bluuebunny/crossref_metadata_2025 huggingface dataset:
Induction of labour with retrievable prostaglandin vaginal inserts: outcomes following retrieval due to an intrapartum adverse event
Authors: Rugarn O , Tipping D , Powers B , Wing DA
Published: June 2016

Objective

To assess adverse event (AE) resolution, delivery mode and neonatal outcomes after misoprostol or dinoprostone vaginal insert (MVI or DVI) retrieval due to AE during induction of labour (IOL).

Design

Randomised, double‐blind trial, EXPEDITE.

Setting

Thirty five obstetric departments, USA.

Population

Consisted of 1358 pregnant women with modified Bishop score ≤4 eligible for pharmacological IOL.

Methods

Post hoc analysis.

Main outcome measures

AEs prompting insert retrieval, times to AE resolution, delivery, delivery mode and neonatal intensive care unit (NICU) admissions.

Results

77/678 (11.4%) and 27/680 (4.0%) women had MVI and DVI retrieved due to AE, respectively (P < 0.001). The most common AEs prompting retrieval were uterine tachysystole with fetal heart rate (FHR) involvement and category II/III FHR pattern. Time to AE resolution varied for both treatments depending on the type of AE. For uterine tachysystole with FHR involvement, median resolution times were 1 hour 34.5 minutes (n = 36) and 8.5 minutes (n = 8) for MVI and DVI, respectively. Caesarean delivery occurred in a high proportion of women with insert retrieved due to AE (MVI: 44/77 (57.1%); DVI: 19/27 (70.4%)); the majority of caesareans were performed at least several hours after insert retrieval. Median times from retrieval to any delivery were not increased for women with insert retrieved due to AE. NICU admissions were 8/77 (10.4%) and 1/27 (3.7%) for MVI and DVI, respectively (P = 0.440).

Conclusions

AEs leading to insert retrieval were primarily uterine tachysystole with FHR involvement and category II/III FHR patterns. Insert retrieval due to an AE did not prolong time to delivery for either prostaglandin insert.

Tweetable abstract

Induction with prostaglandin vaginal inserts: outcomes following retrieval due to intrapartum adverse event.
The Nursing Diagnosis Development of Unemployment Disorder: Content Validation With Nursing Experts
Authors: Bocchino Anna , Medialdea María Jesús , Lepiani Isabel , Mejías Concepción , Dueñas María
Published: June 2016

PURPOSE

This study aimed to validate the definition and define the characteristics and related factors of unemployment disorder, a proposed nursing diagnosis.

METHODS

Using Fehring's diagnostic content validity model, Spanish experts were asked to assess the adequacy of the label, defining the characteristics and other related factors.

FINDINGS

The content validity index was 0.8690. A total of 16 defining characteristics reached major criteria (>0.80).

CONCLUSION

The present study supports the proposed development of a nursing diagnosis for the human response to unemployment.

PRACTICE IMPLICATIONS

The results suggest that the inclusion of the “unemployment disorder” diagnostic NANDA‐I taxonomy would allow nursing professionals to identify the disorder and its causes and manifestations, and therefore provide the information needed for planning more relevant interventions and results.

OBJETIVO

Validación de la definición, características definitorias y factores relacionados de trastorno por desempleo, una propuesta de diagnóstico enfermero.

METODOLOGÍA

Usando el modelo de validación de contenido de Fehring, se consensuó mediante expertos españoles la denominación de la etiqueta, las características definitorias y otros factores relacionados.

RESULTADOS

El índice de validez de contenido global fue 0.8690. Un total de 16 características definitorias alcanzaron carácter crítico (>0.80).

CONCLUSIÓN

El presente estudio apoya la propuesta de elaborar un diagnóstico de enfermería para la respuesta humana al desempleo.

IMPLICACIONES PRÁCTICAS

Los resultados obtenidos sugieren que la inclusión en la taxonomía NANDA‐I del diagnóstico “trastorno por desempleo” permitiría a los profesionales de enfermería identificar el problema, sus causas y manifestaciones, y por lo tanto ofrecerían la información necesaria para planificar las intervenciones y resultados más pertinentes.
Heat stress‐induced phosphorylation of FoxO3a signalling in rat skeletal muscle
Authors: Yoshihara T. , Kobayashi H. , Kakigi R. , Sugiura T. , Naito H.
Published: June 2016

Aim

A recent study demonstrated that FoxO3a was directly induced by the overexpression of Hsp72 in rat soleus muscle. However, whether heat stress treatment induces FoxO3a phosphorylation in rat skeletal muscle remains unclear. This study examined the effects of heat stress on the regulation of the FoxO3a signalling pathway in rat skeletal muscle.

Methods

Thirty‐two male Wistar rats (15 weeks old) were randomly assigned into two groups; sedentary control group (Sed, n = 8) and experimental group (n = 24). After an overnight fast, one leg of each rat (HS leg) in the experimental group was immersed in hot water (43 °C) for 30 min, and the soleus and plantaris muscles in both legs were removed immediately (0 min), 30 min, 60 min, or 24 h after the heat stress (n = 6 each group). The contralateral, non‐heated leg in the experimental group served as an internal control (CT leg).

Results

Heat stress treatment resulted in a significant increase in FoxO3a phosphorylation (Ser253) in the soleus and plantaris muscles of heat‐stressed legs after 24 h. Hsp72 expression in heat‐stressed legs was significantly higher at 60 min and 24 h in these muscles. Activation of the PTEN/Akt and MEK/ERK pathways was also observed in these muscles immediately after stress, but not at 24 h. There were no differences in FoxO1 and AMPKα phosphorylation in either muscle.

Conclusion

Heat stress in rat skeletal muscle induces phosphorylation of FoxO3a signalling, and it may be related to Hsp72 upregulation, and the activation of the PTEN/Akt and MEK/ERK pathways.
Dexamethasone promotes long‐term functional recovery of neuromuscular junction in a murine model of tourniquet‐induced ischaemia–reperfusion
Authors: Zhang D. , Wang D. , Pipinos I. I. , Muelleman R. L. , Li Y.‐L.
Published: June 2016

Aim

Tourniquet‐induced ischaemia and subsequent reperfusion cause serious ischaemia–reperfusion (IR) injury in the neuromuscular junction (NMJ) and skeletal muscle. Here, we investigated whether dexamethasone (Dex) promotes long‐term functional recovery of the NMJ and skeletal muscle in tourniquet‐induced hindlimb IR.

Methods

Unilateral hindlimb of C57/BL6 mice was subjected to 3 h of ischaemia following 6 weeks of reperfusion (6‐wk IR). Dex treatment began on the day of IR induction and lasted for different periods. Sciatic nerve‐stimulated gastrocnemius muscle contraction was detected in situ. Function of the NMJ was measured in situ using electrophysiological recording of the miniature endplate potential (mEPP) and endplate potential (EPP). Western blot was used to detect protein expression of nicotinic acetylcholine receptors (nAChRs) in gastrocnemius muscles.

Results

Gastrocnemius muscle contraction in mice with 6‐wk IR was about 60% of normal skeletal muscle contraction recorded in age‐matched sham mice. The amplitude of the mEPP and EPP was lower in mice with 6‐wk IR, compared to sham mice. Dex treatment for 1 or 3 days did not restore the function of the NMJ and improve gastrocnemius muscle contraction in mice with 6‐wk IR. Dex treatment for 1 week exerted a maximum effect on improving the function of the NMJ and skeletal muscle, with the effect of Dex gradually lessening with prolonged Dex treatment. There are no significant differences in protein expression of nAChR‐α1 and nAChR‐β1 subunits in the gastrocnemius muscle among all groups.

Conclusion

Dex promotes repair of the NMJ and subsequently restores skeletal muscle contractile function in tourniquet‐induced 6‐wk IR.
Embryonic stem cell gene expression signatures in the canine mammary tumor: a bioinformatics approach
Authors: Zamani‐Ahmadmahmudi Mohamad
Published: June 2016

Canine breast cancer was considered as an ideal model of comparative oncology for the human breast cancer, as there is significant overlap between biological and clinical characteristics of the human and canine breast cancer. We attempt to clarify expression profile of the embryonic stem cell (ES) gene signatures in canine breast cancer. Using microarray datasets (GSE22516 and GSE20718), expression of the three major ES gene signatures (modules or gene‐sets), including Myc, ESC‐like, and PRC modules, was primarily analyzed through Gene‐Set Enrichment Analysis (GSEA) method in tumor and healthy datasets. For confirmation of the primary results, an additional 13 ES gene‐sets which were categorized into four groups including ES expressed (ES exp1 and ES exp2), NOS targets (Nanog targets, Oct4 targets, Sox2 targets, NOS targets, and NOS TFs), Polycomb targets (Suz12 targets, Eed targets, H3K27 bound, and PRC2 targets), and Myc targets (Myc targets1, and Myc targets2) were tested in the tumor and healthy datasets. Our results revealed that there is a valuable overlap between canine and human breast cancer ES gene‐sets expression profile, where Myc and ESC‐like modules were up‐regulated and PRC module was down‐regulated in metastatic canine mammary gland tumors. Further analysis of the secondary gene‐sets indicated overexpression of the ES expressed, NOS targets (Nanog targets, Oct4 targets, Sox2 targets, and NOS targets), and Myc targets and underexpression of the Polycomb targets in metastatic canine breast cancer.
Muramyl dipeptide and anti‐CD10 monoclonal antibody immunoconjugate enhances anti‐leukemia immunity of T lymphocytes
Authors: Wang Ling‐zhen , Zhang Li , Wang Ling‐Li , Lu Yuan , Chen Lei , Sun Yan , Zhao Hong‐guo , Song Liang , Sun Li‐Rong
Published: June 2016

It is necessary to completely eliminate minimal residual disease (MRD) to cure acute leukemia. Monoclonal antibodies (MAb) have been shown to be effective to eliminate MRD. In this study we aimed to investigate the effect of anti‐CD10 MAb conjugated to muramyl dipeptide immunoconjugate (MDP‐Ab) on the function of lymphocytes and activated lymphocytes using leukemia xenografts in nude mice as a model. Peripheral blood mononuclear cells were isolated from children with acute lymphoblastic leukemia and induced into dendritic cells (DCs) and lymphocytes. Cytotoxic activity of lymphocytes was detected by LDH release assay. Leukemia xenografts in nude mice were established to assess tumor growth. We found that the killing rate was significantly higher in MDP‐Ab group, LPS group and MDP‐Ab+LPS group than in control group, and was the highest in MDP‐Ab+LPS group. Tumor‐bearing mice in MDP‐Ab group showed obvious coagulation necrosis. In conclusion, our data suggest that MDP‐Ab could effectively prime DCs to improve the anti‐tumor immunity of T lymphocytes and inhibit the tumor growth. MDP‐Ab may be used as suitable candidate for eliminating residual leukemia cells to prevent relapse.
Microstructural and Componential Characterization of the Plating Technology on Chinese Han Dynasty Bronze Fragments
Authors: Jin P. J. , Ruan F. H. , Yang X. G. , Zou H. X. , Yi J. , Zhang Y. , Zhao Y.
Published: June 2016

The bronze wares of the Han Dynasty excavated in Chongqing are decorated with plating patterns, maintaining an exquisite lustre right up to modern times after the covering patina is cleared away. In this paper, a plated fragment of the Han Dynasty from the Wushan County Museum was characterized by combining optical microscopy (OM), scanning electron microscopy with X‐ray energy‐dispersive spectrometry (SEM–EDS), X‐ray fluorescence analysis (XRF), X‐ray diffraction (XRD) and X‐ray photoelectron spectroscopy (XPS). The results showed that the bronze fragment was gilded with a ~ 3 μm thick gilded layer and a ~ 20 μm thick silvered layer. The high concentration of Hg and Hg‐rich intermetallic compounds confirmed the existence of mercury gilding/silvering technology, for example, Au9Hg in the gilded layer and Ag13Hg7 in the silvered layer. An ordered stripe structure was observed in the gilded surface, corresponding to the formation of rod‐like, intermetallic Au–Hg compounds. Specifically, a high concentration of Au was detected in the silvered layer. The exploration of gilded/silvered bronze casts light on this ancient technology and the benefit of identifying, protecting and reproducing it.
Dilemma of modernity: interrogating cross‐border ethnic identities at China's southwest frontier
Authors: Qian Junxi , Tang Xueqiong
Published: June 2016

Recent theoretical advancement in human geography has reconceptualised the border as a process and becoming, which is appropriated and constructed by myriad actors to yield diverse and changing meanings, and accommodate various needs and interests. This enables us to appreciate the dual qualities of the border, both as a barrier to be overcome and an enabling factor for practices and meanings. In particular, cross‐border mobility plays an essential role in mediating meanings of the border and identities of those whose lifeworlds are affected by the very existence of the border. On the one hand, mobilities transgress territorial orders imposed by official conceptions of the border. But, on the other hand, the distinctions between economic, social and political milieus at the two sides of the border may give rise to heightened senses of difference and lead to diverging identities. Building on these insights, this article argues for a more nuanced, dynamic understanding of the relationship between border crossing and belonging. It examines two empirical cases: the cross‐border attendance of Huashan Festival celebration for Miao people at the Sino‐Vietnamese borderland, and the trans‐border mobility of Buddhist monks from the Myanmar city Muse to the Chinese border city Ruili. Overall, this paper argues that the potentials of the border to both connect and differentiate are inscribed in the lifeworlds in the borderlands in equally visible ways. Also, this paper adds some twists to Scott's thesis on Zomia, and argues that we must not downplay the importance of the frame of nation‐states in shaping the lifeworlds of border inhabitants.
Financial Performance Adjustment in English Local Governments
Authors: Arcas Maria Jose , Martí Caridad
Published: June 2016

This paper analyses financial performance adjustment in English local governments and the specific accruals used to achieve it. Based on statistical approaches used in previous literature, our results indicate the use of abnormal accruals in English local governments in order to report surpluses/deficits close to zero as well as to avoid reporting big deficits. We find that depreciation and impairment expense of fixed assets is the item most significantly related to abnormal accruals. Consistent with the conservatism theory, local governments with higher leverage use more income‐decreasing accounting policies.
The origins of urinary stone disease: upstream mineral formations initiate downstream Randall's plaque
Authors: Hsi Ryan S. , Ramaswamy Krishna , Ho Sunita P. , Stoller Marshall L.
Published: June 2016

Objectives

To describe a new hypothesis for the initial events leading to urinary stones. A biomechanical perspective on Randall's plaque formation through form and function relationships is applied to functional units within the kidney, we have termed the ‘medullo‐papillary complex’ – a dynamic relationship between intratubular and interstitial mineral aggregates.

Methods

A complete MEDLINE search was performed to examine the existing literature on the anatomical and physiological relationships in the renal medulla and papilla. Sectioned human renal medulla with papilla from radical nephrectomy specimens were imaged using a high resolution micro X‐ray computed tomography. The location, distribution, and density of mineral aggregates within the medullo‐papillary complex were identified.

Results

Mineral aggregates were seen proximally in all specimens within the outer medulla of the medullary complex and were intratubular. Distal interstitial mineralisation at the papillary tip corresponding to Randall's plaque was not seen until a threshold of proximal mineralisation was observed. Mineral density measurements suggest varied chemical compositions between the proximal intratubular (330 mg/cm3) and distal interstitial (270 mg/cm3) deposits. A review of the literature revealed distinct anatomical compartments and gradients across the medullo‐papillary complex that supports the empirical observations that proximal mineralisation triggers distal Randall's plaque formation.

Conclusion

The early stone event is initiated by intratubular mineralisation of the renal medullary tissue leading to the interstitial mineralisation that is observed as Randall's plaque. We base this novel hypothesis on a multiscale biomechanics perspective involving form and function relationships, and empirical observations. Additional studies are needed to validate this hypothesis.
Utility of clinical high‐depth next generation sequencing for somatic variant detection in the PIK3CA‐related overgrowth spectrum
Authors: Hucthagowder V. , Shenoy A. , Corliss M. , Vigh‐Conrad K.A. , Storer C. , Grange D.K. , Cottrell C.E.
Published: June 2016

Next‐generation sequencing (NGS) has revolutionized the approach of studying sequence variation, and has been well described in the clinical laboratory setting for the detection of constitutional alterations, as well as somatic tumor‐associated variants. It is increasingly recognized that post‐zygotic somatic alteration can be associated with congenital phenotypic abnormalities. Variation within the PI3K/AKT/mTOR pathway, including PIK3CA, has been described in somatic overgrowth syndromes and vascular malformations. Detection of PIK3CA somatic alteration is challenging because of low variant allele frequency (VAF) along with the need to assay involved tissue, thus necessitating a highly sensitive methodology. Here we describe the utility of target hybrid capture coupled with NGS for the identification of somatic variation in the PIK3CA‐related overgrowth spectrum (PROS) among 14 patients submitted for clinical testing. Assay detection of low allelic fraction variation is coverage dependent with >90% sensitivity at 400× unique read depth for VAF of 10%, and approaching 100% at 1000×. Average read depth among the patient dataset across PIK3CA coding regions was 788.4. The diagnostic yield among this cohort was 71%, including the detection of two PIK3CA alterations novel in the setting of PROS. This report expands the mutational scope and phenotypic attributes of PROS disorders.
Ginkgolide B Protects Against Ischemic Stroke Via Modulating Microglia Polarization in Mice
Authors: Shu Zhao‐Ma , Shu Xiao‐Dong , Li Hui‐Qin , Sun Yi , Shan Han , Sun Xi‐Yang , Du Ren‐Hong , Lu Ming , Xiao Ming , Ding Jian‐Hua , Hu Gang
Published: June 2016

Aim

Ginkgolide B (GB) has shown neuroprotective effect in treating ischemic stroke, related to its property of anti‐inflammation. Nevertheless, it is unclear whether GB is able to modulate microglia/macrophage polarization, which has recently been proven to be vital in the pathology of ischemic stroke.

Methods

We performed transient middle cerebral artery occlusion (tMCAO) on C57BL/6J male mice and induced cultured BV2 microglia and primary bone marrow‐derived macrophages to be M1/2 phenotype by LPS+ interferon‐γ and IL‐4, respectively. Immunofluorescence and flow cytometry were used for detecting the specialized protein expression of M1/2, such as CD206 and CD16/32. qPCR was utilized to detect the signature gene change of M1/2.

Results

GB significantly reduced cerebral ischemic damage and ameliorated the neurological deficits of mice after tMCAO. More importantly, our experiments proved that GB promoted microglia/macrophage transferring from inflammatory M1 phenotype to a protective, anti‐inflammatory M2 phenotype in vivo or vitro. CV3988 and silencing the platelet activator factor (PAF) receptor by siRNA demonstrated that PAF receptor was involved in the modulation of microglia/macrophage polarization.

Conclusion

Our results reveal a novel pharmacological effect of GB in modulating microglia/macrophage polarization after tMCAO, thus deepening our understanding of neuroprotective mechanisms of GB in treatment of ischemic stroke. Furthermore, this new mechanism may allow GB to be used in many other microglia/macrophage polarization‐related inflammatory diseases.
The Importance of Reading Naturally: Evidence From Combined Recordings of Eye Movements and Electric Brain Potentials
Authors: Metzner Paul , von der Malsburg Titus , Vasishth Shravan , Rösler Frank
Published: June 2016

How important is the ability to freely control eye movements for reading comprehension? And how does the parser make use of this freedom? We investigated these questions using coregistration of eye movements and event‐related brain potentials (ERPs) while participants read either freely or in a computer‐controlled word‐by‐word format (also known as RSVP). Word‐by‐word presentation and natural reading both elicited qualitatively similar ERP effects in response to syntactic and semantic violations (N400 and P600 effects). Comprehension was better in free reading but only in trials in which the eyes regressed to previous material upon encountering the anomaly. A more fine‐grained ERP analysis revealed that these regressions were strongly associated with the well‐known P600 effect. In trials without regressions, we instead found sustained centro‐parietal negativities starting at around 320 ms post‐onset; however, these negativities were only found when the violation occurred in sentence‐final position. Taken together, these results suggest that the sentence processing system engages in strategic choices: In response to words that don't match built‐up expectations, it can either explore alternative interpretations (reflected by regressions, P600 effects, and good comprehension) or pursue a “good‐enough” processing strategy that tolerates a deficient interpretation (reflected by progressive saccades, sustained negativities, and relatively poor comprehension).
Conservation (In)Action: Renewing the Relevance of UNESCO Biosphere Reserves
Authors: Reed Maureen G.
Published: June 2016

The research and policy landscape for biodiversity conservation is changing. Protected areas are now expected to meet a broad range of objectives including effective and equitable management. In this new landscape, organizations strive to find ways to ensure the rights of local and Indigenous peoples are respected while conservation scientists have endorsed the need for platforms for international research and practice. For 40 years, a growing international network of sites support such research and practice, yet, it has been underutilized and largely ignored by scientists and decision‐makers alike. To better understand this paradox, this article explores the evolution of the World Network of UNESCO Biosphere Reserves internationally and its application in Canada. Analysis of archived materials, a national survey of practitioners, and interviews with past and present members of Canada's national committee reveals an expanded mandate for biosphere reserves beyond conservation science and biodiversity protection. The article recommends that to support the expanded conservation agenda, biosphere reserves work with governments and conservation scientists to connect more effectively with global concerns and initiatives such as the Convention on Biological Diversity and Sustainable Development Goals; establish appropriate, reliable, and active transdisciplinary partnerships; and meaningfully engage a broader range of knowledge holders.
Alcohol‐attributable cancer deaths under 80 years of age in New Zealand
Authors: Connor Jennie , Kydd Robyn , Maclennan Brett , Shield Kevin , Rehm Jürgen
Published: June 2016

Introduction and Aims

Cancer deaths made up 30% of all alcohol‐attributable deaths in New Zealanders aged 15–79 years in 2007, more than all other chronic diseases combined. We aimed to estimate alcohol‐attributable cancer mortality and years of life lost by cancer site and identify differences between Māori and non‐Māori New Zealanders.

Design and Methods

We applied the World Health Organization's comparative risk assessment methodology at the level of Māori and non‐Māori subpopulations. Proportions of specific alcohol‐related cancers attributable to alcohol were calculated by combining alcohol consumption estimates from representative surveys with relative risks from recent meta‐analyses. These proportions were applied to both 2007 and 2012 mortality data.

Results

Alcohol consumption was responsible for 4.2% of all cancer deaths under 80 years of age in 2007. An average of 10.4 years of life was lost per person; 12.7 years for Māori and 10.1 years for non‐Māori. Half of the deaths were attributable to average consumption of <4 standard drinks per day. Breast cancer comprised 61% of alcohol‐attributable cancer deaths in women, and more than one‐third of breast cancer deaths were attributable to average consumption of <2 standard drinks per day. Mortality data from 2012 produced very similar findings.

Discussion and Conclusions

Alcohol is an important and modifiable cause of cancer. Risk of cancer increases with higher alcohol consumption, but there is no safe level of drinking. Reduction in population alcohol consumption would reduce cancer deaths. Additional strategies to reduce ethnic disparities in risk and outcome are needed in New Zealand. [Connor J, Kydd R, Maclennan B, Shield K, Rehm J. Alcohol‐attributable cancer deaths under 80 years of age in New Zealand. Drug Alcohol Rev 2017;36:415–423]
Per rectal endoscopic myotomy for the treatment of adult Hirschsprung's disease: First human case (with video)
Authors: Bapaye Amol , Wagholikar Gajanan , Jog Sameer , Kothurkar Aditi , Purandare Shefali , Dubale Nachiket , Pujari Rajendra , Mahadik Mahesh , Vyas Viral , Bapaye Jay
Published: June 2016

Hirschsprung's disease (HD) is a congenital disorder characterized by the absence of intrinsic ganglion cells in submucosal and myenteric plexuses of the hindgut; and presents with constipation, intestinal obstruction and/or megacolon. HD commonly involves the rectosigmoid region (short segment HD), although shorter and longer variants of the disease are described. Standard treatment involves pull‐through surgery for short segment HD or posterior anorectal myotomy in selected ultrashort segment candidates. Third space endoscopy has evolved during the past few years. Per oral endoscopic myotomy and per oral pyloromyotomy are described for treatment of achalasia cardia and refractory gastroparesis, respectively. Using the same philosophy of muscle/sphincter disruption for spastic bowel segments, per rectal endoscopic myotomy could be considered as a treatment option for short segment HD. A 24‐year‐old male patient presented with refractory constipation since childhood, and habituated to high‐dose laxative combinations. Diagnosis was confirmed as adult short segment HD by barium enema, colonoscopic deep suction mucosal biopsies and anorectal manometry. Histopathology confirmed aganglionosis in the distal 15 cm. By implementing principles of third space endoscopy, per rectal endoscopic myotomy 20 cm in length was successfully carried out. At 24‐week follow up, the patient reported significant relief of constipation and associated symptoms. Sigmoidoscopy, anorectal manometry and barium enema confirm improved rectal distensibility and reduced rectal pressures. The present case report describes the first human experience of per rectal endoscopic myotomy for successful treatment of adult short segment HD.
Evidence for genetic regulation of the human parieto‐occipital 10‐Hz rhythmic activity
Authors: Salmela Elina , Renvall Hanna , Kujala Jan , Hakosalo Osmo , Illman Mia , Vihla Minna , Leinonen Eira , Salmelin Riitta , Kere Juha
Published: June 2016

Several functional and morphological brain measures are partly under genetic control. The identification of direct links between neuroimaging signals and corresponding genetic factors can reveal cellular‐level mechanisms behind the measured macroscopic signals and contribute to the use of imaging signals as probes of genetic function. To uncover possible genetic determinants of the most prominent brain signal oscillation, the parieto‐occipital 10‐Hz alpha rhythm, we measured spontaneous brain activity with magnetoencephalography in 210 healthy siblings while the subjects were resting, with eyes closed and open. The reactivity of the alpha rhythm was quantified from the difference spectra between the two conditions. We focused on three measures: peak frequency, peak amplitude and the width of the main spectral peak. In accordance with earlier electroencephalography studies, spectral peak amplitude was highly heritable (h2 > 0.75). Variance component‐based analysis of 28 000 single‐nucleotide polymorphism markers revealed linkage for both the width and the amplitude of the spectral peak. The strongest linkage was detected for the width of the spectral peak over the left parieto‐occipital cortex on chromosome 10 (LOD = 2.814, nominal P < 0.03). This genomic region contains several functionally plausible genes, including GRID1 and ATAD1 that regulate glutamate receptor channels mediating synaptic transmission, NRG3 with functions in brain development and HRT7 involved in the serotonergic system and circadian rhythm. Our data suggest that the alpha oscillation is in part genetically regulated, and that it may be possible to identify its regulators by genetic analyses on a realistically modest number of samples.
Strategic down‐regulation of attentional resources as a mechanism of proactive response inhibition
Authors: Langford Zachary D. , Krebs Ruth M. , Talsma Durk , Woldorff Marty G. , Boehler C. N.
Published: June 2016

Efficiently avoiding inappropriate actions in a changing environment is central to cognitive control. One mechanism contributing to this ability is the deliberate slowing down of responses in contexts where full response cancellation might occasionally be required, referred to as proactive response inhibition. The present electroencephalographic (EEG) study investigated the role of attentional processes in proactive response inhibition in humans. To this end, we compared data from a standard stop‐signal task, in which stop signals required response cancellation (‘stop‐relevant’), to data where possible stop signals were task‐irrelevant (‘stop‐irrelevant’). Behavioral data clearly indicated the presence of proactive slowing in the standard stop‐signal task. A novel single‐trial analysis was used to directly model the relationship between response time and the EEG data of the go‐trials in both contexts within a multilevel linear models framework. We found a relationship between response time and amplitude of the attention‐related N1 component in stop‐relevant blocks, a characteristic that was fully absent in stop‐irrelevant blocks. Specifically, N1 amplitudes were lower the slower the response time, suggesting that attentional resources were being strategically down‐regulated to control response speed. Drift diffusion modeling of the behavioral data indicated that multiple parameters differed across the two contexts, likely suggesting the contribution from independent brain mechanisms to proactive slowing. Hence, the attentional mechanism of proactive response control we report here might coexist with known mechanisms that are more directly tied to motoric response inhibition. As such, our study opens up new research avenues also concerning clinical conditions that feature deficits in proactive response inhibition.
MicroRNA‐23b‐3p regulates human keratinocyte differentiation through repression of TGIF1 and activation of the TGF‐ß–SMAD2 signalling pathway
Authors: Barbollat‐Boutrand Laetitia , Joly‐Tonetti Nicolas , Dos Santos Morgan , Metral Elodie , Boher Aurélie , Masse Ingrid , Berthier‐Vergnes Odile , Bertolino Philippe , Damour Odile , Lamartine Jérôme
Published: June 2016

MicroRNAs (miRNAs) are a class of short non‐coding RNAs capable of repressing gene expression at the post‐transcriptional level. miRNAs participate in the control of numerous cellular mechanisms, including skin homeostasis and epidermal differentiation. However, few miRNAs involved in these processes have been identified so far in human skin, and the gene networks they control remain largely unknown. Here, we focused on miR‐23b‐3p, a miRNA that is expressed during the late step of human keratinocyte differentiation. We report that miR‐23b‐3p silencing modulates epidermal differentiation in human skin reconstructs. The SMAD transcriptional corepressor TGIF1 was identified on bioinformatic analysis as a potential target of miR‐23b‐3p. Expression analysis and reporter gene assays confirmed direct regulation of TGIF1 expression by miR‐23b‐3p. Finally, we showed that miR‐23‐3p was able to activate TGF‐ß signalling in human keratinocytes by increasing SMAD2 phosphorylation through TGIF1 repression. Taken together, these data identify miR‐23b‐3p as a new regulator of human epidermal differentiation in line with TGF‐ß signalling.
Low doses of paclitaxel enhance liver metastasis of breast cancer cells in the mouse model
Authors: Li Qi , Ma Zhuang , Liu Yinhua , Kan Xiaoxi , Wang Changjun , Su Bingnan , Li Yuchen , Zhang Yingmei , Wang Pingzhang , Luo Yang , Na Daxiang , Wang Lanlan , Zhang Guoying , Zhu Xiaoxin , Wang Lu
Published: June 2016

Paclitaxel is the most commonly used chemotherapeutic agent in breast cancer treatment. In addition to its well‐known cytotoxic effects, recent studies have shown that paclitaxel has tumor‐supportive activities. Importantly, paclitaxel levels are not maintained at the effective concentration through one treatment cycle; rather, the concentration decreases during the cycle as a result of drug metabolism. Therefore, a comprehensive understanding of paclitaxel's effects requires insight into the dose‐specific activities of paclitaxel and their influence on cancer cells and the host microenvironment. Here we report that a low dose of paclitaxel enhances metastasis of breast cancer cells to the liver in mouse models. We used microarray analysis to investigate gene expression patterns in invasive breast cancer cells treated with low or clinically relevant high doses of paclitaxel. We also investigated the effects of low doses of paclitaxel on cell migration, invasion and metastasis in vitro and in vivo. The results showed that low doses of paclitaxel promoted inflammation and initiated the epithelial–mesenchymal transition, which enhanced tumor cell migration and invasion in vitro. These effects could be reversed by inhibiting NF‐κB. Furthermore, low doses of paclitaxel promoted liver metastasis in mouse xenografts, which correlated with changes in estrogen metabolism in the host liver. Collectively, these findings reveal the paradoxical and dose‐dependent effects of paclitaxel on breast cancer cell activity, and suggest that increased consideration be given to potential adverse effects associated with low concentrations of paclitaxel during treatment.

Database

Gene expression microarray data are available in the GEO database under accession number GSE82048.
The effects of elevated CO2 and eutrophication on surface elevation gain in a European salt marsh
Authors: Reef Ruth , Spencer Tom , Mӧller Iris , Lovelock Catherine E. , Christie Elizabeth K. , McIvor Anna L. , Evans Ben R. , Tempest James A.
Published: June 2016

Salt marshes can play a vital role in mitigating the effects of global environmental change by dissipating incident storm wave energy and, through accretion, tracking increasing water depths consequent upon sea level rise. Atmospheric CO2 concentrations and nutrient availability are two key variables that can affect the biological processes that contribute to marsh surface elevation gain. We measured the effects of CO2 concentrations and nutrient availability on surface elevation change in intact mixed‐species blocks of UK salt marsh using six open‐top chambers receiving CO2‐enriched (800 ppm) or ambient (400 ppm) air. We found more rapid surface elevation gain in elevated CO2 conditions: an average increase of 3.4 mm over the growing season relative to ambient CO2. Boosted regression analysis to determine the relative influence of different parameters on elevation change identified that a 10% reduction in microbial activity in elevated CO2‐grown blocks had a positive influence on elevation. The biomass of Puccinellia maritima also had a positive influence on elevation, while other salt marsh species (e.g. Suaeda maritima) had no influence or a negative impact on elevation. Reduced rates of water use by the vegetation in the high CO2 treatment could be contributing to elevation gain, either directly through reduced soil shrinkage or indirectly by decreasing microbial respiration rates due to lower redox levels in the soil. Eutrophication did not influence elevation change in either CO2 treatment despite doubling aboveground biomass. The role of belowground processes (transpiration, root growth and decomposition) in the vertical adjustment of European salt marshes, which are primarily minerogenic in composition, could increase as atmospheric CO2 concentrations rise and should be considered in future wetland models for the region. Elevated CO2 conditions could enhance resilience in vulnerable systems such as those with low mineral sediment supply or where migration upwards within the tidal frame is constrained.
Does bilateral seminal vesicle invasion at radical prostatectomy predict worse prognosis than unilateral invasion among patients with pT3b prostate cancers?
Authors: Lee Hyun Jung , Han Jun‐Hee , Lee Dong Hoon , Nam Jong Kil , Kim Tae Nam , Chung Moon Kee , Park Sung‐Woo
Published: June 2016

Objectives

To determine whether bilateral seminal vesicle invasion is associated with worse biochemical recurrence‐free survival than unilateral seminal vesicle invasion after radical prostatectomy.

Methods

We reviewed the clinicopathological data of 598 men who underwent radical prostatectomy between 2008 and 2015. Among them, 107 (17.9%) had seminal vesicle invasion. After excluding cases with neo‐/adjuvant hormone treatment or radiotherapy, 93 were included in the analysis. We compared biochemical recurrence‐free survival rates in subgroups with or without bilateral seminal vesicle invasion using Kaplan–Meier estimates. Cox proportional hazard regression models were used to determine the predictors of biochemical recurrence‐free survival.

Results

Bilateral prostatic lobes and bilateral seminal vesicles were involved by prostate cancers in 85 (91.4%) and 35 patients (37.6%), respectively. Actuarial 3‐year and 5‐year biochemical recurrence‐free survival rates in patients with pT3b tumors with/without bilateral seminal vesicle invasion were 13.0%/34.3%, and 4.3%/19.8%, respectively. On multivariable analysis, preoperative prostate‐specific antigen (hazard ratio 1.01, 95% confidence interval 1.00–1.02, P = 0.034), lymph node metastasis (hazard ratio 2.88, 95% confidence interval 1.43–5.81, P = 0.003) and bilateral seminal vesicle invasion (hazard ratio 1.75, 95% confidence interval 1.01–3.05, P = 0.047) were independent predictors of biochemical recurrence‐free survival. After excluding cases with lymph node metastasis, preoperative prostate‐specific antigen, surgical margin status and bilateral seminal vesicle invasion were independent predictors of biochemical recurrence‐free survival.

Conclusions

Although most men with seminal vesicle invasion experience biochemical recurrences after radical prostatectomy, their survival outcome is not uniform. Bilateral seminal vesicle invasion seems to represent an independent prognostic factor for pT3b patients, together with the preoperative prostate‐specific antigen and lymph node status.
Non‐compliance with minimum wage laws in Latin America: The importance of institutional factors
Authors: MARINAKIS Andrés
Published: June 2016

Based on household survey data, the author compares the level of minimum wages in 16 Latin American countries with average wages, GDP, poverty lines and purchasing power. He then estimates the degree of non‐compliance with minimum wage laws and its correlation with the minimum wage/average wage ratio. Comparing the situation in Chile, Costa Rica, Peru and Uruguay, he concludes that, when the minimum wage is very low or very high relative to average wages, the degree of compliance will depend on the quality of the institutional system, particularly the labour inspection system, in which regard he recommends a number of improvements.
Structural and Electrical Characteristics of (1−x)Pb(Lu1/2Nb1/2)O3–xPbTiO3 Ceramics with Low PbTiO3
Authors: Yang Xiaoming , He Chao , Liu Ying , Li Xiuzhi , Wang Zujian , Han Shujuan , Pan Shilie , Long Xifa
Published: June 2016

A solid solution of (1−x)Pb(Lu1/2Nb1/2)O3–xPbTiO3 with composition of 0.01 ≤ x ≤ 0.08 have been prepared successfully. XRD analysis indicates the crystal structure adopts an orthorhombic (O) phase in 0.01 ≤ x ≤ 0.06 interval and becomes the coexistence of O and rhombohedral (R) phase at x = 0.07, then turns into R phase mostly at x = 0.08. In addition, two sets of superlattice reflections due to B‐site ordering and antiparallel cation displacement are distinguished by XRD and the superstructures which arise from antiparallel cation displacement disappear gradually with the increasing x. The grain size increases gradually with the increasing x, and then becomes the bimodal microstructure at x ≥ 0.06 due to the coexistence of O and R phase. The dielectric spectra exhibit Curie temperature decreases from 248°C to 147°C with increasing x from 0.01 to 0.08. As 0.01 ≤ x ≤ 0.04, the samples display typical double hysteresis loops, suggesting antiferroelectric nature, then turn into ferroelectric gradually at x = 0.05. Finally, it exhibit typical ferroelectric hysteresis loops in 0.06 ≤ x ≤ 0.08 interval.
Rate‐Dependent Mechanical Behavior and Amorphization of Ultrafine‐Grained Boron Carbide
Authors: DeVries Matthew , Pittari John , Subhash Ghatu , Mills Kendall , Haines Chris , Zheng James Q.
Published: June 2016

An investigation into mechanical properties and amorphization behavior of ultrafine‐grained (0.3 μm) boron carbide (B4C) is conducted and compared to a baseline coarse‐grained (10 μm) boron carbide. Static and dynamic uniaxial compressive strength, and static and dynamic Vickers indentation hardness were determined, and Raman spectroscopy was then conducted on indented regions to quantify and compare the intensity of amorphization. In relation to coarse‐grained B4C the ultrafine‐grained material exhibited, on average, a 33% higher static compressive strength, 20% higher dynamic compressive strength, 10% higher static Vickers hardness, and 23% higher dynamic Vickers hardness. In addition, there was an 18% reduction in indentation‐induced radial crack length in ultrafine‐grained B4C, which corresponded to an increase in estimated fracture toughness. Although traditional coarse‐grained B4C exhibits an 8.6% decrease in hardness from the static to dynamic regimes, ultrafine‐grained B4C showed only negligible change under similar conditions, suggesting a reduced propensity for amorphization. Raman spectroscopic analysis confirmed this result by revealing significantly lower amorphization intensity in ultrafine‐B4C compared to coarse‐grained B4C. These results may have significant positive implications in the implementation of ultrafine‐grained boron carbide as a material for improved performance in impact and other high‐pressure applications.
Improvement in Retinal Capillary Rarefaction After Valsartan Treatment in Hypertensive Patients
Authors: Jumar Agnes , Harazny Joanna M. , Ott Christian , Kistner Iris , Friedrich Stefanie , Schmieder Roland E.
Published: June 2016

Decreased capillary density influences vascular resistance and perfusion. The authors aimed to investigate the influence of the renin‐angiotensin receptor blocker valsartan on retinal capillary rarefaction in hypertensive patients. Retinal vascular parameters were measured noninvasively and in vivo by scanning laser Doppler flowmetry before and after 4 weeks of treatment with valsartan in 95 patients with hypertension stage 1 or 2 and compared with 55 healthy individuals. Retinal capillary rarefaction was determined with the parameters intercapillary distance (ICD) and capillary area (CapA). In hypertensive patients, ICD decreased (23.4±5.5 μm vs 21.5±5.6 μm, P<.001) and CapA increased (1564±621 vs 1776±795, P=.001) after valsartan treatment compared with baseline. Compared with healthy normotensive controls (ICD 20.2±4.2 μm, CapA 1821±652), untreated hypertensive patients showed greater ICD (P<.001) and smaller CapA (P=.019), whereas treated hypertensive patients showed no difference in ICD (P=.126) and CapA (P=.728). Therapy with valsartan for 4 weeks diminished capillary rarefaction in hypertensive patients.
HOTAIRM1 as a potential biomarker for diagnosis of colorectal cancer functions the role in the tumour suppressor
Authors: Wan Ledong , Kong Jianlu , Tang Jinlong , Wu Yihua , Xu Enping , Lai Maode , Zhang Honghe
Published: June 2016

Recent studies have revealed many different long noncoding RNAs (lncRNA), however, the investigation for their function and clinical value as tumour biomarkers has scarcely begun. Here, we found that expression of HOTAIRM1 was reduced in colorectal cancer (CRC) tissues compared with matched normal tissues, and plasma HOTAIRM1 levels in CRC patients were less than in controls. The cut‐off point was chosen as 0.003 with a sensitivity of 64.00% and a specificity of 76.50% in the validation set. The performance of HOTAIRM1 was highly comparable to carcinoembryonic antigen (CEA), and better than CA19‐9 and CA125. The combined assay of HOTAIRM1 and CEA raised the sensitivity and specificity to 84.00%. HOTAIRM1 knockdown resulted in obvious changes in expression of the cell proliferation related to genes and promoted cell proliferation. HOTAIRM1 plays a role of tumour suppressor in CRC; Down‐regulation of HOTAIRM1 can serve as a biomarker for CRC, and combined HOTAIRM1 and CEA assay might provide a promising diagnosis for CRC.
Suppressive effect of epigallocatechin‐3‐O‐gallate on endoglin molecular regulation in myocardial fibrosis in vitro and in vivo
Authors: Lin Chiu‐Mei , Chang Hang , Wang Bao‐Wei , Shyu Kou‐Gi
Published: June 2016

Epigallocatechin‐3‐O‐gallate (EGCG), derived from green tea, has been studied extensively because of its diverse physiological and pharmacological properties. This study evaluates the protective effect of EGCG on angiotensin II (Ang II)‐induced endoglin expression in vitro and in vivo. Cardiac fibroblasts (CFs) from the thoracic aorta of adult Wistar rats were cultured and induced with Ang II. Western blotting, Northern blotting, real‐time PCR and promoter activity assay were performed. Ang II increased endoglin expression significantly as compared with control cells. The specific extracellular signal‐regulated kinase inhibitor SP600125 (JNK inhibitor), EGCG (100 μM) and c‐Jun N‐terminal kinase (JNK) siRNA attenuated endoglin proteins following Ang II induction. In addition, pre‐treated Ang II‐induced endoglin with EGCG diminished the binding activity of AP‐1 by electrophoretic mobility shift assay. Moreover, the luciferase assay results revealed that EGCG suppressed the endoglin promoter activity in Ang II‐induced CFs by AP‐1 binding. Finally, EGCG and the JNK inhibitor (SP600125) were found to have attenuated endoglin expression significantly in Ang II‐induced CFs, as determined through confocal microscopy. Following in vivo acute myocardial infarction (AMI)‐related myocardial fibrosis study, as well as immunohistochemical and confocal analyses, after treatment with endoglin siRNA and EGCG (50 mg/kg), the area of myocardial fibrosis reduced by 53.4% and 64.5% and attenuated the left ventricular end‐diastolic and systolic dimensions, and friction shortening in hemodynamic monitor. In conclusion, epigallocatechin‐3‐O‐gallate (EGCG) attenuated the endoglin expression and myocardial fibrosis by anti‐inflammatory effect in vitro and in vivo, the novel suppressive effect was mediated through JNK/AP‐1 pathway.