bluuebunny/crossref_metadata_2025 huggingface dataset:
Growth‐faults from delta collapse – structural and sedimentological investigation of the Last Chance delta, Ferron Sandstone, Utah
Authors: Braathen Alvar , Midtkandal Ivar , Mulrooney Mark J. , Appleyard Tyler R. , Haile Beyene Girma , van Yperen Anna E.
Published: November 2017

Investigations of syn‐sedimentary growth faults in the Last Chance delta (Ferron Sandstone, Utah, USA) show that fault‐bounded half‐grabens arrested high amounts of sand in the mouth bar and/or distributary channel areas. Fault‐controlled morphology causes changes in routing of the delta top to delta front drainage towards the long axis of half‐grabens. Faulting was spatially and temporally non‐systematic, and polyphase, with 3D cusp/listric fault geometries instigated by linkage of variously oriented segments. Hanging wall rollover folds consisting of wedge‐shaped syn‐kinematic sand attest to rapid <1‐m slip increments on faults followed by mild erosion along crests of fault blocks and sedimentary infill of adjacent accommodation. Triangle‐zones in prodelta to delta front muds are located underneath steeper faults and interconnected rotated fault‐flats. Their geometry is that of antiformal stack duplexes, in an arrangement of low‐angle‐to‐bedding normal faults at the base, replaced by folded thrusts upwards. These faults show a brittle, frictional flow deformation mechanism ascribed to early compaction of mud. For syn‐kinematic sand, there is a change from general granular/hydroplastic flow in shear zones to later brittle failure and cataclasis, a transition instigated by precipitation of calcite cement. Extensional faulting in the Last Chance delta was likely controlled by gravity driven collapse towards the delta slope and prodelta, as is commonly observed in collapsing deltas. The trigger and driving mechanism is envisioned as localized loads from sand deposited within distributary channels/mouth bars and fault‐controlled basins along the delta top. A regional tilt and especially displacement of compacted mud below sand bodies towards less compacted muds also contributed to the faulting.
Childhood cancer incidence and survival in Japan and England: A population‐based study (1993‐2010)
Authors: Nakata Kayo , Ito Yuri , Magadi Winnie , Bonaventure Audrey , Stiller Charles A. , Katanoda Kota , Matsuda Tomohiro , Miyashiro Isao , Pritchard‐Jones Kathy , Rachet Bernard
Published: November 2017

The present study aimed to compare cancer incidence and trends in survival for children diagnosed in Japan and England, using population‐based cancer registry data. The analysis was based on 5192 children with cancer (age 0‐14 years) from 6 prefectural cancer registries in Japan and 21 295 children diagnosed in England during 1993‐2010. Differences in incidence rates between the 2 countries were measured with Poisson regression models. Overall survival was estimated using the Kaplan–Meier method. Incidence rates for Hodgkin lymphoma, renal tumors and Ewing sarcomas in England were more than twice as high as those in Japan. Incidence of germ cell tumors, hepatic tumors, neuroblastoma and acute myeloid leukemia (AML) was higher in Japan than in England. Incidence of all cancers combined decreased in Japan throughout the period 1993 to 2010, which was mainly explained by a decrease in registration of neuroblastoma in infants. For many cancers, 5‐year survival improved in both countries. The improvement in survival in chronic myeloid leukemia (CML) was particularly dramatic in both countries. However, 5‐year survival remained less than 80% in 2005‐2008 in both countries for AML, brain tumors, soft tissue sarcomas, malignant bone tumors and neuroblastoma (age 1‐14 years). There were significant differences in incidence of several cancers between countries, suggesting variation in genetic susceptibility and possibly environmental factors. The decrease in incidence for all cancers combined in Japan was related to the cessation of the national screening program for neuroblastoma. The large improvement in survival in CML coincided with the introduction of effective therapy (imatinib).
PRDM14 directly interacts with heat shock proteins HSP90α and glucose‐regulated protein 78
Authors: Moriya Chiharu , Taniguchi Hiroaki , Nagatoishi Satoru , Igarashi Hisayoshi , Tsumoto Kouhei , Imai Kohzoh
Published: November 2017

PRDM14 is overexpressed in various cancers and can regulate cancer phenotype under certain conditions. Inhibiting PRDM14 expression in breast and pancreatic cancers has been reported to reduce cancer stem‐like phenotypes, which are associated with aggressive tumor properties. Therefore, PRDM14 is considered a promising target for cancer therapy. To develop a pharmaceutical treatment, the mechanism and interacting partners of PRDM14 need to be clarified. Here, we identified the proteins interacting with PRDM14 in triple‐negative breast cancer (TNBC) cells, which do not express the three most common types of receptor (estrogen receptors, progesterone receptors, and HER2). We obtained 13 candidates that were pulled down with PRDM14 in TNBC HCC1937 cells and identified them by mass spectrometry. Two candidates—glucose‐regulated protein 78 (GRP78) and heat shock protein 90‐α (HSP90α)—were confirmed in immunoprecipitation assay in two TNBC cell lines (HCC1937 and MDA‐MB231). Surface plasmon resonance analysis using GST‐PRDM14 showed that these two proteins directly interacted with PRDM14 and that the interactions required the C‐terminal region of PRDM14, which includes zinc finger motifs. We also confirmed the interactions in living cells by NanoLuc luciferase‐based bioluminescence resonance energy transfer (NanoBRET) assay. Moreover, HSP90 inhibitors (17DMAG and HSP990) significantly decreased breast cancer stem‐like CD24− CD44+ and side population (SP) cells in HCC1937 cells, but not in PRDM14 knockdown HCC1937 cells. The combination of the GRP78 inhibitor HA15 and PRDM14 knockdown significantly decreased cell proliferation and SP cell number in HCC1937 cells. These results suggest that HSP90α and GRP78 interact with PRDM14 and participate in cancer regulation.
Downregulation of dual‐specificity tyrosine‐regulated kinase 2 promotes tumor cell proliferation and invasion by enhancing cyclin‐dependent kinase 14 expression in breast cancer
Authors: Imawari Yoshimi , Mimoto Rei , Hirooka Shinichi , Morikawa Toshiaki , Takeyama Hiroshi , Yoshida Kiyotsugu
Published: November 2017

Tumor progression is the main cause of death in patients with breast cancer. Accumulating evidence suggests that dual‐specificity tyrosine‐regulated kinase 2 (DYRK2) functions as a tumor suppressor by regulating cell survival, differentiation, proliferation and apoptosis. However, little is known about the mechanisms of transcriptional regulation by DYRK2 in cancer progression, particularly with respect to cancer proliferation and invasion. Here, using a comprehensive expression profiling approach, we show that cyclin‐dependent kinase 14 (CDK14) is a target of DYRK2. We found that reduced DYRK2 expression increases CDK14 expression, which promotes cancer cell proliferation and invasion in vitro, in addition to tumorigenicity in vivo. CDK14 and DYRK2 expression inversely correlated in human breast cancer tissues. We further identified androgen receptor (AR) as a candidate of DYRK2‐dependent transcription factors regulating CDK14. Taken together, our findings suggest a mechanism by which DYRK2 controls CDK14 expression to regulate tumor cell proliferation and invasion in breast cancer. Targeting of this pathway may be a promising therapeutic strategy for treating breast cancer.
Understanding aneurysmal type 1 neovascularization (polypoidal choroidal vasculopathy): a lesson in the taxonomy of ‘expanded spectra’ – a review
Authors: Dansingani Kunal K , Gal‐Or Orly , Sadda Srinivas R , Yannuzzi Lawrence A , Freund K Bailey
Published: November 2017

The term aneurysmal type 1 neovascularization is derived from terminology, which is established in the literature but has fallen out of use. We believe that aneurysmal type 1 neovascularization accurately describes the lesions which define the entity known as polypoidal choroidal vasculopathy (PCV). Over the last three decades, the clinical spectrum of PCV has expanded to recognize the occurrence of the aneurysmal (polypoidal) lesions in different contexts, resulting in a complex and unwieldy taxonomy based sometimes on circumstantial findings rather than mechanistic considerations. Advances in multimodal imaging provides increasingly convincing evidence that the lesions which define various forms of PCV are indeed vascular and arise from type 1 neovascular networks. The understanding of PCV as type 1 neovascularization with aneurysms renews focus on the question as to why some patients with type 1 neovascularization develop aneurysms while others do not. Conceptual themes and potential for further study are discussed.
Early impairment of the full‐field photopic negative response in patients with Stargardt disease and pathogenic variants of the ABCA4 gene
Authors: Abed Edoardo , Placidi Giorgio , Campagna Francesca , Federici Matteo , Minnella Angelo , Guerri Giulia , Bertelli Matteo , Piccardi Marco , Galli‐Resta Lucia , Falsini Benedetto
Published: November 2017

Background

To study the photopic negative response of the full‐field photopic electroretinography (ERG) in Stargardt patients with pathogenic variants in the ABCA4 gene.

Methods

A retrospective analysis of 35 Stargardt patients with ABCA4 gene pathogenic variants, compared to normal age‐matched controls. Patients were clinically followed at the Ophthalmology Department of Fondazione Policlinico Universitario A. Gemelli/Università Cattolica del Sacro Cuore, Rome, Italy.

Results

The photopic negative response of the full‐field photopic ERG was compromised in most Stargardt patients. In the presence of a normal B‐wave, the amplitude ratio between the photopic negative response and the B‐wave displayed a 97% accuracy in detecting diseased eyes (receiver operating characteristic curves).

Conclusions

In Stargardt patients with ABCA4 pathogenic mutations, the photopic negative response of the full‐field photopic ERG is a very sensitive disease read‐out. Its inclusion in standard ERG analysis would be a no‐cost addition of practical consequence in the follow‐up of Stargardt disease. The early impairment of the photopic negative response suggests that inner retinal function might be affected in Stargardt disease earlier than previously acknowledged.
Flow dynamics of cerebrospinal fluid between the intracranial cavity and the subarachnoid space of the optic nerve measured with a diffusion magnetic resonance imaging sequence in patients with normal tension glaucoma
Authors: Boye Dirk , Montali Margherita , Miller Neil R , Pircher Achmed , Gruber Philipp , Killer Hanspeter E , Remonda Luca , Berberat Jatta
Published: November 2017

Importance

This study offers a new approach for the quantification of CSF dynamics.

Background

Non‐invasive method to quantify the CSF dynamics in the subarachnoid space of the optic nerve is highly desirable. The aim of the study was to measure slow‐flow CSF velocities in healthy controls and normal tension glaucoma patients between the intracranial cavity and the subarachnoid space of the optic nerve.

Design

Prospective observational study.

Participants

Eleven age‐matched healthy volunteers and 15 normal tension glaucoma patients.

Methods

Using phase contrast images, the phase shift in MRI diffusion images can be used to determine the flow velocity. Flow‐range ratio between the intracranial cavity and the subarachnoid space of the optic nerve was calculated.

Main Outcome Measure

Flow‐range ratio between the intracranial cavity and the subarachnoid space of the optic nerve was calculated.

Results

First, phantom measurements were provided to validate the slow‐flow velocity calculations. Second, flow‐range ratio was validated for the healthy controls (0.63 ± 0.05), with the range being similar for the right and left optic nerve (P = 0.1). Statistically significant results were obtained (P < 0.05) when comparing the flow‐range ratio in the optic nerve of healthy controls (n = 22 eyes, 0.63 ± 0.05) with the flow‐range ratio in pathological optic nerves (n = 23, 0.55 ± 0.08) of normal tension glaucoma patients. MANOVA revealed no dependency between flow‐range ratio and patient dependent variables.

Conclusion and Relevance

Diffusion‐weighted imaging provides a method to evaluate CSF flow within the subarachnoid space of the optic nerve in a non‐invasive manner. Compared to healthy controls, patients with normal tension glaucoma measure a significantly lower flow‐range ratio. This finding suggests a possible role of impaired CSF dynamics in the pathophysiology in normal tension glaucoma.
Hypermanganesemia with dystonia, polycythemia and cirrhosis in 10 patients: Six novel SLC30A10 mutations and further phenotype delineation
Authors: Zaki M.S. , Issa M.Y. , Elbendary H.M. , El‐Karaksy H. , Hosny H. , Ghobrial C. , El Safty A. , El‐Hennawy A. , Oraby A. , Selim L. , Abdel‐Hamid M.S.
Published: November 2017

Biallelic mutations in the SLC30A10 gene cause an inborn error of Mn metabolism characterized by hypermanganesemia, polycythemia, early‐onset dystonia, and liver cirrhosis (HMDPC). To date, only 14 families from various ethnic groups have been reported. Here, we describe 10 patients from 7 unrelated Egyptian families with HMDPC. Markedly elevated blood Mn levels, the characteristic basal ganglia hyperintensity on T1‐weighted images, and variable degrees of extrapyramidal manifestations with or without liver disease were cardinal features in all patients. Eight patients presented with striking early diseased onset (≤2 years). Unexpectedly, early hepatic involvement before the neurological regression was noted in 3 patients. Mutational analysis of SLC30A10 gene revealed 6 novel homozygous mutations (c.77T > C (p.Leu26Pro), c.90C > G (p.Tyr30*), c.119A > C (p.Asp40Ala), c.122_124delCCT (p.Ser41del), c.780_782delCAT (p.Iso260del) and c.957 + 1G > C). Treatment using 2,3 dimercaptosuccinic acid as a manganese chelating agent showed satisfactory results with improvement of biochemical markers, hepatic manifestations and relative amelioration of the neurological symptoms. Our findings present a large cohort of patients with HMDPC from same ethnic group. The majority of our patients showed severe and early presentation with clear phenotypic variability among sibship. Moreover, we extend the phenotypic and mutational spectrum and emphasize the importance of early diagnosis and treatment of this potentially fatal disorder.
Risk of recurrence of sigmoid volvulus: a single‐centre cohort study
Authors: Johansson N. , Rosemar A. , Angenete E.
Published: November 2017

Aim

Sigmoid volvulus is a condition with a tendency to recur if treated conservatively. Little is known about the best type of treatment or when to perform definitive surgery. The aim of this study was to review treatment, and assess the outcome, of sigmoid volvulus in adult patients treated at a Swedish university hospital.

Method

The medical records of patients treated for sigmoid volvulus at Sahlgrenska University Hospital, Sweden from January 2000 to September 2016 were reviewed retrospectively. Median follow‐up time was 8.3 years.

Results

One hundred and sixty‐eight patients were included with a total of 453 admissions for sigmoid volvulus. Nonoperative decompression was attempted as the initial treatment in 438/453 (97%), with a success rate of 92% (403/438), which was not influenced by whether it was the first episode or a recurrence. Without planned surgery, recurrence occurred after 84% of successful nonoperative decompressions with a median of two recurrences (1–16). Recurrence was less common after the first episode compared with subsequent episodes. Median time until recurrence was 58 days. Mortality after planned surgery following successful decompression was 3.3% (2/61) compared with 13% (6/46) following emergency surgery.

Conclusion

In our cohort, the recurrence rate of sigmoid volvulus following successful nonoperative decompression was high. Still, more than 20% of patients did not experience a recurrence after their first episode. Nonoperative decompression could thus be suggested as the sole treatment for the first episode of volvulus. However, after the second episode it is probable that early planned surgery would improve outcome and reduce health‐care consumption.
The relationship between 18F‐FDG‐PETCT‐derived markers of tumour metabolism and systemic inflammation in patients with recurrent disease following surgery for colorectal cancer
Authors: McSorley S. T. , Khor B. Y. , Tsang K. , Colville D. , Han S. , Horgan P. G. , McMillan D. C.
Published: November 2017

Aim

18F‐fluorodeoxyglucose positron emission tomography‐computed tomography (18F‐FDG‐PETCT)‐derived markers of tumour metabolism have been reported to have prognostic significance in a variety of tumours. Host inflammation is also recognized to have prognostic significance. The aim of the present study was to investigate the relationship between these markers and host systemic inflammation in patients undergoing elective surgery for colorectal cancer.

Method

Patients with histologically confirmed colorectal cancer who underwent elective surgery between 2008 and 2015 and also underwent 18F‐FDG‐PETCT at a single centre were included (n = 103). The neutrophil–lymphocyte ratio (NLR) and modified Glasgow Prognostic Score (mGPS) were derived from routine blood tests. The maximum standardized uptake (SUVmax), peak standardized uptake (SUVpeak), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) were measured.

Results

There was no association between 18F‐FDG‐PETCT measures of tumour metabolism and systemic inflammation in the 33 patients who underwent preoperative imaging. Of the 70 patients with recurrent disease who underwent 18F‐FDG‐PETCT during follow‐up, patients with NLR ≥ 5 had a significantly higher SUVmax (20 vs 7, P = 0.002), SUVpeak (14 vs 5, P < 0.001), MTV (29 g vs 2 g, P = 0.001) and TLG (338 g vs 9 g, P < 0.001). Similarly, patients with a mGPS of 1–2 at the time of 18F‐FDG‐PETCT had a significantly higher median SUVmax (11 vs 6, P = 0.048), SUVpeak (8 vs 4, P = 0.046), MTV (13 ml vs 2 ml, P = 0.005) and TLG (146 g vs 10 g, P = 0.004).

Conclusion

The present study reports a direct association between 18F‐FDG‐PETCT‐derived measures of tumour metabolism and systemic inflammation in patients with recurrent colorectal cancer.
Ileus Management International (IMAGINE): protocol for a multicentre, observational study of ileus after colorectal surgery
Authors:   EuroSurg Collaborative
Published: November 2017

Aim

The management of postoperative ileus following colorectal surgery remains controversial. It is the commonest complication after elective colorectal resection and is associated with an increased incidence of postoperative adverse events. The prevention and management of postoperative ileus remains unstandardized. This study aims to describe an international profile of gastrointestinal recovery after colorectal surgery and will assess the role of non‐steroidal anti‐inflammatory drugs, when used as postoperative analgesia, in expediting the return of gastrointestinal function.

Methods

A multicentre, student‐ and trainee‐led, prospective cohort study will be conducted across both Europe and Australasia. Adult patients undergoing elective colorectal resection during 2‐week data collection periods between January and April 2018 will be included. A site‐specific questionnaire will capture compliance to Enhanced Recovery after Surgery components at participating centres. The primary outcome is time to gastrointestinal recovery, measured using a composite outcome of bowel function and oral tolerance. The impact of non‐steroidal anti‐inflammatory drugs on gastrointestinal recovery will be evaluated along with safety data with respect to anastomotic leak, acute kidney injury and complications within 30 days of surgery.

Discussion

This protocol describes the methodology of an international, observational assessment of gastrointestinal recovery after colorectal surgery. It discusses key challenges and describes how the results will impact on future investigation. The study will be conducted across a large student‐ and trainee‐led collaborative network, with prospective quality assurance and data validation strategies.
Presence of stratum corneum serum in non‐palmoplantar psoriasis
Authors: Chahal Sunisha , Tallon Ben
Published: November 2017

Background

Psoriasis is a common, chronic skin eruption characterized by abnormal hyperproliferation of the epidermis. When assessing psoriasis histologically, it is historically considered a “dry” disease, with significant amounts of serum not expected within lesional stratum corneum. However, this specific feature is not often mentioned within the literature. A retrospective study was undertaken to assess prevalence of serum within stratum corneum in cases of non‐palmoplantar psoriasis.

Methods

We evaluated 27 specimens diagnosed histologically as psoriasis between January 2015 and June 2016. In addition to serum, we assessed for psoriasiform hyperplasia, hypogranulosis, suprapapillary thinning and parakeratosis with neutrophils. The cases were then categorized as either diagnostic for, or consistent with, psoriasis and were followed up with clinicians to assess whether the clinical course was consistent with psoriasis.

Results

A total of 27 hematoxylin and eosin (H&E)‐stained biopsies were examined from 21 patients, with periodic acid‐Schiff (PAS) performed on 20 of the biopsies. Of these, 12 biopsies had serum present (44.4%). Of the 12 lesions considered to clinically and histologically represent psoriasis, 5 (41.7%) had serum.

Conclusion

Our results suggest serum within stratum corneum is possibly an acceptable feature within the spectrum of psoriasis histopathology and should not necessarily detract from the diagnosis.
Low annual frequency of HbA1c testing in people with Type 2 diabetes in primary care practices in Germany
Authors: Kostev K. , Jacob L. , Lucas A. , Rathmann W.
Published: November 2017

Aims

To analyse the annual frequency of HbA1c testing, as well as the factors associated with higher or lower testing frequency, in people with Type 2 diabetes mellitus in general practices and specialist diabetes practices in Germany.

Methods

A total of 43 509 people diagnosed with Type 2 diabetes between January 2016 and December 2016 in 557 medical practices (51% of all practices) were included in this study. The primary outcome was the annual recorded frequency of HbA1c testing in 2016. Multivariable logistic regression analyses were performed to identify variables associated with the odds of HbA1c concentration being tested at least twice in 2016, using predefined demographic and clinical variables.

Results

The mean (sd) number of reported HbA1c tests was 2.7 (1.6) in 2016. Overall, 74% of individuals had at least two annual HbA1c measurements. The likelihood of receiving ≥2 HbA1c tests was inversely associated with stroke (odds ratio 0.81, 95% CI 0.74–0.89), shorter diabetes duration (≤1 year: odds ratio 0.77, 95% CI 0.70–0.84) and higher mean HbA1c concentration (≥8.5%: odds ratio 0.85, 95% CI 0.76–0.94) and was positively associated with specialist diabetes care (odds ratio 1.24, 95% CI 1.14–1.36), hypertension (odds ratio 1.10, 95% CI 1.04–1.17), hyperlipidaemia (odds ratio 1.48, 95% CI 1.41 to 1.55), renal complications (odds ratio 1.41, 95% CI 1.32 to 1.50), neuropathy (odds ratio 1.27, CI 1.20 to 1.35) and retinopathy (odds ratio 1.38, 95% CI 1.25 to 1.52).

Conclusions

Only three out of four individuals with Type 2 diabetes underwent at least two HbA1c tests in Germany in 2016, which means that 25% of individuals underwent fewer tests than required by German guidelines.
MicroRNA‐145 regulates disabled‐2 and Wnt3a expression in cardiomyocytes under hyperglycaemia
Authors: Wang Bao‐Wei , Fang Wei‐Jen , Shyu Kou‐Gi
Published: November 2017

Aims

MicroRNA‐145 (miR‐145) could protect cardiomyocyte apoptosis against oxidative stress and repair infarcted myocardium. Angiotensin II (Ang II), a pro‐inflammatory cytokine could modulate myocardial remodelling. However, the role of hyperglycaemia on miR‐145 expression in cardiomyocyte or diabetes is not known. The effect of Ang II on miR‐145 expression under hyperglycaemia in cardiomyocytes remains unknown. We sought to investigate the effect of hyperglycaemia and Ang II on miR‐145 expression in cardiomyocytes.

Methods

Rat cardiomyocytes were cultured under high glucose concentration (25 mmol/L), and streptozotocin‐induced diabetic rats were established. TaqMan® MicroRNA real‐time quantitative assay was used to quantitate miR‐145.

Results

Sustained high glucose concentration (hyperglycaemia) significantly decreased miR‐145 expression in cardiomyocytes. Hyperglycaemia significantly increased Ang II mRNA expression and secretion from rat cardiomyocytes. Ang II suppressed miR‐145 expression in cardiomyocytes. Hyperglycaemia increased Dab2 and decreased Wnt3a/ß‐catenin expression in cardiomyocytes. Repression of miR‐145 expression by Ang II resulted in increased Dab2 and decreased Wnt3a and ß‐catenin expression under hyperglycaemia. In contrast, overexpression of miR‐145 significantly decreased Dab2 mRNA and protein expression, whereas the mRNA and protein levels for Wnt3a and ß‐catenin were significantly reduced in left ventricular myocardium from 5 days to 28 days in diabetic rats. The protein expression patterns of Dab2 and Wnt3a/ß‐catenin in left ventricular myocardium of diabetic rats could be reversed upon treatment with valsartan.

Conclusions

Ang II downregulates miR‐145 to regulate Dab2 and Wnt3a/ß‐catenin expression in cardiomyocytes under high glucose concentration. Ang II plays a critical role in the regulation of miR‐145 in cardiomyocytes under hyperglycaemic conditions.
E‐selectin gene in essential hypertension: a case‐control study
Authors: Srivastava Kamna , Chandra Sudhir , Narang Rajiv , Bhatia Jagriti , Saluja Daman
Published: November 2017

Background

Hypertension is associated with endothelial cell dysfunction. E‐selectin, an endothelial cell adhesion molecule, is specific for endothelial cell activation. Polymorphism in E‐selectin gene has recently been identified among which Leu554Phe E‐selectin gene polymorphism is least investigated in essential hypertension. This study reports the association of E‐selectin gene Leu554Phe polymorphism and the expression of E‐selectin gene in patients with essential hypertension.

Materials and methods

We analysed the Leu554Phe polymorphism and expression of E‐selectin gene in 250 patients with essential hypertension and 250 normal healthy controls. Genotyping of Leu554Phe polymorphism was performed by polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP), and the expression of E‐selectin gene at mRNA and protein levels were carried out by real‐time PCR and Western blot, respectively.

Results

A significant association of E‐selectin genotypes (CT + TT) with essential hypertension (P < .0001, Odds ratio = 2.2 [1.58‐3.24] at 95% CI) was observed. The expression of mRNA for E‐selectin gene in patients with essential hypertension was ~12‐fold higher as compared to control. We observed an elevated level of E‐selectin protein expression (up to 1.9 times) in patients as compared to controls.

Conclusions

A significant association of E‐selectin (Leu554Phe) gene and increased expression of E‐selectin gene at mRNA and protein levels in patients might be related to the genetic predisposition to develop essential hypertension.
Sublingual functional capillary rarefaction in chronic heart failure
Authors: Wadowski Patricia P. , Hülsmann Martin , Schörgenhofer Christian , Lang Irene M. , Wurm Raphael , Gremmel Thomas , Koppensteiner Renate , Steinlechner Barbara , Schwameis Michael , Jilma Bernd
Published: November 2017

Background and objective

Microcirculatory changes contribute to clinical symptoms and disease progression in chronic heart failure (CHF). A depression of coronary flow reserve is associated with a lower myocardial capillary density in biopsies. We hypothesized that changes in cardiac microcirculation might also be reflected by a systemic reduction in capillaries and visualized by sublingual videomicroscopy. The aim was to study in vivo capillary density and glycocalyx dimensions in patients with CHF vs healthy controls.

Methods

Fifty patients with ischaemic and nonischaemic CHF and standard treatment were compared to 35 healthy age‐matched subjects in a prospective cross‐sectional study. Sublingual microcirculation was visualized using a sidestream darkfield videomicroscope. Functional and perfused total capillary densities were compared between patients and controls. A reduced glycocalyx thickness was measured by an increased perfused boundary region (PBR).

Results

Median functional and total perfused capillary densities were 30% and 45% lower in patients with CHF (both P < .001). Intake of oral vitamin K antagonists was associated with significantly lower capillary densities (P < .05), but not independent of NT‐proBNP. Dimensions of the glycocalyx were marginally lower in CHF patients than in healthy controls (<7% difference). However, PBR correlated significantly with inflammation markers (fibrinogen: r = .58; C‐reactive protein: r = .42), platelet counts (r = .36) and inversely with measures of liver/renal function such as bilirubin (r = −.38) or estimated glomerular filtration rate (r = −.34) in CHF patients.

Conclusion

CHF patients have got a markedly lower functional and total perfused capillary density in sublingual microvasculature when compared to controls, indicating a systemic decrease in microcirculation.
Thinking about cases: Applying Kant's universal law formula
Authors: Bojanowski Jochen
Published: November 2017

According to a widespread view, Kant's claim that moral wrongness has its ground in a contradiction underlying every immoral action is a “bluff” rooted in “dogmatic moralism”. Ever since Benjamin Constant's exchange with Kant, counterexamples have played a crucial role in showing why Kant's “universalization procedure” fails to determine the moral validity of our judgments. Despite recent attempts to bring Kant's ethics closer to Aristotle's, these counterexamples have prevailed. Most recently, Jesse Prinz has launched another attack along the same lines. Prinz insists that Kant's universalization procedure fundamentally begs the question and fails to generate plausible results. Even authors who are very sympathetic to Kant, such as Allen Wood, have tried to downplay universalization, focusing instead on other formulations of the categorical imperative. In this paper, I respond directly to four of the most prominent counterexamples. In each case, I aim to show how we can uphold Kant's fundamental claim that the universal law formulation of the categorical imperative articulates the form of our particular moral judgments.
Autoimmune glial fibrillary acidic protein astrocytopathy in Chinese patients: a retrospective study
Authors: Long Y. , Liang J. , Xu H. , Huang Q. , Yang J. , Gao C. , Qiu W. , Lin S. , Chen X.
Published: November 2017

Background and purpose

The aim was to describe the clinical, radiological and pathological features of an autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy.

Methods

Data from 19 patients with positiveGFAP‐immunoglobulin G in cerebrospinal fluid (CSF) were retrospectively analyzed.

Results

The main disease manifestations included myelitis (68.4%), headache (63.2%), abnormal vision (63.2%), fever (52.6%), ataxia (36.8%), psychosis (31.6%), dyskinesia (15.8%), dementia (15.8%) and seizure (10.5%). Seventeen patients had brain abnormalities (89.5%), of which eight (42.1%) revealed the characteristic radial enhancing and laminar patterns. Cortical abnormalities were found in four patients (21.1%). Other abnormalities were found in the hypothalamus, midbrain, pons, medulla cerebellum, meninges and skull. Eleven patients had longitudinally extensive spinal cord lesions.CSFabnormalities were detected in all patients. Pathological examinations of four patients revealed extensive inflammation, with prominent perivascular B cells and T cells. Abundant antibody‐secreting cells were noted in the interstitial and perivascular spaces. Immunohistochemical analysis showed loss of astrocytes and neurons.

Conclusion

The present patients with positiveGFAP‐immunoglobulin G are highly similar to autoimmuneGFAPastrocytopathy, described in a recent report. The features of the neuropathology and immunopathology ofGFAPastrocytopathies were perivascular inflammation and loss of astrocytes and neurons.
Visualization of dendritic cells’ responses in atopic dermatitis: Preventing effect of emollient
Authors: Mias Céline , Le Digabel Jimmy , Filiol Jérôme , Gontier Etienne , Gravier Eléonore , Villaret Aurélie , Nocera Thérèse , Questel Emmanuel , Rossi Ana‐Beatris , Redoulès Daniel , Josse Gwendal
Published: November 2017

Atopic dermatitis (AD) is a chronic and multifactorial inflammatory skin disease involving various dendritic cells such as epidermal Langerhans cells (LC) and inflammatory dendritic epidermal cells (IDECs). Most of the clinical studies was performed on isolated cells, and thus, it would be useful to characterize directly on the human epidermal tissue the first cellular events occurred during the AD. The suction blister method was used to obtain whole epidermis samples and interstitial cutaneous fluids. Employing multiphoton microscopy, we analyzed the early dynamic behavior of inflammatory cells using Dermatophagoides pteronyssinus atopy patch test (Derp‐APT) and evaluated the effects of emollient pre‐application. Derp‐APT application provoked rapid and strong infiltration of IDECs, and proliferation and activation of LC in the AD subjects’ epidermis. Moreover, emollient pre‐application strengthened the defective skin barrier and had positive effects on inflammatory cells’ behavior, characterized by the complete inhibition of IDEC influx and the presence of immature LC.
BRAF mutations might be more common than supposed in vulvar melanomas
Authors: Wylomanski Sophie , Denis Marc G. , Théoleyre Sandrine , Bouquin Réjane , Vallée Audrey , Knol Anne‐Chantal , Saint‐Jean Mélanie , Peuvrel Lucie , Dréno Brigitte , Quéreux Gaëlle
Published: November 2017

Data on BRAF, NRAS and KIT mutations are scarce in patients with vulvo‐vaginal melanomas and are associated with important therapeutic issues. We investigated their prevalence in a cohort of patients with female lower genital tract melanomas between 2003 and 2017. Of the 22 patients, 5 (22.7%) harboured a BRAF mutation, which was much higher than the rate of 5% reported in the literature. One patient, who was tested negative on the primary melanoma, had a NRAS mutation in a cutaneous metastasis. Our data provide a rationale for prospective and repeated mutations testing in female lower genital tract melanomas.
Comparative study of amlodipine vs. cilnidipine for the prevention of hepatic ischemia‐reperfusion injury in rat model
Authors: Fouda Abdel‐Motaal , Youssef Amany R. , Sharaf Eldin Osama
Published: November 2017

Ca2+ signaling plays crucial role in ischemia and reperfusion (I/R) injury. Although blockade of L‐type Ca2+ channels by amlodipine (AML) has been shown to suppress hepatic I/R injury in several animal models, information is still needed regarding the hepatoprotective effects of the dual L/N‐type Ca2+ channel blockers, cilnidipine (CIL). We examined the effect of pretreatment with AML or CIL (100 μg/kg i.p.) 45 min before induction of 60 min of liver ischemia followed by reperfusion, on oxidative stress markers, liver enzymes, serum tumor necrosis factor‐α, interleukin‐1β, apoptosis markers, and nuclear factor KB after 6 and 24 h of hepatic reperfusion. Both drugs significantly ameliorated biochemical and histological markers of hepatic I/R injury, but protection with CIL was more significant at the 6‐h time point where protection with AML outlasted that of CIL. Both drugs offered significant protection against hepatic I/R damage, but the protection with CIL seemed more potent but of shorter duration than that observed with AML possibly due to the shorter half‐life of CIL.
The role of nonsteroidal anti‐inflammatory drugs intramuscular injection in the development and severity of deep soft tissue infection in mice
Authors: Ture Zeynep , Demiraslan Hayati , Kontas Olgun , Alp Emine , Doganay Mehmet
Published: November 2017

The aim of this study was to determine the role of nonsteroidal anti‐inflammatory drugs (NSAID) injection on the severity of local infection and the effect on the progression of soft tissue infection (STI).The mouse model of STI with Group A streptococcus (GAS) was developed and treated with diclofenac sodium (DS) intramuscularly. Mice were divided into five groups: administered DS for 48 h before GAS (Group 1), GAS‐DS and maintained DS for 48 h (Group 2), DS for 48 h (Group 3), GAS on zero time (Group 4), and control (Group 5). In vitro, a high concentration (40 mg/L) of DS inhibited GAS growth, whereas a lower concentration (0.4 mg/L) was not effective. Sepsis was observed in animals with DS and GAS inoculation (group 1 and 2). Group 4 had statistically significant higher bacterial load than groups 1 and 2. All groups had a higher inflammation rate than the control group. The median of TNF‐alpha and mean IL‐6 in the groups 1, 2, and 4 was significantly higher than those in the control group. Even if the animals that were treated with DS injection prior to the GAS inoculation had similar inflammation score, similar cytokine levels and low bacterial load in the tissue, they had a rather high rate of sepsis. In conclusion, DS injection prior to bacterial inoculation might predispose to bacteremia and sepsis.
BCL‐XL binds and antagonizes RASSF6 tumor suppressor to suppress p53 expression
Authors: Xu Xiaoyin , Iwasa Hiroaki , Hossain Shakhawoat , Sarkar Aradhan , Maruyama Junichi , Arimoto‐Matsuzaki Kyoko , Hata Yutaka
Published: November 2017

RASSF6, a member of the tumor suppressor Ras‐association domain family proteins, induces apoptosis in the caspase‐dependent and caspase‐independent manners. RASSF6 interacts with MDM2 and stabilizes p53. BCL‐XL is a prosurvival member of BCL‐2 family proteins. BCL‐XL directly inhibits proapoptotic BAX and BAK. BCL‐XL also traps tBID, a proapoptotic activator BH3‐only protein, and sequesters p53. In addition, BCL‐XL regulates the mitochondrial membrane permeability via voltage‐dependent anion channel. In these manners, BCL‐XL plays an antiapoptotic role. We report the interaction of BCL‐XL with RASSF6. BCL‐XL inhibits the interaction between RASSF6 and MDM2 and suppresses p53 expression. Consequently, BCL‐XL antagonizes RASSF6‐mediated apoptosis. Thus, the inhibition of RASSF6‐mediated apoptosis also underlies the prosurvival role of BCL‐XL.
Cicatricial organising pneumonia mimicking a fibrosing interstitial pneumonia
Authors: Churg Andrew , Wright Joanne L , Bilawich AnaMaria
Published: November 2017

Aims

Organising pneumonia (OP) is composed of loose granulation tissue plugs in distal airspaces; these disappear with steroid treatment. Recently a variant labelled ‘cicatricial’ OP has been described in which the granulation tissue organised to much denser fibrous tissue but still retained the usual pattern of OP. Here we report 10 patients thought to have an interstitial lung disease, and who on biopsy had a variant of cicatricial OP characterised by linear bands or small nodular masses of dense fibrous tissue that does not resemble ordinary OP.

Methods and results

The bands/nodules were usually distributed randomly but occasionally resembled fibrotic non‐specific interstitial pneumonia in local areas. Small foci of loose granulation tissue at the edge of the fibrotic bands sometimes mimicked fibroblast foci. Recognisable conventional OP was always present, but often in very small amounts. Four cases, including one patient with Ehlers–Danlos syndrome, showed formation of bone in the fibrotic bands and nodules. On computerised tomography (CT) scan of the chest some cases looked like typical OP, but some demonstrated only irregularly distributed linear opacities, sometimes with associated calcification. Follow‐up imaging on six cases showed that the process either markedly improved or remained stable over time; no case had progressive disease.

Conclusions

Cicatricial OP with this pathological pattern represents an uncommon form of OP that appears to be a generally benign process which may have persisting linear opacities on CT scan but that does not progress; however, it can be confused on biopsy and CT with a fibrosing interstitial pneumonia.
The role of radar wind profilers in ornithology
Authors: Weisshaupt Nadja , Arizaga Juan , Maruri Mercedes
Published: November 2017

In the past 70 years radar technology has been increasingly applied in ornithological research in various geographical areas worldwide and has contributed greatly to a better understanding of bird migration. Many different radar types have been used, such as tracking, ship or weather radars. However, radar wind profilers (RWPs) have been largely neglected in avian research. RWPs continuously measure three‐dimensional winds and, despite the low frequency range at which these systems operate, available literature provides evidence that birds are recorded at many sites. So far the potential of RWPs in ornithological research has not been fully explored and studies deal predominantly with birds in the context of clutter removal. However, based on their broad implementation in networks (e.g. E‐PROFILE in Europe) situated in areas that are strategically important for bird migration, they could offer a valuable complement to already established or planned large‐scale bird monitoring schemes by radar. The objective of this paper is to serve as a reference for those who wish to consider RWP data in a biological context. To that end, we provide an overview of the evolution and establishment of operational RWPs as well as of their mode of operation, in order to depict their role in meteorology and to evaluate their potential in ornithology. The assessment is based on available literature on RWPs and radar ornithology outlining the past, present and potential future role of wind profilers. In the past, birds were discarded as contamination and eliminated as far as possible from the meteorological data. Only recently have the echo signatures of biological targets been scrutinized thoroughly in raw data and used successfully for ornithological investigation. On this basis it is possible to consider the potential future utility of this promising data source as a complement to other remote‐sensing instruments and other sampling techniques used in avian research. Weather independence of ornithological information was found to be a particular benefit. However, as the development of the bird‐specific method is only in an early stage, more detailed studies are necessary in the future to fully assess the potential of this type of radar.
Low‐frequency, threatened habitats drive the large‐scale distribution of Andean Condors in southern Patagonia
Authors: Pérez‐García Juan M. , Sánchez‐Zapata José A. , Lambertucci Sergio A. , Hiraldo Fernando , Donázar José A.
Published: November 2017

The analysis of factors that determine the distribution of top‐scavengers at large scales can provide clues to understanding important ecological processes and may be useful in establishing conservation and management strategies. Here, we conducted a large‐scale survey to study the distribution of the threatened Andean Condor Vultur gryphus in relation to environmental factors in southern Patagonia. This area has undergone the settlement of livestock and the introduction of exotic wildlife, although to a lesser extent than in the distribution of Condors in northern Patagonia. The aim of this study was to determine the relevance of different factors such as the availability of food resources, the availability of suitable nesting and roosting places and the presence of humans on large‐scale condor distribution. Our results show that the presence of meadows was the primary factor shaping Andean Condor distribution, despite the fact that this habitat occupies only 4% of the Patagonian landscapes. However, this habitat has a high probability of herbivore presence, so Condors seem to optimize their searching. The availability of nesting and roosting cliffs also contributed to explaining the observed distributions. Our results suggest that Condor distribution in southern Patagonia is a compromise between the spatial locations of two low‐frequency habitats – meadows and cliffs. A successful Condor conservation strategy in southern Patagonia should include the protection of these habitats and the regulation of farming expansion, including the recovery of meadows.
Differences in wing morphology between juvenile and adult European Turtle DovesStreptopelia turtur: implications for migration and predator escape
Authors: Cabodevilla Xabier , Moreno‐Zarate Lara , Arroyo Beatriz
Published: November 2017

Behaviour has direct links to wing morphology in bird species. Many studies have postulated migration to be one of the most important forces of selection acting on wing morphology, particularly in relation to wing pointedness. Studies in passerines have found that adults have longer and more pointed wings than juveniles, especially in migratory species. We analysed differences in wing morphology between age groups of the European Turtle Dove, a non‐passerine migratory species that benefits from rounded wings during their daily activity, due to its ground‐feeding behaviour and acrobatic flight style. Our results show that adults of this species have longer but more rounded wings than juveniles. This suggests that in this species wing morphology in juveniles is selected to facilitate the first migration, whereas other selection forces (e.g. flight manoeuvrability) are more important after the first moult. These data also explain why juveniles are not as adept at escaping from predators or hunters as adults.
Importance of artificial stopover sites through avian migration flyways: a landfill‐based assessment with the White StorkCiconia ciconia
Authors: Arizaga Juan , Resano‐Mayor Jaime , Villanúa Diego , Alonso Daniel , Barbarin Juan M. , Herrero Alfredo , Lekuona Jesús M. , Rodríguez Ricardo
Published: November 2017

Open landfills seem to be playing an increasing role as target feeding areas for several species, not only in their breeding areas or during the winter, but also during the migration period. Evaluating the extent to which landfill sites are used by migrants is crucial to understanding their role in driving stopover decisions during migration, and in the potential health risks linked to feeding on refuse. The aim of this study was to evaluate the role of two open landfills located just before (France) and after (Spain) the East‐Atlantic flyway enters Iberia through the western Pyrenees as potentially important stopover sites for the White Stork populations moving along this route. Overall, we detected that these sites were used by storks that had been ringed from many western European breeding populations, mainly during the migration period, but also in winter. The mean distance between the stork breeding/ringing origin and the landfill sites increased from summer to winter, suggesting that storks breeding further away pass through Iberia later in the season, reflecting population‐specific timing of migration. During the autumn migration period (August–September), the first encountered landfill in France was estimated to be used byc. 1200 storks, and the other in Spain by 4000 storks. Our study hence contributes to a better understanding of the current and potentially hazardous role played by landfill sites in White Stork ecology, which is essential in order to provide management recommendations, and to evaluate the consequences of proposed open landfill closures in Europe.