bluuebunny/crossref_metadata_2025 huggingface dataset:
Using camera trap data to characterise terrestrial larger‐bodied mammal communities in different management sectors of the Dja Faunal Reserve, Cameroon
Authors: Bruce Tom , Amin Rajan , Wacher Tim , Fankem Oliver , Ndjassi Constant , Ngo Bata Madeleine , Fowler Andrew , Ndinga Hilaire , Olson David
Published: November 2018

Camera trap surveys can be useful in characterising terrestrial larger‐bodied mammal communities in Central Africa forests. Two 40‐trap, minimum of 100 days, survey grids conducted in the Dja Faunal Reserve of southern Cameroon showed differences in the mammal communities of two sites 32 km apart. Mammal richness, diversity, guild structure, body‐size patterns and relative abundance of taxa were measured by trapping rates and occupancy of the two mammal communities. One of the survey sites was (a) less rich in terrestrial mammal species; (b) missing disturbance‐sensitive felids and white‐bellied duiker (Cephalophus leucogaster, subsp, leucogaster, Gray, 1873); (c) greater in abundance of some disturbance‐tolerant species; and (d) lower in abundance of larger‐bodied species. Several indicators suggest a higher hunting pressure at this site, and this may be a contributing factor to these differences.
Reduced pain thresholds and signs of sensitization in women with persistent pelvic pain and suspected endometriosis
Authors: Grundström Hanna , Gerdle Björn , Alehagen Siw , Berterö Carina , Arendt‐Nielsen Lars , Kjølhede Preben
Published: November 2018

Introduction

Endometriosis is a gynecological disorder that may cause considerable pelvic pain in women of fertile age. Determining pain mechanisms is necessary in order to optimize the treatment of the disease. The objective of the study was to evaluate pain thresholds in women with persistent pelvic pain with and without confirmed endometriosis, and healthy, unaffected controls, and analyze how pain thresholds in these cohorts related to duration of pelvic pain, quality of life, and symptoms of anxiety and depression.

Material and methods

Pain thresholds for heat, cold and pressure were assessed with quantitative sensory testing on six locations on a reference group of 55 healthy women and on 37 women with persistent pelvic pain who had been admitted for diagnostic laparoscopy on the suspicion of endometriosis. Validated instruments were applied to assess quality of life and symptoms of anxiety and depression. Data were analyzed by means of uni‐ and multivariate analysis of variance and Spearman's rank‐order correlation.

Results

The women with persistent pelvic pain had significantly lower pain thresholds compared with the reference women. In the women with pain, no differences were observed in pain thresholds between women with (n = 13) and women without (n = 24) biopsy‐proven endometriosis. The duration of pelvic pain correlated significantly positively with reduced pain thresholds, ie, the longer the duration, the more sensitization. In the persistent pelvic pain group, pain thresholds for heat correlated significantly with the Short Form Health Survey 36 dimension of bodily pain, and thresholds for cold correlated with Short Form Health Survey 36 bodily pain and with symptoms of depression.

Conclusions

Our results showed widespread alterations in pain thresholds in women with persistent pelvic pain that are indicative of central sensitization and a time‐dependent correlation. Women with pelvic pain and suspicion of endometriosis should probably be treated more thoroughly to prevent or at least minimize the concomitant development of central sensitization.
Outcomes of monoamniotic twin pregnancies managed primarily in outpatient care—a Danish multicenter study
Authors: Madsen Caroline , Søgaard Kirsten , Zingenberg Helle , Jørgensen Finn S. , Rosbach Hanne , Hoseth Eva , Pedersen Lars H. , Petersen Olav B.
Published: November 2018

Introduction

Monoamniotic twin pregnancies are high‐risk pregnancies, and management by inpatient or frequent outpatient care is recommended. We report the outcomes of a national cohort of monoamniotic twin pregnancies managed primarily as outpatients.

Material and methods

We prospectively analyzed the recorded data from the Danish Fetal Medicine Database, local databases, and medical records of all monoamniotic twin pregnancies diagnosed at the first trimester scan or later, and managed at the six major fetal medicine centers in Denmark over a 10‐year period.

Results

Sixty‐one monoamniotic twin pregnancies were included. Thirteen pregnancies were terminated early. Of the remaining 48 pregnancies with a normal first trimester scan, there were 36 fetal losses (25 spontaneous miscarriages <22+0 weeks, 3 late terminations and 8 intrauterine deaths >22 weeks) and 60 liveborn children (62.5%), all of whom were delivered by cesarean delivery at a median gestational age of 33+0 weeks. Three children had minor malformations and there was 1 pregnancy with twin‐to‐twin transfusion syndrome. After 26+0 weeks, 78.8% were managed as outpatients. Intrauterine death occurred in 3.8% of outpatients and in 28.6% of inpatients (admitted due to complications). At weeks 32, 33 and 34, the prospective risk of intrauterine death was 6.9%, 4.2% and 5.9%, respectively.

Conclusion

In this nationwide, unselected population, only 62.5% of fetuses with a normal first trimester scan were born alive. In contrast, the mortality was 3.8% after 26 weeks among the 78.8% of the cohort that was managed as outpatients. More knowledge is still needed to predict which pregnancies are at the highest risk of intrauterine death.
Self‐reported physical activity during leisure time was favourably associated with body composition in Norwegian adolescents
Authors: Aars Nils Abel , Jacobsen Bjarne K. , Furberg Anne‐Sofie , Grimsgaard Sameline
Published: November 2018

Aim

We studied the cross‐sectional association between self‐reported physical activity and body composition in adolescents.

Methods

The Norwegian Fit Futures Cohort Study was conducted in the Tromsø and Balsfjord municipalities during 2010–2011. All 1,117 students in their first year of upper secondary high school were invited to attend an examination at the Clinical Research Unit at the University Hospital of Northern Norway and 93% agreed. After exclusions, we analysed 945 participants (51% boys) with a mean age of 16.1 years (range 15.5–17.5 years) with valid measurements. The associations between self‐reported weekly hours of physical activity during leisure time and four measures of body composition were explored using linear regression.

Results

Self‐reported physical activity was significantly associated with the fat mass index (p < 0.03) and lean mass index (p < 0.001) in both genders. The lean mass index increased with higher levels of activity and the fat mass index decreased. Physical activity was not associated with body mass index for either gender, but there was an inverse association with waist circumference in girls (p = 0.04).

Conclusion

Physical activity was favourably associated with body composition in Norwegian adolescents and showed contrasting associations with the fat mass and lean mass indexes.
Validation of the International Guide for Monitoring Child Development demonstrates good sensitivity and specificity in four diverse countries
Authors: Ozturk Ertem Ilgi , Krishnamurthy Vibha , Mulaudzi Mphelekedzeni C. , Sguassero Yanina , Bilik Burcu , Srinivasan Roopa , Balta Hakan , Gulumser Ozlem , Gan Geliang , Calvocoressi Lisa , Johnson Benjamin , Shabanova Veronika , Forsyth Brian W.C.
Published: November 2018

Aim

It is of critical importance to have internationally constructed tools to address early childhood development. The aim of this second phase of a two‐phase study was to examine the sensitivity and specificity of the Guide for Monitoring Child Development (GMCD) in identifying developmental delay in four diverse countries.

Methods

The first phase of this 2011–2015 back‐to‐back study included 4949 children up to 42 months of age from primary healthcare centres in Argentina, India, South Africa and Turkey. Distribution curves were generated to show the ages when the children attainedGMCDmilestones and those that could be used across sexes and countries were placed in age ranges corresponding to the 85th and 97th percentile point estimates. Phase two examined a separately recruited sample of children in those countries to determine sensitivity and specificity of theGMCD.

Results

The validation phase of the 85 milestones in theGMCDidentified delayed development in 30% of the 1731 children in the four countries. The sensitivity and specificity ranged from 0.71–0.94 and 0.69–0.82, respectively, for the total sample and the different age groups.

Conclusion

TheGMCDstandardised in four diverse countries has appropriate accuracy for identification of children with developmental delay.
Interorganisational Relationships in Times of Decline: Implications for Organisational Resilience
Authors: Brueller Daphna , Brueller Nir N. , Brueller Raviv , Carmeli Abraham
Published: November 2018

We seek to delineate the processes by which work relationships between employees from buyer and supplier organisations can enhance the supplier's resilience. A micro‐foundations perspective is taken to study the effect of individual‐level relationships on these higher‐level processes in the context of a declining organisation—a supplier that has been experiencing a period of size decline, following the transition of some of its stronger competitors to a more advanced generation of products. The findings of a qualitative study indicate that the work relationships built between employees from the supplier and the customers around current product and services offerings can help a declining organisation to cope with setbacks and difficulties. Expanding on the three C's of hardiness (challenge, control, and commitment), we discuss the implications of our research for the study of resilience through the lens of interorganisational work relationships and highlight the different pathways that build these coping and adaptation qualities for the organisation. Specifically, the challenge of transitioning to new products can negatively influence these work relationships unless the supplier organisation provides supportive context by allowing employees to retain the necessary control over what it takes to serve their customers. Furthermore, the supplier should display strong commitment to integrate the new offerings while customers need to mirror this commitment by developing a willingness to adopt these new offerings by the supplier. The findings further suggest that these new offerings can be translated into higher levels of adaptation.
Recovery of Mediterranean steppe vegetation after cultivation: Legacy effects on plant composition, soil properties and functional traits
Authors: Helm Juliane , Dutoit Thierry , Saatkamp Arne , Bucher Solveig F. , Leiterer Matthias , Römermann Christine
Published: November 2018

Questions

Are the vegetation structure and soil properties of fallows similar to adjacent species‐rich Mediterranean steppe communities 35 years after abandonment? Is there a spontaneous redevelopment towards the original steppe vegetation after reintroduction of the traditional grazing system? Can differences in functional trait composition be identified according to different land‐use types? Do traits of selected species affect the ability to recolonize fallow land?

Location

Mediterranean steppe of La Crau (Southeastern France).

Methods

We conducted 80 vegetation surveys and soil analyses in the steppe and adjacent fallow land in six locations in La Crau in 2015; for three locations, data from 2001 were included. To compare the functional composition of steppe vs fallow land, community‐weighted means (CMW) of specific leaf area (SLA), leaf dry matter content (LDMC) and canopy height were calculated. To test whether trait variability is associated with the recolonization success of 12 selected target species, we measured SLA, LDMC, canopy height, plant width and aboveground biomass on eight replicate individuals per site and species.

Results

Fallow land was characterized by lower species richness and elevated phosphorus and potassium content in the soil. Comparing vegetation relevés between 2001 and 2015 revealed that the fallows were developing towards steppe vegetation. CWMs of SLA were significantly lower and CWM of LDMC higher in steppe than in fallow land. There was no similarity in trait composition between steppe species that successfully recolonized the fallow‐land community, and no evidence that intraspecific trait variability is associated with recolonization success of these species.

Conclusions

Even after decades of abandonment and reintroduction of the grazing system, the vegetation structure, soil properties and plant functional trait composition of fallows differ from those of adjacent steppe communities. These results illustrate the need for active restoration to accelerate the recovery of former arable land to the target steppe communities.
Bisphosphonate use and risk of renal cell carcinoma: A population‐based case‐control study
Authors: Chung Benjamin I. , Hellfritzsch Maja , Ulrichsen Sinna P. , Sørensen Henrik T. , Ehrenstein Vera
Published: November 2018

The purpose of this study was to evaluate the association between the use of bisphosphonates and the risk of developing renal cell carcinoma (RCC). We conducted a case‐control study in Denmark, using data linked from population‐based health and administrative registries. We identified all cases of RCC from 1996 to 2013 and sampled population controls in a 10:1 ratio from the underlying population free of RCC, while matching on sex, birth year and calendar time. Bisphosphonate use before RCC diagnosis, excluding the year leading up to the diagnosis, was measured using outpatient prescription dispensations. We used conditional logistic regression to compute crude and adjusted odds ratios (ORs) comparing ever vs. never bisphosphonate use in doses indicated for treatment of osteoporosis, overall and stratified by sex, with the OR estimating the incidence rate ratio. We also examined the effects by cumulative dose and specific agent. There were 2748 RCC cases and 27 480 controls. The adjusted ORs for ever vs never bisphosphonate use were 1.07 (95% confidence interval: 0.94‐1.22) overall; 1.15 (1.00‐1.32) for women; and 0.78 (0.54‐1.12) for men. Smoking could not be directly controlled for in the analysis. We found a weak association between use of oral bisphosphonates and risk of renal cell carcinoma in females. The observed association could be due to confounding by cigarette smoking, and future studies are required to assess this association further.
Effect of pharmacist intervention on blood conservation therapy in total knee arthroplasty: A retrospective, observational study
Authors: Zhou Ling , Ma Jingjing , Bao Jianan
Published: November 2018

Background

Total knee arthroplasty (TKA) is associated with blood loss and an increased risk of transfusion. Guidelines for antifibrinolytic drug tranexamic acid (TXA) treatment in TKA patients are available. We evaluated the effects of anticoagulant pharmacist intervention on perioperative blood conservation treatment in TKA patients.

Methods

In a retrospective, observational experimental study, patients admitted for TKA were allocated into the control or pharmacist intervention group. In the intervention phase, multiple interventions of TXA treatment based on guidelines were implemented. The primary endpoint was blood loss. Other outcome included postoperative haemoglobin and haematocrit levels, allogeneic blood transfusion, cost savings and safety.

Results

A total of 177 patients were included (88 and 89 in the control and intervention group, respectively). In the intervention group, 24.72% orders of TXA dosage, 20.22% orders of drug choice, 26.97% orders of TXA timing and 30.34% orders of TXA administration manner were adjusted. Eighty‐nine (100%) patients received blood conservation therapy compared with 21 (23.86%) patients in the control group (P < 0.001). Total blood loss was 1133.31 ± 627.08 mL in the control group compared with 604.34 ± 459.09 mL in the intervention group (P < 0.001). Postoperative drops in haemoglobin and haematocrit in the control group were greater than in the intervention group (P < 0.001). The rate of allogeneic blood transfusion was 40.91% in the control group compared with 21.35% in the intervention group (P = 0.01). Pharmacist intervention was conducted to cost savings resulting from reduced transfusion, but with comparable safety profile.

Conclusions

Anticoagulant pharmacist intervention on blood conservation treatment of TKA patients leads to favourable clinical and economic outcome.
Compliance with the guidelines for laboratory monitoring of patients treated with lithium: A retrospective follow‐up study among ambulatory patients in the Netherlands
Authors: Nederlof Mariëtte , Egberts Toine CG , van Londen Liesbeth , de Rotte Maurits CFJ , Souverein Patrick C , Herings Ron MC , Heerdink Eibert R
Published: November 2018

Objectives

Laboratory monitoring of patients using lithium is important to prevent harm and to increase effectiveness. The aim of this study is to determine compliance with the guidelines for laboratory monitoring of patients treated with lithium overall and within subgroups.

Methods

Patients having at least one lithium dispensing for 6 months or longer between January 2010 and December 2015 were identified retrospectively using data from the Dutch PHARMO Database Network. Laboratory monitoring was defined as being compliant with the Dutch Multidisciplinary Clinical Guideline Bipolar Disorders when lithium serum levels, creatinine and thyroid‐stimulating hormone (TSH) had been measured at least every 6 months during lithium use.

Results

Data were analyzed from 1583 patients with a median duration of 7‐ to 6‐months period of lithium use. Results indicated that patients had been monitored over 6‐month period for lithium serum levels 65% of the time, for creatinine 73% of the time and for TSH 54% of the time. Just over one seventh (16%) of patients had been monitored in compliance with the guidelines for all three parameters during total follow‐up. Especially males, patients aged below 65 years, patients receiving prescriptions solely from general practitioners, prevalent users of lithium, patients without interacting co‐medication, and patients without other days with laboratory measurements had been monitored less frequently in compliance with the guidelines.

Conclusions

A considerable proportion of patients had not been monitored in accordance with the guidelines. Further research is needed to understand the reasons for noncompliance and to implement strategies with the ultimate goal of optimizing safety and effectiveness for patients treated with lithium.
Behçet’s syndrome as a tool to dissect the mechanisms of thrombo-inflammation: clinical and pathogenetic aspects
Authors: Becatti M , Emmi G , Bettiol A , Silvestri E , Di Scala G , Taddei N , Prisco D , Fiorillo C
Published: November 2018

Behçet’s syndrome (BS) is a complex disease with different organ involvement. The vascular one is the most intriguing, considering the existence of a specific group of patients suffering from recurrent vascular events involving the venous and, more rarely, the arterial vessels. Several clinical clues suggest the inflammatory nature of thrombosis in BS, especially of the venous involvement, thus BS is considered a model of inflammation-induced thrombosis. Unique among other inflammatory conditions, venous involvement (together with the arterial one) is currently treated with immunosuppressants, rather than with anti-coagulants. Although many in-vitro studies have suggested the different roles of the multiple players involved in clot formation, in-vivo models are crucial to study this process in a physiological context. At present, no clear mechanisms describing the pathophysiology of thrombo-inflammation in BS exist. Recently, we focused our attention on BS patients as a human in-vivo model of inflammation-induced thrombosis to investigate a new mechanism of clot formation. Indeed, fibrinogen displays a critical role not only in inflammatory processes, but also in clot formation, both in the fibrin network and in platelet aggregation. Reactive oxygen species (ROS)-derived modifications represent the main post-translational fibrinogen alterations responsible for structural and functional changes. Recent data have revealed that neutrophils (pivotal in the pathogenetic mechanisms leading to BS damage) promote fibrinogen oxidation and thrombus formation in BS. Altogether, these new findings may help understand the pathogenetic bases of inflammation-induced thrombosis and, more importantly, may suggest potential targets for innovative therapeutic approaches.
An evaluation of the quality and content of web‐based stoma information
Authors: Connelly T. M. , Khan M. S. , Alzamzami M. , Cooke F.
Published: November 2018

Aim

Although the internet is commonly the first port of call for medical information, it provides unregulated data of variable quality. We aimed to evaluate commonly accessed web‐based information on intestinal stomas using validated and novel scoring systems.

Method

The keywords ‘stoma’, ‘colostomy’, ‘ileostomy’ and ‘bowel bag’ were entered into the most commonly used internet search engines (Google, Bing and Yahoo). The first ten websites from each search were analysed using the validated Journal of the American Medical Association (JAMA) benchmark criteria and DISCERN scoring systems. A novel stoma‐specific score was devised and applied.

Results

Forty‐three unique websites were identified. The majority (49%) were from nonprofit or governmental agencies and 9% were from commercial entities. The mean total DISCERN score for all websites was 42.4 ± 10.2 (maximum possible score = 75). The mean JAMA and stoma‐specific scores were 2.1 ± 1.0 (maximum possible score = 4) and 12.9 ± 6.1 (maximum possible score = 27). The lowest JAMA scores were in the category of attribution, with 70% of websites lacking references for the information provided. A total of 88% displayed disclosure/paid advertiser information. Surgery was described in 67%. An image or diagram was provided in 58% and in 72% a stoma therapist/nurse was mentioned. Information on when to seek medical help was provided in 51%.

Conclusion

Web‐based information on stomas is of variable content and quality. Authorship and information sources are often unclear. Only half provided information on when to seek medical help for complications including high output and dehydration. These findings should be highlighted to patients who utilize the internet to obtain information on stomas.
Paediatric asthma prevalence: The first national population‐based survey in Iran
Authors: Fazlollahi Mohammad Reza , Najmi Mehdi , Fallahnezhad Mojtaba , Sabetkish Nastaran , Kazemnejad Anoshirvan , Bidad Katayoon , Shokouhi Shoormasti Raheleh , Mahloujirad Maryam , Pourpak Zahra , Moin Mostafa
Published: November 2018

Background

The actual prevalence of paediatric asthma as a worldwide chronic disease has been surveyed in developed countries. However, no sufficient survey has been conducted in most of the eastern developing countries. Herein, we took measures to evaluate the prevalence of paediatric asthma in Iran.

Methods

In this national cross‐sectional study, the prevalence of asthma symptoms was estimated throughout the country using a randomized multistage stratified cluster sampling method in 16 410 and 16 850 individuals aged 6‐7 and 13‐14 years, respectively. A validated questionnaire including core questions of the International Study of Asthma and Allergies in Childhood (ISAAC) was applied between November 2015 and February 2016.

Results

The total prevalence of asthma was 10.9% (n = 3624) (95% confidence interval [CI]: 10.6%‐11.2%) which was significantly higher among 13‐ to 14‐year olds compared to a younger age group (12.4% vs. 9.4%, P < 0.001), males versus females (12.1% vs. 9.8%, P < 0.001) and residents of urban compared to rural areas (P = 0.003). The prevalence of severe asthma was 3.9%, being significantly more prevalent in higher age groups and male individuals (P < 0.001). A significant relationship was found between asthma and passive smoking in both 6‐ to 7‐ and 13‐ to 14‐year olds (P < 0.001).

Conclusions

The prevalence of asthma and severe asthma in the paediatric population of Iran was similar to other developing countries. It is recommended to pay special attention to urban regions, male individuals and higher age groups for better controlling of asthma. Nevertheless, further national surveys are necessary to determine the trend of paediatric asthma in Iran.
Risk of adverse maternal and fetal outcomes during pregnancy in living kidney donors: A matched cohort study
Authors: Davis Scott , Dylewski James , Shah Pratik B. , Holmen John , You Zhiying , Chonchol Michel , Kendrick Jessica
Published: November 2018

Background

We examined the risk of adverse pregnancy outcomes in primiparous kidney donors compared to matched controls.

Methods

Fifty‐nine women with a history of kidney donation prior to their first pregnancy with normal renal function and no history of kidney disease, diabetes or chronic hypertension were matched 1:4 by age (within 2 years) and race to women with two kidneys using data from an integrated healthcare delivery system. Adverse pregnancy outcomes were defined as preterm delivery (delivery <37 weeks), delivery via cesarean section, gestational hypertension, preeclampsia/eclampsia, gestational diabetes, length of stay in the hospital >3 days, infant death/transfer to acute facility and low birthweight (<2500 g).

Results

Living kidney donors did not have a higher risk of adverse outcomes compared to matched controls. There was a trend toward an increased risk of preeclampsia/eclampsia in kidney donors but it did not reach statistical significance (Odds ratio [OR]: 2.96, 95% CI: 0.98‐8.94, P = 0.06). However, in kidney donors ≤30 years of age, there was a fourfold increased risk of preeclampsia/eclampsia (OR: 4.09, 95% CI: 1.07‐15.59, P = 0.04).

Conclusion

Overall, the risk of pregnancy‐associated complications following kidney donation is small but potential female kidney donors should be counseled on the possible increased risk of preeclampsia.
Genetic variation for egg‐to‐adult survival in Drosophila melanogaster in a set of recombinant inbred lines reared under heat stress in a natural thermal environment
Authors: Borda Miguel Angel , Sambucetti Pablo Daniel , Gomez Federico Hernan , Norry Fabian Marcelo
Published: November 2018

Quantitative trait loci (QTL) for thermotolerance were previously identified for adult flies in several mapping populations of Drosophila melanogaster Meigen (Diptera: Drosophilidae) in the laboratory. However, laboratory assays may not necessarily reflect the performance under heat stress in the field. For instance, do the heat‐resistance QTL regions in the field match the QTL for thermotolerance in laboratory studies? To address this and related questions we used a set of recombinant inbred lines (RIL), which were originally used to identify QTL in the laboratory. We tested egg‐to‐adult survival (EAS) QTL in a field experiment under naturally varying heat‐stress temperatures in fly cultures reared on a rotting fruit (banana) in summer. EAS under heat stress was found to be 3–6× lower (depending on RIL) in the field than in the corresponding control at benign temperature (25 °C). Five QTL for EAS were significant in the field experiment under heat stress, four of them co‐located with plasticity QTL, and none of the QTL was significant at control temperature. All significant QTL overlapped (co‐localized) with thermotolerance QTL previously identified in the laboratory. A previously found QTL in the middle of chromosome 2 explained near 30% of the phenotypic variance in EAS under heat stress in previous studies in the laboratory, but this QTL explained only 8% of the EAS variation in our field assay. The largest effect on EAS was found for an X‐linked QTL (cytological range 7B3‐10C3) in the heat‐stress field experiment, explaining a high percentage (14–45%) of the phenotypic variation in EAS. The ecological relevance of QTL implicated in this study is discussed.
The influence of clinical experience on dental students' ethical awareness
Authors: Hertrampf Katrin , Groß Dominik , Karsten Gudrun , Wenz Hans‐Jürgen
Published: November 2018

Introduction

There has been no structured integration of ethical issues into the dental curriculum and currently no data for certain ethics modules exists in Germany. The study aimed at evaluating the attitudes to ethical issues that affect students at the Dental School in Kiel during patient treatment.

Material and methods

In the summer of 2017, students were recruited from the 6th and 10th semesters. A qualitative study design with interviews was chosen. The dimensions included, for example, experience with ethical issues, definitions and expectations of teaching content and methods. A qualitative content analysis was performed.

Results

Twelve and eleven students from semesters (32% each) participated. No student was able to name an ethical question based on his own experience (private/study). The need to address ethical issues was justified solely by personal treatment experiences.

Discussion

The study revealed a lack of basic ethical knowledge resulting in a lack of ability to deal with ethical issues. Instead, participants described experiences of psychological pressure, feelings of helplessness.

Conclusion

The results suggest that ethical‐theoretical foundations should be taught before the beginning of patient treatment. A didactic combination with clinical facts and case vignettes is recommended.
Inflammatory functional iron deficiency common in myelofibrosis, contributes to anaemia and impairs quality of life. From the Nordic MPN study Group
Authors: Birgegard Gunnar , Samuelsson Jan , Ahlstrand Erik , Ejerblad Elisabeth , Enevold Christian , Ghanima Waleed , Hasselbalch Hans , Nielsen Claus H. , Knutsen Håvar , Pedersen Ole B. , Sørensen Anders , Andreasson Björn
Published: November 2018

Objectives

The study investigates the hypothesis that inflammation in myelofibrosis (MF) like in myeloma and lymphoma, may disturb iron distribution and contribute to anaemia.

Methods

A cross‐sectional study of 80 MF and 23 ET patients was performed.

Results

About 35% of anaemic MF patients had functional iron deficiency (FID) with transferrin saturation <20 and normal or elevated S‐ferritin (<500 µg/L). In ET, FID was rare. In MF patients with FID, 70.6% were anaemic, vs 29.4% in patients without FID (P = 0.03). Hepcidin was significantly higher in MF patients with anaemia, including transfusion‐dependent patients, 50.6 vs 24.4 µg/L (P = 0.01). There was a significant negative correlation between Hb and inflammatory markers in all MF patients: IL‐2, IL‐6 and TNF‐α, (P < 0.01‐0.03), LD (P = 0.004) and hepcidin (P = 0.03). These correlations were also seen in the subgroup of anaemic MF patients (Table ). Tsat correlated negatively with CRP (P < 0.001). Symptom burden was heavier in MF patients with FID, and MPN‐SAF quality of life scores correlated with IL‐6 and CRP.

Conclusions

The inflammatory state of MF disturbs iron turnover, FID is common and contributes to anaemia development and impairment of QoL. Anaemic MF patients should be screened for FID.
Striatal GABAergic interneuron dysfunction in the Q175 mouse model of Huntington's disease
Authors: Holley Sandra M. , Galvan Laurie , Kamdjou Talia , Cepeda Carlos , Levine Michael S.
Published: November 2018

The pathological hallmark of Huntington's disease (HD) is the massive loss of striatal and cortical neurons. Until recently, it was believed that striatal interneurons were spared from degeneration. This view has changed after the demonstration that parvalbumin (PV)‐expressing interneurons also are vulnerable in humans. Here we compared morphological and functional changes of striatal fast‐spiking interneurons (FSIs) and low‐threshold spiking (LTS) interneurons in the Q175 mouse model of HD at presymptomatic (2 months) and symptomatic (12 months) stages of the disease. Electrophysiological intrinsic and synaptic properties of FSIs were significantly altered in symptomatic mice compared to wild‐type (WT) littermates. Overall, FSIs became more excitable with disease progression. Sholl analysis also revealed a significant loss of dendritic complexity and excitatory synaptic inputs. The basic membrane and synaptic properties of LTS interneurons were similar in Q175 and WT mice regardless of disease stage. The resilience of LTS interneurons could be related to their sparsity of excitatory synaptic inputs compared with FSIs. However, in symptomatic mice, a subpopulation of LTS interneurons displayed an increase in action potential firing within oscillating bursts. Thus, we conclude that while both FSI and LTS interneurons demonstrate increases in excitability, the HD mutation differentially affects their membrane and synaptic properties as well as their ability to respond to compensatory challenges presented during the late stage of the disease. Alterations in GABAergic interneuron intrinsic activity and responsiveness to incoming signals may significantly affect SPN output thus contributing to abnormal motor movements in patients afflicted with HD.
Spontaneous pre‐stimulus oscillatory activity shapes the way we look: A concurrent imaging and eye‐movement study
Authors: Paoletti Davide , Braun Christoph , Vargo Elisabeth Julie , van Zoest Wieske
Published: November 2018

Previous behavioural studies have accrued evidence that response time plays a critical role in determining whether selection is influenced by stimulus saliency or target template. In the present work, we investigated to what extent the variations in timing and consequent oculomotor controls are influenced by spontaneous variations in pre‐stimulus alpha oscillations. We recorded simultaneously brain activity using magnetoencephalography (MEG) and eye movements while participants performed a visual search task. Our results show that slower saccadic reaction times were predicted by an overall stronger alpha power in the 500 ms time window preceding the stimulus onset, while weaker alpha power was a signature of faster responses. When looking separately at performance for fast and slow responses, we found evidence for two specific sources of alpha activity predicting correct versus incorrect responses. When saccades were quickly elicited, errors were predicted by stronger alpha activity in posterior areas, comprising the angular gyrus in the temporal‐parietal junction (TPJ) and possibly the lateral intraparietal area (LIP). Instead, when participants were slower in responding, an increase of alpha power in frontal eye fields (FEF), supplementary eye fields (SEF) and dorsolateral pre‐frontal cortex (DLPFC) predicted erroneous saccades. In other words, oculomotor accuracy in fast responses was predicted by alpha power differences in more posterior areas, while the accuracy in slow responses was predicted by alpha power differences in frontal areas, in line with the idea that these areas may be differentially related to stimulus‐driven and goal‐driven control of selection.
Engineering synucleinopathy‐resistant human dopaminergic neurons by CRISPR‐mediated deletion of the SNCA gene
Authors: Chen Yixi , Dolt Karamjit Singh , Kriek Marco , Baker Terry , Downey Patrick , Drummond Nicola J. , Canham Maurice A. , Natalwala Ammar , Rosser Susan , Kunath Tilo
Published: November 2018

An emerging treatment for Parkinson's disease (PD) is cell replacement therapy. Authentic midbrain dopaminergic (mDA) neuronal precursors can be differentiated from human embryonic stem cells (hESCs) and human induced pluripotent stem cells (iPSCs). These laboratory‐generated mDA cells have been demonstrated to mature into functional dopaminergic neurons upon transplantation into preclinical models of PD. However, clinical trials with human fetal mesenchephalic cells have shown that cell replacement grafts in PD are susceptible to Lewy body formation suggesting host‐to‐graft transfer of α‐synuclein pathology. Here, we have used CRISPR/Cas9n technology to delete the endogenous SNCA gene, encoding for α‐synuclein, in a clinical‐grade hESC line to generate SNCA+/− and SNCA−/− cell lines. These hESC lines were first differentiated into mDA neurons, and then challenged with recombinant α‐synuclein preformed fibrils (PFFs) to seed the formation for Lewy‐like pathology as measured by phosphorylation of serine‐129 of α‐synuclein (pS129‐αSyn). Wild‐type neurons were fully susceptible to the formation of protein aggregates positive for pS129‐αSyn, while SNCA+/− and SNCA−/− neurons exhibited significant resistance to the formation of this pathological mark. This work demonstrates that reducing or completely removing SNCA alleles by CRISPR/Cas9n‐mediated gene editing confers a measure of resistance to Lewy pathology.
A Kiss to drive rhythms in reproduction
Authors: Simonneaux Valérie
Published: November 2018

Reproduction, like many other biological functions, exhibits marked daily and seasonal rhythms in order to anticipate and adapt breeding activity to environmental challenges. In recent years, studies investigating the neuroendocrine mechanisms driving rhythms in reproduction have unveiled the pivotal role of hypothalamic neurons expressing kisspeptin in integrating and forwarding daily and seasonal cues to the reproductive system. The objective of this review is to summarize the knowledge on the effect and role of this neuropeptide on the mammalian hypothalamo‐pituitary‐gonadal axis and describe how it is involved in the daily control of ovulation in females and long‐term adaptation of reproduction in seasonal breeders.
Safety of urgent endarterectomy in acute non‐disabling stroke patients with symptomatic carotid artery stenosis: an international multicenter study
Authors: Roussopoulou A. , Tsivgoulis G. , Krogias C. , Lazaris A. , Moulakakis K. , Georgiadis G. S. , Mikulik R. , Kakisis J. D. , Zompola C. , Faissner S. , Chondrogianni M. , Liantinioti C. , Hummel T. , Safouris A. , Matsota P. , Voumvourakis K. , Lazarides M. , Geroulakos G. , Vasdekis S. N.
Published: November 2018

Background and purpose

International recommendations advocate that carotid endarterectomy (CEA) should be performed within 2 weeks from the index event in symptomatic carotid artery stenosis (sCAS) patients. However, there are controversial data regarding the safety of CEA performed during the first 2 days of ictus. The aim of this international, multicenter study was to prospectively evaluate the safety of urgent (0–2 days) in comparison to early (3–14 days) CEA in patients with sCAS.

Methods

Consecutive patients with non‐disabling (modified Rankin Scale scores ≤2) acute ischaemic stroke or transient ischaemic attack due to sCAS (≥70%) underwent urgent or early CEA at five tertiary‐care stroke centers during a 6‐year period. The primary outcome events included stroke, myocardial infarction or death during the 30‐day follow‐up period.

Results

A total of 311 patients with sCAS underwent urgent (n = 63) or early (n = 248) CEA. The two groups did not differ in baseline characteristics with the exception of crescendo transient ischaemic attacks (21% in urgent vs. 7% in early CEA; P = 0.001). The 30‐day rates of stroke did not differ (P = 0.333) between patients with urgent (7.9%; 95% confidence interval 3.1%–17.7%) and early (4.4%; 95% confidence interval 2.4%–7.9%) CEA. The mortality and myocardial infarction rates were similar between the two groups. The median length of hospitalization was shorter in urgent CEA [6 days (interquartile range 4–6) vs. 10 days (interquartile range 7–14); P < 0.001].

Conclusions

Our findings highlight that urgent CEA performed within 2 days from the index event is related to a non‐significant increase in the risk of peri‐procedural stroke. The safety of urgent CEA requires further evaluation in larger datasets.
High‐frequency repetitive transcranial magnetic stimulation and intermittent theta‐burst stimulation for spasticity management in secondary progressive multiple sclerosis
Authors: Korzhova J. , Bakulin I. , Sinitsyn D. , Poydasheva A. , Suponeva N. , Zakharova M. , Piradov M.
Published: November 2018

Background and purpose

The spasticity phenomenon is a significant factor in the development of disability. Repetitive transcranial magnetic stimulation (rTMS) is a promising treatment method for this disorder. Our aim was to compare the effects of two protocols of rTMS – the high‐frequency (HF) rTMS (20 Hz) and the intermittent theta‐burst stimulation (iTBS) – on the level of spasticity and concomitant symptoms in patients with secondary progressive multiple sclerosis with an analysis of the duration of the effects up to 12 weeks after the stimulation course.

Methods

Thirty‐four patients with secondary progressive multiple sclerosis and lower spastic paraparesis were randomized into three groups: (i) HF‐rTMS (20 Hz); (ii) iTBS; (iii) sham stimulation. Spasticity and spasticity‐associated symptoms were assessed by the Modified Ashworth Scale, the Subjective Evaluating Spasticity Scale (SESS), the numerical analog scale, the Modified Fatigue Impact Scale and the pain level scale.

Results

The Modified Ashworth Scale was significantly reduced after the stimulation course in the HF‐rTMS and iTBS groups. The SESS was reduced post‐intervention and at the two follow‐ups in the iTBS group, whilst HF‐rTMS produced an SESS reduction only at the 2‐week follow‐up, with no effects in the sham group. Conversely, reduction in pain and fatigue was found in the HF‐rTMS group.

Conclusions

The results show that HF‐rTMS and iTBS significantly reduce spasticity measured by the Modified Ashworth Scale, in contrast to sham stimulation. Some evidence was found in favor of a longer‐lasting effect of iTBS on the SESS and of a reduction in pain and fatigue after HF‐rTMS.
Concentrations of indomethacin and its metabolite desmethylindomethacin in plasma and urine after repeated indomethacin topical application to Thoroughbreds
Authors: Kusano K. , Minamijima Y. , Mashita S. , Kunii H. , Yamashita S. , Nagata S.
Published: November 2018

Background

Repeated topical application of indomethacin is common in Japanese racehorses, despite the lack of pharmacokinetic data.

Objectives

To determine the concentrations of indomethacin and its metabolite, desmethylindomethacin, in plasma and urine of Thoroughbreds topically treated repeatedly with indomethacin.

Study design

In vivo experimental.

Methods

Seven female Thoroughbreds were topically treated with 50 g of 1% indomethacin cream per horse to the back and hips (500 mg of indomethacin/head/2400 cm2, 0.21 g/cm2) for 3 consecutive days. Samples were pretreated by protein precipitation for plasma and liquid‐liquid extraction with ethyl acetate after hydrolysis with hydrochloric acid for urine. The concentrations of indomethacin and desmethylindomethacin in plasma and urine were measured by liquid chromatography‐mass spectrometry.

Results

Indomethacin was quantifiable in plasma up to 48–72 h and in urine up to 96 h after the final application. Desmethylindomethacin was quantifiable in plasma up to 48 h and in urine up to 72–96 h after the final application.

Main limitations

The relationship between the local and systemic indomethacin concentrations after the topical application was not clarified.

Conclusions

Pharmacokinetic data were acquired for repeated topical administration of 1% indomethacin cream to Thoroughbreds. Hydrolysing urine samples with hydrochloric acid was effective for the analysis of indomethacin and its metabolite, and indomethacin may be an excellent marker analyte for doping tests. The estimated withdrawal time based on the limit of detection was 342 h.
The relationship between sagittal hoof conformation and hindlimb lameness in the horse
Authors: Pezzanite L. , Bass L. , Kawcak C. , Goodrich L. , Moorman V.
Published: November 2018

Background

Lameness can be multifactorial and may result from the accumulation of multiple seemingly unrelated causes. The identification of factors associated with lameness could be one method to decrease incidence of lameness and prolong the equine athlete's competitive life.

Objectives

To determine if there is an association between hoof balance in the sagittal plane and hindlimb lameness.

Study design

Case‐control study.

Methods

Eighty client‐owned horses with hindlimb lameness (cases) and 80 horses with no detectable hindlimb lameness (controls) were prospectively enroled following lameness evaluation as either cases (lameness localised with regional anaesthesia) or controls (no hindlimb lameness). Lameness cases were divided based on location (stifle, tarsus, proximal metatarsus and other sites). Lateromedial radiographs were performed on hind hooves and plantar angle of the distal phalanx (PADP) was determined. The prevalence of negative/neutralPADPand medianPADPs were calculated. Conditional logistic regression and Wilcoxon signed rank tests were used to analysePADPs, and odds ratios were calculated. Significance was set at P<0.05.

Results

The meanPADPwas significantly smaller in cases compared to controls. The meanPADPwas significantly smaller in horses with lameness localised to tarsus and proximal suspensory, but not the stifle. Lameness in horses was associated with a negative/neutralPADP(Odds ratio [OR] 3.87, 95% confidence interval [95%CI] 1.97–7.61, P<0.01), with lameness localised to the tarsus (OR4.98, 95%CI1.34–18.54, P = 0.01) and proximal suspensory (OR5.16, 95%CI1.11–23.89, P = 0.03) being associated with a negative/neutralPADP.

Main limitations

It is unknown whether the negative/neutralPADPcontributed to lameness or lameness resulted in lowerPADP.

Conclusions

Horses with hindlimb lameness localised to the distal tarsus and proximal metatarsus, but not the stifle, were more likely to have negative/neutralPADPs. Corrective farriery to improvePADPmay be investigated further as one component in the treatment of hindlimb lameness localised to regions proximal to the foot.

The Summary is available in Portuguese – see Supporting Information