bluuebunny/crossref_metadata_2025 huggingface dataset:
Controversies on the prognostic value of interim FDG‐PET in advanced‐stage Hodgkin lymphoma
Authors: Adams Hugo J. A. , Kwee Thomas C.
Published: August 2016

Hodgkin lymphoma, even in advanced‐stage, is a highly curable malignancy, but treatment is associated with short‐term toxicity and long‐term side effects. Early predictive markers are required to identify those patients who do not require the full‐length standard therapy (and thus qualify for therapy de‐escalation) and those patients who will not be cured by standard therapy (and thus qualify for therapy escalation). Multiple trials have assessed the value of 18F‐fluoro‐2‐deoxy‐d‐glucose positron emission tomography (FDG‐PET) after a few cycles of chemotherapy (also known as ‘interim FDG‐PET’) in predicting outcome in advanced‐stage Hodgkin lymphoma. Furthermore, multiple interim FDG‐PET‐adapted trials, in which patients with positive interim FDG‐PET scans are assigned to escalated therapies, and patients with negative interim FDG‐PET scans are assigned to de‐escalated therapies, have recently been published or are currently ongoing, with generally heterogeneous results. The present article reports the currently available evidence (and controversies) on the prognostic value of interim FDG‐PET in advanced‐stage Hodgkin lymphoma in patients with positive and negative interim FDG‐PET findings following continuation of standard chemotherapy or escalated/de‐escalated therapy.
Switching between two targets with non‐constant velocity profiles reveals shared internal model of target motion
Authors: Hainque E. , Apartis E. , Daye P. M.
Published: August 2016

Several experiments have shown that smooth pursuit and saccades interact while tracking an object moving across the visual scene. It was proposed two decades ago that the amplitude of saccades triggered during smooth pursuit (‘catch‐up saccades’) were corrected by a delayed sensory signal to account for the ongoing target displacement during catch‐up saccades. However, recent studies used targets with non‐constant velocity profiles and suggested that the correction of catch‐up saccade amplitude must be done through an internal model of target motion. It is widely accepted that an internal model of target motion is also used by the central nervous system (CNS) to cancel inherent delays between visual input and smooth pursuit motor output, ensuring accurate tracking of moving targets. Our study proposes a new paradigm in which the target switches unexpectedly from one target with a non‐constant periodic velocity profile to another with a non‐constant aperiodic velocity profile. Our results confirm the hypothesis that the CNS uses an internal model of target motion to correct catch‐up saccade amplitude. In addition, we reconcile the sensory delayed and the internal model of target motion hypotheses and show that a common internal model of target motion is shared within the CNS to control smooth pursuit and to correct catch‐up saccade amplitude.
Differences in spatial and temporal frequency interactions between central and peripheral parts of the feline area 18
Authors: Zhao Chunzhen , Hata Ryosuke , Okamura Jun‐ya , Wang Gang
Published: August 2016

The visual system demonstrates significant differences in information processing abilities between the central and peripheral parts of the visual field. Optical imaging based on intrinsic signals was used to investigate the difference in stimulus spatial and temporal frequency interactions related to receptive field eccentricity in the cat area 18. Changing either the spatial or the temporal frequency of grating stimuli had a significant impact on responses in the cortical areas corresponding to the centre of the visual field and more peripheral parts at 10 degrees eccentricity. The cortical region corresponding to the centre of the gaze was tuned to 0.4 cycles per degree (c/deg) for spatial frequency and 2 Hz for temporal frequency. In contrast, the cortical region corresponding to the periphery of the visual field was tuned to a lower spatial frequency of 0.15 c/deg and a higher temporal frequency of 4 Hz. Interestingly, when we simultaneously changed both the spatial frequency and the temporal frequency of the grating stimuli, the responses were significantly different from those estimated with an assumption of independence between the spatial and temporal frequency in the cortical region corresponding to the periphery of the visual field. However, in the cortical area corresponding to the centre of the gaze, spatial frequency showed significant independence from temporal frequency. These properties support the notion of relative specialization of visual information processing for peripheral representations in cortical areas.
Post‐thrombolytic blood pressure and symptomatic intracerebral hemorrhage
Authors: Waltimo T. , Haapaniemi E. , Surakka I. L. , Melkas S. , Sairanen T. , Sibolt G. , Tatlisumak T. , Strbian D.
Published: August 2016

Background and purpose

Most guidelines for intravenous thrombolysis (IVT) in acute ischaemic stroke patients advise keeping systolic blood pressure (BP) below 180/105 mmHg prior to the bolus injection. Less is known about optimal management of BP thereafter. We assessed temporal changes in post‐thrombolytic systolic BP values and their impact on development of symptomatic intracerebral hemorrhage (sICH).

Methods

The study cohort included 1868 consecutive acute ischaemic stroke patients treated with IVT at the Helsinki University Central Hospital. sICH was defined according to the European Cooperative Acute Stroke Study II (ECASS‐II) (primary outcome), National Institute of Neurological Disorders and Stroke, and Safe Implementation of Thrombolysis in Stroke criteria. We evaluated BP at admission, prior to IVT and at 2, 4, 8, 12, 24 and 48 h after thrombolysis. We used univariate and multivariable models to test the effect of BP at various time‐points on development of post‐thrombolytic sICH.

Results

Prevalence of sICH in the cohort was 5.8% (ECASS‐II). Patients with sICH had significantly higher systolic BP at several time‐points after IVT compared with those without sICH (P < 0.01 at 2 and 4 h; P < 0.05 at 12 and 48 h). The odds ratios for development of sICH per 10 mmHg increase in BP were 1.14 [95% confidence interval (CI), 1.03–1.25], 1.14 (95% CI, 1.03–1.25), 1.12 (95% CI, 1.01–1.23) and 1.12 (95% CI, 1.01–1.23), respectively. At 8 h, we observed a trend (P = 0.07) for ECASS‐II and a significant effect (P < 0.05) for National Institute of Neurological Disorders and Stroke, and Safe Implementation of Thrombolysis in Stroke criteria. Thus, the only time‐point with no difference observed was 24 h.

Conclusions

Patients with post‐thrombolytic sICH have significantly higher systolic BP at several time‐points compared with patients without sICH.
Genetic risk factors for antiepileptic drug–induced hypersensitivity reactions in Israeli populations
Authors: Israel Shoshana , Maggio Nicola , Ekstein Dana , Zaid Huda , Firer Maria , Bederovsky Yana , Noyman Iris , Gandelman‐Marton Revital , Blatt Ilan , Brautbar Chaim , Marom Eli , Nahlieli Dil Dorit , Berman Erez , Sabag David , Ingber Arieh , Eyal Sara
Published: August 2016

The human leukocyte antigen (HLA) alleles B*15:02 and A*31:01 have been identified as predictive markers of adverse cutaneous effects of carbamazepine and phenytoin in Asian and North European populations, respectively. Our aim was to estimate the distribution of these alleles in Jewish and Arab populations in Israel. The HLA‐B*15:02 and HLA‐A*31:01 carrier rate was estimated based on data from the Hadassah Bone Marrow Registry. Data on Stevens‐Johnson syndrome (SJS)– and toxic epidermal necrolysis (TEN)–related hospitalizations were obtained from the Israeli Ministry of Health (MOH) registries and from four Israeli medical centers. Of 83,705 Jewish and Arab‐Muslim donors, 81 individuals of known origin carried the HLA‐B*15:02. Among them, 66 were Jews of India‐Cochin descent. Of the Cochin Jewish donors, 12.7% were B*15:02 carriers. HLA‐A*31:01 carrier incidence among Arab and Jewish Israeli populations (3.5% and 2.2%, respectively) was within the range reported in other countries. We did not identify SJS‐ or TEN‐related hospitalizations of Jews of Indian descent. Yet, this population should be considered at greater risk for antiepileptic drug–induced SJS and TEN. Until further data on actual risk are available, such patients should be typed for HLA‐B before treatment with carbamazepine or phenytoin.
Continuous spike‐waves during slow‐wave sleep in a mouse model of focal cortical dysplasia
Authors: Sun Qian‐Quan , Zhou Chen , Yang Weiguo , Petrus Daniel
Published: August 2016

Objective

To examine if mice with focal cortical dysplasia (FCD) develop spontaneous epileptic seizures and, if so, determine the key electroencephalography (EEG) features.

Methods

Unilateral single freeze lesions to the S1 region (SFLS1R) were made in postnatal day 0–1 pups to induce a neocortical microgyrus in the right cortical hemisphere. Continuous 24‐h recordings with intracranialEEGelectrodes and behavioral tests were performed in adultSFLS1R and sham‐control mice to assess neurologic status.

Results

A high percentage of adultSFLS1R animals (89%, 40/45) exhibited at least one or more spontaneous nonconvulsive seizure events over the course of 24 h. Of these animals, 60% (27/45) presented with a chronic seizure state that was persistent throughout the recording session, consisting of bursts of rhythmic high‐amplitude spike‐wave activities and primarily occurring during periods of slow‐wave sleep. In comparison, none of the control, age‐matched, mice (0/12) developed seizures. The epileptic discharge pattern closely resembled a pattern of continuous spike‐waves during slow‐wave sleep (CSWS) of the human syndrome described as an electrical status epilepticus during slow‐wave sleep (ESES). Key findings in theSFLS1R model indicated that the observedCSWS(1) were more prevalent in female (18/23) versus male (9/22, p < 0.05), (2) were strongest in the right S1 region although generalized to other brain regions, (3) were associated with significant cognitive and behavioral deficits, (4) were temporarily alleviated by ethosuximide treatment or optogenetic activation of cortical γ‐aminobutyric acid (GABA)ergic neurons, and (5) theta and alpha band rhythms may play a key role in the generalization of spike‐wave activities.

Significance

This is the first report of an in vivo animalFCDmodel that induces chronic spontaneous electrographic brain seizures. Further characterization of the abnormal oscillations in this mouse model may lead to a better understanding of the mechanisms ofCSWS/ESES.
Neurodegeneration in equine grass sickness is not attributable to niacin deficiency
Authors: McGorum B. C. , Jago R. C. , Cillan‐Garcia E. , Pirie R. S. , Keen J. A. , Reardon R. J. M. , Saffu P. Y. , Miller N. J.
Published: August 2016

Background

The aetiology of equine grass sickness (EGS) is currently unknown. We hypothesised that an acute deficiency of niacin (vitamin B3), which plays a key role in neural homeostasis, may contribute to neurodegeneration inEGS. Niacin deficiency can potentially result from ingestion of niacin antagonists produced by pasture mycotoxigenic fungi.

Objectives

To compare the niacin status ofEGSand control grazing horses. A secondary objective was to compare blood concentrations of vitamins B1, B2 and B6 inEGSand control grazing horses to determine if the status of these vitamins was altered inEGS.

Study design

Case–control study.

Methods

Indices of niacin status, namely the erythrocyte nicotinamide adenine dinucleotide:nicotinamide adenine dinucleotide phosphate ratio (NAD:NADPratio) and erythrocyte concentrations ofNADandNADP, were compared in blood collected fromEGSand healthy control grazing horses. Blood concentrations of vitamins B1, B2 and B6 were also compared.

Results

There was no significant intergroup difference in theNAD:NADPratio, the main index of functional niacin status (control group: median 2.1, interquartile range [IQR] 1.8–2.6;EGSgroup: median 2.1,IQR1.9–2.6).EGShorses had significantly higher (median value increased by 25%) concentrations ofNADP. There were no intergroup differences in blood concentrations of vitamins B1, B2 and B6.

Main limitations

The interpretation of data was limited by the lack of previously defined equine reference ranges for many of the analytes. Sample size was low.

Conclusions

Niacin deficiency does not contribute toEGSneurodegeneration.
Hopanoids play a role in stress tolerance and nutrient storage in the cyanobacterium Nostoc punctiforme
Authors: Ricci J. N. , Morton R. , Kulkarni G. , Summers M. L. , Newman D. K.
Published: August 2016

Hopanes are abundant in ancient sedimentary rocks at discrete intervals in Earth history, yet interpreting their significance in the geologic record is complicated by our incomplete knowledge of what their progenitors, hopanoids, do in modern cells. To date, few studies have addressed the breadth of diversity of physiological functions of these lipids and whether those functions are conserved across the hopanoid‐producing bacterial phyla. Here, we generated mutants in the filamentous cyanobacterium, Nostoc punctiforme, that are unable to make all hopanoids (shc) or 2‐methylhopanoids (hpnP). While the absence of hopanoids impedes growth of vegetative cells at high temperature, the shc mutant grows faster at low temperature. This finding is consistent with hopanoids acting as membrane rigidifiers, a function shared by other hopanoid‐producing phyla. Apart from impacting fitness under temperature stress, hopanoids are dispensable for vegetative cells under other stress conditions. However, hopanoids are required for stress tolerance in akinetes, a resting survival cell type. While 2‐methylated hopanoids do not appear to contribute to any stress phenotype, total hopanoids and to a lesser extent 2‐methylhopanoids were found to promote the formation of cyanophycin granules in akinetes. Finally, although hopanoids support symbiotic interactions between Alphaproteobacteria and plants, they do not appear to facilitate symbiosis between N. punctiforme and the hornwort Anthoceros punctatus. Collectively, these findings support interpreting hopanes as general environmental stress biomarkers. If hopanoid‐mediated enhancement of nitrogen‐rich storage products turns out to be a conserved phenomenon in other organisms, a better understanding of this relationship may help us parse the enrichment of 2‐methylhopanes in the rock record during episodes of disrupted nutrient cycling.
A Theoretical Model of Psychometric Effects of Faking on Assessment Procedures: Empirical findings and implications for personality at work
Authors: Salgado Jesús F.
Published: August 2016

This article proposes a theoretical model for explaining the psychometric effects of faking on assessment procedures (e.g., biodata, interviews, assessment center, personality inventories, and self‐reported measures). The model hypothesizes that faking is a phenomenon of homogenization of scores, consisting of a double mechanism that increases the mean, on one hand, and decreases the standard deviation of distributions of scores, on the other. Subsequently, this affects the covariance, reliability, and validity of assessment procedures negatively. The model predicts that a mean ratio (faking ratio) greater than 1 and a coefficient of homogeneity u smaller than 1 characterizes faking. Meta‐analysis was used to test several predictions of the theoretical model in the case of the personality measures. A database of 46 independent studies was created. All the studies used the NEO‐PI‐R for assessing the Big Five and their facets. The general pattern of data fully supported the model predictions. Implications for personnel assessment and, particularly, for personality assessment are discussed.
If You Are Emotionally Intelligent: The effects of customer‐related social stressors on counterproductive work behavior for front‐line service employees
Authors: Zhang Ran , Redfern Kylie , Newman Meredith A. , Ferreira‐Meyers Karen
Published: August 2016

Recent literature in the area of employee–customer interactions suggests that stressful encounters contribute to negative outcomes for service employees. Few studies, however, have focused on the effects of customer‐related social stressors (CSS) on counterproductive work behavior (CWB) among front‐line service employees. The researchers tested a moderated mediation model of the effects of CSS on CWB with the key objective of exploring the mediation effects of emotional exhaustion and the moderating effects of emotional intelligence on this relationship. Based on a sample of 244 call center representatives in China, the research revealed that CSS led to emotional exhaustion, which, in turn, related to CWB for service employees. Furthermore, emotional intelligence acted as a buffer on the effects of CSS on CWB via emotional exhaustion.
Context Matters, but How Much? Latent state–trait analysis of cognitive ability assessments
Authors: Hermes Michael , Stelling Dirk
Published: August 2016

Cognitive abilities are thought to represent temporally stable constructs, however, accumulating evidence suggests that effects of the measurement situation could affect its measurement (e.g., effects of test motivation, stress level). The present study modeled these effects explicitly in a latent variables approach. In contrast to previous studies, we investigated participants (job candidates) in repeated high‐stakes settings (N = 188). We found that cognitive ability measurements in high‐stakes settings not only reflect a stable latent trait and random measurement error, but also systematic effects of the test setting. Our results support the application of cognitive ability tests in organizational contexts but have implications for its use in applied settings such as personnel selection.
Medication appropriateness tool for co‐morbid health conditions in dementia: consensus recommendations from a multidisciplinary expert panel
Authors: Page A. T. , Potter K. , Clifford R. , McLachlan A. J. , Etherton‐Beer C.
Published: August 2016

Background

Medication management for people living with dementia is a complex task as it is unclear what constitutes optimal medication management in this population due to the shifting focus of health priorities and the balance between the benefits and harms of medications.

Aim

This study sought expert opinion to create a consensus list to define appropriate medication management of co‐morbidities for people with dementia.

Methods

This study used the Delphi technique. We invited multidisciplinary experts in geriatric therapeutics including pharmacists, doctors, nurse practitioners, a patient advocate and a psychologist to participate. Participants were asked to engage into three or more rounds of questioning. Round 1 was a questionnaire comprised of one question defining dementia and seven open‐ended questions about appropriate management of co‐morbidities in people with dementia. Two investigators qualitatively analysed the responses to questions from Round 1 using thematic analysis. The results of this analysis were provided to participants as statements in the Round 2 survey. The participants were asked to rate their agreement with each statement on a 5‐point Likert scale. The median and interquartile range (IQR) were calculated for the responses to each statement. Consensus was pre‐specified as an IQR less than or equal to 1. Statements where consensus was not achieved were presented to participants in Round 3. The Round 2 median and IQR values were provided and participants were again asked to rate their agreement with each statement on a 5‐point Likert scale. The statements where participants agreed or strongly agreed were included in the Medication Appropriateness Tool for Co‐morbid Health conditions in Dementia criteria.

Results

Fifty‐seven experts agreed to participate in the study, of whom 58% were pharmacists and 36% were medical practitioners. Fifty‐five participants completed the Round 1 (95% response rate). A total of 128 statements was included in the Round 2 survey. Consensus was reached on 93 statements in Round 2 (n = 48 responders, 84% response rate) and on 18 statements in Round 3 (n = 43 responders, 75% response rate). The participants reached consensus on 111 of 128 statements. Of these statements, 67 statements were included in the Medication Appropriateness Tool for Co‐morbid Health conditions in Dementia criteria. The statements were in the broad themes of preventative medication, symptom management, disease progression, psychoactive medication, treatment goals, principles of medication use, side‐effects and medication reviews.

Discussion

This research provides consensus‐based guidance for clinicians who manage co‐morbid health conditions in people with dementia.
Return to sender: the need to re‐address patient antibiotic allergy labels in Australia and New Zealand
Authors: Trubiano J. A. , Worth L. J. , Urbancic K. , Brown T. M. , Paterson D. L. ,   on behalf of the Australasian Society for Infectious Diseases Clinical Research Network, Lucas M. ,   on behalf of the Australasian Society of Clinical Immunology and Allergy, Phillips E.
Published: August 2016

Background/Aim

Antibiotic allergies are frequently reported and have significant impacts upon appropriate prescribing and clinical outcomes. We surveyed infectious diseases physicians, allergists, clinical immunologists and hospital pharmacists to evaluate antibiotic allergy knowledge and service delivery in Australia and New Zealand.

Methods

An online multi‐choice questionnaire was developed and endorsed by representatives of the Australasian Society of Clinical Immunology and Allergy (ASCIA) and the Australasian Society of Infectious Diseases (ASID). The 37‐item survey was distributed in April 2015 to members of ASCIA, ASID, the Society of Hospital Pharmacists of Australia and the Royal Australasian College of Physicians.

Results

Of 277 respondents, 94% currently use or would utilise antibiotic allergy testing (AAT) and reported seeing up to 10 patients/week labelled as antibiotic‐allergic. Forty‐two per cent were not aware of or did not have AAT available. Most felt that AAT would aid antibiotic selection, antibiotic appropriateness and antimicrobial stewardship (79, 69 and 61% respectively). Patients with the histories of immediate hypersensitivity were more likely to be referred than those with delayed hypersensitivities (76 vs 41%, P = 0.0001). Lack of specialist physicians (20%) and personal experience (17%) were barriers to service delivery. A multidisciplinary approach was a preferred AAT model (53%). Knowledge gaps were identified, with the majority overestimating rates of penicillin/cephalosporin (78%), penicillin/carbapenem (57%) and penicillin/monobactam (39%) cross‐reactivity.

Conclusions

A high burden of antibiotic allergy labelling and demand for AAT is complicated by a relative lack availability or awareness of AAT services in Australia and New Zealand. Antibiotic allergy education and deployment of AAT, accessible to community and hospital‐based clinicians, may improve clinical decisions and reduce antibiotic allergy impacts. A collaborative approach involving infectious diseases physicians, pharmacists and allergists/immunologists is required.
New P–T constraints on the Tamayen glaucophane‐bearing rocks, eastern Taiwan: Perple_X modelling results and geodynamic implications
Authors: Baziotis I. , Tsai C.‐H. , Ernst W. G. , Jahn B.‐M. , Iizuka Y.
Published: August 2016

New pseudosection modelling was applied to better constrain the P–T conditions and evolution of glaucophane‐bearing rocks in the Tamayen block of the Yuli belt, recognized as the world's youngest known blueschist complex. Based on the predominant clinoamphibole, textural relationships, and mineral compositions, these glaucophane‐bearing high‐P rocks can be divided into four types. We focused on the three containing garnet. The chief phase assemblages are (in decreasing mode): amphibole + quartz + epidote + garnet + chlorite + rutile/titanite (Type‐I), phengite + amphibole + quartz + garnet + chlorite + epidote + titanite + biotite + magnetite (Type‐II), and amphibole + quartz + albite + epidote + garnet + rutile + hematite + titanite (Type‐III). Amphibole exhibits compositional zoning from core to rim as follows: glaucophane → pargasitic amphibole → actinolite (Type‐I), barroisite → Mg‐katophorite/taramite → Fe‐glaucophane (Type‐II), glaucophane → winchite (Type‐III). Using petrographic data, mineral compositions and Perple_X modelling (pseudosections and superimposed isopleths), peak P–T conditions were determined as 13 ± 1 kbar and 550 ± 40 °C for Type‐I, 10.5 ± 0.5 kbar and 560 ± 30 °C for Type‐II (thermal peak) and 11 ± 1 kbar and 530 ± 30 °C for Type‐III. The calculations yield higher pressures and temperatures than previously thought; the difference is ~1–6 kbar and 50–200 °C. The three rock types record similar P–T retrograde paths with clockwise trajectories; all rocks followed trajectories with substantial pressure decrease under near‐isothermal conditions (Type‐I and Type‐III), with the probable exception of Type‐II where decompression followed colder geotherms. The P–T paths suggest a tectonic environment in which the rocks were exhumed from maximum depths of ~45 km within a subduction channel along a relative cold geothermal gradient of ~11–14 °C km−1.
Mapping the alterations in glutamate with GluCEST MRI in a mouse model of dopamine deficiency
Authors: Bagga Puneet , Crescenzi Rachelle , Krishnamoorthy Guruprasad , Verma Gaurav , Nanga Ravi Prakash Reddy , Reddy Damodar , Greenberg Joel , Detre John A. , Hariharan Hari , Reddy Ravinder
Published: August 2016

Glutamate chemical exchange saturation transfer (GluCEST) MRI was used to measure metabolic changes in mice treated with 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) by mapping regional cerebral glutamate. The GluCEST contrast following MPTP treatment was correlated with 1H‐MR spectroscopy, motor function, and immunohistochemical measures. The GluCEST contrast was found to be significantly higher in the striatum and motor cortex of mice treated with MPTP than in controls (p < 0.001), which was confirmed by localized 1H‐MR spectroscopy. Elevated striatal GluCEST was positively associated with local astrogliosis measured by immunohistochemistry for glial fibrillary acidic protein. Additionally, a negative correlation was found between motor function, measured by the four‐limb grip strength test, and GluCEST of the striatum (R = −0.705, p < 0.001) and the motor cortex (R = −0.617, p < 0.01), suggesting a role of elevated glutamate in the abnormal cerebral motor function regulation. The GluCEST contrast and glial fibrillary acidic protein immunostaining were unaltered in the thalamus indicating glutamate elevation was localized to the striatum and the motor cortex. These findings suggest that in addition to measuring spatial changes in glutamate, GluCEST may serve as an in vivo biomarker of metabolic and functional changes that may be applied to the assessment of a broad range of neuropathologies.

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Read the Editorial Highlight for this article on page 346.
Pathogenic mechanisms of prion protein, amyloid‐β and α‐synuclein misfolding: the prion concept and neurotoxicity of protein oligomers
Authors: Ugalde Cathryn L. , Finkelstein David I. , Lawson Victoria A. , Hill Andrew F.
Published: August 2016

Proteinopathies represent a group of diseases characterized by the unregulated misfolding and aggregation of proteins. Accumulation of misfolded protein in the central nervous system (CNS) is associated with neurodegenerative diseases, such as the transmissible spongiform encephalopathies (or prion diseases), Alzheimer's disease, and the synucleinopathies (the most common of which is Parkinson's disease). Of these, the pathogenic mechanisms of prion diseases are particularly striking where the transmissible, causative agent of disease is the prion, or proteinaceous infectious particle. Prions are composed almost exclusively of PrPSc; a misfolded isoform of the normal cellular protein, PrPC, which is found accumulated in the CNS in disease. Today, mounting evidence suggests other aggregating proteins, such as amyloid‐β (Aβ) and α‐synuclein (α‐syn), proteins associated with Alzheimer's disease and synucleinopathies, respectively, share similar biophysical and biochemical properties with PrPSc that influences how they misfold, aggregate, and propagate in disease. In this regard, the definition of a ‘prion’ may ultimately expand to include other pathogenic proteins. Unifying knowledge of folded proteins may also reveal common mechanisms associated with other features of disease that are less understood, such as neurotoxicity. This review discusses the common features Aβ and α‐syn share with PrP and neurotoxic mechanisms associated with these misfolded proteins.

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Several proteins are known to misfold and accumulate in the central nervous system causing a range of neurodegenerative diseases, such as Alzheimer's, Parkinson's, and the prion diseases. Prions are transmissible misfolded conformers of the prion protein, PrP, which seed further generation of infectious proteins. Similar effects have recently been observed in proteins associated with Alzheimer's disease and the synucleinopathies, leading to the proposition that the definition of a ‘prion’ may ultimately expand to include other pathogenic proteins. Unifying knowledge of misfolded proteins may also reveal common mechanisms associated with other features of disease that are less understood, such as neurotoxicity.
Heterologous regulation of the cannabinoid type 1 receptor by angiotensin II in astrocytes of spontaneously hypertensive rats
Authors: Haspula Dhanush , Clark Michelle A.
Published: August 2016

Brainstem and cerebellar astrocytes have critical roles to play in hypertension and attention‐deficit hyperactivity disorder, respectively. Angiotensin (Ang) II, via the astroglial Ang type 1 receptor (AT1R), has been demonstrated to elevate pro‐inflammatory mediators in the brainstem and the cerebellum. The activation of astroglial cannabinoid type 1 receptor (CB1R), a master regulator of homeostasis, has been shown to neutralize inflammatory states. Factors that drive disease progression are known to alter the expression of CB1Rs. In this study, we investigated the role of Ang II in regulating CB1R protein and mRNA expression in astrocytes isolated from the brainstem and the cerebellum of spontaneously hypertensive rats (SHRs). The results were then compared with their normotensive counterpart, Wistar rats. Not only was the basal expression of CB1R protein and mRNA significantly lower in SHR brainstem astrocytes, but treatment with Ang II resulted in lowering it further in the initial 12 h. In the case of cerebellum, Ang II up‐regulated the CB1R protein and mRNA in SHR astrocytes. While the effect of Ang II on CB1R protein was predominantly mediated via the AT1R in SHR brainstem; both AT1R‐ and AT2R‐mediated Ang II's effect in the SHR cerebellum. These data are strongly indicative of a potential new mode of cross‐talk between components of the renin angiotensin system and the endocannabinoid system in astrocytes. The consequence of such a cross‐talk could be a potential reduced endocannabinoid tone in brainstem in hypertensive states, but not in the cerebellum under the same conditions.

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Analysis of pregnancy outcome and decline of anti‐Müllerian hormone after laparoscopic cystectomy for ovarian endometriomas
Authors: Taniguchi Fuminori , Sakamoto Yasuko , Yabuta Yuko , Azuma Yukihiro , Hirakawa Eriko , Nagira Kei , Uegaki Takashi , Deura Imari , Hata Koukichi , Harada Tasuku
Published: August 2016

Aim

Excision of ovarian endometrioma (OE) may induce the reduction of ovarian reserve. We evaluated pregnancy outcomes after laparoscopic cystectomy (LC), and the pre‐ and postoperative levels of anti‐Müllerian hormone (AMH) to consider the ovarian reserve.

Methods

We enrolled 40 women with OE and 16 women with benign ovarian tumors who hoped to have a child and who underwent LC. To evaluate the ovarian reserve of 40 patients (OE group, n = 24; non‐OE group, n = 16), we measured serum AMH levels before and after the surgery.

Results

In the 40 women who underwent LC for OE, the cumulative pregnancy rate was 50%. Prior to the cystectomy, serum AMH levels in the OE group, especially in patients over the age of 35, were significantly lower than those in the non‐OE group. Rate of decline in serum AMH in the OE group was significant compared with that in the non‐OE group 6 months after surgery. In patients over the age of 35 in the OE group, AMH levels 1 year after surgery decreased noticeably.

Conclusion

LC for OE could be a preferred surgical approach, but effective therapeutic strategies will have to be developed to prevent damage to the ovarian reserve, especially for older patients.
Survey of attitudes of Chinese perinatologists and obstetricians toward non‐invasive prenatal genetic testing
Authors: Zhai Jinguo , Cai Wenzhi , Li Cuilan , Chen Min , Huang Lijuan , Zhong Mei
Published: August 2016

Aim

The clinical application of non‐invasive prenatal testing (NIPT) is still very limited in China. We carried out a survey to assess the willingness of Chinese obstetricians to offer NIPT and to determine how they would implement it and what resources they would need for the testing.

Methods

Between June 2014 and June 2015, a survey was conducted at a large academic referral center with data obtained from 392 registered perinatologists and obstetricians who completed an entire questionnaire.

Results

Most respondents (72.5%) agreed or strongly agreed that the percentage of women patients refusing to accept NIPT would increase if they were charged directly for the test. Most respondents (82.7%) answered affirmatively that the national health administration agencies should formulate a standard charge for NIPT. The most important factors that influence the application of NIPT are the popularity of the test and its cost. The majority of respondents indicated that there are appropriate reasons for NIPT.

Conclusion

The importance of NIPT and guidelines for the application of NIPT should be clarified in current clinical practice in China. Extensive education regarding NIPT application is necessary prior to mass implementation.
Perinatal outcomes of abnormal umbilical coiling according to a modified umbilical coiling index
Authors: Ohno Yasumasa , Terauchi Mikio , Tamakoshi Koji
Published: August 2016

Aim

The aim of this study was to determine the relation between perinatal outcomes and umbilical cord coiling as evaluated by a modified umbilical coiling index.

Methods

In this retrospective study, 200 consecutive umbilical cords were examined. An umbilical venous and arterial coiling index was calculated by dividing the total number of umbilical venous and arterial coils by the length of cord individually. Umbilical cords with umbilical venous coiling indices in the lowest decile, the highest decile, and the remaining deciles were defined as hypocoiled, hypercoiled, and normocoiled, respectively. The perinatal outcomes of the subjects with hypocoiled and hypercoiled umbilical cords were compared with those with normocoiled umbilical cords.

Results

In 69.5% of subjects, a difference in the degree of coiling was detected between the umbilical veins and arteries. While all umbilical venous twisting demonstrated the same direction, the direction of the arterial twisting reversed at a certain point along the umbilical cord in 19.0% of the subjects. The arteriovenous coiling difference was small in the hypercoiled group and large in the hypocoiled group. A hypocoiled umbilical cord evaluated by umbilical venous coiling index was found to be associated with prolonged deceleration (odds ratio [OR], 4.18; 95% confidence interval [CI], 1.54–11.38), operative delivery (OR, 2.67; 95%CI, 1.01–7.09), and nuchal cord entanglement (OR, 3.21; 95%CI, 1.23–8.33).

Conclusion

Umbilical coiling abnormalities were investigated using a novel umbilical venous coiling index. A hypocoiled umbilical cord evaluated by umbilical venous coiling index was found to be associated with fetal heart rate abnormalities, operative delivery, and nuchal cord entanglement.
Current status of fetal neurodevelopmental assessment: Four‐dimensional ultrasound study
Authors: Hata Toshiyuki
Published: August 2016

With the latest advent of four‐dimensional (4‐D) ultrasound, fetal neurobehavioral or neurodevelopmental assessment can be easily and readily performed. Using this technique, typical fetal movements and behavioral patterns have become apparent in all three trimesters of pregnancy. In twin pregnancy, 4‐D ultrasound facilitates the precise evaluation of inter‐twin contact and intra‐pair stimulation. New fetal neurobehavioral assessment tests, such as Kurjak's Antenatal Neurodevelopmental Test and the Fetal Observable Movement System, may reflect the normal and abnormal neurological development of the fetus, and will facilitate more precise assessments of fetal neurobehavior or neurodevelopment, and fetal brain and central nervous system functions. In this review article, I also discuss interesting topics regarding maternal and fetal stress, fetal pain, and fetal consciousness. Four‐dimensional ultrasound has opened the door to new scientific fields, such as ‘fetal neurology’ and ‘fetal psychology,’ and fetal neurobehavioral science is at the dawn of a new era. Knowledge on fetal neurobehavior and neurodevelopment will be advanced through fetal behavioral research using this technique.
Oncologic and obstetric outcomes of early stage cervical cancer with abdominal radical trachelectomy: Single‐institution experience
Authors: Tamauchi Satoshi , Kajiyama Hiroaki , Sakata Jun , Sekiya Ryuichiro , Suzuki Shiro , Mizuno Mika , Utsumi Fumi , Niimi Kaoru , Kotani Tomomi , Shibata Kiyosumi , Kikkawa Fumitaka
Published: August 2016

Aim

Radical trachelectomy (RT) is a widely used fertility‐sparing treatment for patients with early cervical cancer (CCA). RT, however, is an investigational treatment, and its gynecological and obstetric efficacy are being investigated. We retrospectively assessed the efficacy of abdominal RT (ART) as a fertility‐sparing surgery.

Methods

From 2010 to 2014, patients with stage IA2–IB1 CCA (tumor ≤2 cm) who wished to preserve their fertility underwent ART. The major outcomes were mortality, recurrence, pregnancy complications, and obstetric outcome.

Results

Twenty‐eight patients received ART. Adjuvant chemotherapy was performed in seven patients because of lymphovascular space invasion. During the median follow‐up of 43 months, no recurrences occurred. Twelve women attempted to conceive, and eight of them became pregnant. A total of five children were born, and one baby was full term. Three cases of second trimester, and one case of third trimester preterm births were recorded.

Conclusions

Fertility was preserved after ART in a moderate number of patients. The pregnancy and birth rates after ART have been improving, and increasing the full‐term birth rate is the next goal. In addition, development of further types of minimally invasive surgery for CCA can be expected.
Effect of medical institution change on gestational duration after the Great East Japan Earthquake: The Fukushima Health Management Survey
Authors: Suzuki Kohta , Goto Aya , Fujimori Keiya
Published: August 2016

Aim

The aim of this study was to examine the association between medical institution change for perinatal care and gestational duration after the Great East Japan Earthquake using data from the Fukushima Health Management Survey.

Methods

The data of pregnant women who experienced the earthquake in Fukushima prefecture and participated in the Pregnancy and Birth Survey as part of the Fukushima Health Management Survey were analyzed. The primary and secondary outcomes of this study were gestational duration and preterm birth, respectively. The main study factor was prenatal checkup institution (only one institution, changed institution due to self‐referral, changed institution due to medical indication, and went to parents' home for childbirth). Self‐referral was considered as indicative of relocation after the disaster. Multiple linear and logistic regression analyses were conducted to examine the effect of earthquake on each outcome.

Results

A total of 5593 (60.2%) participants experienced the earthquake between the 4th and 37th weeks of their gestational period. After controlling for variables, pregnant women who changed their perinatal checkup institution due to medical indication were significantly associated with shorter gestational duration (β = −10.6, P < 0.001) and preterm birth (adjusted odds ratio, 8.5; 95% confidence interval, 5.8–12.5) compared with women who visited only one institution. Self‐referral, however, was not significantly associated with the outcomes.

Conclusion

According to prenatal checkup status, our results suggest that the effect on gestational duration of the Great East Japan Earthquake and the subsequent Fukushima Daiichi nuclear disaster was not significant.
Successful conservative management of placenta percreta: Investigation by serial magnetic resonance imaging of the clinical course and a literature review
Authors: Sawada Masaaki , Matsuzaki Shinya , Mimura Kazuya , Kumasawa Keiichi , Endo Masayuki , Kimura Tadashi
Published: August 2016

Placenta percreta is a rare condition that presents a risk of massive intraoperative hemorrhage. To decrease maternal morbidity in such cases, conservative management was recently adopted as an option. Nevertheless, severe morbidity occurs in 42% of cases. In addition, the clinical course of conservative management remains unclear. We encountered a case of placenta percreta that was successfully treated by conservative management without complications or other clinical interventions. Serial magnetic resonance imaging (MRI) was performed to investigate the natural course of conservative management of placenta percreta. MRI on postoperative day (POD) 99 showed a decrease in placental size without gadolinium enhancement. MRI on POD 162 showed that the residual placenta was approximately 4 cm in size without gadolinium enhancement. On POD 265, the placenta had almost disappeared. This is the first series of MRI of conservative management of placenta percreta without clinical interventions. We present our case and a literature review.
LAMC2 is a predictive marker for the malignant progression of leukoplakia
Authors: Nguyen Chi Thi Kim , Okamura Takeshi , Morita Kei‐ichi , Yamaguchi Satoshi , Harada Hiroyuki , Miki Yoshio , Izumo Toshiyuki , Kayamori Kou , Yamaguchi Akira , Sakamoto Kei
Published: August 2016

Background

LAMC2 plays an important role in cancer invasion. The aim of this study was to (i) compare the immunoexpression of LAMC2 in different stages of oral squamous cell carcinoma (OSCC), early and advanced, and (ii) to evaluate LAMC2 as a marker of malignant transformation in leukoplakia.

Materials and Methods

The expression of LAMC2 was examined by immunohistochemistry in 50 surgical specimens of advanced OSCC assembled as tissue microarrays, and by cDNA microarray in 43 surgical specimens of advanced OSCC. LAMC2 expression was further examined in 39 surgical specimens of early OSCC and in 93 incisional biopsy specimens of leukoplakia of the tongue, which exhibited epithelial dysplasia. The relationship of LAMC2 expression score with clinico‐pathological characteristics was analyzed.

Results

LAMC2 was remarkably upregulated in OSCC at the cancer–stroma interface. The grade of LAMC2 expression was significantly associated with the pattern and depth of invasion of OSCC. Foci of LAMC2‐positive cells were observed in some cases of leukoplakia. The number and size of LAMC2‐positive foci were significantly associated with the grade of dysplasia. The presence of LAMC2‐positive foci was a significant predictive factor for the malignant progression of leukoplakia. LAMC2‐positive leukoplakia had an approximately 11‐fold increased risk of malignancy compared with LAMC2‐negative leukoplakia.

Conclusions

The results of this study highlight the value of LAMC2 as a marker of cancer invasion. LAMC2‐positive foci in leukoplakia suggest an imminent risk of cancer. LAMC2 immunostaining is expected to contribute to a more precise assessment of the malignancy of leukoplakia.
SPATIAL DISCONTINUITY FOR THE IMPACT ASSESSMENT OF THE EU REGIONAL POLICY: THE CASE OF ITALIAN OBJECTIVE 1 REGIONS*
Authors: Giua Mara
Published: August 2016

The economic impact of the Regional Policy of the European Union is still controversial. This paper exploits administrative boundaries as spatial discontinuity to estimate the causal effect of this policy on the Italian Objective 1 regions’ employment. The analysis, developed both in a border strategy framework (municipalities contiguous to the policy‐change boundary) and with more traditional RDD models balanced by spatial forcing variables (centroids’ distance and coordinates), shows that the EU Regional Policy produced a positive impact on employment levels, without any displacement of economic activities away from nontreated regions and a concentration of the impact in key economic sectors.
Asymmetric Punishment as an Instrument of Corruption Control
Authors: BASU KARNA , BASU KAUSHIK , CORDELLA TITO
Published: August 2016

The control of bribery is a policy objective in many developing countries. It has been argued that asymmetric punishments could reduce bribery by incentivizing whistle‐blowing. This paper investigates the role played by asymmetric punishment in a setting where bribe size is determined by Nash bargaining, detection is costly, and detection rates are set endogenously. First, if whistle‐blowing is infeasible, the symmetry properties of punishment are irrelevant to bribery deterrence but not to bribe size. Bribery disappears if expected penalties are sufficiently high; otherwise, bribe sizes rise as expected penalties rise. Second, when the bribe‐giver may whistle‐blow, a switch from symmetric to asymmetric punishment eliminates bribery only if whistle‐blowing is cheap and the stakes are low. When bribery persists, multiple bribe sizes could survive in equilibrium. The paper derives parameter values under which each of these outcomes occurs, and discusses implications for welfare and the design of policy.
The role of negative and positive memories in fear of dental treatment
Authors: Risløv Staugaard Søren , Jøssing Marit , Krohn Christina
Published: August 2016

Objectives

Most young adults transition from childhood dental care to adult dental care without problems. However, a substantial minority leaves childhood dental care with considerable fear of dental treatment. In the present study, we hypothesized that fear of dental treatment in the young adult is influenced by memories of positive and negative childhood experiences with dental care. More specifically, we predicted that the emotional impact, sense of reliving, rehearsal, and belief in the accuracy of a negative treatment memory would be associated with increased dental fear, while positive treatment memories would show the opposite relation.

Methods

One hundred thirty‐six young adults leaving childhood dental care responded to a online measures of dental fear, the most negative and most positive memory of dental treatment, and symptoms of posttraumatic stress disorder.

Results

Negative memories of events that involved pain and dentist behaviors such as impatience or scolding were frequently described and significantly associated with dental fear and symptoms of posttraumatic stress. Positive memories were more frequent, but did not show a consistent relationship with dental fear.

Conclusions

The importance of negative memories suggests an avenue for intervention against dental fear that focuses on restructuring those memories to emphasize positive aspects.