bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of placental weight centiles is useful to estimate cause of fetal growth restriction
Authors: Hasegawa Junichi , Arakawa Kaori , Nakamura Masamitsu , Matsuoka Ryu , Ichizuka Kiyotake , Katsufumi Otsuki , Sekizawa Akihiko , Okai Takashi
Published: July 2011

Aim:  To establish a nomogram of placental weight at delivery and to clarify the associations among standardized placental weights and known risk factors of fetal growth restriction (FGR).

Material and Methods:  Consequent cases who delivered singleton babies after 22 weeks of gestation at our hospital between 2005 and 2009 were retrospectively analyzed using the hospital database. The data of neonatal birth weight, placental weight, maternal demographics and variables associated with FGR were collected. From these data, we established the nomogram of neonatal and placental weight, and fetal : placental weight ratio against gestational age at the delivery. According to regression formula, the z‐score of the neonatal and placental weights were calculated, and the relation between the standardized placental weights and risk factors associated with growth restriction were analyzed.

Results:  Nomograms of neonatal and placental weight, and fetal : placental weight ratio were demonstrated using 3434 cases. Z‐scores of placental weights were low in cases with low maternal body mass index, preeclampsia, abnormal placental forms and short umbilical cord. They were also low in cases with ‘placental dysfunction’, which we usually defined when any other known risk factor was not seen in FGR cases.

Conclusion:  A standard curve of placental weight would be a useful tool to explain a certain degree of placental development and the cause of FGR, and to use for further research.
Fetal hemodynamic changes following maternal betamethasone administration in monochorionic twin pregnancies featuring one twin with selective growth restriction and abnormal umbilical artery Doppler
Authors: Chang Yao‐Lung , Chang Shuenn‐Dyh , Chao An‐Shine , Hsieh Peter C. C. , Wang Chao‐Nin , Wang Tzu‐Hao
Published: July 2011

Aim:  To evaluate fetal hemodynamic changes following maternal betamethasone administration in monochorionic twin pregnancies featuring one twin with selective intrauterine growth restriction (sIUGR) and absence of end‐diastolic velocity in umbilical artery (UA) Doppler.

Material and Methods:  sIUGR was defined as fetal weight below the 10th percentile in one twin and inter‐twin birth weight discordance >25%. The results of Doppler examinations including UA, middle cerebral artery (MCA) and ductus venosus directly prior to (D0), at 24 h (D1) and 48 h (D2) after administration of the first dose of betamethasone were recorded. Cerebral‐placenta ratio was defined as MCA pulsatility index (PI) divided by UA‐PI.

Results:  In four (20%) of the 20 cases, the UA Doppler of the growth‐restricted twin returned to positive end‐diastolic velocity after betamethasone administration. The UA‐PI and MCA‐PI of the sIUGR twin changed significantly after betamethasone administration: UA‐PI was decreased at D1, the MCA‐PI was reduced at both D1 and D2, and the cerebral‐placenta ratio was not altered after betamethasone administration in the sIUGR twin.

Conclusion:  The hemodynamic changes after betamethasone administration were different between the two monochorionic twin fetuses where one presented with sIUGR and absence of UA end‐diastolic velocity. The etiology of a low rate of return of end‐diastolic velocity in the sIUGR twin needs further evaluation.
Predictors associated with severity of pelvic actinomycosis
Authors: Koo Yu‐Jin , Kwon Yong‐Soon , Shim Jae‐Uk , Mok Jung‐Eun
Published: July 2011

Aim:  To evaluate the clinical features of pelvic actinomycosis and to identify predictive factors associated with severity of pelvic actinomycosis.

Material and Methods:  Medical records of 25 patients diagnosed with pelvic actinomycosis and treated by surgery between September 1994 and March 2010 at Cheil General Hospital and Women's Healthcare Center were reviewed retrospectively.

Results:  Of the 25 patients, 15 (60%) had mild pelvic actinomycosis with adhesion and abscess but no complications. The other 10 patients (40%) had an aggressive state of pelvic actinomycosis accompanied by diverse complications, such as hydroureter, abscess rupture, bowel obstruction and cystoenteric fistula. The aggressive actinomycosis correlated with fever, higher neutrophil percentage and a higher white blood cell count to hemoglobin ratio compared to those with mild pelvic actinomycosis. However, there were no significant differences in the use of intrauterine devices, C‐reactive peptide level or mass size between those with mild and aggressive pelvic actinomycosis.

Conclusion:  Using the clinical factors, such as fever, neutrophil percentage and white blood cell count to hemoglobin ratio, the surgeons can more accurately predict the severity of pelvic actinomycosis, thus being helpful for more proper disease management.
Metastatic urachal carcinoma of the ovary
Authors: Jo Eun Ju , Choi Chel Hun , Bae Duk‐Soo , Park Se Hoon , Hong Sung‐Ran , Lee Je‐Ho
Published: July 2011

A 52‐year‐old woman had undergone a partial cystectomy for a cystic mass at the dome of the urinary bladder in 1997. The pathological diagnosis was a urachal mucinous cystadenoma with borderline malignancy. Twelve years later, multiple masses were noted on the uterus, ovaries and abdominal wall. She underwent debulking surgery, including a total hysterectomy, bilateral salpingo‐oophorectomy, pelvic lymph node dissection, infracolic omentectomy, appendectomy, colon mass removal and abdominal wall mass removal. Remnants of the tumor were seeded throughout the abdominal cavity. The pathological evaluation confirmed metastatic urachal mucinous adenocarcinoma in both ovaries, the abdominal wall, the colon mass, the uterosacral ligament and the bladder. Adjuvant chemotherapy with paclitaxel and carboplatin was administered, which showed stable disease. She is now undergoing second‐line chemotherapy.
Impact of a single perioperative dose of dexamethasone on the incidence of surgical site infections: A case–control study
Authors: Eberhart Leopold H. J. , Holdorf Stefanie , Albert Ute S. , Kalder Matthias , Kerwat Klaus , Kranke Peter , Morin Astrid M.
Published: July 2011

Aims:  Dexamethasone is recommended in several international guidelines to prevent postoperative nausea and vomiting, a problem especially frequent in gynecological patients. Despite the increasing use of dexamethasone for this indication there are limited data concerning potential harmful effects of corticosteroids in surgical patients, especially the potential negative impact on wound healing and surgical site infection (SSI). This case–control study was conducted to look for potentially harmful effects of a single perioperative dose of dexamethasone with respect to the occurrence of SSI in gynecological and obstetric surgery patients.

Materials and Methods:  We retrospectively analyzed 3449 patients undergoing inpatient gynecological or obstetric surgical procedures for the occurrence of deep SSI requiring surgical intervention or prolonged antibiotic treatment. These case patients were matched to control patients according to the surgeon performing the procedure, the type of surgery, biometric data, and known risk factors for SSI. Furthermore, timely linearity of dexamethasone use and SSI rate was exploratorily analyzed using several auto‐regressive, integrated, moving‐average models.

Results:  Forty patients with deep SSI were matched to 158 controls. The risk profile for wound infections of both groups was comparable. Forty‐five percent (95% confidence interval: 29–62%) of the case patients were treated with dexamethasone and 49% (95% confidence interval: 41–57%) of the control group received the drug. An increasing use of dexamethasone over time was not followed by an increased SSI rate. There were no timely correlations between dexamethasone usage and the occurrence of SSI.

Conclusion:  In this case–control study we could not detect any evidence for an increased risk for SSI after a single‐dose of dexamethasone (4–8 mg) in gynecological patients.
Reciprocal Associations Between Family and Peer Conflict in Adolescents’ Daily Lives
Authors: Chung Grace H. , Flook Lisa , Fuligni Andrew J.
Published: July 2011

Using a daily diary method, this study assessed daily episodes of family and peer conflict among 578 adolescents in the 9th grade to examine potential bidirectional associations between the family and peer domains. Adolescents completed a daily diary checklist at the end of each day over a 14‐day period to report events of conflict and their emotional states for a given day. Overall, the within‐person models provided evidence for the bidirectional nature of family peer linkages across gender and ethnicity. Adolescents experienced more peer conflict on days in which they argued with parents or other family members, and vice versa. Effect of family conflict further spilled over into peer relationships the next day and 2 days later, whereas peer conflict predicted only the following day family conflict. Adolescents’ emotional distress partially explained these short‐term spillovers between family and peer conflict.
Fast continuous‐discrete DAF‐filters
Authors: Mazzoni Thomas
Published: July 2011

This article introduces a new method for nonlinear continuous‐discrete filtering. It is shown that the Fokker–Planck‐equation can be solved numerically by using distributed approximating functionals (DAFs). The approximation is very accurate and resolves the time interval between observations in one calculation step. Additionally, the operator matrix has to be evaluated only once and not necessarily online. Therefore, the method is very efficient.
PET in coma and in vegetative state
Authors: Heiss W. –D.
Published: July 2011

Advances in resuscitation and critical care management have resulted in the survival of many patients despite severe brain damage. These patients may remain in coma or in vegetative state. The probability of recovery of conscious function is dependent on the extent of structural brain damage, which is difficult to assess by clinical, laboratory or functional tests. Positron emission tomography (PET) of 18F‐fluordeoxyglucose (FDG) can be used to investigate metabolic and functional impairment of the brain. In acute vegetative state (AVS, duration < 1 month), overall glucose utilization was significantly reduced in comparison with age‐matched controls. In a few cases with locked‐in syndrome, cortical metabolism was in the normal range. 11C‐Flumazenil (FMZ) measures the density of benzodiazepine receptors (BZRs) and thereby furnishes an estimate of neuronal integrity. PET with this tracer demonstrated a considerable reduction in BZRs in cortical areas, but indicated that the cerebellum was spared from neuronal loss. The comparison of FDG‐ and FMZ‐PET findings in AVS demonstrates that alterations of cerebral glucose consumption do not represent mere functional inactivation, but also irreversible structural damage. In some cases with minimally conscious state, auditory stimuli with emotional valence induced more brain activation (investigated by H215O‐PET) than meaningless noise; such studies can be used to detect residual cortical function. To improve prognostication of chances for recovery, a combination of functional activation studies and assessment of the extent of neuronal damage might be the optimal procedure and should be tested in larger cohorts of patients with comatose states of different severity.
Rooted Cosmopolitanism: Spaces of Multiplicity in Cusco, Peru
Authors: LAWHON MARY , CHION MIRIAM
Published: July 2011

Cosmopolitanism has recently been revived as a concept through which to explore increasing global interactions. While many theoretical advances have been made, these conversations focus on urban centers in the global North and remain caught up in binary concepts such as the global/local. In our article, we start with an empirical set of social processes and spatial practices in Cusco, a global South city with extensive international connections. To this we add theoretical concepts of rooted cosmopolitanism and multiplicity of space to move beyond the global/local dichotomy. We then formulate our theorization of the production of cosmopolitan places and propose a revised conceptualization of rooted cosmopolitanism. The multiple stories of Cusco allowed us to recognize the production of rooted cosmopolitan places through three interrelated processes: openness to diversity and difference, valuing of own aesthetics based on personal preferences and local traditions, and territorial commitment to shared space and its people. We provide examples of these processes, and posit the need for them to occur simultaneously, to show the potential for a rooted cosmopolitanism. Our intention is not to establish a set of criteria for development but to contribute to conversations on understanding, evaluating and negotiating diverse flows in place.

Dernièrement, le cosmopolitisme a réapparu en tant que concept permettant d'explorer les interactions mondiales croissantes. De nombreux progrès théoriques ont été réalisés, mais les débats se focalisent sur les centres urbains des pays du Nord, restant prisonniers de notions binaires tels que mondial/local. Cet article présente d'abord un ensemble empirique de processus sociaux et de pratiques spatiales propres à Cuzco, ville mondiale du Sud dotée de vastes connexions internationales. Viennent s'ajouter les concepts théoriques de cosmopolitisme enraciné et de multiplicité de l'espace pour échapper à la dichotomie du mondial/local. Ce travail aboutit à une théorisation de la production de lieux cosmopolites et reformule la conceptualisation du cosmopolitisme enraciné. En partant des multiples récits sur Cuzco, il est possible de reconnaître la production de lieux cosmopolites enracinés grâce à trois processus liés: l'ouverture à la diversité et à la différence; la valorisation d'une esthétique propre basée sur des préférences personnelles et des traditions locales; un engagement territorial à l'égard de l'espace partagé et de sa population. Le potentiel du cosmopolitisme enraciné est montréà l'aide d'exemples de ces processus, ceux‐ci devant, par principe, se produire simultanément. Il ne s'agit pas ici de définir une liste de critères de développement, mais de contribuer aux échanges sur la compréhension, l'évaluation et la négociation des divers flux existants.
Emotional reactivity to emotional and smoking cues during smoking abstinence: Potentiated startle and P300 suppression
Authors: Engelmann Jeffrey M. , Gewirtz Jonathan C. , Cuthbert Bruce N.
Published: July 2011

Negative affect is thought to be an important factor in the maintenance of cigarette smoking, and thus it is important to further develop objective measures of smoking‐related emotional responses. Nonsmokers, nonabstinent smokers, and abstinent smokers participated in a cue reactivity task where eyeblink startle amplitude and startle probe P300 (P3) suppression were measured during the presentation of emotional pictures. During unpleasant pictures, the amplitude of both measures was smaller in nonabstinent smokers than in nonsmokers or abstinent smokers. P3 suppression, but not startle amplitude, was larger in abstinent smokers than in nonsmokers. Abstinence‐induced increases in cigarette craving were associated with P3 suppression during tobacco‐related pictures. Results suggest that tobacco abstinence increases emotional reactivity to unpleasant stimuli, which is consistent with negative reinforcement models of tobacco addiction.
Pregnancy incidence and outcome among patients with cervical intraepithelial neoplasia: a retrospective cohort study
Authors: Kalliala I , Anttila A , Dyba T , Hakulinen T , Halttunen M , Nieminen P
Published: July 2011

Please cite this paper as: Kalliala I, Anttila A, Dyba T, Hakulinen T, Halttunen M, Nieminen P. Pregnancy incidence and outcome among patients with cervical intraepithelial neoplasia: a retrospective cohort study. BJOG 2012;119:227–235.

Objective  To investigate the effect of cervical intraepithelial neoplasia (CIN) treatment on incidence of pregnancy and pregnancy outcome.

Design  Retrospective cohort study.

Setting  Helsinki University Central Hospital, Finland, the sole reference centre in the Helsinki–Uusimaa region for women referred for colposcopy.

Population  A cohort of 6179 women treated for CIN between 1974 and 2001, and a randomly selected, age‐ and municipality‐matched, reference population of 30 436 women.

Methods  Based on nationwide registers, all women were followed‐up for pregnancy outcomes until death, emigration, sterilization, or until the end of 2004.

Main outcome measures  Incidence of any pregnancy, livebirths, miscarriages, extrauterine pregnancies, molar pregnancies, and terminations of pregnancies (TOPs) before and after CIN treatment, estimated by calculating hazard ratios (HRs) with stratified Cox regression and Poisson regression.

Results  After CIN treatment, both incidence of pregnancy (HR 1.20; 95% CI 1.15–1.26; P < 0.001) and incidence of livebirths (HR 1.12; 95% CI 1.06–1.18; P < 0.001) were higher among the treated women than among the reference population. Before treatment, only incidence of pregnancy had been elevated among those treated (HR 1.06; 95% CI 1.04–1.09; P < 0.001). The incidence of extrauterine pregnancies and of TOPs was significantly elevated among those treated both before and after CIN treatment.

Conclusions  No clear evidence emerged of adverse effects resulting from the CIN treatment itself, because the women treated had more pregnancies and more children than their reference population. TOPs and extrauterine pregnancies were more common among the treated women already before the CIN treatment.
A Study of Bistable Laminates of Generic Lay‐Up for Adaptive Structures
Authors: Bowen C. R. , Betts D. N. , Giddings P. F. , Salo A. I. T. , Kim H. A.
Published: July 2011

Abstract:  Asymmetric laminates are known to exhibit two stable cylindrical states and one unstable saddle state. Such bistability has attracted attention in aerospace applications because of the potential low energy requirement to achieve a large deflection or change in shape. This paper presents experimental observations of a generic asymmetric [−30/60] laminate with and without piezoelectric actuation and compares against both energy‐based analytical and finite element (FE) models. It is observed that the analytical model offers a qualitative understanding of bistable behaviour, degree of curvature and overall shape but is unable to model the distinctive curvature changes near the boundaries which can be captured by the FE model. The investigation also presents the use of piezoelectric actuation to achieve snap‐through in both analytical and FE models, which is compared and validated with experimental characterisation.
World class? An investigation of globalisation, difference and international student mobility
Authors: Findlay Allan M , King Russell , Smith Fiona M , Geddes Alistair , Skeldon Ronald
Published: July 2011

This paper explores the motivations and meanings of international student mobility. Central to the discussion are the results of a large questionnaire survey and associated in‐depth interviews with UK students enrolled in universities in six countries from around the world. The results suggest, first, that several different dimensions of social and cultural capital are accrued through study abroad. It is argued that the search for ‘world class’ education has taken on new significance. Second, the paper argues that analysis of student mobility should not be confined to a framework that separates study abroad from the wider life‐course aspirations of students. It is argued that these insights go beyond existing theorisations of international student mobility to incorporate recognition of diverse approaches to difference within cultures of mobility, including class reproduction of distinction, broader notions of distinction within the life‐plans of individual students, and how ‘reputations’ associated with educational destinations are structured by individuals, institutions and states in a global higher education system that produces differentially mediated geographies of international student mobility.
The thermo‐TRP ion channel family: properties and therapeutic implications
Authors: Vay Laura , Gu Chunjing , McNaughton Peter A
Published: July 2011

The thermo‐transient receptor potentials (TRPs), a recently discovered family of ion channels activated by temperature, are expressed in primary sensory nerve terminals where they provide information about thermal changes in the environment. Six thermo‐TRPs have been characterised to date: TRP vanilloid (TRPV) 1 and 2 are activated by painful levels of heat, TRPV3 and 4 respond to non‐painful warmth, TRP melastatin 8 is activated by non‐painful cool temperatures, while TRP ankyrin (TRPA) 1 is activated by painful cold. The thermal thresholds of many thermo‐TRPs are known to be modulated by extracellular mediators, released by tissue damage or inflammation, such as bradykinin, PG and growth factors. There have been intensive efforts recently to develop antagonists of thermo‐TRP channels, particularly of the noxious thermal sensors TRPV1 and TRPA1. Blockers of these channels are likely to have therapeutic uses as novel analgesics, but may also cause unacceptable side effects. Controlling the modulation of thermo‐TRPs by inflammatory mediators may be a useful alternative strategy in developing novel analgesics.
2′‐Methoxy‐6‐methylflavone: a novel anxiolytic and sedative with subtype selective activating and modulating actions at GABAA receptors
Authors: Karim Nasiara , Curmi John , Gavande Navnath , Johnston Graham AR , Hanrahan Jane R , Tierney M Louise , Chebib Mary
Published: July 2011

BACKGROUND AND PURPOSE Flavonoids are known to have anxiolytic and sedative effects mediated via actions on ionotropic GABA receptors. We sought to investigate this further.

EXPERIMENTAL APPROACH We evaluated the effects of 2′‐methoxy‐6‐methylflavone (2′MeO6MF) on native GABAA receptors in new‐born rat hippocampal neurons and determined specificity from 18 human recombinant GABAA receptor subtypes expressed in Xenopus oocytes. We used ligand binding, two‐electrode voltage clamp and patch clamp studies together with behavioural studies.

KEY RESULTS 2′MeO6MF potentiated GABA at α2β1γ2L and all α1‐containing GABAA receptor subtypes. At α2β2/3γ2L GABAA receptors, however, 2′MeO6MF directly activated the receptors without potentiating GABA. This activation was attenuated by bicuculline and gabazine but not flumazenil indicating a novel site. Mutation studies showed position 265 in the β1/2 subunit was key to whether 2′MeO6MF was an activator or a potentiator. In hippocampal neurons, 2′MeO6MF directly activated single‐channel currents that showed the hallmarks of GABAA Cl‐ currents. In the continued presence of 2′MeO6MF the single‐channel conductance increased and these high conductance channels were disrupted by the γ2(381–403) MA peptide, indicating that such currents are mediated by α2/γ2‐containing GABAA receptors. In mice, 2′MeO6MF (1–100 mg·kg−1; i.p.) displayed anxiolytic‐like effects in two unconditioned models of anxiety: the elevated plus maze and light/dark tests. 2′MeO6MF induced sedative effects at higher doses in the holeboard, actimeter and barbiturate‐induced sleep time tests. No myorelaxant effects were observed in the horizontal wire test.

CONCLUSIONS AND IMPLICATIONS 2′MeO6MF will serve as a tool to study the complex nature of the activation and modulation of GABAA receptor subtypes.
On the inhibition of 5‐lipoxygenase product formation by tryptanthrin: mechanistic studies and efficacy in vivo
Authors: Pergola C , Jazzar B , Rossi A , Northoff H , Hamburger M , Sautebin L , Werz O
Published: July 2011

BACKGROUND AND PURPOSE Leukotrienes (LTs) are pro‐inflammatory mediators produced by 5‐lipoxygenase (5‐LO). Currently available 5‐LO inhibitors either lack efficacy or are toxic and novel approaches are required to establish a successful anti‐LT therapy. Here we provide a detailed evaluation of the effectiveness of the plant‐derived alkaloid tryptanthrin as an inhibitor of LT biosynthesis.

EXPERIMENTAL APPROACH We analysed LT formation and performed mechanistic studies in human neutrophils stimulated with pathophysiologically relevant stimuli (LPS and formyl peptide), as well as in cell‐free assays (neutrophil homogenates or recombinant human 5‐LO) and in human whole blood. The in vivo effectiveness of tryptanthrin was evaluated in the rat model of carrageenan‐induced pleurisy.

KEY RESULTS Tryptanthrin potently reduced LT‐formation in human neutrophils (IC50= 0.6 µM). However, tryptanthrin is not a redox‐active compound and did not directly interfere with 5‐LO activity in cell‐free assays. Similarly, tryptanthrin did not inhibit the release of arachidonic acid, the activation of MAPKs, or the increase in [Ca2+]i, but it modified the subcellular localization of 5‐LO. Moreover, tryptanthrin potently suppressed LT formation in human whole blood (IC50= 10 µM) and reduced LTB4 levels in the rat pleurisy model after a single oral dose of 10 mg·kg−1.

CONCLUSIONS AND IMPLICATIONS Our data reveal that tryptanthrin is a potent natural inhibitor of cellular LT biosynthesis with proven efficacy in whole blood and is effective in vivo after oral administration. Its unique pharmacological profile supports further analysis to exploit its pharmacological potential.
Pyridoxine inhibits endothelial NOS uncoupling induced by oxidized low‐density lipoprotein via the PKCα signalling pathway in human umbilical vein endothelial cells
Authors: Xie Liping , Liu Zhen , Lu Hui , Zhang Wen , Mi Qiongyu , Li Xiaozhen , Tang Yan , Chen Qi , Ferro Albert , Ji Yong
Published: July 2011

BACKGROUND AND PURPOSE One key mechanism for endothelial dysfunction is endothelial NOS (eNOS) uncoupling, whereby eNOS generates superoxide (O2•−) rather than NO. We explored the effect of pyridoxine on eNOS uncoupling induced by oxidized low‐density lipoprotein (ox‐LDL) in human umbilical vein endothelial cells (HUVECs) and the potential molecular mechanism.

EXPERIMENTAL APPROACH HUVECs were incubated with ox‐LDL with/without pyridoxine, NG‐nitro‐L‐arginine methylester (L‐NAME), chelerythrine chloride (CHCI) or apocynin. Endothelial O2•− was measured using lucigenin chemiluminescence, and O2•−‐sensitive fluorescent dye dihydroethidium (DHE). NO levels were measured by chemiluminescence, PepTag Assay for non‐radioactive detection of PKC activity, depletion of PKCα and p47phox by siRNA silencing and the states of phospho‐eNOS Thr495, total‐eNOS, phospho‐PKCα/βII, total PKC, phospho‐PKCα, total PKCα and p47phox were measured by Western blot.

KEY RESULTS Ox‐LDL significantly increased O2•− production and reduced NO levels released from HUVECs; an effect reversed by eNOS inhibitor, L‐NAME. Pyridoxine pretreatment significantly inhibited ox‐LDL‐induced O2•− generation and preserved NO levels. Pyridoxine also prevented the ox‐LDL‐induced reduction in phospho‐eNOS Thr495 and PKC activity. These protective effects of pyridoxine were abolished by the PKC inhibitor, CHCI, or siRNA silencing of PKCα. However, depletion of p47phox or treatment with the NADPH oxidase inhibitor, apocynin, had no influence on these effects. Also, cytosol p47phox expression was unchanged by the different treatments.

CONCLUSIONS AND IMPLICATIONS Pyridoxine mitigated eNOS uncoupling induced by ox‐LDL. This protectant effect was related to phosphorylation of eNOS Thr495 stimulated by PKCα, not via NADPH oxidase. These results provide support for the use of pyridoxine in ox‐LDL‐related vascular endothelial dysfunction.
Inhibitory kappa B kinases as targets for pharmacological regulation
Authors: Gamble Carly , McIntosh Kathryn , Scott Rebecca , Ho Ka Ho , Plevin Robin , Paul Andrew
Published: July 2011

The inhibitory kappa B kinases (IKKs) are well recognized as key regulators of the nuclear factor kappa B (NF‐κB) cascade and as such represent a point of convergence for many extracellular agents that activate this pathway. The IKKs generally serve to transduce pro‐inflammatory and growth stimulating signals that contribute to major cellular processes but also play a key role in the pathogenesis of a number of human diseases. Therefore, the catalytic IKKs represent attractive targets for intervention with small molecule kinase inhibitors. IKK isoforms are assembled as variable multi‐subunit IKK complexes that regulate not only NF‐κB dimers, but also protein substrates out‐with this cascade. Consequently, close consideration of how these individual complexes transduce extracellular signals and more importantly what impact small molecule inhibitors of the IKKs have on functional outcomes are demanded. A number of adenosine triphosphate (ATP)‐competitive IKKβ‐selective inhibitors have been developed but have demonstrated a lack of activity against IKKα. A number of these chemicals have also exhibited detrimental outcomes such as cellular toxicity and immuno‐suppression. The impact of small molecule inhibitors of IKK catalytic activity will therefore be reappraised, examining the advantages and potential disadvantages to this type of intervention strategy in the treatment of diseases such as arthritis, intestinal inflammation and cancer. Furthermore, we will outline some emerging strategies, particularly the disruption of protein–protein interactions within the IKK complex, as an alternative route towards the development of novel pharmacological agents. Whether these alternatives may negate the limitations of ATP‐competitive molecules and potentially avoid the issues of toxicity will be discussed.
Specimen‐Based Modeling, Stopping Rules, and the Extinction of the Ivory‐Billed Woodpecker
Authors: GOTELLI NICHOLAS J. , CHAO ANNE , COLWELL ROBERT K. , HWANG WEN‐HAN , GRAVES GARY R.
Published: July 2011

Abstract:  Assessing species survival status is an essential component of conservation programs. We devised a new statistical method for estimating the probability of species persistence from the temporal sequence of collection dates of museum specimens. To complement this approach, we developed quantitative stopping rules for terminating the search for missing or allegedly extinct species. These stopping rules are based on survey data for counts of co‐occurring species that are encountered in the search for a target species. We illustrate both these methods with a case study of the Ivory‐billed Woodpecker (Campephilus principalis), long assumed to have become extinct in the United States in the 1950s, but reportedly rediscovered in 2004. We analyzed the temporal pattern of the collection dates of 239 geo‐referenced museum specimens collected throughout the southeastern United States from 1853 to 1932 and estimated the probability of persistence in 2011 as <6.4 × 10−5, with a probable extinction date no later than 1980. From an analysis of avian census data (counts of individuals) at 4 sites where searches for the woodpecker were conducted since 2004, we estimated that at most 1–3 undetected species may remain in 3 sites (one each in Louisiana, Mississippi, Florida). At a fourth site on the Congaree River (South Carolina), no singletons (species represented by one observation) remained after 15,500 counts of individual birds, indicating that the number of species already recorded (56) is unlikely to increase with additional survey effort. Collectively, these results suggest there is virtually no chance the Ivory‐billed Woodpecker is currently extant within its historical range in the southeastern United States. The results also suggest conservation resources devoted to its rediscovery and recovery could be better allocated to other species. The methods we describe for estimating species extinction dates and the probability of persistence are generally applicable to other species for which sufficient museum collections and field census results are available.
Stability of sapphirine + quartz in the oxidized rocks of the Wilson Lake terrane, Labrador: calculated equilibria in NCKFMASHTO
Authors: KORHONEN F. J. , POWELL R. , STOUT J. H.
Published: July 2011

The equilibrium coexistence of sapphirine + quartz is inferred to record temperatures in excess of 980 °C, based on the stability of this assemblage in the simplified chemical system FeO–MgO–Al2O3–SiO2 (FMAS) system. However, the potential for sapphirine to contain significant Fe3+ suggests that the stability of sapphirine + quartz could extend to lower temperatures than those constrained in this ideal system. The Wilson Lake terrane in the Grenville Province of central Labrador preserves sapphirine + quartz‐bearing assemblages in highly oxidized bulk compositions, and provides an opportunity to explore the stability of sapphirine + quartz in such rock compositions within the Na2O–CaO–K2O–FeO–MgO–Al2O3–SiO2–H2O–TiO2–O (NCKFMASHTO) chemical system. Starting with the phase equilibria in FeO–MgO–Al2O3–SiO2–TiO2–O (FMASTO), expansion into K2O–FeO–MgO–Al2O3–SiO2–H2O–TiO2–O (KFMASHTO) allows the effect of the stability of the additional phases, biotite, K‐feldspar and melt, on the stability of sapphirine + quartz to be assessed. These phase relations are evaluated generally using P–T projections, and the ultimate extension into NCKFMASHTO is done with pseudosections. Conditions of peak metamorphism in the Wilson Lake terrane are constrained using P–T pseudosections, and the appropriate H2O and O contents to use in the modelled compositions are investigated using T–MH2O and T–MO pseudosections. The peak P–T estimates from a sapphirine + quartz‐bearing sample are ∼960 to 935 °C at ∼10 to 8.6 kbar, similar to estimates from orthopyroxene + sillimanite + quartz ± garnet‐bearing samples. Whereas the sapphirine + quartz‐bearing sample is more Fe‐rich than the orthopyroxene + sillimanite‐bearing sample on an all‐Fe‐as‐FeO basis, once the oxidation state is taken into account, the former is effectively more magnesian than the latter, accounting for the sapphirine occurrence.
Headache in Systemic Lupus Erythematosus vs Multiple Sclerosis: A Prospective Comparative Study
Authors: Katsiari Christina G. , Vikelis Michail , Paraskevopoulou Eleftheria S. , Sfikakis Petros P. , Mitsikostas Dimos D.
Published: July 2011

Objective.— To clarify whether headache, and particularly migraine, belongs to the spectrum of neurologic manifestations of systemic lupus erythematosus (SLE), the archetypal autoimmune disease.

Methods.— Consecutive SLE patients were matched 1:1 for age, gender, and level of education with healthy control subjects. A representative subgroup of SLE patients were also matched with patients suffering from multiple sclerosis (MS), a nervous system‐specific autoimmune disease. All study participants were assessed for headache present in the previous year. Anxiety, depression, and quality of life were also estimated at baseline. During the following year, all participants were assessed every 3 months using specific headache diaries.

Results.— Seventy‐two SLE/control pairs and 48 MS patients completed 12 months of follow‐up. Prevalence of migraine, with or without aura, was similar between SLE patients (21%), MS patients (23%), and controls (22%), as was the prevalence of frequent tension‐type headache. Duration and severity of migraine attacks were milder in SLE patients than controls. Only chronic tension‐type headache was significantly more prevalent in SLE patients (12.5%) compared to controls (1.4%). MS patients also presented increased frequency of chronic tension‐type headache (8.3%). No associations of any headache type with particular clinical manifestations, autoantibody, or disease activity, either in SLE or MS patient groups, were found. Irrespective of the presence of headache, anxiety symptoms and impaired quality of life were more frequent among SLE than MS patients or controls.

Conclusion.— Migraine should be no longer considered a neurologic manifestation of systemic or organ‐specific autoimmunity. Increased migraine prevalence in these patients found in previous studies could be due to methodological weaknesses.
Bioactive Coils Cause Headache and Fever After Endovascular Treatment of Intracranial Aneurysms
Authors: Takigawa Tomoji , Matsumaru Yuji , Nakai Yasunobu , Nakamura Kazuhiro , Hayakawa Mikito , Tsuruta Wataro , Matsumura Akira
Published: July 2011

Background.— Based on our encounters with patients who have been treated for unruptured intracranial aneurysms by endovascular coil embolization using bioactive coils, we observed that such patients often present with headaches and fever.

Objective.— The purpose of this study was to evaluate the incidence of headache and fever after coil embolization using bioactive coils.

Methods.— A database of 92 intracranial unruptured aneurysm patients (88 patients who did not have chronic headaches or migraines before treatment) on whom coil embolization had been performed between July 2007 and October 2010 was retrospectively assessed. Forty‐five aneurysms (43 patients) were treated using bioactive coils and the other aneurysms were treated using bare coils. We analyzed the incidence and duration of headache, temperature, C‐reactive protein, and white blood cell count before and after coil embolization and compared the 2 groups.

Results.— Forty‐one patients (46.6%) reported onset of headaches just after treatment. Headache incidences were significantly greater in the patients treated with bioactive coils (bioactive coil group: 62.8% [27/43] vs bare coil group: 31.1% [14/45], P = .003), and the duration of headaches was significantly longer in the bioactive coil group (bioactive coil group: 3.44 ± 1.22 days vs bare coil group: 2.40 ± 1.17 days, P = .027). Seventy‐one patients (80.7%) had incidences of fever (over 37°C) after treatment (bioactive coil group: 83.7% [36/43] vs bare coil group: 77.8% [35/45], P = .663). The duration of fever was significantly longer in the bioactive coil group (bioactive coil group: 2.9 ± 1.4 days vs bare coil group: 1.9 ± 1.1 days, P = .0017), and temperatures at 1, 2, or 3 days after treatment were significantly higher in the bioactive coil group (respective temperatures at 1, 2, 3 days after treatment: bioactive coil group: 37.42 ± 0.49, 37.19 ± 0.45, 37.00 ± 0.49 vs bare coil group: 37.14 ± 0.38, 36.96 ± 0.41, 36.63 ± 0.51, P = .009, P = .0246, P = .0032). There were no significant differences in C‐reactive protein level and white blood cell count 1 and 3 days after treatment between 2 groups.

Conclusions.— Bioactive coils induce headache and fever after coil embolization for intracranial aneurysms due to the inflammatory effects of polyglycolic acid used to accelerate aneurysm fibrosis and neointimal formation.
Long‐Term Evaluation of Sumatriptan and Naproxen Sodium for the Acute Treatment of Migraine in Adolescents
Authors: McDonald Susan A. , Hershey Andrew D. , Pearlman Eric , Lewis Donald , Winner Paul K. , Rothner David , Linder Steven L. , Runken M. Chris , Richard Nathalie E. , Derosier Frederick J.
Published: July 2011

Objectives.— To evaluate the long‐term safety, tolerability, effectiveness, impact on quality of life, and medication satisfaction of sumatriptan/naproxen sodium in the acute treatment of migraine headache in adolescents.

Methods.— This 12‐month, multicenter, open‐label, safety study was conducted in adolescents (aged 12‐17 years) with an average of 2‐8 migraines/month typically lasting >2 hours untreated for >6 months prior to initiation. Subjects were instructed to treat migraines as early as possible and were allowed to rescue 2 hours post dose with a single dose of a naproxen‐containing product, over‐the‐counter pain reliever, or anti‐emetics. Subjects were advised not to take a second tablet of sumatriptan/naproxen sodium without at least a 24‐hour headache‐free period. Safety evaluations included adverse events, laboratory tests, and vital signs and electrocardiogram evaluation. Other evaluations included freedom from pain, quality of life, and medication satisfaction.

Results.— Of the 656 subjects enrolled, 622 (95%) treated at least 1 migraine with sumatriptan/naproxen sodium, of which 435 (70%) and 363 (58%) completed 6 and 12 months of the study, respectively. Overall, there were 12,927 exposures to sumatriptan/naproxen sodium: on average 2.5 tablets were taken per month per subject. The most common treatment‐related adverse events were nausea (7%), dizziness (3%), muscle tightness (3%), and chest discomfort (3%). There were no deaths; 4 subjects had 5 serious adverse events (suicide attempt, hemolytic anemia and syncope, suicidal ideation, spontaneous abortion) unrelated to sumatriptan/naproxen sodium and resolved without sequelae. Seven percent of subjects discontinued participation in the study because of an adverse event; 5% of subjects discontinued due to lack of efficacy. Overall, 42% of the migraine attacks were pain‐free within 2 hours of treatment with sumatriptan/naproxen sodium, subjects reported improvements from baseline in 2 of 3 quality of life domains over time, and were generally satisfied with the efficacy and overall treatment at the end of the study.

Conclusion.— In adolescent migraineurs, after up to 12 months and over 12,000 exposures to sumatriptan/naproxen sodium, there were no new or clinically significant findings in the safety parameters, including the frequency and nature of adverse events, as compared to the individual components or to the adverse event profile in adults. In addition, sumatriptan/naproxen sodium provided freedom from pain over time, improvements in quality of life and medication satisfaction.
The Point Prevalence of Dizziness or Vertigo in Migraine – and Factors That Influence Presentation
Authors: Calhoun Anne H. , Ford Sutapa , Pruitt Amy P. , Fisher Karen G.
Published: July 2011

Objective.— To ascertain and characterize the point prevalence of dizziness or vertigo in migraineurs presenting for routine appointments at a specialty headache clinic.

Background.— Migraine, dizziness, and vertigo are all common in the general population, affecting 13%, 20‐30%, and 5‐10% respectively. Thereby, chance concurrence of migraine with either dizziness or vertigo would be expected in roughly 4% of the general population. It is the authors' clinical impression that severe attacks of migraine are far more commonly associated with these complaints than chance would predict.

Methods.— This is a prospective, cross‐sectional study of 462 consecutive patients who presented for consultation at a specialty headache clinic over a 4‐month period of time. During routine check‐in procedures, patients were asked to report their headache pain on a 1‐10 Likert scale. Patients were also asked to report if they were currently experiencing dizziness or vertigo. Responses to these questions were recorded along with vital signs. Diagnosis of migraine with or without aura was made by headache medicine specialists in accordance with International Classification of Headache Disorders – second edition criteria. Chi‐square analysis was used to examine the prevalence of vertigo or dizziness in subjects with varying intensity of headache, and by history of aura.

Results.— Of the 425 evaluable subjects, 28% experienced aura. Subjects' average age was 43.8 years (range 15 to 76 years); 89.5% were female. At the time of evaluation, 72.4% of subjects reported some degree of ongoing headache pain and 15.7% reported concurrent dizziness or vertigo. The prevalence of dizziness or vertigo was twice as high (24.5% vs 12.1%) in migraine with aura compared to migraine without aura (P < .01), and prevalence increased with age (P < .05). There was a strong correlation between migraine pain and subjective complaint of vertigo (P < .001). When migraine pain was present at an intensity of 7 or greater (on a scale of 1‐10), almost half of the subjects (47.5%) reported concomitant dizziness or vertigo.

Conclusions.— Subjective complaints of dizziness or vertigo appear to be relatively common accompaniments of migraine, particularly migraine with aura, and prevalence increases with age. Disequilibrium symptoms have a strong and positive association with the severity of migraine pain. With co‐occurrence higher than expected by chance, the relationship either reflects comorbidity or these symptoms may be part of the migraine presentation. With a point prevalence of 15.7%, and factors that link expression both to the intensity of migraine pain and to migraine aura, the authors believe that the true relationship may prove to be the latter.
Translation of an Evidence‐Based Social Skills Intervention for Children with Prenatal Alcohol Exposure in a Community Mental Health Setting
Authors: O’Connor Mary J. , Laugeson Elizabeth A. , Mogil Catherine , Lowe Evy , Welch‐Torres Kathleen , Keil Vivien , Paley Blair
Published: July 2011

Background: Children with prenatal alcohol exposure (PAE) have significant social skills deficits and are often treated in community mental health settings. However, it remains unclear whether these children can be effectively treated using manualized, evidence‐based interventions that have been designed for more general mental health populations.

Methods: To shed light on this issue, the effectiveness of Children’s Friendship Training (CFT) versus Standard of Care (SOC) was assessed for 85 children ages 6 to 12 years with and without PAE in a community mental health center.

Results: Children participating in CFT showed significantly improved knowledge of appropriate social skills, improved self‐concept, and improvements in parent‐reported social skills compared to children in the SOC condition. Moreover, results revealed that within the CFT condition, children with PAE performed as well as children without PAE. Findings indicated that CFT, an evidence‐based social skills intervention, yielded greater gains than a community SOC social skills intervention and was equally effective for children with PAE as for those without PAE.

Conclusions: Results suggest that children with PAE can benefit from treatments initiated in community settings in which therapists are trained to understand their unique developmental needs, and that they can be successfully integrated into treatment protocols that include children without PAE.