleep Apnoea (OSA) suggests some benefits, although more research is needed to clarify this effect. Prefabricated functional appliances (PFAs) are sometimes advocated as part of myofunctional training programs. In the past decade, controlled clinical investigations have demonstrated that PFAs can improve Class II Division 1 malocclusions in compliant patients. Compared with traditional functional appliances, PFAs might be more cost effective; however, this must be balanced against compliance problems and evidence suggesting that other types of functional appliances might give better treatment results in a comparable time frame.
Systematic review of rectal stump management during and after emergency total colectomy for acute severe ulcerative colitis
Authors: Bedrikovetski Sergei , Dudi‐Venkata Nagendra , Kroon Hidde M. , Liu Jianliang , Andrews Jane M. , Lewis Mark , Lawrence Matthew , Sammour Tarik
Published: March 2019

Background

There is no consensus about the optimal management of the rectal stump after an emergency subtotal colectomy in patients with acute severe ulcerative colitis (ASUC). The aim was to perform a systematic review of the published literature on the surgical and medical management of the rectal stump after an emergency (sub) total colectomy in patients with ASUC.

Methods

The following databases were searched, MEDLINE (PubMed), EMBASE and OVID SP, from January 1993 to March 2018. Studies that reported post‐operative outcomes after surgical and/or medical management of the rectal stump after emergency (sub) total colectomy in adults with ASUC were included. Two independent assessors reviewed eligible articles.

Results

A total of 11 studies met the inclusion criteria. All were case series and included 476 patients. Regarding surgical management, five studies reported on closed subcutaneous placement of the rectal stump, seven on intraperitoneal placement and two on the formation of a formal mucous fistula. The lowest reported pelvic sepsis rate was in patients with subcutaneous closure of the rectal stump (n = 144, 2%) and lowest wound infection rate was reported after intraperitoneal closure (n = 268, 7.8%). The highest rate of mortality was reported after intraperitoneal placement of the rectal stump (n = 268, 1.5%). There were insufficient data reported on medical management for any comparison.

Conclusion

Subcutaneous placement of the rectal stump was associated with the lowest morbidity and mortality rate, although data are of limited quality and insufficient to guide practice recommendations.
Corruption at the Border: Intersections between US Labour Demands, Border Control, and Human Smuggling Economies
Authors: Izcara Palacios Simón Pedro
Published: March 2019

Based on a qualitative methodology that includes in‐depth interviews conducted between 2008 and 2017 with 180 migrant smugglers from Mexico, the objective of this paper is to analyse the way US employers' interest in having access to cheap labour feeds migrant smuggling, and is connected to corruption in US border enforcement. We conclude that corruption on the US side of the border could be systematic and not a matter of a few bad apples. Corruption is manifested in selective enforcement, which is a pragmatic practice that justifies enhanced immigration enforcement, and benefits US immigration agents, US employers and Mexican smugglers, while undocumented border crossers suffer the monstrous effects of militarised border enforcement.
Performing Resistance: Liminality, Infrapolitics, and Spatial Contestation in Contemporary Russia
Authors: Fröhlich Christian , Jacobsson Kerstin
Published: March 2019

This article explores protest tactics in Russian cities, stressing the liminality of spatial contestation practices. In this authoritarian context, spatial contestation typically has a liminal character, where citizens employ strategic ambiguity of their actions vis‐á‐vis (a) legal regulations, (b) official discourse, and (c) transcripts of legitimate behaviour. Showing how urbanites develop creative and subversive infrapolitical forms of resistance, the article contributes an analysis of the ways in which public space in the city can be appropriated from below, temporary protest communities formed and active citizenship claimed under non‐democratic regime conditions.
Editorial: metabolomic biomarkers for colorectal adenocarcinoma and in the differentiation between irritable bowel syndrome and ulcerative colitis in clinical remission—confounded by the gut microbiome?
Authors: Leong Rupert W. L. , Kaakoush Nadeem O. , Yau Yunki Y. , Wasinger Valerie C.
Published: March 2019

Linked Content

This article is linked to Keshteli et al, Bond et al, and Bond and Probert papers. To view these articles, visit https://doi.org/10.1111/apt.15141, https://doi.org/10.1111/apt.15140, https://doi.org/10.1111/apt.15196 and https://doi.org/10.1111/apt.15200.
Letter: distinct hepatitis B virus relapse rates after discontinuing tenofovir and entecavir therapy in chronic hepatitis B patients—author's reply
Authors: Chen Chien‐Hung
Published: March 2019

Linked Content

This article is linked to Kuo et al and Huang et al papers. To view
these articles, visit https://doi.org/10.1111/apt.15053 and https://doi.org/10.1111/apt.15150.
Review article: treatment options for functional dyspepsia
Authors: Masuy Imke , Van Oudenhove Lukas , Tack Jan
Published: March 2019

Background

Functional dyspepsia, consisting of epigastric pain syndrome and postprandial distress syndrome, is a prevalent functional gastrointestinal disorder. To date, only limited treatment options are available and conflicting results in terms of efficacy have been reported. Consequently, nonpharmacological treatment options are increasingly being explored for functional dyspepsia.

Aim

To provide an overview of current pharmacological and nonpharmacological treatment options for functional dyspepsia.

Methods

A literature search was conducted on Pubmed and other sources to identify relevant studies.

Results

Acid suppressive therapy reduced symptoms in 30%‐70% of the patients, with higher benefit in epigastric pain syndrome and superior effectiveness for proton pump inhibitors compared to H2‐antagonists. Prokinetic agents, primarily used to treat postprandial distress syndrome, showed variable efficiency: 59%‐81% responder rate for dopamine receptor antagonists, 32%‐91% for serotonin‐4‐receptor agonists and 31%‐80% for muscarinic receptor antagonists. H Pylori eradication, recommended in infected patients, was effective in 24%‐82%. Refractory symptoms are addressed with neuromodulators. However, their efficacy in functional dyspepsia remains incompletely elucidated, available data showing symptom reduction in 27%‐71% of the patients. Regarding herbal agents, peppermint oil reduced symptoms in 66%‐91%, rikkunshito in 29%‐34% and iberogast in 20%‐95%. Lastly, acupuncture, cognitive behavioural therapy and hypnotherapy may help to provide symptom control, but research on their efficacy remains sparse.

Conclusions

None of the available therapies is effective in the majority of patients without being associated with major side effects. Developing new treatment options is challenging due to the heterogeneity of functional dyspepsia, the lack of readily identified target mechanisms and the poor association between pathophysiological disturbances and symptoms.
Editorial: should we abandon HCV genotype testing? Maybe
Authors: Plaz Torres Maria Corina , Aghemo Alessio
Published: March 2019

Linked Content

This article is linked to Mettikanont et al paper. To view this article,
visit https://doi.org/10.1111/apt.15100.
Editorial: importance of an elevated mean platelet volume for prediction of major adverse cardiovascular events in non‐alcoholic fatty liver disease – authors’ reply
Authors: Mullish Benjamin H. , Forlano Roberta , Abeles Robin Daniel , Thursz Mark R. , Manousou Pinelopi
Published: March 2019

Linked Content

This article is linked to Abeles et al and Targher and Lippi papers. To
view these articles, visit https://doi.org/10.1111/apt.15192, and https://doi.org/10.1111/apt.15208.
Is the keystone role of figs maintained across a gradient of increasing human disturbance?
Authors: Peabotuwage Indika , Goodale Uromi Manage , Goodale Eben
Published: March 2019

Fig trees provide important resources to tropical animals, but is their keystone role affected by human disturbance? In Sri Lanka, we found that more bird species were found in close association with fruiting figs in urban areas, suggesting their role is accentuated there, and justifying their planting.
Does Exposure to Code‐Switching Influence Language Performance in Bilingual Children?
Authors: Kaushanskaya Margarita , Crespo Kimberly
Published: March 2019

This study investigated whether the effect of exposure to code‐switching on bilingual children's language performance varied depending on verbal working memory (WM). A large sample of school‐aged Spanish–English bilingual children (N = 174, Mage = 7.78) was recruited, and children were administered language measures in English and Spanish. The frequency with which the children were exposed to code‐switching was gathered through parent report. For children with high verbal WM, greater exposure to code‐switching was associated with higher levels of language ability. In contrast, for children with lower verbal WM, greater exposure to code‐switching was associated with lower levels of language ability. These findings indicate that children's cognitive processing capacity dictates whether exposure to code‐switching facilitates or hinders language skills.
Diagnostischer Nutzen der Konfokalmikroskopie als weiterführende Untersuchungsmethode von Gesichtsläsionen
Authors: Ahlgrimm‐Siess Verena , Weitzer Friedrich , Arzberger Edith , Laimer Martin , Hofmann‐Wellenhof Rainer
Published: March 2019

Hintergrund und Zielsetzung

Benigne und maligne Läsionen der Gesichtshaut können klinisch und dermatoskopisch schwierig zu differenzieren sein. Die vorliegende Studie zielte darauf ab, den diagnostischen Nutzen der In‐vivo‐Konfokalmikroskopie (RCM) als weiterführende Untersuchungsmethode für Neubildungen der Gesichtshaut zu untersuchen.

Patienten und Methodik

Retrospektive und verblindete Untersuchung von 160 konsekutiven Gesichtsläsionen in zwei getrennten Schritten: zuerst Auswertung der klinischen und dermatoskopischen Bilder, gefolgt von einer kombinierten Beurteilung der klinischen, dermatoskopischen und RCM‐Bilder. Unsere Studie schloss 60 % maligne Läsionen ein, bestehend aus 43 % Melanomen, 9 % Basalzellkarzinomen, 5 % In‐situ‐Plattenepithelkarzinomen und 3 % Lymphomen.

Ergebnisse

Die zusätzliche RCM verbesserte die diagnostische Spezifität für die Erkennung von Malignomen im Vergleich zur klinisch‐dermatoskopischen Auswertung allein deutlich (58 % vs. 28 %). Die Sensitivität war für die RCM‐basierte Auswertung jedoch wegen der Fehlbeurteilung eines In‐situ‐Plattenepithelkarzinoms und eines Lymphoms etwas erniedrigt (93 % vs. 95 %). Im Bezug auf die Melanomdiagnose schnitt die RCM‐basierte Bildauswertung generell besser ab; die Sensitivität war nur gering erhöht (88 % vs. 87 %), die Spezifität jedoch deutlich (84 % vs. 58 %).

Schlussfolgerungen

Die RCM stellt ein wertvolles diagnostisches Hilfsmittel im Gesichtsbereich dar; die Anzahl unnötiger Biopsien in diesem kosmetisch sensiblen Areal könnte, ohne ein Melanom zu übersehen, um ein Drittel reduziert werden.
Deprescribing in der Dermatologie: Ein systematisches Review aktueller dermatologischer Leitlinien
Authors: Darr‐Foit Susanne , Elsner Peter , Tittelbach Jörg
Published: March 2019

Als „Deprescribing“ wird der systematische Prozess der Identifikation, der Dosisreduktion und des Absetzens individuell ineffektiver und/oder potenziell schädigender Arzneimittel bezeichnet. Die hier vorgenommene Analyse befasst sich mit diesem Begriff im Rahmen der Anwendungsempfehlungen von Systemmedikationen innerhalb aktueller dermatologischer Leitlinien unter Betrachtung verschiedener Gesichtspunkte. Untersucht wurden 16 Leitlinien der Deutschen Dermatologischen Gesellschaft (DDG). Bei der Auswertung fiel auf, dass bei vielen Leitlinien keine oder keine vollständigen Hinweise für das Deprescribing der erwähnten Systemtherapien gegeben wurden. Daher wird empfohlen, im Rahmen der Leitlinienerstellung oder ‐aktualisierung standardisiert Hinweise zum Absetzen oder der Dosisanpassung für die vorgeschlagenen Systemtherapien zu integrieren.
S2k‐Leitlinie Haut‐ und WeichgewebeinfektionenAuszug aus „Kalkulierte parenterale Initialtherapie bakterieller Erkrankungen bei Erwachsenen – Update 2018“
Authors: Sunderkötter Cord , Becker Karsten , Eckmann Christian , Graninger Wolfgang , Kujath Peter , Schöfer Helmut
Published: March 2019

Diese erste deutschsprachige S2k‐Leitlinie zu bakteriellen Haut‐ und Weichgewebeinfektionen ist im Rahmen der „Empfehlungen zur kalkulierten parenteralen Initialtherapie bakterieller Erkrankungen“ unter Federführung der Paul‐Ehrlich‐Gesellschaft für Chemotherapie e.V. entstanden und wird in wichtigen Auszügen hier wiedergegeben.

Voraussetzung für gut kalkulierte Antibiotikatherapien ist eine genaue diagno­stische Zuordnung. So wird das Erysipel definiert als nichteitrige Infektion als deren Erreger β‐­hämolysierende Streptokokken gelten, und das klinisch diagnostiziert wird aufgrund eines hellroten Erythems und initial auftretenden Fiebers oder Fröstelns. Therapie der Wahl ist Penicillin. Begrenzte Phlegmonen dagegen werden meist durch Staphylococcus (S.) aureus verursacht, gehen häufig von Wunden aus, zeigen lividrote Erytheme und sind initial meist nicht von Fieber begleitet. Die Behandlung erfolgt mit einem Cephalosporin der Gruppe 1 oder 2 oder Flucloxacillin (parenteral). Schwere Phlegmonen sind eitrige, teilweise nekrotische, im Gewebe sich ausbreitende und bis an die Faszie reichende Infektionen, welche neben der Antibiotikabehandlung zusätzlich einer chirurgischen Versorgung bedürfen. Sie erfüllen oft auch die Kriterien für komplizierte Weichgewebeinfektionen, wie sie von der Food and Drug Administration für klinische Studien definiert worden sind (u. a. Komorbiditäten wie schlecht eingestellter Diabetes mellitus, periphere arterielle Verschlusskrankheit, Neutropenie). Hierfür werden Antibiotika empfohlen, die neben S. aureus auch anaerobe Bakterien und/oder gramnegative Bakterien erfassen. Die sogenannten nekrotisierenden Weichgewebeinfektionen sind eigenständige, rasch progrediente, akut lebensbedrohliche Infektionen infolge besonderer bakterieller Toxine, die zu ischämischen Nekrosen und Schock führen und ein schnelles radikales chirurgisches Débridement sowie entsprechende Anitbiotika erfordern. Abszesse müssen in erster Linie gut drainiert werden und erfordern nur unter bestimmten Umständen zusätzlich Antibiotika (Lokalisation im Gesicht, Hand‐ oder Genitoanalbereich, schwieriger Drainage etc.).

Die Leitlinie enthält zusätzlich Konsensus‐basierte Empfehlungen für höhere als in Studien geprüfte oder üblicherweise verabreichte Dosierungen. Ziel ist eine rationale Antibiotikatherapie, die wirksam und verträglich ist und keinen unnötigen Selektionsdruck in Richtung (multi‐)resistenter Erreger ausübt.
Identification and characterization of splenic adherent cells forming densely‐packed colonies
Authors: Hirasaki Masataka , Mizuno Yosuke , Ida Yui , Murakoshi Takayuki , Okuda Akihiko , Kotani Norihiro
Published: March 2019

It is thought that the spleen contains stem cells that differentiate into somatic cells other than immune cells. We investigated the presence of these hypothetical splenic cells with stem cell characteristics and identified adherent cells forming densely‐packed colonies (Splenic Adherent Colony‐forming Cell; SACC) in the spleen. Splenic Adherent Colony‐forming Cell was positive for alkaline phosphatase staining and stage‐specific embryonic antigen (SSEA)‐1 antigen. However, the self‐renewal properties of SACCs were limited because they stopped cell proliferation once colonies visible to the naked eye were formed. Gene expression analyses by semi‐quantitative RT‐PCR revealed the significant expression of c‐Myc and Klf4, whereas faint or no expression was evident for Nanog, Oct3/4, and Sox2. Global expression analyses by DNA microarray and subsequent gene ontology analyses revealed that the expression levels of genes related to the immune system were significantly lower in SACCs than in control splenic cells. In contrast, genes unrelated to the immune system, such as those involved in cell adhesion and axon guidance, were relatively highly expressed in SACCs compared with control splenic cells. Taken together, we identified a novel cell type residing in the spleen that is different from the hypothetical splenic stem cell, but which bears some, but not all, characteristics that represent an undifferentiated state.
Fidelity scales, performance measures and early intervention in psychosis services
Authors: Malla Ashok , Kinkaid Miriam
Published: March 2019

This commentary refers to the article by D. Addington, p 1235–1242 of this issue EIP 12:6.
Central thalamic inactivation impairs the expression of action‐ and outcome‐related responses of medial prefrontal cortex neurons in the rat
Authors: Francoeur Miranda J. , Wormwood Benjamin A. , Gibson Brett M. , Mair Robert G.
Published: March 2019

The mediodorsal (MD) and adjacent intralaminar (IL) and midline nuclei provide the main thalamic input to the medial prefrontal cortex (mPFC) and are critical for associative learning and decision‐making. MD neurons exhibit activity related to actions and outcomes that mirror responses of mPFC neurons in rats during dynamic delayed non‐match to position (dDNMTP), a variation of DNMTP where start location is varied randomly within an open octagonal arena to avoid confounding behavioral events with spatial location. To test whether the thalamus affects the expression of these responses in mPFC, we inhibited the central thalamus unilaterally by microinjecting muscimol at doses and sites found to affect decision‐making when applied bilaterally. Unilateral inactivation reduced normalized task‐related responses in the ipsilateral mPFC without disrupting behavior needed to characterize event‐related neuronal activity. Our results extend earlier findings that focused on delay‐related activity by showing that central thalamic inactivation interferes with responses related to actions and outcomes that occur outside the period of memory delay. These findings are consistent with the broad effects of central thalamic lesions on behavioral measures of reinforcement‐guided responding. Most (7/8) of the prefrontal response types affected by thalamic inactivation have also been observed in MD during dDNMTP. These results support the hypothesis that MD and IL act as transthalamic gates: monitoring prefrontal activity through corticothalamic inputs; integrating this information with signals from motivational and sensorimotor systems that converge in thalamus; and acting through thalamocortical projections to enhance expression of neuronal responses in the PFC that support adaptive goal‐directed behavior.
Genome‐wide association study of psoriasis in an Egyptian population
Authors: Bejaoui Yosra , Witte Mareike , Abdelhady Mohamed , Eldarouti Mohammad , Abdallah Nermeen M. A. , Elghzaly Ashraf Antar , Tawhid Ziyad , Gaballah Mohammad Ali , Busch Hauke , Munz Matthias , Wendorff Mareike , Ellinghaus Eva , Franke Andre , Ibrahim Saleh M.
Published: March 2019

Psoriasis is a chronic inflammatory disorder of the skin, with genetic factors reportedly involved in the disease pathogenesis. Numerous studies reported psoriasis candidate genes. However, these tend to involve mostly in the European and Asian populations. Here, we report the first genome‐wide association study (GWAS) in an Egyptian population, identifying susceptibility variants for psoriasis using a two‐stage case‐control design. In the first discovery stage, we carried out a genome‐wide association analysis using the Infinium® Global Screening Array‐24 v1.0, on 253 cases and 449 control samples of Egyptian descent. In the second replication stage, 26 single‐nucleotide polymorphisms (SNPs) were selected for replication in additional 321 cases and 253 controls. In concordance with the findings from previous studies on other populations, we found a genome‐wide significant association between the MHC locus and the disease at rs12199223 (Pcomb = 6.57 × 10−18) and rs1265181 (Pcomb = 1.03 × 10−10). Additionally, we identified a novel significant association with the disease at locus, 4q32.1 (rs12650590, Pcomb = 4.49 × 10−08) in the vicinity of gene GUCY1A3, and multiple suggestive associations, for example rs10832027 (Pcomb = 7.28 × 10−06) and rs3770019 (Pcomb = 1.02 × 10−05). This proposes the existence of important interethnic genetic differences in psoriasis susceptibility. Further studies are necessary to elucidate the downstream pathways of the new candidate loci.
The acute myeloid leukemia‐associated Nucleophosmin 1 gene mutations dictate amyloidogenicity of the C‐terminal domain
Authors: La Manna Sara , Scognamiglio Pasqualina Liana , Roviello Valentina , Borbone Fabio , Florio Daniele , Di Natale Concetta , Bigi Alessandra , Cecchi Cristina , Cascella Roberta , Giannini Cinzia , Sibillano Teresa , Novellino Ettore , Marasco Daniela
Published: March 2019

Nucleophosmin 1 (NPM1) is a nucleus‐cytoplasm shuttling protein ubiquitously expressed and highly conserved. It is involved in many cellular processes and its gene is mutated in ~ 50–60% of Acute Myeloid Leukemia (AML) patients. These mutations cause its cytoplasmic mislocation and accumulation (referred to as NPM1c+) and open the door to rational targeted therapy for AML diseases with mutated NPM1. Currently, there is limited knowledge on the mechanism of action of NPM1c+ and on structural determinants of the leukemogenic potential of AML mutations. Numerous previous studies outlined an unexpected amyloid‐like aggregation tendency of several regions located in the C‐terminal domain that, in wild‐type form, fold as a three‐helical‐bundle. Here, using a combination of different techniques including Thioflavin T fluorescence, congo red absorbance, CD spectroscopy, Scanning Electron Microscopy (SEM) and wide‐angle X‐ray scattering on a series of peptides bearing mutations, we evidence that the amyloidogenicity of NPM1 mutants is directly linked to AML. Noticeably, AML point mutations strongly affect the amyloid cytotoxic effects in neuroblastoma cells and the morphologies of deriving fibrils. This study paves the way to deepen our understanding of AML‐associated NPM1 mutants, and could help to break new ground for the identification of novel drugs targeting NPM1c+ for treatment of AML.
Sexual intimacy in later life: From the perspectives of older couples in Malaysia
Authors: Minhat Halimatus S , Mat Din Hazwan , Hamid Tengku A , Hassan Nudin Siti S
Published: March 2019

Aim

To identify the determinants of sexual intimacy among married older people in Malaysia.

Methods

A cross‐sectional study was carried out among 1294 married Malaysian older couples who were randomly selected from all 14 states in Malaysia. The data were collected by trained enumerators using a set of validated questionnaires consisting of eight sections, namely sociodemographic characteristics, chronic diseases, perceived health status, life satisfaction, body mass index, disability status (World Health Organization Disability Assessment Schedule), social support (Lubben Social Network Scale) and sexual intimacy.

Results

Having good social support (AOR 0.57, 95% CI 0.45–0.74) from family and friends were protective determinants against poor sexual intimacy in later life. Meanwhile, those who were aged 70–79 years (AOR 1.81, 95% CI 1.35–2.42), aged >80 years (AOR 35.49, 95% CI 4.80–262.18), women (AOR 1.47, 95% CI 1.13–1.90), non‐Malay (AOR 1.93, 95% CI 1.50–2.48), received only informal education (AOR 1.81, 95% CI 1.35–2.42), had gastritis (AOR 2.62, 95% CI 1.58–4.34), had a stroke (AOR 3.83, 95% CI 1.04–14.12), perceived their current health status was satisfactory (AOR 1.52, 95% CI 1.15–2.00) and disabled based on the World Health Organization Disability Assessment Schedule (AOR 3.14, 95% CI 1.34–7.36) were at risk of poor sexual intimacy.

Conclusions

The majority of older Malaysian couples were having poor sexual intimacy despite being still married and sleeping with their partners, reflecting the presence of underlying barriers towards sexual intimacy in later life among older Malaysians. Geriatr Gerontol Int 2019; 19: 492–496.
Cardio‐ankle vascular index and circulating CD34‐positive cell levels as indicators of endothelial repair activity in older Japanese men
Authors: Shimizu Yuji , Yamanashi Hirotomo , Noguchi Yuko , Koyamatsu Jun , Nagayoshi Mako , Kiyoura Kairi , Fukui Shoichi , Tamai Mami , Kawashiri Shin‐Ya , Kondo Hideaki , Maeda Takahiro
Published: March 2019

Aim

The cardio‐ankle vascular index (CAVI) reflects functional arterial stiffness, which is related to endothelial dysfunction. CD34‐positive cells carry out an important function in endothelial repair. However, there have been no reports assessing the association between CAVI and the number of circulating CD34‐positive cells.

Methods

We carried out a cross‐sectional study of 249 Japanese men, aged 60–69 years, who underwent annual health checkups between 2013 and 2015. As individuals with high levels of circulating CD34‐positive cells might indicate the influence of consumptive reduction of circulating CD34‐positive cells as a result of aggressive endothelial repair, participants were stratified by circulating CD34‐positive cell levels, using the median value in this population (0.95 cells/μL) as the cut‐off.

Results

For participants with low circulating CD34‐positive cell levels, logarithmic values of circulating CD34‐positive cells were inversely associated with CAVI (multivariable standardized parameter estimate [β] = −0.22, P = 0.014), but not for participants with high levels (β = −0.04, P = 0.638). In addition, even when no significant associations between CAVI and carotid intima‐media thickness were detected for participants with low circulating CD34‐positive cell levels (β = −0.02, P = 0.865), significant positive associations were identified for participants with high levels (β = 0.22, P = 0.028).

Conclusions

As circulating CD34‐positive cell count might indicate endothelial repair activity, the present results show that CAVI is affected by insufficient endothelial repair in individuals with low circulating CD34‐positive cell counts. Our results also show that a positive association between CAVI and carotid intima‐media thickness exists only in individuals with aggressive endothelial repair, which indicates the presence of organic arterial disease, such as atherosclerosis. Geriatr Gerontol Int 2019; 19: 557–562.
Milk and Montasio‐type cheese fatty acid composition from cows grazing on timothy and reed canarygrass pasture or fed indoor
Authors: Lee Bae‐Hun , Corazzin Mirco , Piasentier Edi , Huh Chul‐Sung , Sung Kyung-Il , Park Seung‐Yong
Published: March 2019

The objective of this study was to compare the fatty acid (FA) profile of cheese and milk produced from cows grazing on timothy and reed canarygrass pasture or fed indoor. Twenty multiparous dairy cows were selected from a single farm in Pyeongchang (South Korea) and assigned to two experimental groups (TMR and PAST). TMR was kept indoor and fed with a total mixed ration, while PAST was maintained on timothy and reed canarygrass (70%–30%) pasture for 5 months (beginning of June–end of October). At approximately 6‐day interval during this period, Montasio‐type cheeses were produced for each experimental group, and at the same day, bulk milk for each group was collected. Chemical composition and FA profile of cheeses and milk and the texture of cheeses were carried out. The diet affected milk fat content, which was higher in PAST than in TMR (p < 0.05). The pasture feeding increased C18:0 (p < 0.01), C18:1n‐9cis (p < 0.01), C18:3n‐3 (p < 0.05), monounsaturated FA (p < 0.05) and n‐3 polyunsaturated FA (PUFA, p < 0.05), and reduced C12:0 (p < 0.01), C16:0 (p < 0.01), C18:2n‐6cis (p < 0.05), C20:3n‐6 (p < 0.05), saturated FA (p < 0.05) and n‐6:n‐3 PUFA ratio (p < 0.01) of both milk and cheese compared with those of TMR. From FA composition point of view, pasture‐based feeding system increased the healthiness of dairy products.
Use of dabigatran with antiretrovirals
Authors: Perram J , O'Dwyer E , Holloway C
Published: March 2019

Objectives

Theoretical and untested interactions between antiretrovirals and direct‐acting oral anticoagulants have limited the use of this new class of anticoagulant in people with HIV infection. This case series, the first of its kind, reports on the successful concurrent use of the direct‐acting oral anticoagulant dabigatran and antiretroviral therapy.

Methods

This series involved 14 patients requiring anticoagulation for management of atrial fibrillation, who were either unable or unwilling to take warfarin, and who were receiving concurrent treatment for HIV infection. Participants were treated with dabigatran with dose monitoring to establish the safety and efficacy of concurrent use with antiretrovirals. All were commenced on 110 mg twice daily, increased to 150 mg twice daily if the trough level was < 69.3 ng/mL.

Results

In the 14 patients treated with dabigatran and antiretrovirals, there were no thromboembolic or bleeding complications. Dabigatran treatment was discontinued in one patient because of undetectable dabigatran levels despite dose escalation. Dabigatran levels fell within the fivefold variance seen in the Randomized Evaluation of Long‐Term Anticoagulation Therapy (RE‐LY) study at a dose of either 110 or 150 mg twice daily.

Conclusions

This case series represents the largest published population to date successfully receiving antiretroviral and direct‐acting oral anticoagulant therapy. Given the significant health care burden faced by people living with HIV, the availability of safe anticoagulant therapy without the requirement for monitoring is an important option in this patient population.
Lukewarm Nationalism: The 2020 Tokyo Olympics, Social Media and Affective Communities
Authors: Mōri Yoshitaka
Published: March 2019

This article considers the way in which a new nationalism is being created in the age of the Internet and social media by looking at the 2020 Tokyo Olympic Games and other Games in the past. The development of media technology from film, radio, and television to the Internet and social media has changed the character of the Olympic Games as media event. It has been argued that these developments have created a shared consciousness, a sense of belonging and enthusiastic nationalism in the age of modern nation‐state. While the spread of the Internet and social media was originally expected to contribute to globalization or to the emergence of global citizens in a global village, as McLuhan once predicted, it seems that the world is more divided, fragmented, and fluid than ever. At the same time, the digital media organize various layers of community not only by ideology but also by affect: affective communities. This often leads to the rise of chauvinistic nationalism in developed countries. With reference to McLuhan's famous argument on hot and cool media, the article tries to examine the character of contemporary lukewarm nationalism in the age of digital media.
Association between grandparent coresidence and weight change among first‐grade Japanese children
Authors: Morita Ayako , Ochi Manami , Isumi Aya , Fujiwara Takeo
Published: March 2019

Background

The prevalence of grandparent coresidence is increasing. However, the impact of grandparent coresidence on weight change among school‐age children remains unclear.

Objectives

The objective of the study is to examine the association between grandparent coresidence and obesity‐related behaviours and change in body mass index (BMI) z scores among school‐age children.

Methods

In total, 3422 caregivers of first‐grade children in Adachi City, Tokyo, participated in surveys and health checkups in 2016 and 2017 with no change in their grandparent coresidence status (response rate: 80.1% and 81.4%, respectively). Association between grandparent coresidence and obesogenic dietary, physical activity, and screen‐based sedentary behaviours was measured using Poisson regression with robust error variance analysis, while change in BMI z scores was determined by linear regression and adjusting for potential covariates.

Results

Grandparent coresidence was associated with increased prevalence rate (PR) of irregular snack foods intake (PR: 1.38, 95% confidential interval (CI): 1.19, 1.61); however, children who live with grandparents showed a lower BMI z scores in the second grade (coefficient: −0.048, 95% CI: −0.094 to −0.0013) after adjustment for BMI z scores in the first grade, family sociodemographics, and obesogenic behaviours.

Conclusion

Grandparent coresidence is associated with lower BMI z scores among early primary school‐age Japanese children living in urban areas.
Commentary: Broadening the scope of educational neuroscience, reflections on Thomas, Ansari, and Knowland (2019)
Authors: Mackey Allyson P.
Published: March 2019

Educational neuroscience is more than the basic science of reading and math, and its translational potential extends far beyond the knowledge, and misconceptions, that have made their way into the classroom so far. Thomas, Ansari, and Knowland synthesize progress in educational neuroscience and set out an ambitious set of goals for its future. Their conceptualization of the field encourages scientists across disciplines to think about how their work can inform a more holistic understanding of how the brain shapes learning, and how learning shapes the brain.