bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of 10‐day Sitafloxacin‐Containing Third‐Line Rescue Therapies for Helicobacter pylori Strains Containing the gyrA Mutation
Authors: Mori Hideki , Suzuki Hidekazu , Matsuzaki Juntaro , Tsugawa Hitoshi , Fukuhara Seiichiro , Miyoshi Sawako , Hirata Kenro , Seino Takashi , Matsushita Misako , Masaoka Tatsuhiro , Kanai Takanori
Published: November 2015

Background and Aim

Sitafloxacin‐containing Helicobacter pylori eradication therapy is a promising third‐line therapeutic approach, but there is no previous studies between gyrA mutation status of H. pylori strains and the efficacy of 10‐day sitafloxacin‐containing regimens. Here, we assessed the efficacy of 2 different 10‐day sitafloxacin‐containing rescue regimens.

Methods

Patients who failed first‐ and second‐line eradication therapies were enrolled. The minimum inhibitory concentrations (MICs) of sitafloxacin, amoxicillin, and metronidazole and the gyrA mutation status of the H. pylori strains were determined before treatment. The patients were randomized to receive a 10‐day triple therapy containing either esomeprazole (20 mg, b.i.d.), amoxicillin (500 mg, q.i.d.), and sitafloxacin (100 mg, b.i.d.) (EAS regimen) or esomeprazole (20 mg, b.i.d.), metronidazole (250 mg, b.i.d.), and sitafloxacin (100 mg, b.i.d.) (EMS regimen). Eradication rates were evaluated by the [13C] urea breath test or the H. pylori stool antigen test.

Results

All patients with gyrA mutation‐negative strains (24 in EAS and 16 in EMS) showed successful eradication, irrespective of the regimen they received. In patients with gyrA mutation‐positive strains, we found eradication rates of 70.3% (26/37) and 66.7% (26/39) in the EAS and EMS groups in per‐protocol population, respectively (p = .81). According to logistic regression analyses, the MICs of sitafloxacin, which were strongly associated with gyrA mutation status, were independently associated with successful eradication in both groups. This study was registered in the UMIN Clinical Trials Registry as UMIN000006483.

Conclusion

There is no significant difference in the eradication rates between EAS and EMS, regardless of the gyrA mutation status of the H. pylori strains. GyrA mutation status was an important factor in predicting successful eradication with sitafloxacin‐containing rescue therapies.
Hp‐normogram (normo‐graham) for Assessing the Outcome of H. pylori Therapy: Effect of Resistance, Duration, and CYP2C19 Genotype
Authors: Graham David Y.
Published: November 2015

There have been hundreds of H. pylori eradication trials and yet doubt remains regarding the best regimen for any situation. With most regimens, treatment failure is the result of resistance to one component (e.g., clarithromycin). Thus, if one knows the treatment success with two groups (all with susceptible and with all with resistant infections), one can construct a normogram that provides a reliable estimate of the outcome at any prevalence of resistance. The same data can be used to estimate the prevalence of resistance in any clinical trial, the effects duration of therapy, and effects of any procedures to improve outcome (e.g., increasing the proton‐pump inhibitor dose, the duration of therapy, etc.). Because the Hp‐normo‐graham can reliably predict the outcome of clinical trials, it can also obviate the need for many clinical trials in populations where resistance is common. Here, we illustrate the construction of Hp‐normo‐graham and its use to describe the effects of resistance, duration of therapy, attempts to improve results, and the prevalence of resistance and to obviate the need for many clinical trials.
Empirical Advances in the Study of Early European Nationalisms
Authors: Kostantaras Dean
Published: November 2015

This article discusses several recent monographs and edited volumes that reconsider the standing of ‘the nation’ in early modern European culture. The emphasis is placed on empirical interventions that condition the picture received from some famous works of the modernist‐constructivist school, while debunking older ‘dichotomies’ regarding presumed differences in the nature of Eastern and Western European thought. Although adhering themselves to a modernist perspective, the contributions cited below show that far from springing on the scene, as Benedict Anderson wrote ‘towards the late 18th century,’ the nation figured much earlier in European culture and it was from this inheritance that thinkers of Enlightenment‐era vintage obtained a number of conceptual and heuristic devices employed in their works. The nation enjoyed a particular rise in status on the basis of its serviceability, based again on older conventions, for the anthropological pursuits of the age. These insights offer a major advance for historians in narrative coherence by demonstrating the extent to which Enlightenment endeavors in this vein were culturally‐mediated and, in turn, influenced the terms of subsequent political debate.
A New Politics of the Middle Ages: A Global Middle Ages for a Global Modernity
Authors: McClure Julia
Published: November 2015

This paper outlines the new politics of the Middle Ages in an age of ‘global modernity’, a term coined by Arif Dirlik to describe the appearance of ‘alternative’ or ‘multiple’ modernities. The politics of the Middle Ages has been recognised by a number of medieval and postcolonial scholars who have understood the role that the category of the Middle Ages has played in the historic construction of Western modernity and Western imperialism. This political use of the Middle Ages in constructing Western imperialism and modernity was underpinned by the colonial discourse identified by Johannes Fabian as the ‘denial of coevalness’. Yet, in an age of multiple modernities, we need to understand the changing political frontiers of multiple medievalisms. This paper indicates the particular way in which radical Islamist movements, especially ISIL, use and relate to the Islamic past and calls for further analysis of the new politics of the Middle Ages. This paper discusses the global turn and the shift in the politics of the Middle Ages, from the denial of coevalness to contemporaneity, and signposts problems and future directions that this shift indicates for medieval history.
The Fourth Stage: Wole Soyinka and the Social Character of Ibadan.
Authors: Ibironke Olabode
Published: November 2015

This article traces the origin and development of modern African literature in Ibadan, in the 1960s. It argues that Soyinka's famous concept, the Fourth Stage, is his attempt to capture the unique and transformative character of the city of Ibadan. A major portion of African literary history is mostly available through writers' autobiographies such as Soyinka's Ibadan. This article promotes the idea of reading more of these autobiographies as literary history in order to recover the specificity and spirit of African literary production. Indeed, the ways in which the founding texts of African literature are reflective of the social character of the city might be lost if the history of local publication is not resurrected. By locating the origins of the idea of the Fourth Stage in Ibadan, I set the stage for the sequel to this paper that argues that although the African Writers Series published by Heinemann Educational Books canonized African literature, the process of that canonization was already well underway through Mbari publication that was located in Ibadan. Taken together, these two articles underscore the significance of Mbari publication as the outcome of literary activities centered on the Mbari literary club in the heart of Ibadan; the club and the publication were unique to the social character of the city as such.
Fission track and U–Pb zircon ages of psammitic rocks from the Harushinai unit, Kamuikotan metamorphic rocks, central Hokkaido, Japan: constraints on metamorphic histories
Authors: Okamoto Ayumi S. , Takeshita Toru , Iwano Hideki , Danhara Tohru , Hirata Takafumi , Nishido Hirotsugu , Sakata Shuhei
Published: November 2015

Accurate pressure–temperature–time (P–T–t) paths of rocks from sedimentation through maximum burial to exhumation are needed to determine the processes and mechanisms that form high‐pressure and low‐temperature type metamorphic rocks. Here, we present a new method combining laser ablation–inductively coupled plasma–mass spectrometry (LA–ICP–MS) U–Pb with fission track (FT) dates for detrital zircons from two psammitic rock samples collected from the Harushinai unit of the Kamuikotan metamorphic rocks. The concordant zircon U–Pb ages for these samples vary markedly, from 1980 to 95 Ma, with the youngest age clusters in both samples yielding Albian‐Cenomanian weighted mean ages of 100.8 ± 1.1 and 99.3 ± 1.0 Ma (2σ uncertainties). The zircon U–Pb ages were not reset by high‐P/T type metamorphism, because there is no indication of overgrowth within the zircons with igneous oscillatory zoning. Therefore, these weighted mean ages are indicative of the maximum age of deposition of protolithic material. By comparison, the zircon FT data yield a pooled age of ca. 90 Ma, which is almost the same as the weighted mean age of the youngest U–Pb age cluster. This indicates that the zircon FT ages were reset at ca. 90 Ma while still at their source, but have not been reset since. This conclusion is supported by recorded temperature conditions of less than about 300 °C (the closure temperature of zircon FTs), as estimated from microstructures in the deformed detrital quartz grains in psammitic rocks, and no shortening of fission track lengths in the zircon. Combining these new data with previously reported white mica K–Ar ages indicates that the Harushinai unit was deposited after ca. 100 Ma, and underwent burial to its maximum depth before being subjected to a localized thermal overprint during exhumation at ca. 58 Ma.
Recognition of shear heating on a long‐lived major fault using Raman carbonaceous material thermometry: implications for strength and displacement history of the MTL, SW Japan
Authors: Mori Hiroshi , Wallis Simon , Fujimoto Koichiro , Shigematsu Norio
Published: November 2015

The extent to which movement on major faults causes long term shear heating is a contentious issue and an important aspect in the debate about the strength of major faults in the crust. Comparing the results of experimental work on the kinetics of crystallization of carbonaceous material with results of thermal modeling show that the Raman carbonaceous material (CM) geothermometer is well suited to studying shear heating on geological time scales in suitable lithologies exposed around exhumed major fault zones. The Median Tectonic Line (MTL), SW Japan, is the largest on‐land fault in Japan with a length of > 800 km. Application of Raman CM thermometry to pelitic schist adjacent to the fault reveals the presence of a rise in peak temperature of around 60 °C over a distance of around 150 m perpendicular to the MTL fault plane. The spatial association of this thermal anomaly with the fault implies it is due to shear heating. Thermal modeling shows the recorded thermal anomaly and steep temperature gradient is compatible with very high rates of displacement over time scales of a few thousand years. However, the implied displacement rates lie outside those generally observed. An alternative explanation is that an originally broader thermal anomaly that developed during strike slip faulting was shortened due to the effects of normal faulting. Constraints on displacement rate, width of the original anomaly, duration of heating and peak temperature imply a coefficient of friction, μ, greater than 0.4.
Reaction‐Bonded B4C with High Hardness
Authors: Li Xiaoguang , Jiang Dongliang , Zhang Jingxian , Zhu Yunzhou , Chen Zhongming , Huang Zhengren
Published: November 2015

Reaction‐bonded B4C (RBBC) was fabricated through molten Si infiltrating porous B4C preforms. A preform with a 75% relative green density was obtained by mixing two different sized B4C powders. Carbon black added to the preform slightly reduces average pore size, but increases porosity. RBBC ceramics showed a dense and homogeneous microstructure. Vickers hardness was about 15 GPa for RBBC fabricated from a single type of B4C powder and could reach 22–23 GPa for the carbon‐added samples after infiltration. Morphological evolution and the influence of the microstructure on the Vickers hardness were investigated and discussed.
The development and validation of the student response system benefit scale
Authors: Hooker J.F. , Denker K.J. , Summers M.E. , Parker M.
Published: November 2015

Previous research into the benefits student response systems (SRS) that have been brought into the classroom revealed that SRS can contribute positively to student experiences. However, while the benefits of SRS have been conceptualized and operationalized into a widely cited scale, the validity of this scale had not been tested. Furthermore, subsequent research found the scale to be unreliable. Therefore, this project used two studies and created a reliable and valid SRS benefit scale. First, iterative exploratory factor analysis (EFA) was conducted to determine whether the stated conceptual definitions matched the operational definitions reflected in student responses to survey items. The results of this statistical analysis showed an 8‐item, two‐factor scale demonstrating the benefits of SRS in the large lecture classroom. Study 2 used a new sample for confirmatory factor analysis that confirmed the results of the EFA suggested a good model fit with excellent scale reliability. Implications for future assessment of the benefits of SRS were discussed.
Hypertension Prevalence, Awareness, Treatment, and Control: Should 24‐Hour Ambulatory Blood Pressure Monitoring be the Tool of Choice?
Authors: O'Flynn Anne Marie , Curtin Ronan J. , Perry Ivan J. , Kearney Patricia M.
Published: November 2015

We aimed to examine hypertension prevalence, awareness, treatment and control in a community sample and investigate the impact of using 24 hour ABPM. Office blood pressure (BP) was taken from the electronic health record. Study BP was measured by standardised methods. Participants were invited to undergo ABPM. Hypertension was defined by accepted thresholds or anti‐hypertensive use. Standardised questions assessed awareness and treatment. Control was defined as anti‐hypertensive use with BP below normal threshold. There were 931 (45%) participants with office BP, study BP and ABPM. By study BP, hypertension prevalence was 60%, awareness 59%, 60% were treated and 46% controlled. By daytime ABPM threshold, prevalence was 61%, awareness 59%, 59% were treated and 54% controlled. ABPM reclassified 13.5% from normotensive to hypertensive and 14.5% from hypertensive to normotensive. ABPM may not hugely impact population hypertension prevalence but at an individual level it reduces misclassification and facilitates more appropriate management.
Nrdp1S, short variant of Nrdp1, inhibits human glioma progression by increasing Nrdp1‐mediated ErbB3 ubiquitination and degradation
Authors: Wu Yuxuan , Wang Lei , Bao Hanmo , Zou Shenshan , Fu Chunling , Gong Hui , Gao Yong , Tang Yuan , Yu Rutong , Shi Hengliang
Published: November 2015

The ubiquitin ligase neuregulin receptor degradation protein 1 (Nrdp1) is involved in the induction of apoptosis and suppression of tumour formation. We previously showed that it was expressed at lower levels in human glioma tissues compared with normal brain tissues. However, the mechanism underlying this is unclear. Here, we reported that a novel short variant (Nrdp1S), lacking 71 amino acids at the N‐terminal, was expressed in normal human brain tissue, but absent from glioma tissues. Similar to Nrdp1, Nrdp1S could be degraded by the proteasomal pathway, but exhibited an even longer half‐life than Nrdp1. Nrdp1S was also shown to form a heterodimer with Nrdp1, which increased its stability, thereby augmenting the Nrdp1‐mediated ubiquitination and degradation of ErbB3. EdU incorporation, MTT assay and in vitro colony formation demonstrated that Nrdp1S significantly inhibited the cell tumourigenicity. These results together suggest that Nrdp1S is a tumour suppressor that which potentiates the Nrdp1‐mediated ubiquitination and degradation of ErbB3. An Nrdp1S deficiency may also be an important factor in the loss of Nrdp1.
Fast‐scan cyclic voltammetry demonstrates that L‐DOPA produces dose‐dependent, regionally selective bimodal effects on striatal dopamine kinetics in vivo
Authors: Harun Rashed , Hare Kristin M. , Brough Elizabeth M. , Munoz Miranda J. , Grassi Christine M. , Torres Gonzalo E. , Grace Anthony A. , Wagner Amy K.
Published: November 2015

Parkinson's disease (PD) is a debilitating condition that is caused by a relatively specific degeneration of dopaminergic (DAergic) neurons of the substantia nigra pars compacta. L‐DOPA was introduced as a viable treatment option for PD over 40 years ago and still remains the most common and effective therapy for PD. Though the effects of L‐DOPA to augment striatal DA production are well known, little is actually known about how L‐DOPA alters the kinetics of DA neurotransmission that contribute to its beneficial and adverse effects. In this study, we examined the effects of L‐DOPA administration (50 mg/kg carbidopa + 0, 100, and 250 mg/kg L‐DOPA) on regional electrically stimulated DA response kinetics using fast‐scan cyclic voltammetry in anesthetized rats. We demonstrate that L‐DOPA enhances DA release in both the dorsal striatum (D‐STR) and nucleus accumbens (NAc), but surprisingly causes a delayed inhibition of release in the D‐STR. In both regions, L‐DOPA progressively attenuated reuptake kinetics, predominantly through a decrease in Vmax. These findings have important implications on understanding the pharmacodynamics of L‐DOPA, which may be informative for understanding its therapeutic effects and also common side effects like L‐DOPA‐induced dyskinesias (LID).

image

L‐DOPA is commonly used to treat Parkinsonian symptoms, but little is known about how it affects presynaptic DA neurotransmission. Using in vivo fast‐scan cyclic voltammetry, we show L‐DOPA inhibits DA reuptake in a region‐specific and dose‐dependent manner, and L‐DOPA has paradoxical effects on release. These findings may be important when considering mechanisms for L‐DOPA's therapeutic benefits and adverse side‐effects.
Sex‐Dependent Effects of Prenatal Stress on Social Memory in Rats: A Role for Differential Expression of Central Vasopressin‐1a Receptors
Authors: Grundwald N. J. , Benítez D. P. , Brunton P. J.
Published: November 2015

Prenatal stress (PNS) affects a number of traits in the offspring, including stress axis regulation, emotionality and cognition; however, much less is known about the effects of PNS on social memory and the underlying central mechanisms. In the present study, we investigated social preference, social memory under basal and stress conditions and olfactory memory for social and nonsocial odours in the adult offspring of dams exposed to social stress during late pregnancy. Given the key roles that the central oxytocin and vasopressin systems play in facilitating social memory, we further investigated the effects of PNS on the central expression of mRNA for oxytocin (Oxtr) and vasopressin‐1a (Avpr1a) receptors. PNS did not affect social preference in either sex; however, social memory was impaired under basal conditions in PNS females but not PNS males. Accordingly, Avpr1a mRNA expression in the lateral septum and bed nucleus of stria terminalis (BNST) was unaltered in males but was significantly lower in PNS females compared to controls. No differences in Oxtr mRNA expression were detected between control and PNS offspring in either sex in any of the brain regions examined. Social memory deficits in PNS females persisted when social odours were used; however, this does not appear to be a result of impaired olfaction because memory for nonsocial odours was similar in control and PNS females. Under acute stress conditions, deficits in social memory were observed in both male and female control offspring; however, PNS males were unaffected. Moreover, acute stress facilitated social memory in PNS females and this was associated with an up‐regulation of Avpr1a mRNA in the lateral septum and BNST. Our data support a role for altered signalling via central Avpr1a in PNS‐induced sex‐dependent changes in social memory and may have implications for understanding the aetiology of neurodevelopmental disorders characterised by social behaviour deficits in humans.
The Anatomical Society core regional anatomy syllabus for undergraduate medicine
Authors: Smith C.F. , Finn G.M. , Stewart J. , Atkinson M.A. , Davies D.C. , Dyball R. , Morris J. , Ockleford C. , Parkin I. , Standring S. , Whiten S. , Wilton J. , McHanwell S.
Published: November 2015

The Anatomical Society's core syllabus for anatomy (2003 and later refined in 2007) set out a series of learning outcomes that an individual medical student should achieve on graduation. The core syllabus, with 182 learning outcomes grouped in body regions, referenced in the General Medical Council's Teaching Tomorrow's Doctors, was open to criticism on the grounds that the learning outcomes were generated by a relatively small group of anatomists, albeit some of whom were clinically qualified. We have therefore used a modified Delphi technique to seek a wider consensus. A Delphi panel was constructed involving ‘experts’ (n = 39). The revised core syllabus of 156 learning outcomes presented here is applicable to all medical programmes and may be used by curriculum planners, teachers and students alike in addressing the perennial question: ‘What do I need to know ?’
Preregistration nursing students’ perspectives on the learning, teaching and application of bioscience knowledge within practice
Authors: Molesworth Mark , Lewitt Moira
Published: November 2015

Aims and objectives

This paper aims to explore student nurses’ experiences of bioscience learning, teaching and application within the practice setting. It draws upon the social learning theory of communities of practice to consider the issues raised.

Background

The teaching of bioscience within many nursing curricula has shifted from traditional to more integrated approaches. Student nurses recognise bioscience as a valuable component of their studies, but many find it challenging. The focus of previous research in this area has often focussed on bioscience learning in theoretical rather than practice settings.

Design

A phenomenological study.

Methods

Data were collected via focus group or interview with a total of seven students across two campuses in a Scottish university. Participants were offered the opportunity to share their experiences at both the end of year one and year two of their studies. A thematic analysis was undertaken independently then jointly by the authors.

Results

The findings suggest that although participants recognise the value of bioscience within practice settings, they found that opportunities for learning were often limited. Bioscience‐related learning, teaching and application was perceived to have been given less legitimacy by the practice setting than other aspects of placement activity. To enhance bioscience approaches participants expressed a desire for more structured and integrated approaches within both practice and university along with further peer learning opportunities.

Conclusions

Students recognise that bioscience knowledge is important in relation to the provision of safe and effective care. They request greater structure and consistency in relation to the learning, teaching and application of this topic during their placements.

Relevance to clinical practice

Those with a stake in educating nurses within clinical settings may find the views of student nurses on the topic of bioscience learning useful when planning and facilitating placement experiences.
Fear of dental pain in Italian children: child personality traits and parental dental fear
Authors: D'Alessandro Giovanni , Alkhamis Nadia , Mattarozzi Katia , Mazzetti Michela , Piana Gabriela
Published: November 2015

Objectives

Dental anxiety could impede dental treatment in children. Evidence shows that parents’ fear of dentists contributes to children's anxiety towards dentists. The aim of the present study was to determine whether and to what extent: a) parents’ anxiety and depression personality traits, b) parent's dental fear, and c) child personality traits can predict children's dental anxiety in an Italian population.

Methods

One hundred and four children (5–14 years old) and one of their parents participated in the study. Well‐known and validated questionnaires were administered to children (MCDASf, CFSS‐DS, TAD) and parents (FDPQ, STAI Y1, Y2, and BDI‐II).

Result

Dental anxiety is significantly associated with the anxiety personality trait and depression of the child and with parental fear of dental pain. A hierarchical regression analysis showed that, regardless of age and gender, the best predictor of child dental anxiety is parent's fear of dental pain, rather than relatively stable temperaments of the child.

Conclusions

In line with the literature concerning adults, these findings highlight the children dental anxiety as a complex phenomena consisting of different components, including the child's personality traits (anxiety trait and depression) and parents’ dental fear. Clinical implications of this evidence are discussed.
Capsular polysaccharides facilitate enhanced iron acquisition by the colonial cyanobacterium Microcystis sp. isolated from a freshwater lake
Authors: Li Zheng‐Ke , Dai Guo‐Zheng , Juneau Philippe , Qiu Bao‐Sheng
Published: November 2015

Microcystis sp., especially in its colonial form, is a common dominant species during cyanobacterial blooms in many iron‐deficient water bodies. It is still not entirely clear, however, how the colonial forms of Microcystis acclimate to iron‐deficient habitats, and the responses of unicellular and colonial forms to iron‐replete and iron‐deficient conditions were examined here. Growth rates and levels of photosynthetic pigments declined to a greater extent in cultures of unicellular Microcystis than in cultures of the colonial form in response to decreasing iron concentrations, resulting in the impaired photosynthetic performance of unicellular Microcystis as compared to colonial forms as measured by variable fluorescence and photosynthetic oxygen evolution. These results indicate that the light‐harvesting ability and photosynthetic capacity of colonial Microcystis was less affected by iron deficiency than the unicellular form. The carotenoid contents and nonphotochemical quenching of colonial Microcystis were less reduced than those of the unicellular form under decreasing iron concentrations, indicating that the colonial morphology enhanced photoprotection and acclimation to iron‐deficient conditions. Furthermore, large amounts of iron were detected in the capsular polysaccharides (CPS) of the colonies, and more iron was found to be attached to the colonial Microcystis CPS under decreasing iron conditions as compared to unicellular cultures. These results demonstrated that colonial Microcystis can acclimate to iron deficiencies better than the unicellular form, and that CPS plays an important role in their acclimation advantage in iron‐deficient waters.
Review: Parkinson's disease: from synaptic loss to connectome dysfunction
Authors: Bellucci Arianna , Mercuri Nicola Biagio , Venneri Annalena , Faustini Gaia , Longhena Francesca , Pizzi Marina , Missale Cristina , Spano PierFranco
Published: November 2015

Parkinson's disease (PD) is a common neurodegenerative disorder with prominent loss of nigro‐striatal dopaminergic neurons. The resultant dopamine (DA) deficiency underlies the onset of typical motor symptoms (MS). Nonetheless, individuals affected by PD usually show a plethora of nonmotor symptoms (NMS), part of which may precede the onset of motor signs. Besides DA neuron degeneration, a key neuropathological alteration in the PD brain is Lewy pathology. This is characterized by abnormal intraneuronal (Lewy bodies) and intraneuritic (Lewy neurites) deposits of fibrillary aggregates mainly composed of α‐synuclein. Lewy pathology has been hypothesized to progress in a stereotypical pattern over the course of PD and α‐synuclein mutations and multiplications have been found to cause monogenic forms of the disease, thus raising the question as to whether this protein is pathogenic in this disorder. Findings showing that the majority of α‐synuclein aggregates in PD are located at presynapses and this underlies the onset of synaptic and axonal degeneration, coupled to the fact that functional connectivity changes correlate with disease progression, strengthen this idea. Indeed, by altering the proper action of key molecules involved in the control of neurotransmitter release and re‐cycling as well as synaptic and structural plasticity, α‐synuclein deposition may crucially impair axonal trafficking, resulting in a series of noxious events, whose pressure may inevitably degenerate into neuronal damage and death. Here, we provide a timely overview of the molecular features of synaptic loss in PD and disclose their possible translation into clinical symptoms through functional disconnection.
An autopsied case of unclassifiable sporadic four‐repeat tauopathy presenting with parkinsonism and speech disturbances
Authors: Iwasaki Yasushi , Mori Keiko , Ito Masumi , Tatsumi Shinsui , Mimuro Maya , Kuwano Ryozo , Hasegawa Masato , Yoshida Mari
Published: November 2015

A 48‐year‐old Japanese woman experienced slow‐onset parkinsonism and speech disturbances. Neurological examinations revealed rigidity in the trunk and extremities, bradykinesia and postural instability, although cognitive impairments and psychiatric symptoms were not apparent in the early disease stage. Neuroimaging revealed progressive bilateral frontotemporal lobe atrophy with cerebral blood flow hypoperfusion. No apparent signs of lower motor neuron involvement were observed, such as fasciculation or electromyogram findings. She eventually reached the akinetic mutism state, and gastrostomy and tracheotomy were performed at 4 years after onset. A clinical diagnosis of progressive supranuclear palsy was made prior to her death, which occurred 6 years after onset. Post mortem examinations revealed that the brain weighed 1200 g and showed atrophy of the frontotemporal lobe and brainstem. Severe neuron loss and gliosis were observed in the frontotemporal lobe. The superior and middle frontal gyri were the most severely affected and showed spongiform changes in the superficial layer. The globus pallidus, subthalamic nucleus, cerebellar dentate nucleus, substantia nigra and inferior olivary nucleus also showed neuronal loss with gliosis. Using hyperphosphorylated tau (AT‐8) immunostaining, pretangle‐like neurons, numerous short threads and glial tau pathology were extensively observed. Using Gallyas−Braak silver staining, thin and short threads were also extensively observed, but considerably fewer than those observed by AT‐8 immunostaining. Neither astrocytic plaques nor tuft‐shaped astrocytes were observed. Examination by immunoelectron microscopy showed straight fibrils approximately 15 nm in diameter in the neuronal cytoplasmic inclusions in the cerebral cortex and in the fibrillary structures in the cerebral white matter. Western blot analysis of sarkosyl‐insoluble tau revealed predominantly four‐repeat tau and a banding pattern similar to that seen in progressive supranuclear palsy. No pathogenic mutations were found during the gene analysis of microtubule‐associated protein tau. After completing our comprehensive investigation, we diagnosed this patient with unclassifiable four‐repeat tauopathy.
Endogenous CRF in rat large intestine mediates motor and secretory responses to stress
Authors: Liu S. , Chang J. , Long N. , Beckwith K. , Talhouarne G. , Brooks J. J. , Qu M.‐H. , Ren W. , Wood J. D. , Cooper S. , Bhargava A.
Published: November 2015

Background

Corticotropin‐releasing factor (CRF) mediates our body's overall responses to stress. The role of central CRF in stress‐stimulated colonic motility is well characterized. We hypothesized that transient perturbation in expression of enteric CRF is sufficient to change stress‐induced colonic motor and secretory responses.

Methods

Sprague–Dawley rats (adult, male) were subjected to 1‐h partial restraint stress (PRS) and euthanized at 0, 4, 8, and 24 h. CRF mRNA and peptide levels in the colon were quantified by real‐time RT‐PCR, enzyme immuno‐assay and immunohistochemistry. Double‐stranded RNA (dsRNA) designed to target CRF (dsCRF) was injected into the colonic wall to attain RNA interference‐mediated inhibition of CRF mRNA expression. DsRNA for β‐globin was used as a control (dsControl). Four days after dsRNA injection, rats were subjected to 1‐h PRS. Fecal output was measured. Ussing chamber techniques were used to assess colonic mucosal ion secretion and transepithelial tissue conductance.

Key Results

Exposure to PRS elevated CRF expression and increased CRF release in the rat colon. Injection of dsCRF inhibited basal CRF expression and prevented the PRS‐induced increase in CRF expression, whereas CRF expression in dsControl‐injected colons remained high after PRS. In rats treated with dsControl, PRS caused a significant increase in fecal pellet output, colonic baseline ion secretion, and transepithelial tissue conductance. Inhibition of CRF expression in the colon prevented PRS‐induced increase in fecal output, baseline ion secretion, and transepithelial tissue conductance.

Conclusions & Inferences

These results provide direct evidence that transient perturbation in peripherally expressed CRF prevents colonic responses to stress.
Expression of salivary biomarkers in patients with oral mucositis: evaluation by SELDI‐TOF/MS
Authors: Ardito F , Giuliani M , Perrone D , Giannatempo G , Di Fede O , Favia G , Campisi G , Colella G , Lo Muzio L
Published: November 2015

Objective

This study aims to evaluate changes in proteomic salivary profile of patients with oral mucositis after adjuvant cancer treatments.

Materials and Methods

Samples were collected from patients after adjuvant cancer therapies, and were analyzed by means of SELDI/TOF. Patients were separated in two groups: patients affected by mucositis (MUCOSITIS) and patient without mucositis (NO MUCOSITIS). All patients were divided in function of the anticancer treatment: patients who had radiotherapy (MUCOSITIS RADIO), had not radiotherapy (MUCOSITIS NO RADIO), had chemotherapy (MUCOSITIS CHEMO), and those who had not chemotherapy (MUCOSITIS NO CHEMO). Statistical evaluation PCA (Principal Component Analysis) was conducted with the software BIO‐RAD Data Manager™ (Version 3.5).

Results

We found the increased peaks of 3443, 3487, and 4135 m/z in MUCOSITIS group, while 6237 m/z was reduced. These same peaks would the same modifications in MUCOSITIS RADIO, while in MUCOSITIS CHEMIO are increased 3443 and 6237 m/z but 3487, 4135 m/z are reduced. These data were confirmed by the PCA.

Conclusion

Anticancer therapy influenced the level expression of many salivary biomarkers in mucositis with a good significance. Therefore, 3443, 3487, 4135, and 6237 m/z are good biomarker candidates of oral mucositis.
Basal cell naevoid syndrome with nasopharyngeal carcinoma: a case report
Authors: Kalsi A.S. , Garg M. , Dhariwal D.K.
Published: November 2015

Basal cell naevoid syndrome is a rare autosomal dominant multisystem disorder characterised by multiple basal cell naevi, keratocystic odontogenic tumours, a variety of developmental anomalies and a predisposition to neoplasms, in particular basal cell carcinomas. A 15‐year‐old female patient with basal cell naevoid syndrome presented with severe headaches waking her at night, spontaneous nosebleeds, fatigue, increased sleep and decreased appetite. A CT head showed a large right‐sided nasopharyngeal mass. The patient underwent nasopharyngoscopy with biopsy which confirmed a nasopharyngeal carcinoma. MRI and a contrast‐enhanced CT scan of the head and neck suggested a nasopharyngeal carcinoma with skull base involvement. The carcinoma was treated successfully with chemotherapy and radiotherapy. She remains in remission at 10‐month review. To our knowledge, this is the first report of a basal cell naevoid syndrome patient diagnosed with nasopharyngeal carcinoma. Clinicians should be aware of the possibility of head and neck neoplasms in patients with basal cell naevoid syndrome.
Formula with long‐chain polyunsaturated fatty acids reduces incidence of allergy in early childhood
Authors: Foiles Amanda M. , Kerling Elizabeth H. , Wick Jo A. , Scalabrin Deolinda M. F. , Colombo John , Carlson Susan E.
Published: November 2015

Background

Allergy has sharply increased in affluent Western countries in the last 30 years. N‐3 long‐chain polyunsaturated fatty acids (n‐3 LCPUFAs) may protect the immune system against development of allergy.

Methods

We prospectively categorized illnesses by body system in a subset of 91 children from the Kansas City cohort of the DIAMOND (DHA Intake and Measurement of Neural Development) study who had yearly medical records through 4 years of age. As infants, they were fed either a control formula without LCPUFA (n = 19) or one of three formulas with LCPUFA from docosahexaenoic acid (DHA) and arachidonic acid (ARA) (n = 72).

Results

Allergic illnesses in the first year were lower in the combined LCPUFA group compared to the control. LCPUFAs significantly delayed time to first allergic illness (p = 0.04) and skin allergic illness (p = 0.03) and resulted in a trend to reduced wheeze/asthma (p = 0.1). If the mother had no allergies, LCPUFAs reduced the risk of any allergic diseases (HR = 0.24, 95% CI = 0.1, 0.56, p = 0.0.001) and skin allergic diseases (HR = 0.35, 95% CI = 0.13, 0.93, p = 0.04). In contrast, if the mother had allergies, LCPUFAs reduced wheezing/asthma (HR = 0.26, 95% CI = 0.07, 0.9, p = 0.02).

Conclusions

LCPUFA supplementation during infancy reduced the risk of skin and respiratory allergic diseases in childhood with effects influenced by maternal allergies.
Outpatient outcomes and satisfaction in pediatric population: data from the postoperative phone call
Authors: Brenn B. Randall , Choudhry Dinesh K. , Sacks Karen
Published: November 2015

Background

Quality and patient/parent satisfaction are goals for pediatric perioperative services. As part of the implementation of our operating room electronic medical record (EMR), a postoperative phone call questionnaire was developed to assess patients discharged after outpatient surgery. The goal of this initiative was to determine the rate of common postoperative complications and understand reasons for patient/parent dissatisfaction.

Methods

Institutional Review Board approval was obtained for chart review. The postoperative phone call survey was attempted by our postanesthesia care unit nursing staff on all pediatric outpatients. The call was attempted for 3 days. From 2009 to 2013, more than 37 000 phone records existed in our EMR, Epic Optime (Epic Systems, Verona, WI). These data were extracted to a business intelligence (BI) program, QlikView (Qliktech, Radnor, PA, USA). A BI dashboard was constructed to obtain phone call results for any given time frame from monthly to spanning several years. Complications were logged as 4‐point severity rating scales (none, mild, moderate, severe) with descriptions for each level. The BI dashboard calculated the overall and rates by severity for the following: (i) nausea, (ii) vomiting, (iii) pain, (iv) bleeding, (v) hoarseness, and (vi) difficulty eating.

Results

Of 42 688 outpatient cases, 37 620 postoperative phone calls were completed for an overall response rate of 88%. Pain, at 11.1%, was the highest reported postoperative complication. The rate of dissatisfaction was reported to be 0.31%. Most patients reporting dissatisfaction (62%) did not report any complications. Contingency coefficient showed that there was little relationship between satisfaction and presence of complications.

Conclusion

A postoperative phone survey is cost‐effective and appreciated by patients. We found that satisfaction with our perioperative services was not related to the rates of reported complications. Although reducing complications is of utmost importance, improvements in wait times and other operational issues would yield greater improvements in satisfaction.
Molecular insights into the function of the viral RNA silencing suppressor HCPro
Authors: Ivanov Konstantin I. , Eskelin Katri , Bašić Marta , De Swarnalok , Lõhmus Andres , Varjosalo Markku , Mäkinen Kristiina
Published: November 2015

Potyviral helper component proteinase (HCPro) is a well‐characterized suppressor of antiviral RNA silencing, but its mechanism of action is not yet fully understood. In this study, we used affinity purification coupled with mass spectrometry to identify binding partners of HCPro in potyvirus‐infected plant cells. This approach led to identification of various HCPro interactors, including two key enzymes of the methionine cycle, S–adenosyl‐l–methionine synthase and S–adenosyl‐l–homocysteine hydrolase. This finding, together with the results of enzymatic activity and gene knockdown experiments, suggests a mechanism in which HCPro complexes containing viral and host proteins act to suppress antiviral RNA silencing through local disruption of the methionine cycle. Another group of HCPro interactors identified in this study comprised ribosomal proteins. Immunoaffinity purification of ribosomes demonstrated that HCPro is associated with ribosomes in virus‐infected cells. Furthermore, we show that HCPro and ARGONAUTE1 (AGO1), the core component of the RNA‐induced silencing complex (RISC), interact with each other and are both associated with ribosomes in planta. These results, together with the fact that AGO1 association with ribosomes is a hallmark of RISC‐mediated translational repression, suggest a second mechanism of HCPro action, whereby ribosome‐associated multiprotein complexes containing HCPro relieve viral RNA translational repression through interaction with AGO1.
A highly specific microRNA‐mediated mechanism silences LTR retrotransposons of strawberry
Authors: Šurbanovski Nada , Brilli Matteo , Moser Mirko , Si‐Ammour Azeddine
Published: November 2015

Small RNAs are involved in a plethora of functions in plant genomes. In general, transcriptional gene silencing is mediated by 24‐nucleotide siRNAs and is required for maintaining transposable elements in a silenced state. However, microRNAs are not commonly associated with transposon silencing. In this study, we performed small RNA transcriptome and degradome analyses of the Rosaceae model plant Fragaria vesca (the woodland strawberry) at the genome‐wide level, and identified miRNA families and their targets. We report a highly specific mechanism of LTR retrotransposon silencing mediated by an abundant, ubiquitously expressed miRNA (fve–miR1511) generated from a single locus. This miRNA specifically targets LTR retroelements, silencing them post‐transcriptionally by perfectly pairing to the highly conserved primer binding site for methionyl initiator tRNA that is essential for reverse transcription. We investigated the possible origins of this miRNA, and present evidence that the pre‐miR1511 hairpin structure probably derived from a locus coding for tRNAiMet through a single microinversion event. Our study shows that this miRNA targets retrotransposons specifically and constitutively, and contributes to features such as genome stability, size and architecture in a far more direct way than previously thought.
Hematologic and serum biochemical reference intervals for wild Tasmanian devils (Sarcophilus harrisii)
Authors: Peck Sarah , Corkrey Ross , Hamede Rodrigo , Jones Menna , Canfield Paul
Published: November 2015

Background

The Tasmanian devil (Sarcophilus harrisii) is a carnivorous marsupial threatened with extinction by a fatally infectious cancer known as devil facial tumor disease (DFTD). Conservation efforts including captive breeding and island translocations are underway to address this threat.

Objectives

The objectives of this study were to determine hematologic and serum biochemical reference intervals (RI) to aid in health assessment of Tasmanian devils, and to examine seasonal, sex, reproductive status and age variations.

Methods

We collected jugular blood samples from individual wild Tasmanian devils at 2 different locations over a 2‐year period to determine hematologic and serum biochemical RI by nonparametric methods using the central 0.95 fraction.

Results

A total of 307 blood samples were collected from 187 devils. Significant age differences were found for ALP, CK, cholesterol, calcium, phosphate, albumin, globulins, albumin: globulin ratio, and glucose. Significant differences between sexes were observed for AST, creatinine, and potassium. Significant seasonal or reproductive status variation in adult males or breeding females were observed for PCV, HGB, RBC, MCHC, MCH, MCV, neutrophils and lymphocytes, fibrinogen, total plasma protein, AST, ALP, ALT, GLDH, bilirubin, urea, calcium, chloride, total protein, albumin, A:G, and glucose.

Conclusions

Many of the differences observed between subgroups can be explained by growth requirements, reproductive demands, and seasonal effects on activity. This study has determined comprehensive RI for the Tasmanian devil, which will be used to assess animals targeted for captive breeding and translocations, or affected by DFTD.
The Effect of Gum Chewing, Early Oral Hydration, and Early Mobilization on Intestinal Motility After Cesarean Birth
Authors: Sahin Ebru , Terzioglu Fusun
Published: November 2015

Aim

The aim of the study was to investigate the effect of gum chewing, early oral hydration, and early mobilization after cesarean birth on intestinal sounds, passing gas, and intestinal evacuation.

Design

Randomized controlled study. Setting: This study was conducted at the Obstetrics Service of the one Obstetrics and Child Diseases Hospital.

Participants

A total of 240 females divided into 8 groups of 30 subjects each were included within the scope of the sample.

Methods

The women who underwent cesarean birth were divided into eight groups by using 23 factorial test levels, depending on the use of three different methods of gum chewing, early oral hydration, and early mobilization. No intervention was applied to the women in the control group. For the other seven groups, the intestinal sounds were checked every 30 minutes with a stethoscope over the abdomen and the first time of passing gas and the first evacuation time were recorded by asking the mother. The data were evaluated with numbers, mean, and percentage calculations, Student's t test, one‐way variance analysis, correlation, and Tukey HSD test.

Results

The intestinal sounds were heard earlier, gas was passed earlier, and bowel movements were earlier in the first group that received all interventions compared to the other groups (p < .05). The patient could not be discharged before 48 hours had passed after the cesarean birth according to the hospital protocol and the time of discharge was therefore not affected by interventions.

Linking Evidence to Action

All of the three different interventions, such as gum chewing, early oral hydration, and early mobilization after cesarean birth, increase intestinal motility. The interventions are recommended during postoperative routine care to shorten hospital stay and prevent postoperative ileus.