bluuebunny/crossref_metadata_2025 huggingface dataset:
Adjuvant radiotherapy in node positive prostate cancer patients: a debate still on. when, for whom?
Authors: Marvaso Giulia , Montesano Marianna , Corrao Giulia , De Angelis Simone P. , Gandini Sara , Mazzola Giovanni C. , Augugliaro Matteo , Franzetti Jessica , Zerini Dario , Pepa Matteo , Luzzago Stefano , Mistretta Francesco A. , Musi Gennaro , Nolè Franco , De Cobelli Ottavio , Orecchia Roberto , Jereczek‐Fossa Barbara A.
Published: September 2020

Objective

To evaluate the impact of adjuvant radiotherapy (aRT) in patients with prostate cancer (PCa) found to have pathological positive lymph nodes (pN1s) after radical prostatectomy (RP) and extended pelvic lymph node dissection (ePLND) with regard to distant recurrence‐free survival (RFS), according to both main tumour pathological characteristics and number of positive lymph nodes. Biochemical RFS, local RFS, overall survival (OS) and acute and late toxicity were assessed as secondary endpoints.

Patients and Methods

A retrospective cohort of 187 consecutive patients with pN1 PCa were treated with aRT at the IEO, European Institute of Oncology IRCCS, Milan, Italy. aRT on the tumour bed and pelvis was administered within 6 months of RP. Androgen deprivation therapy was administered according to the guidelines. Univariate and multivariate Cox regression analyses predicting biochemical RFS, local RFS, distant RFS and OS rates were performed to assess whether the number of pN1s represented an independent prognostic factor. The Youden index was computed to find the optimal threshold for the number of pN1s able to discriminate between patients with or without biochemical and clinical relapse.

Results

At 5 years, local RFS, distant RFS, biochemical RFS and OS were 68%, 71%, 56% and 94%, respectively. The median follow‐up was 49 months. The number of pN1s was significantly associated with biochemical RFS, local RFS and distant RFS. The best threshold for discriminating between patients with or without biochemical and clinical relapse was five pN1s. In multivariate analyses, the number of pN1s was confirmed to be an independent predictor of biochemical RFS, local RFS and distant RFS, but not of OS. Multivariate analyses also showed an increased risk of biochemical relapse for increasing values of initial prostate‐specific antigen and for patients with tumour vascular invasion. Local and distant RFS were also inversely correlated with significantly reduced risk for International Society of Urological Pathology grade group <3 (group 1 or 2 compared to group 3).

Conclusions

Our data confirmed the encouraging outcomes of patients with pN1 PCa treated with adjuvant treatments and the key role represented by the number of pN1s in predicting biochemical RFS, clinical RFS and distant RFS. Large prospective cohort studies and randomized clinical trials are needed to confirm these results and to identify the subgroup of patients with pN1 PCa who would most benefit from aRT.
Palaeoenvironmental conditions during MIS 6/MIS 5 transition recorded in speleothems from the Tatra Mountains
Authors: Pawlak Jacek , Błaszczyk Marcin , Hercman Helena , Matoušková Šárka
Published: September 2020

We present 100‐ka multiproxy palaeoenvironmental records from three stalagmites collected in different caves located in the Tatra Mountains on the Polish/Slovakian border. A combination of three records from one mountain region helps to estimate local factors controlling the recorded proxies and separate them from regional/global patterns. The studied stalagmites react to the same environmental changes in different ways due to the differences in their local settings. Furthermore, the analysed records show environmental changes from relatively cold and dry climates to interglacial conditions of MIS 5e. One episode of a colder climate during the MIS 6/MIS 5e transition similar to Dryas periods is observed in all studied stalagmites. The δ18O record from the MAG‐1 stalagmite is most similar to the GRIP record. During the MIS 5e, the δ18O record from the MAG‐1 stalagmite e xhibits a pattern similar to the records from the western part of the European continent. This finding suggests that the Atlantic Ocean was an important source of moisture for the region. The observed rapid change of δ18O, δ13C, Sr and Si proxies from the MAG‐1 and Dz‐1 stalagmites after 109 ka are potentially related to a drier and colder climate.
Rho kinase inhibitor fasudil reduces l‐DOPA‐induced dyskinesia in a rat model of Parkinson's disease
Authors: Lopez‐Lopez Andrea , Labandeira Carmen M. , Labandeira‐Garcia Jose L. , Muñoz Ana
Published: September 2020

Background and Purpose

Rho kinase (ROCK) activation is involved in neuroinflammatory processes leading to progression of neurodegenerative diseases such as Parkinson's disease. Furthermore, ROCK plays a major role in angiogenesis. Neuroinflammation and angiogenesis are mechanisms involved in developing l‐DOPA‐induced dyskinesias (LID). However, it is not known whether ROCK plays a role in LID and whether ROCK inhibitors may be useful against LID.

Experimental Approach

In rats, we performed short‐ and long‐term dopaminergic lesions using 6‐hydroxydopamine and developed a LID model. Effects of dopaminergic lesions and LID on the RhoA/ROCK levels were studied by western blot, real‐time PCR analyses and ROCK activity assays in the substantia nigra and striatum. The effects of the ROCK inhibitor fasudil on LID were particularly investigated.

Key Results

Short‐term 6‐hydroxydopamine lesions increased nigrostriatal RhoA/ROCK expression, apparently related to the active neuroinflammatory process. However, long‐term dopaminergic denervation (completed and stabilized lesions) led to a decrease in RhoA/ROCK levels. Rats with LID showed a significant increase of RhoA and ROCK expression. The development of LID was reduced by the ROCK inhibitor fasudil (10 and 40 mg·kg−1), without interfering with the therapeutic effect of l‐DOPA. Interestingly, treatment of 40 mg·kg−1 of fasudil also induced a significant reduction of dyskinesia in rats with previously established LID.

Conclusion and Implications

The present results suggest that ROCK is involved in the pathophysiology of LID and that ROCK inhibitors such as fasudil may be a novel target for preventing or treating LID. Furthermore, previous studies have revealed neuroprotective effects of ROCK inhibitors.
What skeletal muscle has to say in amyotrophic lateral sclerosis: Implications for therapy
Authors: Manzano Raquel , Toivonen Janne Markus , Moreno‐Martínez Laura , de la Torre Miriam , Moreno‐García Leticia , López‐Royo Tresa , Molina Nora , Zaragoza Pilar , Calvo Ana Cristina , Osta Rosario
Published: September 2020

Amyotrophic lateral sclerosis (ALS) is an adult onset disorder characterized by progressive neuromuscular junction (NMJ) dismantling and degeneration of motor neurons leading to atrophy and paralysis of voluntary muscles responsible for motion and breathing. Except for a minority of patients harbouring genetic mutations, the origin of most ALS cases remains elusive. Peripheral tissues, and particularly skeletal muscle, have lately demonstrated an active contribution to disease pathology attracting a growing interest for these tissues as therapeutic targets in ALS. In this sense, molecular mechanisms essential for cell and tissue homeostasis have been shown to be deregulated in the disease. These include muscle metabolism and mitochondrial activity, RNA processing, tissue‐resident stem cell function responsible for muscle regeneration, and proteostasis that regulates muscle mass in adulthood. This review aims to compile scientific evidence that demonstrates the role of skeletal muscle in ALS pathology and serves as reference for development of novel therapeutic strategies targeting this tissue to delay disease onset and progression.

LINKED ARTICLES

This article is part of a themed issue on Recent advances in ALS pathogenesis and therapeutics. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.6/issuetoc
Glycogen synthase kinase‐3β participates in acquired resistance to gemcitabine in pancreatic cancer
Authors: Uehara Masahiro , Domoto Takahiro , Takenaka Satoshi , Bolidong Dilireba , Takeuchi Osamu , Miyashita Tomoharu , Minamoto Toshinari
Published: September 2020

Acquisition of resistance to gemcitabine is a challenging clinical and biological hallmark property of refractory pancreatic cancer. Here, we investigated whether glycogen synthase kinase (GSK)‐3β, an emerging therapeutic target in various cancer types, is mechanistically involved in acquired resistance to gemcitabine in human pancreatic cancer. This study included 3 gemcitabine‐sensitive BxPC‐3 cell‐derived clones (BxG30, BxG140, BxG400) that acquired stepwise resistance to gemcitabine and overexpressed ribonucleotide reductase (RR)M1. Treatment with GSK3β‐specific inhibitor alone attenuated the viability and proliferation of the gemcitabine‐resistant clones, while synergistically enhancing the efficacy of gemcitabine against these clones and their xenograft tumors in rodents. The gemcitabine‐resensitizing effect of GSK3β inhibition was associated with decreased expression of RRM1, reduced phosphorylation of Rb protein, and restored binding of Rb to the E2 transcription factor (E2F)1. This was followed by decreased E2F1 transcriptional activity, which ultimately suppressed the expression of E2F1 transcriptional targets including RRM1, CCND1 encoding cyclin D1, thymidylate synthase, and thymidine kinase 1. These results suggested that GSK3β participates in the acquisition of gemcitabine resistance by pancreatic cancer cells via impairment of the functional interaction between Rb tumor suppressor protein and E2F1 pro‐oncogenic transcription factor, thereby highlighting GSK3β as a promising target in refractory pancreatic cancer. By providing insight into the molecular mechanism of gemcitabine resistance, this study identified a potentially novel strategy for pancreatic cancer chemotherapy.
Epigenetic methylation in Eosinophilic Esophagitis: Molecular ageing and novel biomarkers for treatment response
Authors: Jensen Elizabeth T. , Langefeld Carl D. , Zimmerman Kip D. , Howard Timothy D. , Dellon Evan S.
Published: September 2020

Background

Treatment failure in eosinophilic esophagitis (EoE) is common. We hypothesize that DNA methylation differs between patients by treatment response to topical steroids (oral viscous budesonide), thus offering the potential to inform targeting therapies.

Objective

We sought to identify differentially methylated sites and affiliated genes in pre‐treatment oesophageal cells between responders and non‐responders and test for accelerated epigenetic ageing in oesophageal cells of EoE patients.

Methods

DNA was extracted from prospectively collected and biobanked oesophageal biopsies from 36 Caucasian treatment naïve EoE patients at diagnosis. Methylation assays were completed using the Infinium HumanMethylation450 BeadChip. Normalizedβvalues for each CpG site were tested (t test) for differential methylation. Further, 353 CpG probes were used to estimate epigenetic age for each patient and a linear regression model tested whether chronologic age and epigenetic age differed. Epigenetic age results were confirmed in an independent cohort of healthy controls.

Results

Eighteen CpG sites were differentially methylated by treatment response (P < .00001). The mean epigenetic age and chronological age were 56.1 ± 11.1 and 36.7 ± 12.3 years, a mean age difference of 19.3 ± 5.2 years (P < .0001); accelerated ageing was not observed in the oesophageal cells of healthy controls.

Conclusions and clinical relevance

EoE patients that respond versus do not respond to treatment have differences in their methylation profile, including enrichment of genes in pathways consistent with cellular injury and repair due to environmental stress and cell adhesion and barrier integrity. EoE also appears to accelerate cellular ageing. Whether treatment can arrest or reverse accelerated epigenetic ageing and the implications for long‐term disease progression is important areas for future research.
Efficacy, safety, and tolerability of adjunctive perampanel in patients from China with focal seizures or generalized tonic‐clonic seizures: Post hoc analysis of phase III double‐blind and open‐label extension studies
Authors: Weiping Liao , Dong Zhou , Zhen Hong , Patten Anna , Dash Amitabh , Malhotra Manoj
Published: September 2020

Abstract

Aims

This post hoc analysis assessed the efficacy and safety/tolerability of adjunctive perampanel in patients from China (aged ≥12 years) with focal seizures (FS), with/without focal to bilateral tonic‐clonic seizures (FBTCS), or generalized tonic‐clonic seizures (GTCS).

Methods

Study centers in China were identified using data from five double‐blind, randomized, phase III studies of adjunctive perampanel (2‐12 mg/day) and their open‐label extensions (OLEx). Efficacy assessments included median percent reduction in seizure frequency per 28 days, and 50% and 75% responder and seizure‐freedom rates. Safety/tolerability assessments included monitoring of treatment‐emergent adverse events (TEAEs).

Results

Overall, 277 patients (placebo, n = 79; perampanel, n = 198) were included in the double‐blind safety analysis set. The full analysis set comprised 274 patients (FS, n = 238 [placebo, n = 60; perampanel, n = 178]; FBTCS, n = 120 [placebo, n = 31; perampanel, n = 89]; GTCS, n = 36 [placebo, n = 18; perampanel, n = 18]). Median percent reductions in seizure frequency for placebo vs perampanel were as follows: 16.6% vs 32.4% (FS; P < 0.05) and 39.1% vs 48.2% (FBTCS; not significant [NS]) at 4‐12 mg/day, and 37.9% vs 82.6% (GTCS; NS) at 8 mg/day; 50% responder rates were 31.7% vs 37.4% (FS; NS), 48.4% vs 51.9% (FBTCS; NS), and 33.3% vs 61.1% (GTCS; NS), respectively. Seizure‐freedom rates were 1.7% vs 9.2%, 16.1% vs 25.3%, and 16.7% vs 44.4%, respectively (all NS). Overall, 262 patients entered the OLEx (FS, n = 228; GTCS, n = 34). Perampanel was efficacious for up to four years for FS and FBTCS and up to two years for GTCS. Across the double‐blind and OLEx studies, TEAEs were reported in 65.7% and 81.3% of perampanel‐treated patients, respectively; the most common was dizziness. Efficacy and safety/tolerability outcomes were generally similar between Chinese and non‐Chinese patients.

Conclusion

Adjunctive perampanel (up to 12 mg/day) may be a suitable treatment for Chinese patients with FS, with/without FBTCS, or GTCS, with similar efficacy and safety/tolerability compared to non‐Chinese patients.
Treatment of faecal incontinence with autologous expanded mesenchymal stem cells: results of a pilot study
Authors: de la Portilla Fernando , Guerrero José Luis , Maestre Maria Victoria , Leyva Laura , Mera Santiago , García‐Olmo Damián , Rodríguez Antonio , Mata Rosario , Lora Fabiola
Published: September 2020

Aim

Management of faecal incontinence (FI) remains challenging because no definitive optimal treatment for this condition has yet been determined. Regenerative medicine could be an attractive therapeutic alternative for treating FI. Here, we aimed to determine the safety and feasibility of autologous expanded mesenchymal stem cells derived from adipose tissue (AdMSCs) in the treatment of patients diagnosed with structural FI.

Method

This was a randomized, multicentre, triple‐blinded, placebo‐controlled pilot study conducted at four sites in Spain with 16 adults with FI and a sphincter defect. Autologous AdMSCs were obtained from patients from surgically excised adipose tissue. These patients were intralesionally infused with a single dose of 4 × 107 AdMSCs or a placebo while under anaesthesia. We assessed the safety and feasibility of the treatment as the cumulative incidence of adverse events and the treatment efficacy using the Cleveland Clinic Faecal Incontinence Score, Faecal Incontinence Quality of Life score and Starck criteria to classify sphincter defects and anorectal physiology outcomes.

Results

Adipose tissue extraction, cell isolation and intralesional infusion procedures were successful in all the patients. There was only one adverse event connected to adipose tissue extraction (a haematoma), and none was associated with the injection procedure. There were no significant differences in any of the assessed clinical, manometric or ultrasonographic parameters.

Conclusion

This study indicates that this infusion procedure in the anal sphincter is feasible and safe. However, it failed to demonstrate efficacy to treat patients with structural FI.
Associations between socio‐environmental factors and landscape‐scale biodiversity recovery in naturally regenerating tropical and subtropical forests
Authors: Crouzeilles Renato , Maurenza Daniel , Prieto Pablo V. , Barros Felipe S. M. , Jakovac Catarina , Ferreira Mariana S. , Chazdon Robin L. , Lindenmayer David B. , Brancalion Pedro H. S. , Ceccon Eliane , Adams Cristina , Lazos‐Chavero Elena , Monteiro Lara , Junqueira André B. , Strassburg Bernardo B. N. , Guariguata Manuel R.
Published: September 2020

Natural regeneration is key for large‐scale forest restoration, yet it may lead to different biodiversity outcomes depending on socio‐environmental context. We combined the results of a global meta‐analysis to quantify how biodiversity recovery in naturally regenerating forests deviates from biodiversity values in reference old‐growth forests, with structural equation modeling, to identify direct and indirect associations between socioeconomic, biophysical and ecological factors and deviation in biodiversity recovery at a landscape scale. Low deviation within a landscape means higher chances of multiple sites in naturally regenerating forests successfully recovering biodiversity compared to reference forests. Deviation in biodiversity recovery was directly negatively associated with the percentage of cropland, forest cover, and positively associated with the percentage of urban areas in the surrounding landscape. These three factors mediated the indirect associations with rural population size, recent gross deforestation, time since natural regeneration started, mean annual temperature, mean annual water deficit, road density, land opportunity cost, percentage cover of strictly protected forest areas, and human population variation in the surrounding landscape. We suggest that natural forest restoration should be prioritized in landscapes with both low socioeconomic pressures on land use conversion to pasturelands and urban areas, and high percentage of forest cover.
Entwicklung und Evaluation eines interprofessionellen Lehrkonzepts zum modernen Wundmanagement
Authors: Bergendahl Lukas , Werner Felix , Schmidt Anita , Ronicke Moritz , Renner Regina , Erfurt‐Berge Cornelia
Published: September 2020

Hintergrund und Zielsetzung

Ziel dieser Arbeit war die Konzeptionierung und Evaluation einer neuartigen interprofessionellen Lehrveranstaltung zum Thema Wundmanagement.

Methoden

Nach einer Überprüfung der Ist‐Situation mittels Befragung von Studierenden der Humanmedizin in der Hauptvorlesung Dermatologie wurde ein 150 Minuten umfassendes Lehrkonzept mit praktischen Inhalten zum Thema Wundmanagement erstellt und innerhalb der bereits etablierten studentischen Übungseinrichtung interprofessionell angeboten. Die Kursteilnehmer wurden vor und nach Kursteilnahme mit Hilfe von Fragebögen hinsichtlich ihres subjektiven Kenntnisstandes befragt.

Ergebnisse

Die Befragung an 190 Studierenden ergab einen deutlichen Wunsch nach praktischer Wissensvermittlung zum Thema Wundmanagement. Bislang konnten 120 Teilnehmer (54,8 % Studierende der Humanmedizin, 45,2 % Auszubildende zum/zur Gesundheits‐ und Krankenpfleger/in) an dem neuen interprofessionellen Kursangebot teilnehmen. Es fand sich eine hohe Nachfrage des angebotenen Konzeptes sowohl von Studierenden als auch Auszubildenden. In allen Bereichen (Diagnostik, Therapie, Anwendung von Wundauflagen, Wunddebridement) konnte ein signifikanter Wissenszuwachs durch die Kursteilnahme erreicht werden.

Schlussfolgerungen

Die Versorgung von Patienten mit chronischen Wunden ist aufgrund der hohen Relevanz für die spätere Praxis für alle Medizinstudierenden von Bedeutung. Gerade der Fachbereich Dermatologie kann für ein besseres Verständnis und auch praktische Kenntnisse in der Wundversorgung sorgen, indem den Bedürfnissen der Studierenden nachgekommen wird und neue Lehrangebote geschaffen werden. Die Thematik bietet dabei beste Voraussetzungen für ein interprofessionelles Lernen.
Drivers of global variation in land ownership
Authors: Kavanagh Patrick H. , Haynie Hannah J. , Kushnick Geoff , Vilela Bruno , Tuff Ty , Bowern Claire , Low Bobbi S. , Ember Carol R. , Kirby Kathryn R. , Botero Carlos A. , Gavin Michael C.
Published: September 2020

Land ownership shapes natural resource management and social–ecological resilience, but the factors determining ownership norms in human societies remain unclear. Here we conduct a global empirical test of long‐standing theories from ecology, economics and anthropology regarding potential drivers of land ownership and territoriality. Prior theory suggests that resource defensibility, subsistence strategies, population pressure, political complexity and cultural transmission mechanisms may all influence land ownership. We applied multi‐model inference procedures based on logistic regression to cultural and environmental data from 102 societies, 71 with some form of land ownership and 31 with no land ownership. We found an increased probability of land ownership in mountainous environments, where patchy resources may be more cost effective to defend via ownership. We also uncovered support for the role of population pressure, with a greater probability of land ownership in societies living at higher population densities. Our results also show more land ownership when neighboring societies also practiced ownership. We found less support for variables associated with subsistence strategies and political complexity.
Weak relationships of parasite infection with sexual and life‐history traits in wild‐caught Texas field crickets (Gryllus texensis)
Authors: Worthington Amy M. , Kelly Clint D. , Proctor Heather
Published: September 2020

Sex differences in immune investment and infection rate are predicted due to the divergent life histories of males and females, where females invest more toward immunity due to the fitness consequences of a reduced lifespan and males allocate less toward immunity due to increased resource investment in traits critical to sexual selection. Consequently, males are expected to fight infection less adeptly, resulting in higher parasite loads relative to females across all taxa.

Wild animals rarely face a single parasite within their given environment, yet nearly all studies on sex‐biased infection rates have focused on a single host–parasite relationship. Here, we investigate how simultaneous natural infections of ecto‐ and endosymbionts (i.e. both parasitic and phoretic taxa) correlate with sex biases in host immune response and reproductive investment in a field‐caught cricket, Gryllus texensis.

Our comprehensive analysis found no significant sex differences in two measures of immune response (melanization and nodulation), and found no strong evidence of a sex bias in the prevalence or intensity of parasitism by the three most common parasites infecting wild G. texensis field crickets (Eutrombidiidae, gregarines, and nematodes).

Two traits related to female fitness, egg number and egg size, showed no relation to parasitic infection; however, males having wider heads and poorer body condition were significantly more infected by eutrombidiid mites, gregarines, and nematodes.

Despite frequent predictions of male‐biased parasitism in the literature, our results concur with many other studies indicating that the divergent life histories of males and females alone are not sufficient to explain natural infection rates in wild insects.
The positive attitude approach for teaching in higher education: An untrodden path for policy and practice
Authors: Miočić Ivana , Brajdić Vuković Marija , Ledić Jasminka
Published: September 2020

This article reports on a study in which a new conceptual framework for fostering a positive attitude towards teaching in higher education (PATTHE) was developed. The PATTHE framework builds on a holistic four‐dimensional theoretical concept and is not limited by the specificity of teaching within a particular discipline or national higher education context. The four dimensions of PATTHE pertain to (a) emotional dimension, (b) professional development, (c) constructivist approaches to teaching, and (d) the teaching and research nexus; all of which are relevant for empowering quality teaching at personal, institutional and/or national higher education policy levels. The purpose of our study was to test and analyse this conceptual framework. Creative qualitative research methods were used including identification of keywords, evoking participant opinions through visual materials, reactions to vignettes, and by documenting discussions regarding the proposed PATTHE conceptual framework. A purposive and critically informed approach was used for the selection of twelve higher education experts as research participants. Responses from the selected education developers were collected through an online protocol system. Research results revealed that participant reflections on a positive attitude towards teaching showed a high level of agreement with the proposed conceptual framework; the proposed theoretical concept is thereby deemed well‐constructed and acceptable with minimal extensions.
What is wrong between ecological science and policy?
Authors: Chassé Pierre , Blatrix Cécile , Frascaria‐Lacoste Nathalie
Published: September 2020

Ecological research is highlighting different kinds of issues concerning biodiversity conservation policies. Based on a historical study on protected areas, we suggest that these issues are not caused by a lack of knowledge or technical tools but rather by a misuse of ecological knowledge during the implementation of policy instruments in part driven by a lack of understanding of the mechanisms underlying the policymaking process. We believe that determining the conditions under which ecological science can enlighten policy decisions is now necessary to address current biodiversity conservation issues. This can only be achieved through the promotion of interdisciplinary research.
Enhancing the communication of functional neurological disorder diagnosis: a multidisciplinary education session
Authors: Cope S. R. , Smith J. G. , Edwards M. J. , Holt K. , Agrawal N.
Published: September 2020

Background and purpose

Functional neurological disorder (FND) is a common diagnosis within neurology. Effective communication of the diagnosis is known to be an important part of treatment and can result in reduction or cessation of symptoms, as well as decreased healthcare utilisation. A single group education session, facilitated by professionals commonly involved in the care of patients with FND, was developed to further enhance patients' and relatives' understanding and acceptance of diagnosis.

Methods

Patients and relatives attending a single education session were asked to complete self‐report ratings of understanding of diagnosis, acceptance of diagnosis, belief in treatability and hopefulness regarding recovery, at the beginning and end of the session. Satisfaction data were also collected.

Results

Data were obtained from 193 patients and 153 relatives. Patients had experienced a median duration of symptoms of 4 years, and more than 80% of patients reported more than one functional neurological symptom. There were significant increases in terms of understanding, acceptance, belief in treatability and hopefulness for patients and relatives. Effect sizes ranged from large for improved understanding of FND to small‐to‐medium for increased agreement with FND diagnosis. High levels of satisfaction were also reported.

Conclusions

A multidisciplinary, single group education session is an effective and acceptable method of increasing understanding and acceptance of an FND diagnosis, even for patients with a long duration of symptoms and high symptom burden. It could help improve readiness for further treatment.
Active immunisation against GnRH as treatment for unilateral granulosa theca cell tumour in mares
Authors: Behrendt Daphne , Burger Dominik , Gremmes Steffen , Szunyog Katja , Röthemeier Selena , Sieme Harald
Published: September 2020

Background

Stallion‐like or aggressive behaviour in mares affected by unilateral granulosa theca cell tumour (GTCT) is well‐known, but use of a GnRH‐vaccine as an alternative to surgical removal of the neoplastic ovary has not been investigated.

Objectives

To determine the effect of immunisation against GnRH on ovarian size, testosterone concentration, Anti‐Müllerian hormone (AMH) concentration, and owner‐reported behaviour in four mares affected by unilateral GTCT.

Study design

Retrospective case report.

Methods

A presumptive diagnosis of GTCT was made in four mares based on clinical signs, behavioural changes, transrectal palpation, and ultrasonography. All mares were vaccinated twice with the GnRH‐vaccine Improvac® on day 0 and on day 13‐33. Further booster vaccinations were administered if aggressive behaviour recurred between days 15 and 498. Before and parallel to the vaccinations, serum levels of oestradiol, progesterone (P4), testosterone, and AMH were evaluated and transrectal ultrasonography was performed.

Results

In all horses, analysis of serum levels of oestradiol, progesterone, testosterone, and AMH confirmed the clinical diagnosis of GTCT. Serum levels of testosterone dropped to baseline levels following the first two of three vaccination in all mares. In addition, AMH serum values decreased shortly after the second vaccination in three of four mares, and in one of the four mares returned to baseline levels. No further GTCT linked behaviour was reported by the owners and the affected ovaries diminished in size in all four cases.

Main limitations

This report is a case series with a limited number of animals, no controls and no standardised immunisation protocol.

Conclusions

Repeated vaccinations with the GnRH‐vaccine Improvac® mitigated owner‐reported behavioural abnormalities and stopped tumour growth in four mares affected by unilateral GTCT over the entire observation period which extends to 7 years in one mare.
Acute interstitial pneumonia in foals: A severe, multifactorial syndrome with lung tissue recovery in surviving foals
Authors: Punsmann Sophia , Hoppe Judith , Klopfleisch Robert , Venner Monica
Published: September 2020

Background

Acute interstitial pneumonia in foals has been sparsely described in literature, and the individual authors disagree on the underlying aetiology. Histopathological follow‐up from surviving foals is not available.

Objectives

Description of clinical and histopathological findings in the course of acute interstitial pneumonia and in recovery. Investigating the aetiology and possible triggering factors of acute interstitial pneumonia.

Study design

Case series.

Methods

Post‐mortem examination of nine affected foals; seven died during the acute phase, and two had recovered from acute interstitial pneumonia. Data from clinical examinations on the day of death were recorded for all foals. Complete necropsy, special histological staining, virological and microbiological examinations were performed.

Results

Seven foals died during the acute phase with severe respiratory distress, fever and increased numbers of comet tail artefacts in lung ultrasound. In post‐mortem examination, a wide variety of possible triggering factors was identified. Microbiology revealedEscherichia coli, Rhodococcus equiandKlebsiella pneumoniaeas the most common bacterial pathogens.Equine herpesvirus 2was detected in all foals by PCR. Those with high viral loads also displayed histopathological changes suggestive of viral infections.Pneumocystis cariniiwas detected in all acutely affected foals. Histopathological changes in lung parenchyma clearly differed between the foals that had recovered from acute interstitial pneumonia and those dying in the acute phase. While lungs in acute phase featured marked parenchymal collapse and necrosis, the recovered foals revealed nearly normal ventilated lung parenchyma and alveolar structure.

Main limitations

Small number of cases. Because all foals are from the same breeding farm with endemic occurrence of pathogens, it is not certain whether the results of this study can be transferred to other foals without restrictions.

Conclusions

Acute interstitial pneumonia seems to be based on a multifactorial aetiology. Lungs from foals that have survived acute interstitial pneumonia appear to be able to regenerate completely, leaving no permanent changes.
The validity and reliability of the Indonesian version of the Summated Xerostomia Inventory
Authors: Wimardhani Yuniardini Septorini , Rahmayanti Febrina , Maharani Diah Ayu , Mayanti Wiwik , Thomson William Murray
Published: September 2020

Objective

To validate and determine the reliability of the Indonesian version of the Summated Xerostomia Inventory (SXI‐ID) questionnaire.

Background

Xerostomia is a common problem in older people, and the SXI is increasingly being used to measure it.

Materials and methods

The SXI questionnaire was cross‐culturally adapted to create an Indonesian version (SXI‐ID), which was assessed for validity and reliability in a cross‐sectional study of older adults living in nursing homes in Jakarta, Indonesia. Each participant signed an informed consent and was interviewed with the SXI‐ID. A subset of participants was interviewed again after two weeks. A standard question was used to check criterion‐related validity, by plotting the mean SXI‐ID scale scores against the ordinal response categories of the standard question. The reliability check included Cronbach's alpha, total and inter‐item correlation, and intraclass correlation for internal consistency, along with test‐retest reliability.

Results

A total of 110 older adults participated. Cronbach's alpha value for the SXI‐ID was .85, and the intraclass correlation coefficient value for test and retest in 15 participants was .9. The SXI‐ID total score showed a strong positive correlation (.87) with the global question. There was a consistent ascending gradient in mean SXI‐ID scores across the ordinal response categories of the global item.

Conclusion

The SXI‐ID is psychometrically valid and reliable for measuring xerostomia in the Indonesian population.
Duodenal microbiome in patients with or without Helicobacter pylori infection
Authors: Suárez‐Jaramillo Andrés , Baldeón Manuel E. , Prado Belén , Fornasini Marco , Cohen Henry , Flores Nancy , Salvador Iván , Cargua Oswaldo , Realpe José , Cárdenas Paul A.
Published: September 2020

Background

Intestinal microbiota are recognized as an organ with important physiological functions whose alterations have been associated with common diseases including inflammatory intestinal conditions, malnutrition, type‐2 diabetes, and cardiovascular diseases. The composition and function of the microbiota in the distal part of the intestine has been mainly described, while there is limited information on the small intestine microbiota. The objective of the present study was to describe the duodenal microbiome in individuals with dyspepsia in the presence or absence of Helicobacter pylori gastric infection.

Materials and Methods

Thirty‐eight biopsies from the proximal duodenum of uninfected and 37 from H pylori‐infected individuals were analyzed. Microbiota composition was assessed by PCR amplification and sequencing of 16S rRNA and ITS genes; sequences were analyzed with QIIME2.

Results and Conclusions

At the phyla level, Proteobacteria, Bacteroidetes, Firmicutes, Actinobacteria, and Fusobacteria were predominant in the mucosal associated duodenal microbiota (MAM); at the genera level, we observed the predominance of Ralstonia, Streptococcus, Pseudomonas, Haemophilus, Herbaspirillum, Neisseria, and Veillonella. Microbiota α‐diversity was higher in H pylori‐infected individuals than in non‐infected ones. In terms of β‐diversity metrics, there was a statistically significant difference between groups. Also, relative abundance of Haemophilus, Neisseria, Prevotella pallens, Prevotella 7, and Streptococcus was greater in H pylori‐infected patients. In infected patients, several types of H pylori were present in duodenal MAM. Finally, the majority of duodenal samples had fungi sequences; the most common taxa observed were Recurvomyces followed by Ascomycota and Basidiomycota.
Bone mineral density, kidney function, weight gain and insulin resistance in women who switch from TDF/FTC/NNRTI to ABC/3TC/DTG
Authors: Ibrahim F , Samarawickrama A , Hamzah L , Vincent R , Gilleece Y , Waters L , Kegg S , Barbini B , Campbell L , Post FA ,   the BESTT Trial Team
Published: September 2020

Objectives

Tenofovir disoproxil fumarate (TDF) is associated with reduced bone mineral density (BMD). We evaluated changes in BMD in women who switched from TDF, emtricitabine and a nonnucleoside reverse transcriptase inhibitor (TDF/FTC/NNRTI) to abacavir, lamivudine and dolutegravir (ABC/3TC/DTG).

Methods

We conducted a randomized controlled trial in which women aged ≥40 years were randomized 1:2 to continue TDF/FTC/NNRTI or switch to ABC/3TC/DTG. The primary endpoint was change in total hip BMD measured by dual‐energy X‐ray absorptiometry at week 48. Secondary endpoints were changes in BMD of the lumbar spine and femoral neck and markers of bone turnover and kidney function up to week 48. We conducted exploratory analyses of weight gain, insulin resistance and metabolic syndrome. Primary and secondary endpoints were analysed by linear regression, with multiple imputation for missing time points.

Results

In all, 91 women [mean age = 50.4 (standard deviation [SD] = 6.6) years, median CD4 cell count = 600 (interquartile range: 479–800) cells/µL] were randomized. Women who switched to ABC/3TC/DTG maintained viral suppression and experienced improvements in total hip BMD (mean adjusted difference = 1%, P = 0.027) and lumbar spine BMD (3%, P = 0.002), with no change in specific markers of bone turnover or renal tubular function. Although participants in the ABC/3TC/DTG arm gained more weight (1.8 kg, P = 0.046), the switch strategy was not associated with reduced insulin sensitivity or new‐onset metabolic syndrome.

Conclusions

Switching from TDF/FTC/NNRTI to ABC/3TC/DTG resulted in improved BMD. Although weight gain was common in women who switched from TDF/FTC/NNRTI to ABC/3TC/DTG, we did not detect adverse effects on glucose homeostasis. Larger studies need to confirm these findings.
Geochemical characteristics of mafic and felsic igneous rocks (1.9–1.75 Ga) in the Lesser Himalaya: Regional variation and its implications for tectonic setting
Authors: Shinjo Ryuichi , Amuro Tomoki , Oura Kohei , Oshiro Kazuya , Tahara Shiro , Sakai Harutaka
Published: September 2020

Major and trace element and Nd–Hf isotopic compositions of Paleoproterozoic meta‐igneous rocks from the lower part of the Lesser Himalayan sequence provide insights into the nature of their source mantle and its tectonic setting. We observed bimodal (basaltic and rhyolitic) magmatic compositions in these rocks; this type of volcanism generally occurs in areas of extensional tectonics, particularly rifts. Two types of mafic rocks are identified: within‐plate type (subduction‐unrelated, enriched mantle derived) rocks and Nb–Ta‐depleted, continental arc‐like rocks. Within‐plate type mafic rocks are dominant in the eastern Nepal, though similar rocks are also found in western Nepal. Although models for the tectonic setting of these igneous rocks remain controversial (e.g. passive margin, continental arc, continental rift with possible hotspot), our new geochemical data support the rift model associated with mantle plume activity, which evolved to a passive margin. The Nb–Ta‐depleted, arc‐like rocks have lower εNd (t) (−1.7 to 1.7) and εHf (t) (0.9–4.4) than within‐plate type rocks; we consider that these rocks are formed from the interaction of mantle‐derived magmas with crustal components. All felsic rocks have similar or slightly lower εNd (t) (−5.2 to −0.1) and εHf (t) (−6.5 to 2.7) values relative to arc‐like mafic rocks, suggesting relatively limited crustal interaction. They may be derived from juvenile crust of underplated mafic magmas. Most of the felsic rocks have remarkably low Nb/Ta ratios (< 5), suggesting modification on their chemical composition by intensive sub‐solidus magmatic‐hydrothermal alteration.
Ni‐Cu‐Zn ferrites with high Curie temperature for multilayer inductors with increased operating temperatures
Authors: Reimann Timmy , Capraro Beate , Bartsch Heike , Töpfer Jörg
Published: September 2020

We studied the sintering behavior and magnetic properties of Ni0.60‐yCuyZn0.42Fe1.98O3.99 ferrites. The shrinkage is shifted toward lower temperature with increasing Cu content y. The addition of Bi2O3 sintering aid induces enhanced shrinkage at T < 900°C and dense ceramics are obtained after sintering at 900°C. Such ferrites exhibit a permeability of µ = 135‐250 depending on the composition, sintering temperature and concentration of sintering additive. Ferrites with y = 0.20 show a high Curie temperature of Tc = 307°C. Multilayer inductors were fabricated and cofired at 900°C using ferrite tapes without and with 0.75 wt% Bi2O3. The compatibility of ferrite tapes with different metal pastes (Ag, AgPd, and Au) was evaluated. Ferrite tapes were also integrated between layers of low‐k dielectric CT708 tapes and successfully cofired at 900°C. Preliminary tests indicate that the multilayer inductors can be operated up to temperatures of 250°C. This demonstrates that high‐Tc Ni‐Cu‐Zn ferrites are promising magnetic materials for inductive components for high operating temperatures.
Preclinical models for studying immune responses to traumatic injury
Authors: Skelton Jessica Katy , Purcell Robert
Published: September 2020

Traumatic injury initiates a large and complex immune response in the minutes after the initial insult, comprising of simultaneous pro‐ and anti‐inflammatory responses. In patients that survive the initial injury, these immune responses are believed to contribute towards complications such as the development of sepsis and multiple organ dysfunction syndrome. These post‐traumatic complications affect a significant proportion of patients and are a major contributing factor for poor outcomes and an increased burden on healthcare systems. Therefore, understanding the immune responses to trauma is crucial for improving patient outcomes through the development of novel therapeutics and refining resuscitation strategies. In order to do this, preclinical animal models must mimic human immune responses as much as possible, and as such, we need to understand the constraints of each species in the context of trauma. A number of species have been used in this field; however, these models are limited by their genetic background and their capacity for recapitulating human immune function. This review provides a brief overview of the immune response in critically injured human patients and discusses the most commonly used species for modelling trauma, focusing on how their immune response to serious injury and haemorrhage compares to that of humans.
The relationships between nurses’ work environments and emotional exhaustion, job satisfaction, and intent to leave among nurses in Saudi Arabia
Authors: Alharbi Amal A. , Dahinten V. Susan , MacPhee Maura
Published: September 2020

Aims

To examine relationships between components of nurses’ work environments and emotional exhaustion, job satisfaction and intent to leave among nurses in Saudi Arabia.

Design

A descriptive correlational study with cross‐sectional data.

Methods

Data were collected in 2017 from 497 Registered Nurses working in a large tertiary hospital in Riyadh, Saudi Arabia. Participants completed an online survey like that used in RN4Cast studies to measure nurses’ perceptions of their work environments and nurse outcomes. Hierarchical linear regression and logistic regression were conducted to examine the relationships between components of nurses’ work environments and nurse outcomes after controlling for nurse and patient characteristics.

Results

Nurse participation in hospital affairs was uniquely associated with all three nurse outcomes, whereas staffing and resource adequacy was associated with emotional exhaustion and job satisfaction, but not intent to leave. These two variables were also the components of the nursing practice environment that received the lowest ratings. Nurse manager ability, leadership and support of nurses, and nurse–physician relationships were associated with job satisfaction only. A nursing foundation for quality of care was not uniquely associated with any of the three outcomes. Finally, nurse emotional exhaustion and job satisfaction fully mediated the relationship between nurse participation in hospital affairs and intent to leave.

Conclusion

Magnet‐like work environments in Saudi Arabia are critical to recruiting and retaining nurses in a country with critical nursing shortages.

Impact

This study addresses a gap in the literature regarding which components of the nurses’ work environment are uniquely associated with emotional exhaustion, job satisfaction and intent to leave among nurses in Saudi Arabia. Study results will assist Saudi hospital administrators and nurse leaders to develop recruitment and retention strategies by focusing on those work environment components most associated with nurse outcomes: participation in hospital affairs and staffing and resource adequacy.
Pseudogene AKR1B10P1 enhances tumorigenicity and regulates epithelial‐mesenchymal transition in hepatocellular carcinoma via stabilizing SOX4
Authors: Hao Fengjie , Fei Xiaochun , Ren Xinping , Xi Xiao Joanna , Chen Yongjun , Wang Junqing
Published: September 2020

Pseudogenes exert potential functions in tumorigenicity and tumour process in human beings. In our previous research on oncogene AKR1B10 in hepatocellular carcinoma (HCC), its pseudogene, AKR1B10P1, was preliminarily noticed being anomalistic transcribed, whereas whether AKR1B10P1 plays any specific function in HCC is poorly understood. By using shRNA transfection and lentiviral infection, we regulated the expression of ARK1B10P1 transcript and the relative targets in two ways. As we discovered, pathological transcription of AKR1B10P1 in HCC cells significantly promotes cell growth and motility either in vitro or in vivo. AKR1B10P1 was correlated with relatively dismal features of HCC. The epithelial‐mesenchymal transition (EMT) was enhanced by up‐regulating AKR1B10P1. And, a potential sequence of AKR1B10P1 transcript was discovered directly interacting with miR‐138. SOX4, a pivotal promotor of EMT, was validated as the down‐streaming target of miR‐138. Mechanistically, degradation of SOX4 mRNA induced by miR‐138 was effectively abrogated by AKR1B10P1. In conclusion, pseudogene AKR1B10P1 exerts stabilizing effect on SOX4 in HCC, associated EMT process, by directly sponging miR‐138, which post‐transcriptionally modulates SOX4’s regulating gene.