bluuebunny/crossref_metadata_2025 huggingface dataset:
A Case Series of Molecular Imaging of Glucagonoma After Initial Therapy—68Ga-DOTATATE PET/CT Reveals Similar Results as in Neuroendocrine Tumors of Other Origin in Follow-up and Re-evaluation
Authors: Rottenburger Christof , Papantoniou Dimitrios , Mandair Dalvinder , Caplin Martyn , Navalkissoor Shaunak
Published: February 2018

Glucagonoma is an extremely rare, glucagon-secreting neuroendocrine tumor of the pancreas. Only sparse data are available about the characteristics of this tumor in somatostatin receptor imaging and only for the situation of initial diagnosis. We present a series of 3 glucagonoma patients who underwent at least 1 68Ga-DOTATATE PET/CT scan. All patients were diagnosed by either histology and/or elevated serum levels of glucagon. The presented cases suggest that somatostatin receptor–based imaging can probably be used for re-evaluation of disease status in patients with glucagonoma in a similar way as it is already established for neuroendocrine tumors of other origin.
Association Between Macroscopic Tongue Ischemia and Enterocyte Injury and Poor Outcome in Patients With Septic Shock: A Preliminary Observational Study
Authors: Sekino Motohiro , Funaoka Hiroyuki , Sato Shuntaro , Okada Kyoko , Inoue Haruka , Yano Rintaro , Matsumoto Sojiro , Ichinomiya Taiga , Higashijima Ushio , Matsumoto Shuhei , Hara Tetsuya
Published: February 2018

A correlation between sublingual and intestinal mucosa microcirculation, and ischemic necrosis of the tongue as a sign of poor prognosis has been reported. However, an association between tongue ischemia and intestinal health and subsequent outcome has never been studied. This preliminary prospective observational study evaluated the association between macroscopic tongue ischemia and enterocyte injury and poor outcome in patients with septic shock. In this study, 57 adults with septic shock on mechanical ventilators were enrolled. Macroscopic tongue ischemia upon intensive care unit (ICU) admission was assessed by two independent intensivists. We used intestinal fatty-acid binding protein (I-FABP) as a biomarker of enterocyte injury and evaluated the association with tongue ischemia. Demographic variables, risk factor data, and 28-day mortality information were also collected. Compared with patients with normal tongues (n = 45), those with ischemic tongues (n = 12) had a significantly higher Acute Physiology and Chronic Health Evaluation II score (29.0 [25.0–34.0] vs. 36.5 [30.5–44.5], P = 0.017), lactate level (2.8 [2.0–5.0] vs. 9.3 [4.5–10.6], P = 0.002), and I-FABP level (1.9 [0.8–4.0] vs. 54.4 [19.5–159.3], P < 0.001) and the all-cause 28-day mortality was significantly higher (7% vs. 83%, P < 0.001). In conclusion, macroscopic tongue ischemia at ICU admission was associated with enterocyte injury and poor outcome in patients with septic shock. Although there is a disadvantage in that assessment of the tongue was subjective, tongue ischemia could be used to gauge the severity of intestinal injury and to estimate poor outcome in the clinical setting.
Surgeon, Hospital, and Geographic Variation in Minimally Invasive Colectomy
Authors: Aquina Christopher T. , Becerra Adan Z. , Justiniano Carla F. , Xu Zhaomin , Boscoe Francis P. , Schymura Maria J. , Noyes Katia , Monson John R. T. , Temple Larissa K. , Fleming Fergal J.
Published: February 2018

Objective:

To identify sources of variation in the use of minimally invasive surgery (MIS) for colectomy.

Background:

MIS is associated with decreased analgesic use, shorter length of stay, and faster postoperative recovery. This study identified factors explaining variation in MIS use for colectomy.

Methods:

The Statewide Planning and Research Cooperative System was queried for scheduled admissions in which a colectomy was performed for neoplastic, diverticular, or inflammatory bowel disease between 2008 and 2015. Mixed-effects analyses were performed assessing surgeon, hospital, and geographic variation and factors associated with an MIS approach.

Results:

Among 45,714 colectomies, 68.1% were performed using an MIS approach. Wide variation in the rate of MIS was present across 1253 surgeons (median 50%, interquartile range 10.9%–84.2%, range 0.3%–99.7%). Calculating intraclass correlation coefficients after controlling for case-mix, 62.8% of the total variation in MIS usage was attributable to surgeon variation compared with 28.5% attributable to patient variation, 7% attributable to hospital variation, and 1.6% attributable to geographic variation. Surgeon-years in practice since residency/fellowship completion explained 19.2% of the surgeon variation, surgeon volume explained 5.2%, hospital factors explained 0.1%, and patient factors explained 0%.

Conclusions:

Wide surgeon variation exists regarding an MIS approach for colectomy, and most of the total variation is attributable to individual surgeon practices—much of which is related to year of graduation. As increasing surgeon age is inversely proportional to the rate of MIS, patient referral and/or providing tailored training to older surgeons may be constructive targets in increasing the use of MIS and reducing healthcare utilization.
Nonsteroidal anti-inflammatory drugs and cancer pain
Authors: Strawson Jenny
Published: February 2018

Purpose of review

This review aims to appraise the most recent evidence for the use of NSAIDS in cancer pain.

Recent findings

The Cochrane review reveals the paucity of high-quality evidence for the use of NSAIDS for cancer pain, highlighting methodological considerations for future research. There is limited evidence for the role of combined NSAIDs (celecoxib and diclofenac) alongside opioids for cancer pain. Recent retrospective data suggests NSAIDS may contribute to better pain control in hospitalized patients. In elderly patients in the last weeks of life, retrospective data shows a reduction in NSAID prescribing, without significant implications for pain relief. A recent systematic review looking at the increased risk of anastomotic leaks versus the survival benefits in cancer patients prescribed NSAIDs post oncological surgery was inconclusive. Considering the prescription of PPIs for gastroprotection, studies in the general population suggest potential risks of long-term use, including renal dysfunction and greater risk of fractures. Although current evidence for the anticancer properties of NSAIDS is based on retrospective cohort studies, there may be a role for aspirin and nonaspirin NSAIDs in reducing the risk of cancer.

Given the lack of quality evidence, NSAIDS should be prescribed on a case by case basis in discussion with the patient, with regular review of efficacy, whilst balancing the ongoing benefits and risks of continued use, taking into account the patient's likely prognosis.
Systematic review of prehospital tourniquet use in civilian limb trauma
Authors: Kauvar David S. , Dubick Michael A. , Walters Thomas J. , Kragh John F.
Published: February 2018

BACKGROUND

Military enthusiasm for limb tourniquet use in combat casualty care has resulted in acceptance by the trauma community for use in the prehospital care of civilian limb injuries. To date, there has been no report synthesizing the published data on civilian tourniquet use. The objective of this systematic review was to compile and analyze the content and quality of published data on the civilian use of tourniquets in limb trauma.

METHODS

The MEDLINE database was searched for studies on civilian limb tourniquet use in adults published between 2001 and 2017. Search terms were tourniquet, trauma, and injury. Military reports and case series lacking systematic data collection were excluded. Counts and percentages were aggregated and weighted for analysis.

RESULTS

Reports were included from six regional trauma centers and one interregional collaboration (total of 572 cases). One national prehospital database report was included but analyzed separately (2,048 cases). All were retrospective cohort studies without prospective data collection. Three reports defined a primary outcome, two had a nontourniquet control group, and no two articles reported the same variables. Limb injury severity and characteristics were inconsistently and incompletely described across reports, as were tourniquet indications and effectiveness. Arterial injury was reported in two studies and was infrequent among cases of tourniquet use. Mortality was low, and limb-specific complications were infrequent but variably reported.

CONCLUSION

The rapid increase in the civilian use of tourniquets for limb hemorrhage control has occurred without a large amount or high quality of data. Adoption of a multicenter registry with standardized data collection specific to limb trauma and tourniquet use can serve to improve the trauma community's understanding of the safety and effectiveness of tourniquet use in civilian trauma settings.

LEVEL OF EVIDENCE

Systematic review, level IV.
Electroencephalography, magnetoencephalography and source localization: their value in epilepsy
Authors: Mégevand Pierre , Seeck Margitta
Published: February 2018

Purpose of review

Source localization of cerebral activity using electroencephalography (EEG) or magnetoencephalography (MEG) can reveal noninvasively the generators of the abnormal signals recorded in epilepsy, such as interictal epileptic discharges (IEDs) and seizures. Here, we review recent progress showcasing the usefulness of these techniques in treating patients with drug-resistant epilepsy.

Recent findings

The source localization of IEDs by high-density EEG and MEG has now been proved in large patient cohorts to be accurate and clinically relevant, with positive and negative predictive values rivaling those of structural MRI. Localizing seizure onsets is an emerging technique that seems to perform similarly well to the localization of interictal spikes, although there remain questions regarding the processing of signals for reliable results. The localization of somatosensory cortex using EEG/MEG is well established. The localization of language cortex is less reliable, although progress has been made regarding hemispheric lateralization. Source localization is also able to reveal how epilepsy alters the dynamics of neuronal activity in the large-scale networks that underlie cerebral function.

Given the high performance of EEG/MEG source localization, these tools should find a place similar to that of established techniques like MRI in the assessment of patients for epilepsy surgery.
Allergy to Carbidopa
Authors: Cansino-Torres Mariana Aurora , Sandoval-Rodríguez Valeria , Sáenz-Farret Michel , Zúñiga-Ramírez Carlos
Published: February 2018

Background

d-Decarboxylase inhibitors, such as carbidopa or benserazide, have been used as adjunct therapy in Parkinson disease shortly after levodopa synthesis in the 1960s. These compounds increase intracerebral drug concentration and decrease adverse effects by blocking peripheral conversion to dopamine. Skin rash as part of an allergic reaction was previously described in subjects who were using levodopa in combination with carbidopa or benserazide; however, etiology was never clear. Allergic reactions to carbidopa have not previously been reported.

Methods

We report a case of a 77-year-old woman with a diagnosis of idiopathic Parkinson disease, who developed autonomic and dermatological signs: conjunctival injection, rhinorrhea, excessive sweating, hypertension, and pruritic generalized rash, among others, immediately after carbidopa/levodopa administration regardless of the manufacturer. Treatment with dexamethasone combined with chloropyramine hydrochloride resulted in complete resolution of the hypersensitivity reaction each time it presented. The autonomic and dermatological manifestations did not reappear after treatment was replaced with benserazide/levodopa.

Conclusions

To the best of our knowledge, this is the first case report of an allergic reaction specific to carbidopa. Our case highlights the importance of identifying the source of a hypersensitivity drug response, whether it is caused by the active component or by the excipients.
Competition‐driven niche segregation on a landscape scale: Evidence for escaping from syntopy towards allotopy in two coexisting sibling passerine species
Authors: Reif Jiří , Reifová Radka , Skoracka Anna , Kuczyński Lechosław
Published: February 2018

The role of interspecific competition for generating patterns in species’ distribution is hotly debated and studies taking into account processes occurring at both large and small spatial scales are almost missing. Theoretically, competition between species with overlapping niches should result in divergence of their niches in sympatry to reduce the costs of competition. Many species show a mosaic distribution within sympatric zones, with the syntopic sites occupied by both species, and allotopic sites where only one species occurs. It is unclear whether such mosaics arise as a consequence of competition‐driven niche segregation or due to the decline of their abundances towards range edges driven by environmental gradients.

If the interspecific competition matters, we should observe (1) a shift in habitat preferences of one or both species between syntopy and allotopy, and (2) between allopatry and allotopy. Moreover, (3) species should show greater divergence in their habitat preferences in allotopy than in allopatry where (4) no differences in habitat preferences may occur. Finally, (5) shifts should be generally greater in the competitively subordinate species than in the dominant species.

We used a unique dataset on abundance of two closely related passerine species, the Common Nightingale (Luscinia megarhynchos) and the Thrush Nightingale (Luscinia luscinia), collected across their syntopy, allotopy and allopatry. The predictions were tested within a generalized mixed‐effects modelling framework.

After accounting for environmental gradients perpendicular to the species’ contact zone, we found a strong support for all but one prediction. Habitat preferences of both species shifted markedly between syntopy and allotopy, as well as between allopatry and allotopy. Whereas the species preferred the same habitats in allopatry, their preferences became strikingly different in allotopy where the abundance of the Common Nightingale increased towards dry and warm sites with low coverage of pastures, while the abundance of the Thrush Nightingale showed exactly opposite trends. Fifth prediction was not supported.

Our results indicate that the competition between closely related species can result in considerable changes in habitat use across their geographic ranges accompanied with divergence in their habitat preferences in sympatry. Here, the species “escape” from competition to allotopic sites covered by habitats avoided by the competitor. Therefore, we argue that the interspecific competition is an important driver of species’ distribution at both large and small spatial scales.
Perinatal outcome of monochorionic and dichorionic twins after spontaneous and assisted conception: a retrospective cohort study
Authors: Hack Karien E.A. , Vereycken Marijn E.M.S. , Torrance Helen L. , Koopman‐Esseboom Corine , Derks Jan B.
Published: February 2018

Introduction

The aim of this study was to compare pregnancy outcomes in twin pregnancies after assisted conception and spontaneous conception, according to chorionicity.

Material and methods

Retrospective cohort study of 1305 twin pregnancies between 1995 and 2015. All spontaneous (n = 731) and assisted conception conceived (n = 574) twin pregnancies with antenatal care and delivery in University Medical Center Utrecht, the Netherlands, a tertiary obstetric care center were studied according to chorionicity.

Results

Maternal age and incidence of nulliparity were higher among the assisted conception twins. Hypertensive disorders also appeared to be more frequent in assisted conception pregnancies, which could largely be explained by the higher proportion of elderly nulliparous women in this group. Spontaneously conceived twins were born earlier than twins after assisted conception, with subsequent lower birthweights and more admissions to a neonatal intensive care unit with increased neonatal morbidity. Monochorionic twins had worse pregnancy outcomes compared with dichorionic twins, irrespective of mode of conception; monochorionic twins conceived by assisted reproduction had more neonatal morbidity (mainly respiratory distress syndrome and necrotizing enterocolitis) and late neonatal deaths compared with spontaneously conceived monochorionic twins.

Conclusions

Spontaneously conceived twins have worse pregnancy outcome compared with twins after assisted conception, probably due to a lower incidence of monochorionicity in the assisted conception group. The already increased perinatal risks in monochorionic twins are even higher in monochorionic twins conceived after infertility treatments compared with spontaneously conceived monochorionic twins, which warrants extra attention to these high‐risk pregnancies.
Effects of l‐Carnosine Supplementation on Sleep Disorders and Disease Severity in Autistic Children: A Randomized, Controlled Clinical Trial
Authors: Mehrazad‐Saber Zahra , Kheirouri Sorayya , Noorazar Seyyed‐Gholamreza
Published: February 2018

Sleep disorders are frequently reported in autistic patients. Evidences suggest that increased oxidative stress and reduced antioxidants may play a major role in the pathogenesis of these disorders. Carnosine acts as an antioxidant, antitoxic and neuroprotective agent. The aim of this trial study was to examine the effects of carnosine supplementation on the sleep disorders and severity of autism core symptoms in autistic patients. In this double‐blind, randomized clinical trial, 43 autistic patients (31 boys and 12 girls; aged 4 to 16 years) were divided into two groups of carnosine and control that received 500 mg of carnosine and 500 mg of placebo per day for 2 months, respectively. Sleep disorders were measured using Children's Sleep Habits Questionnaires. Gilliam Autism Rating Scale 2 was used to assess the effects of carnosine supplementation on the autism severity. Carnosine supplementation did not change anthropometric indices (p > 0.05) and showed no effect on autism severity (p > 0.05), whereas it significantly reduced sleep duration (p = 0.04), parasomnias (p = 0.02) and total sleep disorders score by 7.59% (p = 0.006) when compared with the control group. The results suggest that carnosine supplementation could be effective in improving sleep disturbances, in particular sleep duration and parasomnias subscales.
Characterization of the depocenters and the basement structure, below the central Chile Andean Forearc: A 3D geophysical modelling in Santiago Basin area
Authors: González Felipe Andrés , Maksymowicz Andrei , Díaz Daniel , Villegas Luis , Leiva Maximiliano , Blanco Bárbara , Vera Emilio , Contreras Sergio , Cabrera Daniel , Bonvalot Sylvain
Published: February 2018

Since the last century, several geological and geophysical studies have been developed in the Santiago Basin to understand its morphology and tectonic evolution. However, some uncertainties regarding sedimentary fill properties and possible density anomalies below the sediments/basement boundary remain. Considering that this is an area densely populated with more than 6 million inhabitants in a highly active seismotectonic environment, the physical properties of the Santiago Basin are important to study the geological and structural evolution of the Andean forearc and to characterize its seismic response and related seismic hazard. Two and three‐dimensional gravimetric models were developed, based on a database of 797 compiled and 883 newly acquired gravity stations. To produce a well‐constrained basement elevation model, a review of 499 wells and 30 transient electromagnetic soundings were used, which contribute with basement depth or minimum sedimentary thickness information. For the 2‐D modelling, a total of 49 gravimetric profiles were processed considering a homogeneous density contrast and independent regional trends. A strong positive gravity anomaly was observed in the centre of the basin, which complicated the modelling process but was carefully addressed with the available constrains. The resulting basement elevation models show complex basement geometry with, at least, eight recognizable depocenters with maximum sedimentary infill of ~ 500 m. The 3‐D density models show alignments in the basement that correlates well with important intrusive units of the Cenozoic and Mesozoic. Along with interpreted fault zones westwards and eastwards of the basin, the observations suggest a structural control of Santiago basin geometry, where recent deformation associated with the Andean contractional deformation front and old structures developed during the Cenozoic extension are superimposed to the variability of river erosion/deposition processes.
Novel 3‐substituted N‐methylcarbazole–imidazolium salt derivatives: Synthesis and cytotoxic activity
Authors: Li Yan‐Hua , Zhou Bei , Shi Yi‐Min , Xun Yu‐Peng , Yang Yun‐Han , Yang Li‐Juan
Published: February 2018

A series of novel 3‐substituted N‐methylcarbazole–imidazolium salt derivatives has been prepared and evaluated in vitro against a panel of tumor cell lines (Hep G‐2, Hela and PC12). The results suggest that the presence of substituted 2‐methyl‐imidazole or imidazole ring and substitution of the imidazolyl‐3‐position with a naphthylacyl or 4‐bromophenacyl group were important for improving cytotoxic activity. Compounds 17, 18, 27, and 28 with 4‐bromophenacyl and naphthylacyl groups displayed good activities with IC50 values of 0.09–7.20 μm against three tumor cell lines investigated and more active than DDP. Compound 35 exhibited cytotoxic activity selectively against Hela cell.
Left ventricular function of patients with pregnancy‐induced hypertension evaluated using velocity vector imaging echocardiography and N‐terminal pro‐brain natriuretic peptide
Authors: Yu Li , Zhou Qichang , Peng Qinghai , Yang Zurong
Published: February 2018

Purpose

To investigate whether acute and transient pressure overload in patients with pregnancy‐induced hypertension (PIH) affects left ventricular (LV) systolic function.

Methods

From pregnancy to 3 months after delivery, 82 patients were analyzed: 27, 25, and 30 with gestational hypertension, preeclampsia, and the healthy control group, respectively. Conventional echocardiography and velocity vector imaging (VVI) were performed, and blood levels of N‐terminal pro‐brain natriuretic peptide (NT‐pro‐BNP) were analyzed.

Results

Compared with the control group, patients with gestational hypertension had significantly lower mean LV peak global longitudinal strain. Importantly, during both pregnancy and after delivery, patients with preeclampsia had significantly lower global longitudinal, circumferential, and radial strain compared with the control group. The NT‐pro‐BNP levels were significantly higher in patients with PIH compared with normotensive pregnancies, and this situation continued for 3 months after delivery in women with preeclampsia.

Conclusions

In pregnancies complicated by pregnancy‐induced hypertension, especially preeclampsia, the systolic function is impaired and NT‐pro‐BNP levels are elevated compared with normal pregnancy. Velocity vector imaging (VVI) is more sensitive than left ventricular ejection fraction to evaluate heart function in patients with PIH.
Prenatal diagnosis of Berry syndrome by fetal echocardiography: A report of four cases
Authors: Zhang Xin , Liu Xiao‐Wei , Gu Xiao‐Yan , Han Jian‐Cheng , Hao Xiao‐Yan , Fu Yu‐Wei , He Yi‐Hua
Published: February 2018

Berry syndrome is a rare congenital cardiac malformation. We describe 4 cases of Berry syndrome diagnosed by fetal echocardiography. Based on our experience, the three‐vessel view is important for diagnosing the aortopulmonary window and aortic origin of the right pulmonary artery. Furthermore, the true cross‐sectional and sagittal views obtained by continuously scanning from the three‐vessel‐trachea view to the long‐axis view of the aortic arch are required to image the interruption or coarctation of the aortic arch. An early and accurate prenatal diagnosis of Berry syndrome is feasible and helps to improve patient outcomes.
Probing the limits of alpha power lateralisation as a neural marker of selective attention in middle‐aged and older listeners
Authors: Tune Sarah , Wöstmann Malte , Obleser Jonas
Published: February 2018

In recent years, hemispheric lateralisation of alpha power has emerged as a neural mechanism thought to underpin spatial attention across sensory modalities. Yet, how healthy ageing, beginning in middle adulthood, impacts the modulation of lateralised alpha power supporting auditory attention remains poorly understood. In the current electroencephalography study, middle‐aged and older adults (N = 29; ~40–70 years) performed a dichotic listening task that simulates a challenging, multitalker scenario. We examined the extent to which the modulation of 8–12 Hz alpha power would serve as neural marker of listening success across age. With respect to the increase in interindividual variability with age, we examined an extensive battery of behavioural, perceptual and neural measures. Similar to findings on younger adults, middle‐aged and older listeners’ auditory spatial attention induced robust lateralisation of alpha power, which synchronised with the speech rate. Notably, the observed relationship between this alpha lateralisation and task performance did not co‐vary with age. Instead, task performance was strongly related to an individual's attentional and working memory capacity. Multivariate analyses revealed a separation of neural and behavioural variables independent of age. Our results suggest that in age‐varying samples as the present one, the lateralisation of alpha power is neither a sufficient nor necessary neural strategy for an individual's auditory spatial attention, as higher age might come with increased use of alternative, compensatory mechanisms. Our findings emphasise that explaining interindividual variability will be key to understanding the role of alpha oscillations in auditory attention in the ageing listener.
GABA‐ and serotonin‐expressing neurons take part in inhibitory as well as excitatory input pathways to the circadian clock of the Madeira cockroach Rhyparobia maderae
Authors: Giese Maria , Gestrich Julia , Massah Azar , Peterle Jonas , Wei HongYing , Stengl Monika
Published: February 2018

In the Madeira cockroach, pigment‐dispersing factor‐immunoreactive (PDF‐ir) neurons innervating the circadian clock, the accessory medulla (AME) in the brain′s optic lobes, control circadian behaviour. Circadian activity rhythms are entrained to daily light–dark cycles only by compound eye photoreceptors terminating in the lamina and medulla. Still, it is unknown which neurons connect the photoreceptors to the clock to allow for light entrainment. Here, we characterized by multiple‐label immunocytochemistry the serotonin (5‐HT)‐ir anterior fibre fan and GABA‐ir pathways connecting the AME‐ and optic lobe neuropils. Colocalization of 5‐HT with PDF was confirmed in PDF‐ir lamina neurons (PDFLAs). Double‐labelled fibres were traced to the AME originating from colabelled PDFLAs branching in accessory laminae and proximal lamina. The newly discovered GABA‐ir medial layer fibre tract connected the AME to the medulla′s medial layer fibre system, and the distal tract fibres connected the AME to the medulla. With Ca2+ imaging on primary cell cultures of the AME and with loose‐patch‐clamp recordings in vivo, we showed that both neurotransmitters either excite or inhibit AME clock neurons. Because we found no colocalization of GABA and 5‐HT in any optic lobe neuron, GABA‐ and 5‐HT neurons form separate clock input circuits. Among others, both pathways converged also on AME neurons that coexpressed mostly inhibitory GABA‐ and excitatory 5‐HT receptors. Our physiological and immunocytochemical studies demonstrate that GABA‐ and 5‐HT‐immunoreactive neurons constitute parallel excitatory or inhibitory pathways connecting the circadian clock either to the lamina or medulla where photic information from the compound eye is processed.
Imoxin attenuates high fructose‐induced oxidative stress and apoptosis in renal epithelial cells via downregulation of protein kinase R pathway
Authors: Kalra Jaspreet , Mangali Suresh Babu , Bhat Audesh , Dhar Indu , Udumula Mary Priyanka , Dhar Arti
Published: February 2018

Double‐stranded RNA (dsRNA)‐activated protein kinase R (PKR), a ubiquitously expressed serine/threonine kinase, is a key inducer of inflammation, insulin resistance, and glucose homeostasis in obesity. Recent studies have demonstrated that PKR can respond to metabolic stress in mice as well as in humans. However, the underlying molecular mechanism is not fully understood. The aim of this study was to examine the effect of high fructose (HF) in cultured renal tubular epithelial cells (NRK‐52E) derived from rat kidney and to investigate whether inhibition of PKR could prevent any deleterious effects of HF in these cells. PKR expression was determined by immunofluorescence staining and Western blotting. Oxidative damage and apoptosis were measured by flow cytometry. HF‐treated renal cells developed a significant increase in PKR expression. A significant increase in reactive oxygen species generation and apoptosis was also observed in HF‐treated cultured renal epithelial cells. All these effects of HF were attenuated by a selective PKR inhibitor, imoxin (C16). In conclusion, our study demonstrates PKR induces oxidative stress and apoptosis, is a significant contributor involved in vascular complications and is a possible mediator of HF‐induced hypertension. Inhibition of PKR pathway can be used as a therapeutic strategy for the treatment of cardiovascular and metabolic disorders.
The C‐terminal cytosolic domain of the human zinc transporter ZnT8 and its diabetes risk variant
Authors: Parsons Douglas S. , Hogstrand Christer , Maret Wolfgang
Published: February 2018

A significant aspect of the control of cellular zinc in eukarya is its subcellular re‐distribution. One of the four human vesicular zinc transporters, ZnT8, supplies the millimolar zinc concentrations of insulin granules in pancreatic β‐cells, affecting insulin processing, crystallisation and secretion. ZnT8 has a transmembrane and a C‐terminal cytosolic domain; the latter has important functions and purportedly mediates protein–protein interactions, senses cytosolic zinc and/or channels zinc to the transport site in the transmembrane domain (TMD). A common variant W325R in the C‐terminal domain (CTD) increases the risk to develop type 2 diabetes and affects autoantibody specificity in type 1 diabetes. To investigate the differences between the two protein variants, we purified and biophysically characterised both variants of the ZnT8 CTD [R325 variant of ZnT8 CTD (aa267–369) (ZnT8cR) and W325 variant of ZnT8 CTD (aa267–369) (ZnT8cW)]. The domains fold independently of the TMD. Remarkably, the ZnT8cW variant (diabetes protection in the full‐length protein) is less thermostable than the ZnT8cR variant (diabetes risk in the full‐length protein). The ZnT8cW monomers associate with higher affinity. Both CTD variants bind zinc with a stoichiometry that differs from bacterial homologues, emphasising the limitation of the latter as models for the structure and function of the human proteins. The relatively small but reproducible differences between the two ZnT8 CTD variants begin to provide a molecular basis for the different diabetes susceptibility caused by the full‐length ZnT8 proteins.
Malignant mesothelioma with squamous differentiation
Authors: Tanaka Hiroyuki , Akiyama Yutaka , Kitamura Akiko , Matsumoto Nobuhiro , Tomita Masaki , Kataoka Hiroaki
Published: February 2018

Aims

We report the autopsy findings of a 58‐year‐old man with malignant mesothelioma in the left pleural cavity.

Methods and results

The patient had a history of asbestos exposure, and the chest computed tomography scan on initial admission demonstrated an extrapleural sign, suggesting a nodular lesion in the chest wall. However, no nodular lesions were detectable in either of his lungs. In spite of chemotherapy, he died 4 months after the initial admission. An autopsy revealed markedly thickened pleura in a large section of the left pleural cavity without visible intrapulmonary primary tumour lesions. Histological examination of a biopsy specimen obtained prior to chemotherapy and that of an autopsy specimen showed that the pleural tumour was composed of a mixture of mesothelioma and tumour cells with squamous differentiation mimicking squamous cell carcinoma.

Conclusions

To the best of our knowledge, this is the first case report of mesothelioma with extensive squamous differentiation in the English‐language literature. The extensive squamous differentiation reminiscent of squamous cell carcinoma can be a pitfall in the pathological diagnosis of pleural cytology and that of biopsy specimens from patients with mesothelioma. Here, we report autopsy findings of a case of malignant mesothelioma with portions of extensive squamous differentiation, mimicking a squamous cell carcinoma.
A monoclonal antibody against SV40 large T antigen (PAb416) does not label Merkel cell carcinoma
Authors: Pelletier Daniel J , Czeczok Thomas W , Bellizzi Andrew M
Published: February 2018

Aims

Merkel cell carcinoma represents poorly differentiated neuroendocrine carcinoma of cutaneous origin. In most studies, the vast majority of Merkel cell carcinomas are Merkel cell polyomavirus (MCPyV)‐associated. SV40 polyomavirus immunohistochemistry is typically used in the diagnosis of other polyomavirus‐associated diseases, including tubulointerstitial nephritis and progressive multifocal leukoencephalopathy, given cross‐reactivity with BK and JC polyomaviruses. MCPyV‐specific immunohistochemistry is commercially available, but, if antibodies against SV40 also cross‐reacted with MCPyV, that would be advantageous from a resource‐utilisation perspective.

Methods and results

Tissue microarrays were constructed from 39 Merkel cell carcinomas, 24 small‐cell lung carcinomas, and 18 extrapulmonary visceral small‐cell carcinomas. SV40 large T antigen immunohistochemistry (clone PAb416) was performed; MCPyV large T antigen immunohistochemistry (clone CM2B4) had been previously performed. UniProt was used to compare the amino acid sequences of the SV40, BK, JC and MCPyV large T antigens, focusing on areas recognised by the PAb416 and CM2B4 clones. SV40 immunohistochemistry was negative in all tumours; MCPyV immunohistochemistry was positive in 38% of Merkel cell carcinomas and in 0% of non‐cutaneous poorly differentiated neuroendocrine carcinomas. UniProt analysis revealed a high degree of similarity between SV40, BK, and JC viruses in the region recognised by PAb416. There was less homology between SV40 and MCPyV in this region, which was also interrupted by two long stretches of amino acids unique to MCPyV. The CM2B4 clone recognises a unique epitope in one of these stretches.

Conclusions

The PAb416 antibody against the SV40 large T antigen does not cross‐react with MCPyV large T antigen, and thus does not label Merkel cell carcinoma.
Enolase‐1 expression in the stratum corneum is elevated with parakeratosis of atopic dermatitis and disrupts the cellular tight junction barrier in keratinocytes
Authors: Tohgasaki T. , Ozawa N. , Yoshino T. , Ishiwatari S. , Matsukuma S. , Yanagi S. , Fukuda H.
Published: February 2018

Objective

Previous studies have shown that enolase‐1 (ENO1) in the stratum corneum (SC) is more highly expressed in patients with atopic dermatitis (AD) than in healthy individuals, suggesting that it is a novel biomarker for evaluating skin condition in patients withAD. However, the mechanism underlying highENO1 expression in theSCand its pathological relevance inADare unclear. In this study, the relationship betweenENO1 expression and keratinization of epidermis was investigated, and the role of highENO1 expression in keratinocytes was characterized.

Methods

ENO1 expression and morphological characteristics were examined inSCfrom the cheeks of 24 patients withAD. Additionally, the localization ofENO1 in the excised human epidermis was observed. Moreover, to analyse the role ofENO1 in cellular barrier function, tight junction proteins (TJs) and transepithelial electrical resistance (TEER) in keratinocytes withENO1 overexpression were evaluated. Furthermore, the localization ofENO1 and plasminogen in keratinocytes was evaluated by immunostaining, and the cellular barrier function in keratinocytes was examined after treatment with tranexamic acid (TXA).

Results

ENO1 expression was substantially correlated with the rate of nucleated corneocytes inAD. In addition,ENO1 localized in the basal to spinous layers, but was its expression dramatically decreased in healthy humanSC.ENO1 overexpression in human epidermal keratinocytes reduced the expression ofTJs (claudin‐4, E‐cadherin, tricellulin, and occludin) andTEER, and treatment with anti‐ENO1 IgG reversed these effects.ENO1 colocalized with plasminogen in keratinocytes. Treatment withTXArescued theENO1‐induced reductions inTJandTEERexpression.

Conclusion

We found a substantial correlation betweenENO1 expression and the rate of nucleated corneocytes inADand decreasedENO1 expression with nuclear disappearance. These results suggest that highENO1 expression in theSCofADis caused by deficient keratinization, which is anADcharacteristic. Moreover,ENO1 overexpression in keratinocytes promoted dysfunction ofTJdynamics, leading to reduced integrity of the cellular barrier, and these effects might be mediated by plasmin activity. We propose thatENO1 is a useful indicator of parakeratosis and might have a potential role in cellularTJbarrier function in the epidermis.
Factors associated with influenza vaccination among healthcare workers in acute care hospitals in Canada
Authors: Hussain Hadia , McGeer Allison , McNeil Shelly , Katz Kevin , Loeb Mark , Simor Andrew , Powis Jeff , Langley Joanne , Muller Matthew ,   The Canadian Health Care Worker Study Group, Coleman Brenda L.
Published: February 2018

Background

Influenza vaccine coverage rates among healthcare workers (HCWs) in acute care facilities in Canada remain below national targets.

Objective

To determine factors associated with influenza vaccine uptake among HCWs.

Methods

This secondary analysis of a prospective cohort study included HCWs aged 18‐69 years, working ≥20 h/wk in a Canadian acute care hospital. Questionnaires were administered to participants in the fall of the season of participation (2011/12‐2013/14) which captured demographic/household characteristics, medical histories, occupational, behavioural and risk factors for influenza. Generalized estimating equation logistic regression was used to determine factors associated with vaccine uptake in the season of participation.

Results

The adjusted odds ratio for influenza vaccination in the current season was highest for those vaccinated in 3 of 3 previous seasons (OR 156; 95% CI 98, 248) followed by those vaccinated in 2 of 3 and 1 of 3 previous seasons when compared with those not vaccinated. Compared with nurses, physicians (OR 4.2; 95% CI 1.4, 13.2) and support services staff (OR 1.8; 95% CI 1.3, 2.4) had higher odds ratios for vaccine uptake. Conversely, HCWs identifying as Black had lower odds of uptake compared with those with European ancestry (OR 0.44, 95% CI 0.26‐0.75) when adjusted for other factors in the model.

Conclusion

Healthcare workers differ in their annual uptake of influenza vaccine based on their past vaccination history, occupation and ethnicity. These findings indicate a need to determine whether there are other vaccine‐hesitant groups within healthcare settings and learn which approaches are successful in increasing their uptake of influenza vaccines.
Human infection with avian influenza A(H7N2) virus—Virginia, 2002
Authors: Terebuh Pauline , Adija Akini , Edwards Lindsay , Rowe Thomas , Jenkins Suzanne , Kleene Jennifer , Fukuda Keiji , Katz Jacqueline M. , Bridges Carolyn B.
Published: February 2018

Background

In March 2002, an outbreak of low‐pathogenic avian influenza (LPAI) A(H7N2) was detected among commercial poultry operations in Virginia.

Methods

We performed a serosurvey of 80 government workers involved in efforts to control the outbreak.

Results

One study participant who assisted with disposal of infected birds tested positive for neutralizing antibodies to influenza A(H7N2) by microneutralization assay and H7‐specific IgM antibodies by enzyme‐linked immunosorbent assay (ELISA). The acute infection was temporally associated with an influenza‐like illness that resolved without hospitalization.

Conclusion

This study documents the earliest evidence of human infection with an H7 influenza virus of the North American lineage.
Historical divergences associated with intermittent land bridges overshadow isolation by larval dispersal in co‐distributed species of Tridacna giant clams
Authors: Keyse Jude , Treml Eric A. , Huelsken Thomas , Barber Paul H. , DeBoer Timery , Kochzius Marc , Nuryanto Agus , Gardner Jonathan P. A. , Liu Li‐Lian , Penny Shane , Riginos Cynthia
Published: February 2018

Aim

The aim of this study was to test historical and contemporary influences on population structure in the giant clams, Tridacna maxima (Röding, 1798) and T. crocea (Lamarck, 1819). To refine the location of clade boundaries within a newly resurrected species, Tridacna noae (Röding, 1798).

Location

Indo‐Australian archipelago, including Indonesia, the Philippines, Australia, Papua New Guinea, the Solomon Islands, Republic of Kiribati, the Line Islands and Taiwan.

Methods

We used isolation‐migration (IMa) coalescent models and distance‐based redundancy analyses (dbRDA) to test the relative influence of barriers and continuous distances on historical divergence, gene flow and population structure of T. maxima and T. crocea. Continuous metrics of distance included present‐day and Last Glacial Maximum overwater distances along with probability of larval dispersal (LD) among sampling sites. We combined new mitochondrial cytochrome oxidase subunit I (mtDNA COI) sequences with existing data to compile the largest data set of these species yet analysed.

Results

The Pleistocene land barriers of the Sunda Shelf and Torres Strait were associated with old (>0.5 Myr) divergence times. The western and eastern boundaries of the Halmahera Eddy were also locations of significant, but more recent, divergence. No gene flow was detected across any of the four barriers tested. Larval dispersal distances between sampling sites were significant predictors of T. crocea population structure, accounting for differentiation above and beyond the contribution of barriers. We further delineated the species range of T. noae and showed that its two known clades are sympatric in central Indonesia.

Main conclusions

The strong signature of historical barriers on genetic differentiation argues against the assumption that Indo‐Pacific Tridacna are open meta‐populations. Despite similar life histories, T. maxima and T. crocea differ in their mtDNA population structure. The widespread species (T. maxima) exhibits population structure linked solely with historical factors, whereas T. crocea's population structure reflects both historical factors and LD distances.
Relationship between social engagement and diabetes incidence in a middle‐aged population: Results from a longitudinal nationwide survey in Japan
Authors: Shibayama Taiga , Noguchi Haruko , Takahashi Hideto , Tamiya Nanako
Published: February 2018

Aims/Introduction

Social engagement can positively affect health status, but its effect on diabetes incidence remains unclear. The present study aimed to assess the relationship between social engagement and diabetes incidence in a middle‐aged Japanese population.

Materials and Methods

We analyzed data on 31,615 people aged 50–59 years from a prospective national survey carried out in Japan from 2005 to 2013. Diabetes incidence was measured by asking respondents annually whether they had been diagnosed with diabetes by a physician in the previous year. We used the complementary log–log model for interval‐censored survival time analysis. Social engagement was assessed at baseline as participation in social activities, having the companionship of friends, living with someone and employment status. Covariates including sex, age, health status and health behaviors were also measured at baseline.

Results

After adjusting for covariates measured at baseline, the effect size of social engagement on diabetes incidence was the same as or larger than that of the covariates. Respondents who participated in social activities (hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.87–0.92), had the companionship of friends (HR 0.97, 95% CI: 0.95–1.00), lived with someone (HR 0.85, 95% CI: 0.82–0.89) and were employed (HR 0.94, 95% CI: 0.92–0.96) were significantly less vulnerable to diabetes than were those who did not.

Conclusions

The present study found a prospective association between social engagement and diabetes incidence among a middle‐aged population. Future strategies to prevent diabetes in Japan should focus on both social and personal factors.
Psoriatic arthritis screening by the dermatologist: development and first validation of the ‘PURE‐4 scale’
Authors: Audureau E. , Roux F. , Lons Danic D. , Bagot M. , Cantagrel A. , Dernis E. , Gouyette N. , Hilliquin P. , Jullien D. , Lioté F. , Passeron T. , A Richard M. , Claudepierre P.
Published: February 2018

Background

Dermatologists are recommended to ask psoriasis patients about musculoskeletal complaints to allow early detection and treatment of psoriatic arthritis (PsA). Screening tools have been developed to help identify patients warranting further rheumatologic assessment, but evidence suggests room for improvement in their diagnostic value and ease of use for outpatient practice.

Objective

To develop and internally validate a brief tool for dermatologists to screen patients to refer to a rheumatologist for PsA diagnosis.

Methods

After the literature review, 23 items were selected, covering pain at various locations and inflammatory signs of PsA. The validation study was conducted in medically diagnosed psoriasis patients consecutively recruited between 2012 and 2014 (Saint Joseph Hospital, Paris, France). Patients were enrolled by a dermatologist who helped to complete the questionnaire. Diagnosis of PsA was established by a rheumatologist based on CASPAR criteria. Multivariate logistic regression models were performed to build the scale, assessing discrimination through sensitivity, specificity and area under the ROC curve (AUC). Final model was internally validated using bootstrapping techniques.

Results

One hundred and sixty‐eight patients were recruited, of whom nine were excluded for known PsA and 21 did not attend the rheumatologist consultation. Of 137 included patients (median age 43 years, 59.6% men), 21 (15.3%) had a PsA diagnosis. Final regression model retained four independent items, including evocative signs of dactylitis, inflammatory heel pain, bilateral buttock pain and peripheral joint pain with swelling in patients aged <50. A total score (the PURE‐4) was computed (0–4 points) that demonstrated excellent discriminative power (AUC = 87.6%; Sensitivity = 85.7% and Specificity = 83.6% at the threshold of ≥1/4 points), with no evidence for over‐optimism in bootstrapped internal validation.

Conclusion

These findings demonstrate the good diagnostic properties of a new screening scale using only four easy‐to‐collect items. If confirmed in other populations, it may prove useful in outpatient dermatology clinics for triage of psoriasis patients requiring further assessment by the rheumatologist.