bluuebunny/crossref_metadata_2025 huggingface dataset:
Delivery at 37 weeks' gestation is associated with a higher risk for child behavioural problems
Authors: Robinson Monique , Whitehouse Andrew J.O. , Zubrick Stephen R. , Pennell Craig E. , Jacoby Peter , McLean Neil J. , Oddy Wendy H. , Hammond Geoffrey , Stanley Fiona J. , Newnham John P.
Published: November 2012

Background

Advances in obstetric care have been accompanied by increasing rates of intervention which often involve elective delivery at 37 weeks, soon after term gestation has been achieved.

Aim

The aim of this study was to examine the behavioural sequelae for children born at this early term gestational age compared with those born at later weeks.

Methods

The Western Australian Pregnancy Cohort (Raine) Study provided comprehensive obstetric data from 2900 pregnancies. Offspring were followed up at ages two, five, eight, 10, 14 and 17 years using the parent report Child Behaviour Checklist (CBCL) with clinical cutoffs for overall, internalising (withdrawn, somatic complaints, anxious/depressed) and externalising (delinquent, aggressive) behaviour (T‐score ≥ 60). We used longitudinal logistic regression models incorporating generalised estimating equations (GEE) with step‐wise adjustment for ante‐, peri‐ and postnatal confounding factors.

Results

Approximately 9% of our cohort was born within the range of 370/7 and 376/7 weeks. Those born at 37 weeks' gestation were at increased risk for overall (OR = 1.43, 95% CI = 1.02, 2.01) and externalising (OR = 1.42, 95% CI = 1.01, 2.01) behavioural problems in the fully adjusted model when compared with infants born from 39 weeks onwards. Infants born late preterm (34–36 weeks) and at 38 weeks did not show a significantly increased risk for behavioural problems.

Conclusion

Infants born at 37 weeks' gestation are at increased risk for behavioural problems over childhood and adolescence compared with those born later in gestation. We suggest that 37 weeks' gestation may not be the optimal cutoff for defining perinatal risk as it applies to behavioural development.
Inflammatory mechanisms of ventilator‐induced lung injury: a time to stop and think?
Authors: Wilson M. R. , Takata M.
Published: November 2012

Ventilator‐induced lung injury (VILI) is the phenomenon by which mechanical ventilation exacerbates lung injury in critically ill patients. It is particularly relevant for those suffering from acute respiratory distress syndrome, in which the iatrogenic injury caused by VILI contributes to their high mortality. The innate immune system is widely accepted to play an important role during VILI. However, it is our belief that the identification of inflammatory mediators that are crucial during VILI, and thus may make useful therapeutic targets, has become obscured by the wide variety of pre‐clinical animal models of VILI reported in the literature. We aim here to summarise some of our work addressing this issue over the last 10 years, and thus, we hope, make interpretation of a convoluted field a little clearer.
The Mischievous Bundle: A Case of Varying Degrees of Right Bundle Branch Block on Alternate Beats during Exercise Stress Testing
Authors: Singh Sukhvinder
Published: November 2012

A 78‐year‐old male was referred for exercise stress testing. He developed incomplete right bundle branch block during first stage of exercise and later on developed incomplete and complete right bundle branch block on alternate beats (2:1). During first minute of recovery he developed complete right bundle branch block on all beats (1:1). At 3 minutes of recovery, baseline electrocardiographic pattern was resumed. Variable degree of right bundle branch block on alternate beats is a rare phenomenon. The plausible mechanisms responsible for this phenomenon are being discussed.
Diagnostic Accuracy of Left Ventricular Hypertrophy in Patients with Myocardial Infarction by Computer‐Assisted Electrocardiography (ELECTROPRES)
Authors: Rodríguez‐Padial Luis , Akerström Finn , Robles‐Gamboa Carolina , Andrés Josep , Ruiz‐Baena Jessica
Published: November 2012

Background

Information is limited about the classification accuracy of electrocardiographic (ECG) criteria for left ventricular hypertrophy (LVH) in the presence of myocardial infarction (MI).

Methods

We evaluated LVH classification accuracy for a set of 16 ECG criteria and some combinations derived from them in 1642 patients (105 with MI) suspected of coronary heart disease with two‐dimensional echocardiography evaluation and a standard 12‐lead ECG recorded at the same time. Patients with left bundle branch block had previously been excluded. Measures of classification accuracy included sensitivity, specificity, likelihood ratios, and positive and negative predictive values.

Results

Diagnostic accuracy varied widely for different LVH criteria. The criteria with the best overall performance had highest sensitivity in the presence of MI and sensitivities of approximately 30% with relatively low specificities ranging from 72% to 78%. However, the classification accuracy for them was similar to that for patients without MI. The prevalence of LVH in patients with MI was higher (56%) than in those with no MI (31%). Classification accuracy of the best single previously published LVH criteria was comparable to that of the best combinations of any three of them.

Conclusions

The classification accuracy of LVH criteria in the presence of MI is comparable to that in patients without MI, in part possibly due to the higher LVH prevalence in the MI group. The presence of a well‐validated computer database facilitates comparative evaluation of ECG‐LVH criteria and derivation of optimal combinations of criteria for any given clinical application.
Association of Fragmented QRS Complex with Myocardial Reperfusion in Acute ST‐Elevated Myocardial Infarction
Authors: Hizal Erdem Fatma , Tavil Yusuf , Yazici Hüseyin , Aygül Nazif , Abaci Adnan , Boyaci Bülent
Published: November 2012

In this study, we aimed to evaluate the relationship between TIMI myocardial perfusion (TMP) grade, as an indicator of myocardial reperfusion, and fragmented QRS (fQRS) in standard 12‐lead electrocardiogram. Also, we evaluate fQRS is an additional indicator of myocardial reperfusion. One hundred patients admitted with first STEMI to Coronary Intensive Care Unit and who were used thrombolytic therapy was included in this retrospective study. Standard 12‐lead electrocardiogram records of patients simultaneous with coronary angiography (second day) were assessed and analysed for the presence of fQRS. Also, coronary angiography images were analyzed to identify the infarct related artery, TIMI grade of infarct related artery and TMP grade of infarct related artery. The patients with fQRS demonstrated a significantly lower TMP grade, TIMI grade and ejection fraction compared with the non‐fQRS patients (P = 0.004, P = 0.003, P = 0.02 respectively). The patients with inadequate myocardial reperfusion demonstrated a significantly higher fQRS compared with the adequate myocardial reperfusion patients. (56.9% versus 23.5%, P = 0.002 respectively). On correlation analysis, there was a significant negative correlation between fQRS and left ventricular ejection fraction (r = −232, P = 0.02) TMP grade and adequate myocardial reperfusion (TMP 3) showed significant negative correlation with fQRS (r = −0.370, P = 0.000; r = −0.318, P = 0.001 respectively). Presence of fragmented QRS in STEMI patients was associated with inadequate myocardial reperfusion and it can be used as a simple, noninvasive parameter to evaluate myocardial reperfusion.
Usefulness of Extended Holter ECG Monitoring for Serious Arrhythmia Detection in Patients with Heart Failure and Sleep Apnea
Authors: Uznańska‐Loch Barbara , Trzos Ewa , Wierzbowska‐Drabik Karina , Śmigielski Janusz , Rechciński Tomasz , Cieślik‐Guerra Urszula , Kasprzak Jarosław D. , Kurpesa Małgorzata
Published: November 2012

Background

In patients with systolic heart failure (HF), coexisting sleep apnea may promote arrhythmia. Ambulatory Holter electrocardiogram (ECG) monitoring (AECG) is a method of arrhythmia and apnea evaluation. We hypothesized that 24‐hour AECG in patients with HF who have a high risk of serious arrhythmia may be less accurate than AECG extended to 48 hours and that, moreover, arrhythmia may be related to apnea.

Methods

Eighty‐four recordings of 48‐hour AECG in 84 patients with ischemic HF (mean ejection fraction 34 ± 7%) were analyzed. Day 1, Day 2 were checked for ventricular tachycardia (VT) and supraventricular tachycardia (SVT). Estimated apnea‐hypopnea index (est.AHI) was calculated using Holter, monitoring where est.AHI >15 indicates apnea.

Results

In 48‐hour AECG, VT occurred in 34 patients (40.5%) whereas SVT in 17 patients (20.2%), and patients with est.AHI > 15 had higher VT occurrence. In two‐sample one‐sided test for proportions, 24‐hour AECG from Day 1 showed a significantly lower percentage of patients with detected VT than 48‐hour AECG—it was 23.8% (20 patients), meaning a significant underestimation with P = 0.0089. We assessed VT underestimation in the subgroups with regard to est.AHI, and found that it was present in Day 1 monitoring in the subgroups with est.AHI > 15. It was absent in the subgroups with est.AHI ≤ 15 and also in Day 2 monitoring.

Conclusions

In patients with systolic HF, 24‐hour AECG may have insufficient sensitivity regarding serious arrhythmia occurrence. If significant apnea was detected in the first day, extending the monitoring may be recommended.
Association between Atrial Fibrillatory Rate and Heart Rate Variability in Patients with Atrial Fibrillation and Congestive Heart Failure
Authors: Corino Valentina D. A. , Cygankiewicz Iwona , Mainardi Luca T. , Stridh Martin , Vasquez Rafael , Bayes de Luna Antonio , Holmqvist Fredrik , Zareba Wojciech , Platonov Pyotr G.
Published: November 2012

Background

Even if atrial fibrillatory rate (AFR) has been related to clinical outcome in patients with atrial fibrillation (AF), its relation with ventricular response has not been deeply studied. The aim of this study was to investigate the relation between AFR and RR series variability in patients with AF.

Methods

Twenty‐minute electrocardiograms in orthogonal leads were processed to extract AFR, using spatiotemporal QRST cancellation and time frequency analysis, and RR series in 127 patients (age 69 ± 11 years) with congestive heart failure (NYHA II–III) enrolled in the MUSIC study (MUerte Subita en Insufficiencia Cardiaca). Heart rate variability and irregularity were assessed by time domain parameters and entropy‐based indices, respectively and their correlation with AFR investigated.

Results

Variability measures seem not to be related to AFR, while irregularity measures do. A significant correlation between AFR and variability parameters of heart rate variability during AF was found only in patients not treated with antiarrhythmics drugs (correlation = 0.56 P < 0.05 for pNN50), while this correlation was lost in patients taking rate‐ or rhythm‐control drugs. A significant positive correlation between AFR and indices of RR irregularity was found, showing that a higher AFR is related to a less organized RR series (correlation = 0.33 P < 0.05 for regularity index for all patients, correlation increased in subgroups of patients treated with the same drug).

Conclusions

These results suggest that a higher AFR is associated with a higher degree of irregularity of ventricular response that is observed regardless of the use of rate‐controlling drugs.
High‐Frequency QRS Analysis in Patients with Acute Myocardial Infarction: A Preliminary Study
Authors: Amit Guy , Galante Ori , Davrath Linda R. , Luria Oded , Abboud Shimon , Zahger Doron
Published: November 2012

Background

The 12‐lead electrocardiogram (ECG) is a primary tool in the evaluation and risk stratification of patients with suspected acute myocardial infarction (AMI), even though the initial ECG of these patients is often normal or nondiagnostic. Myocardial ischemia induces depolarization changes that can be quantified by analysis of high‐frequency QRS (HFQRS) components. We aimed to demonstrate the potential usefulness of HFQRS analysis in diagnosing myocardial ischemia by characterizing the morphological patterns of the HFQRS signals in patients with AMI before and following reperfusion.

Methods

Five‐minute high‐resolution ECG was acquired from 30 patients with AMI (age 55 ± 11 years, 26 men) upon their admission to the intensive coronary care unit (ICCU). Serial ECGs were acquired following coronary revascularization and after additional 24 hours (24h). High‐frequency morphology index (HFMI), quantifying the extent of ischemic patterns was computed by a custom software, and its values were compared between the serial ECG measurements.

Results

HFMI values were significantly higher on the admission ECG as compared to the post intervention ECG (4.6 ± 2.9% vs 3.4 ± 2.3%, P < 0.05) and to the 24h ECG (4.6 ± 2.9% vs 2.8 ± 2.1%, P < 0.01). In 79% of the patients who were successfully revascularized HFMI value decreased from admission ECG to 24h ECG.

Conclusions

Analysis of HFQRS morphology in patients with AMI provides information about the existence and severity of myocardial ischemia. HFQRS analysis may aid in risk stratification of patients with suspected myocardial ischemia, complementarily to conventional ECG.
Language experienced in utero affects vowel perception after birth: a two‐country study
Authors: Moon Christine , Lagercrantz Hugo , Kuhl Patricia K
Published: November 2012

Aims

To test the hypothesis that exposure to ambient language in the womb alters phonetic perception shortly after birth. This two‐country study aimed to see whether neonates demonstrated prenatal learning by how they responded to vowels in a category from their native language and another non‐native language, regardless of how much postnatal experience the infants had.

Method

A counterbalanced experiment was conducted in Sweden (n = 40) and the USA (n = 40) using Swedish and English vowel sounds. The neonates (mean postnatal age = 33 h) controlled audio presentation of either native or non‐native vowels by sucking on a pacifier, with the number of times they sucked their pacifier being used to demonstrate what vowel sounds attracted their attention. The vowels were either the English/i/or Swedish/y/in the form of a prototype plus 16 variants of the prototype.

Results

The infants in the native and non‐native groups responded differently. As predicted, the infants responded to the unfamiliar non‐native language with higher mean sucks. They also sucked more to the non‐native prototype. Time since birth (range: 7–75 h) did not affect the outcome.

Conclusion

The ambient language to which foetuses are exposed in the womb starts to affect their perception of their native language at a phonetic level. This can be measured shortly after birth by differences in responding to familiar vs. unfamiliar vowels.
Intrathyroidal epithelial thymoma/carcinoma showing thymus‐like differentiation; comparison with thymic lymphoepithelioma‐like carcinoma and a possibility of development from a multipotential stem cell
Authors: Hirokawa Mitsuyoshi , Miyauchi Akira , Minato Hiroshi , Yokoyama Shigeo , Kuma Seiji , Kojima Masaru
Published: November 2012

The purpose of our article is to describe the immunohistochemical findings of intrathyroidal epithelial thymoma/carcinoma showing thymus‐like differentiation (ITET/CASTLE) of the thyroid in detail, to clarify the difference between ITET/CASTLE and thymic lymphoepithelioma‐like carcinoma (LELC), and to discuss the pathogenesis of ITET/CASTLE. We immunohistochemically examined five ITET/CASTLE and eight LELC cases. All of ITET/CASTLE cases were strongly positive for CD5, P63, high‐molecular‐weight cytokeratin and B‐cell CLL/lymphoma‐2. Carcinoembryonic antigen‐positive carcinoma cells were found in four ITET/CASTLE cases. Neuroendocrine marker‐positive carcinoma cells were scattered in all cases. Immunohistochemical findings in thymic LELC were essentially similar to those in ITET/CASTLE, but the sensitivity was different. There is a possibility that ITET/CASTLE and thymic LELC are not the quite same disease entity. We think that ITET/CASTLE is derived from ectopic thymus, but not related to solid cell nests.
Ultrastructure and distribution of sensilla on the antennae of female fig wasp Eupristina sp. (Hymenoptera: Agaonidae)
Authors: Li Zongbo , Yang Pei , Peng Yanqiong , Yang Darong
Published: November 2012

In the species‐specific and obligate mutualism between the fig (Moraceae: Ficus spp.) and its pollinator (Hymenoptera: Agaonidae), the continuity of lifecycle of both partners completely depends on the female pollinator's ability to detect receptive figs. To better understand the chemical location mechanism, we examined the antennae and their sensilla of the female fig pollinator Eupristina sp. using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The antennae of female Eupristina sp. are geniculated, and in total, there were seven types of sensilla found on the antennae: two types of multiporous placoid sensilla (type 1 is sausage‐like and type 2 is rounded), sensilla trichodea (ST), basiconic sensilla (BS), chaetica sensilla (ChS), coeloconic sensilla (CoS), and one specialized sensillum classified as sensillum obscurum (SO). We described external morphology, abundance, distribution, ultrastructure and discussed putative functions. We inferred from their ultrastructures as chemoreceptors that two types of multiporous placoid sensilla, BS and CoS, were innervated by sensory neurons. The aporous type ST, ChS, and SO were not innervated by dendrites which may function as mechanoreceptor/proprioceptor. These results were also discussed in relation to the interaction between Eupristina sp. and its host fig.
Drug‐conjugated antibodies for the treatment of cancer
Authors: Lambert John M.
Published: November 2012

Despite considerable effort, application of monoclonal antibody technology has had only modest success in improving treatment outcomes in patients with solid tumours. Enhancing the cancer cell‐killing activity of antibodies through conjugation to highly potent cytotoxic ‘payloads’ to create antibody–drug conjuates (ADCs) offers a strategy for developing anti‐cancer drugs of great promise. Early ADCs exhibited side‐effect profiles similar to those of ‘classical’ chemotherapeutic agents and their performance in clinical trials in cancer patients was generally poor. However, the recent clinical development of ADCs that have highly potent tubulin‐acting agents as their payloads have profoundly changed the outlook for ADC technology. Twenty‐five such ADCs are in clinical development and one, brentuximab vedotin, was approved by the FDA in August, 2011, for the treatment of patients with Hodgkin's lymphoma and patients with anaplastic large cell lymphoma, based on a high rate of durable responses in single arm phase II clinical trials. More recently, a second ADC, trastuzumab emtansine, has shown excellent anti‐tumour activity with the presentation of results of a 991‐patient randomized phase III trial in patients with HER2‐positive metastatic breast cancer. Treatment with this ADC (single agent) resulted in a significantly improved progression‐free survival of 9.6 months compared with 6.4 months for lapatinib plus capecitabine in the comparator arm and significantly prolonged overall survival. Besides demonstrating excellent efficacy, these ADCs were remarkably well tolerated. Thus these, and other ADCs in development, promise to achieve the long sought goal of ADC technology, that is, of having compounds with high anti‐tumour activity at doses where adverse effects are generally mild.
The organization of attention in typical development: A new preschool attention test battery
Authors: Breckenridge Kate , Braddick Oliver , Atkinson Janette
Published: November 2012

This article introduces a new battery of attention tests for typically developing and atypically developing children with a mental age of 3–6 years. In the light of adult and child studies supporting a model of distinct networks for specific attentional operations, tests in the current battery were selected with the aim of measuring functions of selective attention, sustained attention and attentional control (executive function). Normative data were collected from 154 typically developing children aged 3–6 years and examined using exploratory factor analysis to determine latent constructs underlying test performance. This analysis suggested increasing differentiation of attention functions over the age range, with support for the hypothesized three‐factor model only after 4½ years of age. Additional analyses supported the validity of the new attention battery with respect to (1) parent/teacher report measures of everyday attention behaviour and (2) later performance on the Test of Everyday Attention for Children (TEA‐Ch), a battery designed for children aged 6–16 years. The results show the developing differentiation of attention functions and support the ecological and predictive validity of the battery as providing early performance‐based measures of attention and an attention ‘profile’ for each individual child, which may aid characterization and remediation of neurodevelopmental disorders.
Plasmacytoid dendritic cells in allergic asthma and the role of inhaled corticosteroid treatment
Authors: Bratke K. , Prieschenk C. , Garbe K. , Kuepper M. , Lommatzsch M. , Virchow J. C.
Published: November 2012

Background

Plasmacytoid dendritic cells (pDCs) infiltrate sites of acute Th2‐dominant inflammation, but their role in allergic asthma remains unclear.

Objective

To characterize circulating pDCs from patients with allergic asthma outside their respective allergen season.

Methods

Adhesion molecules, co‐stimulatory molecules, immunoglobulin receptors and chemokine receptors were quantified on blood pDCs from 20 patients with allergic asthma and 18 healthy controls using flow cytometry. In addition, IL‐6‐, TNF‐α‐ and IFN‐α‐secretion were analysed after stimulating isolated pDCs with TLR7‐ and TLR9‐ligands.

Results

Plasmacytoid dendritic cells from patients with allergic asthma showed an increased expression of chemokine receptors involved in inflamed tissue homing such as CCR2, CCR4, CCR9, CCR10, CXCR2, CXCR5 and CXCR6, while the expression of the lymph node homing receptor CXCR3 was down‐regulated. In addition, these pDCs exhibited a higher expression of activation markers and Th2‐associated molecules such as CD40, CD62L, CD64 and FcεRIα. In contrast, TLR7‐mediated IL‐6‐, TNF‐α‐ and IFN‐α‐secretion was significantly reduced in pDCs from patients with asthma. The TLR9‐mediated cytokine response was only suppressed in those patients who were treated with inhaled corticosteroids (ICS) during previous allergen seasons. The same effect was observed for CD54 and OX40L expression.

Conclusions

We report an increased expression of activation markers, and Th2‐associated molecules, and an increased migratory potential of circulating pDCs in allergic asthma. These changes are accompanied by a reduced TLR7‐mediated cytokine response. In addition, our results suggest a longterm impact of ICS treatment on the characteristics of circulating pDCs.
Protection from articular damage by passive or active anti-tumour necrosis factor (TNF)-α immunotherapy in human TNF-α transgenic mice depends on anti-TNF-α antibody levels
Authors: Semerano L , Biton J , Delavallée L , Duvallet E , Assier E , Bessis N , Bernier E , Dhellin O , Grouard-Vogel G , Boissier M-C
Published: November 2012

Active anti-tumour necrosis factor (TNF)-α immunization with the kinoid of TNF-α (TNF-K) induces polyclonal anti-TNF-α antibodies and ameliorates arthritis in human TNF-α (hTNF-α) transgenic mice (TTg). We compared the efficacy of TNF-K to that of infliximab (IFX) and of TNF-K and IFX co-administration, and evaluated whether the titres of anti-hTNF-α antibodies induced by immunization were a determinant of TNF-K efficacy. Forty-eight TTg mice received one of the following treatments: TNF-K immunization (TNF-K group); weekly IFX throughout the study duration (IFXw0–15); TNF-K plus weekly IFX for 4 weeks (TNF-K + IFX); and weekly IFX for 4 weeks (IFXw0–4); PBS. Animals were killed at week 16. Anti-hTNF-α antibody titres and clinical and histological scores were compared. All TNF-K immunized mice (TNF-K and TNF-K + IFX) produced anti-hTNF-α antibodies. Titres were higher in TNF-K versus TNF-K + IFX (P < 0·001) and correlated inversely with histological inflammation (R = −0·78; P = 0·0001) and destruction (R = −0·67; P = 0·001). TNF-K + IFX had higher histological inflammation and destruction versus TNF-K (P < 0·05). A receiver operating characteristic (ROC) analysis of anti-hTNF-α antibody titres identified the criterion cut-off value to discriminate most effectively between the TNF-K and TNF-K + IFX groups. Mice with high versus low titres had less histological inflammation and destruction (P < 0·05). In a model of TNF-α-dependent arthritis, protection from articular damage by TNF-K correlates with the titres of induced anti-hTNF-α antibodies. The co-administration of TNF-K and a short course of infliximab does not result in less articular damage versus solely TNF-K, due probably to lower anti-hTNF-α antibody production. These results are relevant for future development of active anti-TNF-α immunization in human disease.
Does elastography reduce the need for thyroid FNAs?
Authors: Mehrotra P. , McQueen A. , Kolla S. , Johnson S. J. , Richardson D. L.
Published: November 2012

Objective

Ultrasound elastography (USE) assesses lesion stiffness by evaluating tissue distortion in response to stress; it is emerging as a potentially useful tool to augment the ultrasound characterisation of thyroid nodules. The aim of this study was to assess the accuracy of USE examination of thyroid nodules compared with pathological outcome, especially to determine whether USE could reliably detect benign nodules and reduce the numbers of ultrasound guided fine needle aspiration cytology (USgFNAC).

Design

Over a three‐year period, thyroid nodules were initially characterised by B‐mode ultrasound (US) findings. Where USgFNAC was indicated by clinical concern and/or the sonographic appearances, the lesion was then subjected to USE by an experienced operator prior to the USgFNAC.

Patients

147 thyroid nodules were examined by USE and USgFNAC in 146 patients.

Measurements

The elastographic appearance was subjectively categorized at the time of the examination (soft, intermediate or hard) and subsequently compared with the cytological/histological outcome.

Results

A total of 122 nodules were non‐neoplastic, 5 nodules were benign neoplasms, 10 nodules had indeterminate cytology and 10 were malignant neoplasms. The sensitivity of USE for malignancy was 90·0%, specificity was 79·6%, PPV was 24·3%, NPV was 99·1% and accuracy was 80·3%.

Conclusion

Thyroid nodules that are soft at USE have a high likelihood of being non‐neoplastic and subjective USE assessment of thyroid nodules by an experienced operator can be a useful means of avoiding USgFNAC for benign nodules. In contrast, we suggest that all nodules that are intermediate or hard on USE undergo USgFNAC.
Borderline sebaceous neoplasm in a renal transplant patient without Muir‐Torre syndrome
Authors: Kaminska Edidiong C.N. , Iyengar Vivek , Tsoukas Maria , Shea Christopher R.
Published: November 2012

Borderline sebaceous neoplasms are rare tumors that can be challenging to diagnose because of their admixture of histopathologic features. Most such tumors have been described in patients with Muir‐Torre syndrome (MTS). We report the case of an immunosuppressed, 82‐year‐old African‐American woman without MTS who developed a rapidly growing lesion on the left cheek. Histopathology revealed a borderline sebaceous neoplasm with predominant features of sebaceous adenoma and with focal features raising concern for the possibility of an evolving, well‐differentiated, low‐grade sebaceous carcinoma with a high mitotic index. In the setting of immunosuppression, borderline sebaceous neoplasms may occur outside of MTS; careful evaluation and conservative treatment are recommended in managing such tumors.
ABC3 Part I: a review of the guidelines for terminology, classification and management of cervical cytology in England
Authors: Smith J. H. F.
Published: November 2012

J. H. F. Smith

ABC3 Part I: a review of the guidelines for terminology, classification and management of cervical cytology in England

The provision of guidance on cytology reporting and evaluation, first outlined in 1995 with the publication of Achievable Standards, Benchmarks for Reporting, and Criteria for Evaluating Cervical Cytopathology (ABC), and subsequently revised and expanded in a second edition in 2000, has been pivotal to the success of the National Health Service Cervical Screening Programme (NHSCSP), ensuring that standards are upheld, and that rigorous evaluation and quality assurance take place.

In the last decade, major changes to the NHSCSP, notably the adoption of revised age ranges and screening intervals for all women in England, implementation of liquid‐based cytology and, most recently, the decision to introduce high‐risk human papillomavirus (HR‐HPV) testing for triage of low‐grade and borderline (equivalent to 'atypical') cytological abnormalities and test of cure after treatment of cervical intraepithelial neoplasia (CIN) determined that an updated version of ABC was required.

The third edition of ABC recommends adoption, with minor modification, of the revised British Society for Clinical Cytology terminology and provides guidance on the management of abnormal cytology results linked to this terminology taking account of HR‐HPV testing. To accommodate these changes, expanded result codes, which are electronic codes used to transfer management information to central computers for follow‐up, call and recall of individual women, have been developed. Further guidance on specimen adequacy is also provided. Revised performance indicators are described and explained in a separate article by R. Blanks in this issue of Cytopathology.

All the changes in ABC3 are designed to support the mission statement of the NHSCSP that ‘the objective of cervical screening is to reduce cervical cancer incidence and mortality by screening with a high sensitivity for the detection of CIN2 or worse, whilst maintaining a high specificity’.
Spatial–temporal patterns of Ceratocystis wilt in Eucalyptus plantations in Brazil
Authors: Ferreira M. A. , Harrington T. C. , Gongora‐Canul C. C. , Mafia R. G. , Zauza E. A. V. , Alfenas A. C.
Published: November 2012

Ceratocystis wilt, caused by Ceratocystis fimbriata, has become the most important disease in eucalyptus (Eucalyptus spp. and hybrids) plantations in Brazil. To further our understanding of the epidemiology of this disease, we surveyed eucalyptus plantations in the states of Minas Gerais and Bahia that were known to have Ceratocystis wilt or were thought to have been planted with infected rooted cuttings. There was generally higher disease incidence in the Minas Gerais plantations, which were on former Cerrado forest sites and likely had soilborne inoculum prior to planting eucalyptus. In such plantations, disease incidence was not evident before 20 months after planting but slowly increased up to 50% at 74 months. The symptomatic and killed trees were aggregated, perhaps from uneven distribution of inoculum in the soil. Also, the progression of cumulative disease incidence best fit a monomolecular model, which is typical of soilborne diseases (fixed level of initial inoculum with little or no secondary inoculum during the crop rotation). However, plots where some trees had been harvested during the rotation showed very high levels of disease incidence in the sprouts that arose from stumps, suggesting secondary spread of the pathogen on harvesting tools or machinery. Most of the Bahia plantations were on pastureland prior to eucalyptus cultivation, and the pathogen was likely introduced with infected nursery stock. In such plots, symptoms were evident as soon as 7 months after planting, and most of the mortality occurred within 12 months. The diseased trees on former pastureland sites were sometimes aggregated within planting rows, suggesting that bunches of infected nursery stock were planted together within the rows. Care should be taken in planting disease‐free planting material and spreading the pathogen on tools, but on sites with soilborne inoculum, use of resistant clones may be the only management option.
Hemodynamic responses in amygdala and hippocampus distinguish between aversive and neutral cues during Pavlovian fear conditioning in behaving rats
Authors: McHugh Stephen B. , Marques‐Smith Andre , Li Jennifer , Rawlins J. N. P. , Lowry John , Conway Michael , Gilmour Gary , Tricklebank Mark , Bannerman David M.
Published: November 2012

Lesion and electrophysiological studies in rodents have identified the amygdala and hippocampus (HPC) as key structures for Pavlovian fear conditioning, but human functional neuroimaging studies have not consistently found activation of these structures. This could be because hemodynamic responses cannot detect the sparse neuronal activity proposed to underlie conditioned fear. Alternatively, differences in experimental design or fear levels could account for the discrepant findings between rodents and humans. To help distinguish between these alternatives, we used tissue oxygen amperometry to record hemodynamic responses from the basolateral amygdala (BLA), dorsal HPC (dHPC) and ventral HPC (vHPC) in freely‐moving rats during the acquisition and extinction of conditioned fear. To enable specific comparison with human studies we used a discriminative paradigm, with one auditory cue [conditioned stimulus (CS)+] that was always followed by footshock, and another auditory cue (CS−) that was never followed by footshock. BLA tissue oxygen signals were significantly higher during CS+ than CS− trials during training and early extinction. In contrast, they were lower during CS+ than CS− trials by the end of extinction. dHPC and vHPC tissue oxygen signals were significantly lower during CS+ than CS− trials throughout extinction. Thus, hemodynamic signals in the amygdala and HPC can detect the different patterns of neuronal activity evoked by threatening vs. neutral stimuli during fear conditioning. Discrepant neuroimaging findings may be due to differences in experimental design and/or fear levels evoked in participants. Our methodology offers a way to improve translation between rodent models and human neuroimaging.
Mixotrophic organisms become more heterotrophic with rising temperature
Authors: Wilken Susanne , Huisman Jef , Naus‐Wiezer Suzanne , Van Donk Ellen
Published: November 2012

The metabolic theory of ecology predicts that temperature affects heterotrophic processes more strongly than autotrophic processes. We hypothesized that this differential temperature response may shift mixotrophic organisms towards more heterotrophic nutrition with rising temperature. The hypothesis was tested in experiments with the mixotrophic chrysophyte Ochromonas sp., grown under autotrophic, mixotrophic and heterotrophic conditions. Our results show that (1) grazing rates on bacterial prey increased more strongly with temperature than photosynthetic electron transport rates, (2) heterotrophic growth rates increased exponentially with temperature over the entire range from 13 to 33 °C, while autotrophic growth rates reached a maximum at intermediate temperatures and (3) chlorophyll contents during mixotrophic growth decreased at high temperature. Hence, the contribution of photosynthesis to mixotrophic growth strongly decreased with temperature. These findings support the hypothesis that mixotrophs become more heterotrophic with rising temperature, which alters their functional role in food webs and the carbon cycle.
Petuniaflowers solve the defence/apparency dilemma of pollinator attraction by deploying complex floral blends
Authors: Kessler Danny , Diezel Celia , Clark David G. , Colquhoun Thomas A. , Baldwin Ian T.
Published: November 2012

Flowers recruit floral visitors for pollination services by emitting fragrances. These scent signals can be intercepted by antagonists such as florivores to locate host plants. Hence, as a consequence of interactions with both mutualists and antagonists, floral bouquets likely consist of both attractive and defensive components. While the attractive functions of floral bouquets have been studied, their defensive function has not, and field‐based evidence for the deterrence of floral‐scent constituents is lacking. In field and glasshouse experiments with five lines of transgenicPetunia x hybridaplants specifically silenced in their ability to release particular components of their floral volatile bouquet, we demonstrate that the emission of single floral‐scent compounds can dramatically decrease damage from generalist florivores. While some compounds are used in host location, others prevent florivory. We conclude that the complex blends that comprise floral scents are likely sculpted by the selective pressures of both pollinators and herbivores.
Transcranial brain sonography findings in two main variants of progressive supranuclear palsy
Authors: Kostić V. S. , Mijajlović M. , Smajlović D. , Lukić M. J. , Tomić A. , Svetel M.
Published: November 2012

Background and purpose

Progressive supranuclear palsy (PSP) can occur with two main clinical presentations, classified as classical Richardson's syndrome (PSP‐RS) and as PSP‐parkinsonism (PSP‐P), the most common atypical PSP variant. The differential diagnosis between them is challenging. Therefore, we studied different ultrasound markers by transcranial sonography in individuals with PSP‐RS and PSP‐P, to test their value in the diagnostic work up of these patients.

Methods

Transcranial sonography was performed in 21 patients with PSP‐RS and 11 patients with PSP‐P. Echogenic sizes of the substantia nigra (SN) and the lenticular nuclei (LN), as well as the width of the third ventricle, were measured.

Results

Among the patients with PSP‐RS and PSP‐P, three (14%) and eight (73%) patients had a hyperechogenic SN (P = 0.020), respectively. Uni‐ or bilateral hyperechogenicity of the LN was observed in 67% and 36% of patients with PSP‐RS and PSP‐P, respectively (P = 0.101). Third ventricle was significantly wider in patients with PSP‐RS (11.2 ± 2.3 mm) when compared with patients with PSP‐P (7.5 ± 1.4 mm; P = 0.001).

Conclusion

Our data, possibly reflecting pathological differences, primarily contribute supporting the view that the neurodegenerative process differs in the two PSP variants.
Azelaic acid reduced senescence‐like phenotype in photo‐irradiated human dermal fibroblasts: possible implication of PPARγ
Authors: Briganti Stefania , Flori Enrica , Mastrofrancesco Arianna , Kovacs Daniela , Camera Emanuela , Ludovici Matteo , Cardinali Giorgia , Picardo Mauro
Published: November 2012

Azelaic acid (AzA) has been used for the treatment for inflammatory skin diseases, such as acne and rosacea. Interestingly, an improvement in skin texture has been observed after long‐time treatment with AzA. We previously unrevealed that anti‐inflammatory activity of AzA involves a specific activation of PPARγ, a nuclear receptor that plays a relevant role in inflammation and even in ageing processes. As rosacea has been considered as a photo‐aggravated disease, we investigated the ability of AzA to counteract stress‐induced premature cell senescence (SIPS). We employed a SIPS model based on single exposure of human dermal fibroblasts (HDFs) to UVA and 8‐methoxypsoralen (PUVA), previously reported to activate a senescence‐like phenotype, including long‐term growth arrest, flattened morphology and increased synthesis of matrix metalloproteinases (MMPs) and senescence‐associated β‐galactosidase (SA‐β‐gal). We found that PUVA‐treated HDFs grown in the presence of AzA maintained their morphology and reduced MMP‐1 release and SA‐β‐galactosidase‐positive cells. Moreover, AzA induced a reduction in ROS generation, an up‐modulation of antioxidant enzymes and a decrease in cell membrane lipid damages in PUVA‐treated HDFs. Further evidences of AzA anti‐senescence effect were repression of p53 and p21, increase in type I pro‐collagen and abrogation of the enhanced expression of growth factors, such as HGF and SCF. Interestingly, PUVA‐SIPS showed a decreased activation of PPARγ and AzA counteracted this effect, suggesting that AzA effect involves PPARγ modulation. All together these data showed that AzA interferes with PUVA‐induced senescence‐like phenotype and its ability to activate PPAR‐γ provides relevant insights into the anti‐senescence mechanism.
Signal processing evaluation of myoelectric sensor placement in low‐level gestures: sensitivity analysis using independent component analysis
Authors: Naik Ganesh R. , Kumar Dinesh K. , Palaniswami Marimuthu
Published: November 2012

Surface electromyogram (sEMG) is a technique in which electrodes are placed on the skin overlying a muscle to detect the electrical activity. Multiple electrical sensors are essential for extracting intrinsic physiological and contextual information from the corresponding sEMG signals. The reason, why more than just one sEMG signal capture has to be used, is as follows: Due to signal propagation inside the human body in terms of an electrical conductor, there cannot be a one‐to‐one mapping of activities between muscle fibre groups and corresponding sEMG sensing electrodes. Each of such electrodes rather records a composition of many, and widely activity‐independent signals, and such kind of raw signal capture cannot be efficiently used for pattern matching due to its linear dependency. On the other hand, Independent component analysis (ICA) provides the perfect answer of separating skin surface recordings into a set of independent muscle actions. Hence, there is a need for a method that indicates the quality of the sensor placements in sEMG. The purpose of this paper is to describe the use of source separation for sEMG using ICA. The actual use in practical sEMG experiments is demonstrated, when the number of recording channels for electrical muscle activities is varied.
Genetic manipulation of myoblasts and a novel primary myosatellite cell culture system: comparing and optimizing approaches
Authors: Jackson Melissa F. , Hoversten Knut E. , Powers John M. , Trobridge Grant D. , Rodgers Buel D.
Published: November 2012

The genetic manipulation of skeletal muscle cells in vitro is notoriously difficult, especially when using undifferentiated muscle cell lines (myoblasts) or primary muscle stem cells (myosatellites). We therefore optimized methods of gene transfer by overexpressing green fluorescent protein (GFP) in mouse C2C12 cells and in a novel system, primary rainbow trout myosatellite cells. A common lipid‐based transfection reagent was used (Lipofectamine 2000) along with three different viral vectors: adeno‐associated virus serotype 2 (AAV2), baculovirus (BAC) and lentivirus. Maximal transfection efficiencies of 49% were obtained in C2C12 cells after optimizing cell density and reagent : DNA ratio, although the GFP signal rapidly dissipated with proliferation and was not maintained with differentiation. The transduction efficiency of AAV2 was optimized to 65% by extending incubation time and decreasing cell density, although only 30% of cells retained expression after passing. A viral comparison revealed that lentivirus was most efficient at transducing C2C12 myoblasts as 97% of cells were transduced with only 106 viral genomes (vg) compared to 54% with 108 vg AAV2 and 23% with 109 vg BAC. Lentivirus also transduced 90% of primary trout myosatellites compared to 1–10% with AAV2 and BAC. The phosphoglycerate kinase 1 (pgk) promoter was 10‐fold more active than the cytomegalovirus immediate‐early promoter in C2C12 cells and both were effective in trout myosatellites. Maximal transduction of C2C12 myotubes was achieved by differentiating myoblasts previously transduced with lentivirus and the pgk promoter. Thus, our optimized protocol proved highly effective in diverse muscle cell systems and could therefore help overcome a common technological barrier.
Role of transcription factor Sp1 and RNA binding protein HuR in the downregulation of Dr+Escherichia coli receptor protein decay accelerating factor (DAF or CD55) by nitric oxide
Authors: Banadakoppa Manu , Liebenthal Daniel , Nowak David E. , Urvil Petri , Yallampalli Uma , Wilson Gerald M. , Kishor Aparna , Yallampalli Chandra
Published: November 2012

We previously reported that nitric oxide (NO) reduces the rate of bacteremia and maternal mortality in pregnant rats with uterine infection by Escherichia coli expressing the Dr Fimbria (Dr+). The epithelial invasion of Dr+ E. coli is dependent on the expression level of its cellular receptor decay accelerating factor (DAF). NO reduces the rate of bacteremia by downregulating the expression of DAF. In this study, we elucidated the role of transcription factor Sp1 and RNA binding protein HuR in the downregulation of human DAF by NO. We generated a series of deletion mutant constructs of DAF gene 5′‐untranslated region and mapped the NO‐response region upstream to the core promoter region of the DAF gene. One of the several Sp1 binding sites in the DAF 5′‐untranslated region was located within the NO‐response region. The binding of Sp1 to this site was inhibited by NO. Furthermore, NO also promoted the degradation of DAF mRNA. The 3′‐untranslated region of DAF harbors an AU‐rich element and this element destabilized the mRNA transcript. NO promoted the rapid degradation of DAF mRNA by inhibiting the binding of mRNA stabilizing protein HuR to this AU‐rich region. The inhibition of binding of HuR to the AU‐rich region was due to the S‐nitrosylation of one or more cysteine residues by NO. Thus, these data reveal the molecular mediators of transcriptional and post‐transcriptional regulation of DAF by NO with implications in pathophysiology related to DAF.
Role of GSH/GSSG redox couple in osteogenic activity and osteoclastogenic markers of human osteoblast‐like SaOS‐2 cells
Authors: Romagnoli Cecilia , Marcucci Gemma , Favilli Fabio , Zonefrati Roberto , Mavilia Carmelo , Galli Gianna , Tanini Annalisa , Iantomasi Teresa , Brandi Maria L. , Vincenzini Maria T.
Published: November 2012

This study comprised a comprehensive analysis of the glutathione (GSH) redox system during osteogenic differentiation in human osteoblast‐like SaOS‐2 cells. For the first time, a clear relationship between expression of specific factors involved in bone remodeling and the changes in the GSH/oxidized GSH (GSSG) redox couple induced during the early phases of the differentiation and mineralization process is shown. The findings show that the time course of differentiation is characterized by a decrease in the GSH/GSSG ratio, and this behavior is also related to the expression of osteoclastogenic markers. Maintenance of a high GSH/GSSG ratio due to GSH exposure in the early phase of this process increases mRNA levels of osteogenic differentiation markers and mineralization. Conversely, these events are decreased by a low GSH/GSSG ratio in a reversible manner. Redox regulation of runt‐related transcription factor‐2 (RUNX‐2) activation through phosphorylation is shown. An inverse relationship between RUNX‐2 activation and extracellular signal‐regulated kinases related to GSH redox potential is observed. The GSH/GSSG redox couple also affects osteoclastogenesis, mainly through osteoprotegerin down‐regulation with an increase in the ratio of receptor activator of NF‐κB ligand to osteoprotegerin and vice versa. No redox regulation of receptor activator of NF‐κB ligand expression was found. These results indicate that the GSH/GSSG redox couple may have a pivotal role in bone remodeling and bone redox‐dysregulated diseases. They suggest therapeutic use of compounds that are able to modulate not just the GSH level but the intracellular redox system through the GSH/GSSG redox couple.