bluuebunny/crossref_metadata_2025 huggingface dataset:
Dietary Trans Fats Enhance Doxorubicin‐Induced Cardiotoxicity in Mice
Authors: Mong Mei‐chin , Hsia Te‐chun , Yin Mei‐chin
Published: September 2013

This study investigated the combined effects of trans fat diet (TFD) and doxorubicin upon cardiac oxidative, inflammatory, and coagulatory stress. TFD increased trans fatty acid deposit in heart (P < 0.05), and decreased protein C and antithrombin‐III activities in circulation (P < 0.05). TFD plus doxorubicin treatment elevated activities of plasminogen activator inhibitor‐1, lactate dehydrogenase, and creatine phosphokinase (P < 0.05). This combination also raised xanthine oxidase activity, and enhanced cardiac levels of reactive oxygen species, interleukin (IL)‐6, IL‐10, tumor necrosis factor‐alpha, and monocyte chemoattractant protein‐1 than TFD or doxorubicin treatment alone (P < 0.05). TFD alone increased cardiac nuclear factor kappa B (NF‐κB) activity (P < 0.05), but failed to affect expression of NF‐κB and mitogen‐activated protein kinase (MAPK) (P > 0.05). Doxorubicin treatment alone augmented cardiac activity, mRNA expression, and protein production of NF‐κB and MAPK (P < 0.05). TFD plus doxorubicin treatment further upregulated cardiac expression of NF‐κB p65, p‐p38, and p‐ERK1/2 (P < 0.05). These findings suggest that TFD exacerbates doxorubicin‐induced cardiotoxicity.
Quality of life in patients with endometriosis and the effect of pertubation with lidocaine – a randomized controlled trial
Authors: Wickström Karin , Bruse Christine , Sjösten Anette , Spira Jack , Edelstam Greta
Published: September 2013

Objective

Pertubation with lidocaine has been shown to reduce pain (on a VAS‐scale) in women with endometriosis. A clinical study was performed to evaluate the effect of lidocaine pertubations on quality of life.

Design

Double‐blind, randomized and controlled trial.

Setting

Three outpatient units in Stockholm, Sweden.

Population

Eligible patients had endometriosis with dysmenorrhoic pain >VAS 50 mm.

Methods

The patients were randomized to pre‐ovulatory pertubations with lidocaine (n = 24) or placebo (n = 18) during three consecutive menstrual cycles. The procedure comprised passing the solution through the uterus and the Fallopian tubes via an intracervical balloon catheter. The effect was evaluated with the validated Endometriosis Health Profile‐30 questionnaire before and after treatments.

Main outcome measures

Changes in scores at six and 12 months from baseline were compared between the groups with the Mann–Whitney U‐test.

Results

After 6 months there was a significant difference between the lidocaine (n = 19) and the placebo (n = 16) groups for the dimension social support (median −18.8 vs. −6.3, p = 0.034), whereas there were no significant differences for the other dimensions after 6 or 12 months. The mean changes in the lidocaine group were above the minimal important difference levels in eight of 12 measurements of quality of life dimensions compared with two of 12 in the placebo group.

Conclusions

This clinical trial indicates that pertubations with lidocaine might improve the social support dimension of quality of life in patients with endometriosis.
Comparison of Continuous‐Flow and Pulsatile‐Flow Blood Pumps on Reducing Pulmonary Artery Pressure in Patients With Fixed Pulmonary Hypertension
Authors: Ozturk Pelin , Engin Aysen Yaprak , Nalbantgil Sanem , Oguz Emrah , Ayik Fatih , Engin Cagatay , Yagdi Tahir , Erkul Sinan , Balcioglu Ozlem , Ozbaran Mustafa
Published: September 2013

Pulmonary hypertension (PH) is considered as a risk factor for morbidity and mortality in patients undergoing heart transplantation. Recently, left ventricular assist device (LVAD) implantation has been increasingly used in reducing pulmonary artery pressure (PAP) in patients with PH unresponsive to medical therapy. Herein, we aimed to compare the efficacy of continuous‐flow and pulsatile‐flow blood pumps on the improvement of PH in mechanical circulatory support patients. Twenty‐seven patients with end‐stage heart failure who underwent LVAD implantation surgery were enrolled. Fifteen of them (55.6%) had continuous‐flow pump (HeartWare Ventricular Assist System, HeartWare, Inc., Miramar, FL, USA), and 12 of them (44.4%) had pulsatile pump (Berlin Heart EXCOR ventricular assist device, Berlin Heart AG, Berlin, Germany). The efficacy of LVADs on the improvement of PH was compared between continuous‐flow and pulsatile pumps by the evaluation of systolic PAP, tricuspid annular plane systolic excursion (TAPSE), right ventricular systolic motion (RVSM), right ventricular ejection fraction (RVEF), and grade of tricuspid insufficiency (TI) for each of the study participants. All of the 15 patients who underwent continuous‐flow blood pump implantation surgery (Group 1) were male with a mean age of 46.9 ± 11.7 years, and in pulsatile‐flow blood pump implanted participants (Group 2), the mean age was 40.6 ± 16.8 years, all of whom were also male (P = 0.259). Mean follow‐up was 313.7 ± 241.3 days in Group 1 and 448.7 ± 120.7 days in Group 2 (P = 0.139). In Group 1, mean preoperative and postoperative systolic PAP were measured as 51.7 ± 12.2 mm Hg and 22.2 ± 3.4 mm Hg, respectively, while those in Group 2 were 54.5 ± 7.5 mm Hg and 33.9 ± 6.4 mm Hg, respectively. A significantly greater decrease in systolic PAP was noticed in patients with continuous‐flow blood pumps (P = 0.023); however, no statistically significant difference was found when we considered the change in TAPSE between study groups (P = 0.112). A statistical significance in the alteration of RVEF, RVSM, and the grade of TI during study visits was not found between the study groups (P = 0.472, P = 0.887, and P = 0.237, respectively). Although the two studied types of LVADs were found to be effective in reducing PAP in heart transplantation candidates with PH, lesser postoperative systolic PAP values were achieved in patients who underwent continuous‐flow pump implantation surgery.
New method for evaluation of early phase tear clearance by anterior segment optical coherence tomography
Authors: Zheng Xiaodong , Kamao Tomoyuki , Yamaguchi Masahiko , Sakane Yuri , Goto Tomoko , Inoue Yasushi , Shiraishi Atsushi , Ohashi Yuichi
Published: September 2013

Purpose

To describe a new method of measuring early phase tear clearance by anterior segment optical coherence tomography (AS‐OCT).

Methods

Sixty normal subjects were divided into a young group (30 subjects; 29.6 ± 7.2 years) and an elder group (30 subjects; 71.4 ± 10.8 years). AS‐OCT (CASIA SS‐1000, Tomey, Japan) with customized software was used to record the tear meniscus at the centre of the lower eyelid. Five microlitres of lukewarm saline solution was dropped into the lower conjunctival sac, and an image of the tear meniscus was obtained immediately and again 30 seconds after natural blinking. The tear meniscus height (TMH) and tear meniscus area (TMA) were measured in the AS‐OCT images, and the percentage decrease in the TMH and TMA was used as a measure of the tear clearance. Correlations between tear clearance and clinical features including degree of conjunctivochalasis, degree of protrusion of inferior lacrimal punctum, distance of lacrimal punctum from the Marx line and fluorescein clearance rates were also determined in another healthy population consisting of 30 subjects.

Results

The OCT tear clearance rate was 35.2 ± 11% for TMH and 28.1 ± 12.4% for TMA in the young group, and 12.4 ± 7.3% and 6.2 ± 9.1%, respectively in the elder group. The differences were significant for both the TMH (p = 0.017) and the TMA (p = 0.024). The OCT‐determined tear clearance was positively correlated with the fluorescein clearance rate, and negatively correlated with the distance between the lacrimal punctum and Marx line, degree of conjunctivochalasis and degree of lacrimal punctum protrusion.

Conclusion

AS‐OCT can be used as a rapid, non‐invasive and quantitative method of determining the early phase tear clearance rate in a normal healthy population.
The surgical spectacle: a survey of urologists viewing live case demonstrations
Authors: Elsamra Sammy E. , Fakhoury Mathew , Motato Hector , Friedlander Justin I. , Moreira Daniel M. , Hillelsohn Joel , Duty Brian , Okeke Zeph , Smith Arthur D.
Published: September 2013

Objective

To evaluate perspectives of urologists viewing live case demonstrations (LCD) and taped case demonstrations (TCD).

Method

A 15‐question anonymous survey was distributed to attendees of the live surgery session at the American Urological Association 2012 national meeting (Atlanta) and the second International Challenges in Endourology meeting (Paris).

Results

Of 1000 surveys distributed, 253 were returned completed (response rate 25%). Nearly half of respondents were in the academic practice setting and nearly 75% were beyond training.

Just over 30% had performed a LCD previously. The perceived benefit of an LCD was greater than unedited and edited videos (chi‐squared P = 0.014 and P < 0.001, respectively). Nearly no one selected ‘not helpful’ and a few selected ‘minimally helpful’ for any of the three forms of demonstration.

Most respondents identified that opportunity to ask questions (61%) and having access to the full unedited version (72%), two features inherent to LCD, improved upon the educational benefit of edited videos.

Most (78%) identified LCD as ethical. However, those that did not perceived lower educational benefit from LCD (P = 0.019).

A slim majority (58%) would allow themselves or a family member to be a patient of a LCD and the vast majority (86%) plan to transfer knowledge gained at the LCD session into their practice.

Conclusions

Urologists who attended these LCD sessions identified LCDs as beneficial and applicable to their practice.

LCDs are preferred over videos. The large majority considers LCD ethical, although not as many would volunteer themselves for LCD.

Further studies are necessary to determine if there is actual benefit from LCD over TCD to patient care.
Comparison of contemporary methods for estimating prostate tumour volume in pathological specimens
Authors: Perera Marlon , Lawrentschuk Nathan , Bolton Damien , Clouston David
Published: September 2013

Objective

To evaluate the accuracy of various prostate tumour volume (TV) estimation methods.

To determine the most appropriate estimation method for current clinical practice.

Patients and Methods

Radical prostatectomy (RP) specimens from multiple institutions were analysed by a single uro‐pathologist between September 2009 and May 2011.

Tumour properties including thickness, width and length were collected and TV was established using computer‐assisted image analysis (CAIA).

TV estimation methods including; square, cuboidal and ellipsoidal estimations were calculated using previously reported formulae.

The estimation methods were compared against the ‘gold‐standard’ and the accuracy of identifying clinically significant tumours of TV ≥0.5 cc was determined.

Results

In all, 299 consecutive specimens were analysed by a single uropathologist.

The median index TV on CAIA was 1.42 cc.

Of the four estimation methods, the ellipsoid methods produced the closest correlation with the gold‐standard (r2 0.91, P = 0.71). This correlation lost accuracy when larger tumours (TV >4 cc) were excluded from the analysis (r2 = 0.73, P = 0.003).

Sensitivity and specificity for identifying clinically significant tumours was 94% and 92% respectively, when using the ellipsoid estimation.

Conclusions

In current uro‐pathology, the ellipsoidal estimation method appears to be the most suitable for estimating TV in prostate cancers.

This method is cheap, reproducible and sensitive and can be safely used as a surrogate for CAIA volumes when such technology is not available.
The dilemma of distance: patients with kidney cancer from regional Australia present at a more advanced stage
Authors: Satasivam Prassannah , O'Neill Sarah , Sivarajah Gausihi , Sliwinski Ania , Kaiser Celina , Niall Owen , Goad Jeremy , Brennan Janelle
Published: September 2013

Objective

To determine whether patients from regional areas undergoing surgery for kidney cancer present with more advanced disease as a result of geographic isolation.

Patients and Methods

Retrospective analysis of 221 patients undergoing surgery for renal cell carcinoma (RCC) from January 2004 to June 2012, from both a metropolitan centre and a large inner regional hospital.

Data was collected on age, gender, presentation (incidental or symptomatic), clinical stage and pathological features.

The Australian Standard Geographical Classification‐Remoteness Area (ASGC‐RA) is a system developed to allow quantitative comparisons between metropolitan and rural Australia. A score was assigned to each patient based on their location of residence at the time of surgery: metropolitan, RA1; inner regional, RA2; outer regional, RA3.

Statistical significance was specified as P < 0.05 on Pearson's chi‐square tests.

Results

Patients in each ASGC‐RA group did not differ significantly in age, sex or mode of presentation.

Pathological T stage on presentation increased with increasing ASGC‐RA and thus distance from tertiary centres (P = 0.004).

The proportion of patients with ≥T3 disease rose from 30% of RA1 to 73% of RA3 patients (P = 0.016) treated at our tertiary centre. Similarly, our regional centre had a larger proportion of patients presenting with ≥T3 disease from RA3 (31% vs 5%, P = 0.003).

When the 221 patients with RCC were analysed as a group, clinical T stage was significantly associated with ASGC‐RA (P < 0.001), symptomatic presentation (P < 0.001), N stage (P < 0.001), M stage (P < 0.001) and Fuhrman grade (P < 0.001).

Conclusions

Our data quantifies the detrimental effect of physical distance on the health outcomes of regional Australians with kidney cancer.

Australia's unique geography and rural culture may preclude any attempts to centralise cancer care to specialised metropolitan units, as has occurred in other countries.
Agonist pharmacology at recombinant α1A‐ and α1L‐adrenoceptors and in lower urinary tract α1‐adrenoceptors
Authors: Yoshiki Hatsumi , Uwada Junsuke , Umada Hidenori , Kobayashi Tadashi , Takahashi Toshihiro , Yamakawa Tomio , Yamaguchi Akio , Yokoyama Osamu , Muramatsu Ikunobu
Published: September 2013

Background and Purpose

Two distinct α1‐adrenoceptor phenotypes (α1A and α1L) have recently been demonstrated to originate from a single α1A‐adrenoceptor gene. Here, we examined the agonist profiles of recombinant α1A and α1L phenotypes and of lower urinary tract (LUT) α1‐adrenoceptors.

Experimental Approach

A series of drugs (A61603, Ro 115–1240, NS‐49 , MK017 and ESR1150) originally developed for stress urinary incontinence (SUI) therapy were used to stimulate recombinant α1A‐ and α1L‐adrenoceptor phenotypes, and their potencies and intrinsic activity estimated from Ca2+ responses. Agonist‐induced contractions were also examined in LUT tissues of rats and humans and in human mesenteric artery and rat tail artery.

Key Results

All the drugs were potent agonists of the α1A‐adrenoceptor compared with the α1L‐adrenoceptor phenotype. Among them, Ro 115–1240 was shown to be an α1A‐specific partial agonist that produced partial contractions through α1A‐adrenoceptors in rat prostate and tail artery, but not in the other LUT tissues and human mesenteric artery. In contrast, P‐come 102 showed full agonist activity at α1A‐ and α1L‐adrenoceptors, but was less selective than noradrenaline for α1A‐adrenoceptors. Like noradrenaline, P‐come 102 was highly potent at inducing contractions in all of the LUT tissues tested. However, the potency and intrinsic activity of P‐come 102 were significantly lower than those of noradrenaline in human mesenteric artery.

Conclusions and Implications

The α1A‐ and α1L‐adrenoceptor phenotypes and LUT α1‐adrenoceptors were demonstrated to have distinct agonist profiles. As adrenergic contractions in LUT are predominantly mediated through α1L‐adrenoceptors, the development of α1L‐selective agonists may provide clinically useful drugs for SUI therapy.
Influence of Prosthetic Parameters on Peri‐Implant Bone Resorption in the First Year of Loading: A Multi‐Factorial Analysis
Authors: Hof Markus , Pommer Bernhard , Zukic Nizama , Vasak Christoph , Lorenzoni Martin , Zechner Werner
Published: September 2013

Background

The first year of prosthetic loading is crucial to peri‐implant bone levels; however, contributing factors are yet barely understood.

Purpose

The purpose of the study is to investigate the influence of patient‐, implant‐, and prosthetic‐related parameters on marginal bone resorption in partially edentulous patients within the first year of prosthetic loading.

Materials and Methods

This retrospective multifactorial analysis involved the following influencing factors: patient gender and age, implant diameter, implant location and neck design, insertion torque, insertion depth, splinted versus single‐tooth restorations, crown height space, and crown‐to‐implant ratio.

Results

Mean peri‐implant bone resorption around 200 dental implants was 0.98 ± 0.76 mm and significantly correlated to higher implant insertion depth (p < .001), whereas no association to prosthetic parameters could be observed.

Conclusions

Within the limits of the present analysis, it can be concluded that apical implant positioning may constitute a relevant determinant of early peri‐implant bone resorption.
Mapping Hotspots of Threatened Species Traded in Bushmeat Markets in the Cross–Sanaga Rivers Region
Authors: FA JULIA E. , FARFÁN MIGUEL ANGEL , MARQUEZ ANA LUZ , DUARTE JESÚS , NACKONEY JANET , HALL AMY , DUPAIN JEF , SEYMOUR SARAH , JOHNSON PAUL J. , MACDONALD DAVID W. , VARGAS J. MARIO
Published: September 2013

Bushmeat markets exist in many countries in West and Central Africa, and data on species sold can be used to detect patterns of wildlife trade in a region. We surveyed 89 markets within the Cross–Sanaga rivers region, West Africa. In each market, we counted the number of carcasses of each taxon sold. During a 6‐month period (7594 market days), 44 mammal species were traded. Thirteen species were on the International Union for Conservation of Nature (IUCN) Red List or protected under national legislation, and at least 1 threatened species was traded in 88 of the 89 markets. We used these data to identify market groups that traded similar species assemblages. Using cluster analyses, we detected 8 market groups that were also geographically distinct. Market groups differed in the diversity of species, evenness of species, and dominant, prevalent, and characteristic species traded. We mapped the distribution of number of threatened species traded across the study region. Most threatened species were sold in markets nearest 2 national parks, Korup National Park in Cameroon and Cross River in Nigeria. To assess whether the threatened‐species trade hotspots coincided with the known ranges of these species, we mapped the overlap of all threatened species traded. Markets selling more threatened species overlapped with those regions that had higher numbers of these. Our study can provide wildlife managers in the region with better tools to discern zones within which to focus policing efforts and reduce threats to species that are threatened by the bushmeat trade.

Mapeo de Sitios Críticos para Especies Amenazadas Comercializadas en Mercados de Vida Silvestre en la Región de los Ríos Cross‐Sanaga
The co‐evolution of social institutions, demography, and large‐scale human cooperation
Authors: Powers Simon T. , Lehmann Laurent
Published: September 2013

Human cooperation is typically coordinated by institutions, which determine the outcome structure of the social interactions individuals engage in. Explaining the Neolithic transition from small‐ to large‐scale societies involves understanding how these institutions co‐evolve with demography. We study this using a demographically explicit model of institution formation in a patch‐structured population. Each patch supports both social and asocial niches. Social individuals create an institution, at a cost to themselves, by negotiating how much of the costly public good provided by cooperators is invested into sanctioning defectors. The remainder of their public good is invested in technology that increases carrying capacity, such as irrigation systems. We show that social individuals can invade a population of asocials, and form institutions that support high levels of cooperation. We then demonstrate conditions where the co‐evolution of cooperation, institutions, and demographic carrying capacity creates a transition from small‐ to large‐scale social groups.
Herbicide‐resistant weeds: from research and knowledge to future needs
Authors: Busi Roberto , Vila‐Aiub Martin M. , Beckie Hugh J. , Gaines Todd A. , Goggin Danica E. , Kaundun Shiv S. , Lacoste Myrtille , Neve Paul , Nissen Scott J. , Norsworthy Jason K. , Renton Michael , Shaner Dale L. , Tranel Patrick J. , Wright Terry , Yu Qin , Powles Stephen B.
Published: September 2013

Synthetic herbicides have been used globally to control weeds in major field crops. This has imposed a strong selection for any trait that enables plant populations to survive and reproduce in the presence of the herbicide. Herbicide resistance in weeds must be minimized because it is a major limiting factor to food security in global agriculture. This represents a huge challenge that will require great research efforts to develop control strategies as alternatives to the dominant and almost exclusive practice of weed control by herbicides. Weed scientists, plant ecologists and evolutionary biologists should join forces and work towards an improved and more integrated understanding of resistance across all scales. This approach will likely facilitate the design of innovative solutions to the global herbicide resistance challenge.
Successful treatment of chronic grass sickness in a donkey
Authors: Mellor N. E. , Bladon B. , Foote A. K. , O'Meara B.
Published: September 2013

This case report outlines the successful management of a case of chronic grass sickness in a donkey and highlights that the occurrence of grass sickness may be underestimated in this species. Furthermore, grass sickness should be considered in the differential diagnosis in cases of inappetance and ill thrift in donkeys.
Detection of Herpesvirus anguillae during two mortality investigations of wild European eel in England: implications for fishery management
Authors: Armitage J. , Hewlett N. R. , Twigg M. , Lewin N. C. , Reading A. J. , Williams C. F. , Aprahamian M. , Way K. , Feist S. W. , Peeler E. J.
Published: September 2013

Herpesvirus anguillae (HVA) was detected during disease investigations of European eel, Anguilla anguilla L. at two stillwater fisheries in central England. These represent the first records of HVA from UK eels. Both mortalities were eel‐specific and took place during August 2009 and July 2010 at water temperatures between 17 and 19.4 °C. Pathological changes consistent with HVA infection included haemorrhaging in the fins, skin lesions and necrosis within the gills and liver. Transmission electron microscopy revealed active virion replication within the gill tissue. An initial assessment of risk is presented, indicating that HVA represents a high disease risk to UK eel stocks. However, further studies are required to establish the distribution of HVA before a reliable assessment of impact may be obtained. Until then, the detection of HVA holds important implications for eel conservation and management, in particular eel stocking activity.
Nocturia among elderly men living in a rural area in Egypt, and its impact on sleep quality and health‐related quality of life
Authors: Abdel Rahman Tomader Taha , El Gaafary Maha Mohammed
Published: September 2013

Aim

Nocturia is such a commonplace occurrence in the lives of many older adults that it is frequently overlooked as a potential cause of sleep disturbance. The aim of the present study was to evaluate the prevalence of nocturia among elderly men living in a rural area in Egypt, and its impact on sleep quality and health‐related quality of life (HRQoL).

Method

This was a cross‐sectional study. A total of 1200 elderly men participated in the survey. The Pittsburgh Sleep Quality Index (PSQI) Arabic version and the short form‐36 (SF‐36) were used in this survey.

Results

The prevalence of nocturia in the studied participants (≥1 void/night) was 63.5%. With the criterion (≥2 voids/night) the prevalence was 46.0%. Multivariate logistic regression analysis showed that nocturia is an independent risk factor of poor sleep quality (OR 5.08), and poor sleep is an independent risk factor of the poor physical component of QoL (OR 17.6) and the mental component of QoL (OR 3.2).

Conclusion

Nocturia is widely prevalent among elderly men living in a rural area in Egypt. The adverse effect of nocturia on QoL is related to poor sleep. Geriatr Gerontol Int 2014; 14: 613–619.
Incidence of certified need of care in the long‐term care insurance system and its risk factors in the elderly of Japanese population‐based cohorts: The ROAD study
Authors: Akune Toru , Muraki Shigeyuki , Oka Hiroyuki , Tanaka Sakae , Kawaguchi Hiroshi , Tokimura Fumiaki , Yoshida Hideyo , Suzuki Takao , Nakamura Kozo , Yoshimura Noriko
Published: September 2013

Aim

To examine the incidence of certified need of care in the national long‐term care insurance (LTCI) system, and to determine its risk factors in the elderly of Japanese population‐based cohorts of the Research on Osteoarthritis/Osteoporosis Against Disability (ROAD) study.

Methods

Of the 3040 participants in the baseline examination of the ROAD study, we enrolled 1773 (699 men, 1074 women) aged 65 years or older who were not certified as in need of care level elderly at baseline. Participants were followed for incident certification of need of care in the LTCI system. Associated factors in the baseline examination with occurrence were determined by multivariate Cox proportional hazards regression analysis. Muscle dysfunction was defined in accordance with the European Working Group on Sarcopenia in Older People algorithm for screening sarcopenia.

Results

A total of 54 men and 115 women were certified as in need of care level elderly during the average 4.0‐year follow up. The incidence was 2.0 and 2.5 per 100 person‐years in men and women, respectively. Identified risk factors were region, age, body mass index <18.5 or ≥27.5 kg/m2, grip strength, knee extension torque, usual gait speed, chair stand time and muscle dysfunction.

Conclusions

Both underweight and obesity, as well as low muscle strength and physical ability, are risk factors for certification of need of care. Considering muscle dysfunction is a risk factor for occurrence, screened individuals are recommended to receive early intervention programs regardless of muscle volume. Geriatr Gerontol Int 2014; 14: 695–701.
Intranasal Zolmitriptan for the Treatment of Acute Migraine
Authors: Tepper Stewart J. , Chen Susy , Reidenbach Faith , Rapoport Alan M.
Published: September 2013

Objective

To review the pharmacokinetics, efficacy, tolerability, and patient acceptance of zolmitriptan nasal spray (NS).

Background

Gastroparesis may delay or diminish the absorption of oral triptans, and nausea or vomiting may do the same and/or make it difficult to take a tablet. Some migraineurs require or prefer faster relief than oral medications provide. Injectable triptans provide the fastest drug delivery into the bloodstream, but many patients are reluctant to use them. Nasal sprays may address some of the problems with tablets and injectables while still providing rapid absorption of drug.

Methods

Non‐systematic review.

Results

Significant levels of zolmitriptan NS are detectable in plasma within 2‐5 minutes, and the rapid absorption is due to early uptake through the nasal mucosa. In 2 randomized trials, users of zolmitriptan NS were significantly more likely than placebo recipients to be pain‐free at 15 minutes post‐dose, the first time point measured, and about half of patients had sustained response at 24 hours. Studies in which patients could treat a migraine of any severity have documented significant headache response or relief with zolmitriptan NS at 10 minutes. In one trial, the rate of total symptom relief was significantly better with the NS than with placebo from 30 minutes post‐dose. The most common side effect of zolmitriptan NS is unusual taste. Patient satisfaction studies indicate that zolmitriptan NS is appreciated for its speed of onset, ease of use, reliability, and overall efficacy.

Conclusions

Zolmitriptan NS provides onset of headache relief within 10 minutes for some patients and quickly abolishes some of the major migraine symptoms. Good candidates are migraineurs whose episodes rapidly escalate to moderate‐to‐severe pain and those who have morning migraine, have a quick time to vomiting, or have failed oral triptans.
A bibliometric approach demonstrates the impact of a social care data set on research and policy
Authors: Urquhart Christine , Dunn Sara
Published: September 2013

Background

The National Minimum Dataset for Social Care (NMDS‐SC) has provided detailed data since 2006 on the workforce for adult social care services in England. In 2012, the organisation responsible for the data set commissioned an evaluation into the impact of the data set on researchers and policymakers.

Objective

Discusses how a novel wide‐ranging bibliometric approach, complemented by interviews of key informants, demonstrated the developing impact of the data set.

Methods

The evaluation comprised web metrics to assess NMDS‐SC‐related traffic on relevant websites; bibliometrics to assess the use of NMDS‐SC data in scholarly publications and grey literature; telephone interviews with 12 key users of the data set; and an online survey completed by 24 key users of the data set. A theoretical framework for research impact was used.

Results

The web metrics demonstrated increase in traffic on the relevant pages of the organisation's website. There were references to the data set in 175 separate publications (15% from academic journals, 50% as policy/practice reports and 35% as media communications. Interviews evidenced many impacts, for example provision of robust data for secondary analysis that challenged conventional views about the social care workforce.

Conclusion

Bibliometrics plus interviews provided a rounded picture of the data set's impact.
Disease characteristics of bovine spongiform encephalopathy following inoculation into mice via three different routes
Authors: Vickery Christopher M. , Beck Katy E. , Simmons Marion M. , Hawkins Stephen A. C. , Spiropoulos John
Published: September 2013

Mouse‐adapted transmissible spongiform encephalopathy (TSE) strains are routinely distinguished based on reproducible disease characteristics in a given mouse line following inoculation via a consistent route. We investigated whether different administration routes (oral, intragastric (i.g.) and intracerebral (i.c.)) can alter the disease characteristics in IM mice after serial dilution of a stabilized mouse‐adapted bovine spongiform encephalopathy (BSE) strain (301V). In addition, the infectivity of distal ileum and mesenteric lymph nodes (ln) sampled at three time points (35 days postinoculation (dpi), 70 dpi and terminal disease) after i.g. inoculation of 301V strain was assessed in mice by i.c. challenge. Strain characteristics were assessed according to standard methodology and PrPSc immunohistochemistry deposition patterns. Mean incubation periods were prolonged following oral or i.g. inoculations compared to the i.c. route. Lesion profiles following i.c. challenges were elevated compared to i.g. and oral routes although vacuolation in the dorsal medulla was consistently high irrespective of the route of administration. Nevertheless, the same PrPSc deposition pattern was associated with each route of administration. Distal and mesenteric ln infectivity was detected as early as 35 dpi and displayed consistent lesion profiles and PrPSc deposition patterns. Our data suggest that although 301V retained its properties, some phenotypic parameters were affected by the route of inoculation. We conclude that bioassay data should be interpreted carefully and should be standardized for route of inoculation.
Evaluation of autologous blood clot subsegmental pulmonary thromboembolism in minimally invasive experimental canine model
Authors: Kang Min‐Hee , Park Hee‐Myung
Published: September 2013

The incidence and significance of subsegmental pulmonary (SSP) thromboembolism is currently under investigation. We aimed to evaluate the clinical and diagnostic features of SSP thromboembolism in an experimental canine model. Obstruction of pulmonary arterial branches was induced in three beagle dogs by intravenous injection of a barium‐coated autologous blood clot (size, approximately 1.7 × 5 mm). The clinical signs, haemodynamic changes (blood pressure, electrocardiogram, echocardiography), coagulation (aPTT, PT, FDPs and D‐dimer test) and cytokine variations (TNF‐a, IL‐4, IL‐6, and IL‐10) were evaluated over a 24‐hour period. Multidetector computed tomography (MDCT) with contrast was conducted to evaluate the pulmonary obstruction, and histopathological confirmation was performed. Pulmonary artery pressure gradient (PAPG) was increased 12 h after the autologous blood clot injection (14.2 ± 2.8 mmHg to 23.6 ± 1.7 mmHg, P = 0.003) and normalized 24 h later (P < 0.01). Infused radiopaque clots were confirmed with MDCT and histopathological examination. Pulmonary parenchymal changes such as arterial dilation and inflammatory reactions were also confirmed in histopathological examinations and were barely observable in MDCT. Usually small emboli are not easily detected through CT imaging, and the clinical relevance of these emboli is controversial. In this experimental study, we made radiopaque small emboli and induced SSP thromboembolism. Thus, we infer that obstruction of the small segmental and subsegmental pulmonary arteries does result in a pulmonary thromboembolism (PTE) and PTE‐related pulmonary parenchymal changes which could be clinically significant.
Cardiomyocyte ultrastructural damage in β‐thalassaemic mice
Authors: Sanyear Chanita , Butthep Punnee , Nithipongvanich Ramaneeya , Sirankapracha Pornpan , Winichagoon Pranee , Fucharoen Suthat , Svasti Saovaros
Published: September 2013

β‐thalassaemia is a hereditary anaemia resulting from the absence or reduction in β‐globin chain production. Heart complications related to iron overload are the most serious cause of death in these patients. In this report cardiac pathology of β‐thalassaemic mice was evaluated by light and electron microscopy. The study was carried out in thalassaemic mice carrying human β‐thalassaemia mutation, IVSII‐654 (654), transgenic mice carrying human βE‐globin transgene insertion (E4), thalassaemic mice with human βE‐globin transgene insertion (654/E4) and homozygous thalassaemic mice rescued by the human βE‐globin transgene (R), which is generated by cross‐breeding between the 654 and E4 mice. Histology showed iron deposition in cardiac myocytes of 654 and R mice, but the ultrastructural damage was observed only in the R mice when compared with the wild type, 654, E4 and 654/E4 mice. Histopathological changes in the cardiomyocytes of the R mice included mitochondrial swelling, loss of myofilaments and the presence of lipofuscin, related to the increased level of tissue iron content. The progressive ultrastructural pathology in R mice cardiomyocytes is consistent with the ultrastructural pathology previously studied in patients with thalassaemia. Thus, this R thalassaemic mouse model is suitable for in vivo pathophysiological study of thalassaemic heart.
Long‐lasting morphofunctional remodelling of liver parenchyma and stroma after a single exposure to low and moderate doses of cadmium in rats
Authors: Cupertino Marli C. , Costa Kyvia L. C. , Santos Daiane C. M. , Novaes Rômulo D. , Condessa Suellen S. , Neves Ana C. , Oliveira Juraci A. , Matta Sérgio L. P.
Published: September 2013

Frequent exposure to cadmium (Cd) in low doses is common; however, the long‐lasting effects of this exposure are still poorly understood. Therefore in this study we have evaluated long‐lasting hepatic morphofunctional adaptations in rats exposed to low and moderate doses of Cd. Five experimental groups were tested: control (0.9% saline) and other four receiving single intraperitoneal doses of 0.67, 0.74, 0.86 and 1.1 mg of Cd/kg. The animals were killed after eight weeks and the following parameters were analysed: biometrics, oedema, Cd bio‐accumulation, collagen, glycogen, lipid droplets, superoxide dismutase (SOD) and catalase (CAT), serum transaminases, liver histopathology and stereology. In all groups exposed to Cd there was significant increase in SOD and CAT activities, ALP levels, proportion of binucleated hepatocytes, nuclei/cytoplasm ratio, macrophages (Kupffer cells) and collagen fibres. In these groups, glycogen accumulation by hepatocytes and the proportion of sinusoidal capillaries were significantly reduced compared with controls. The liver somatic index was increased, and liver oedema was evident in animals exposed to higher dose of Cd. Areas of necrosis were found in animals exposed to the three highest doses. These results indicate that Cd is an extremely toxic bioactive heavy metal, which even at low doses is able to disrupt liver homeostasis. At low and moderate doses, Cd exposure induces morphofunctional pathological remodelling of the hepatic stroma and parenchyma, which remain active after eight weeks. In response to injury, the liver tissue triggers a reactive process by enhancing activation of antioxidant enzymes and collagenogenesis.
Troubled by Law: The Subjectivizing Effects of Danish Marriage Reunification Laws
Authors: Schmidt Garbi
Published: September 2013

Between 2002 and 2003, Denmark introduced further limitations on its already restrictive regulations concerning family and marriage reunification. While several studies, both Danish and international, have discussed the effects of these and other family reunification laws on individual practice, we know very little about the their effects on people's self‐perceptions and norms. Based on a qualitative data set, including a total of 89 interviews with young people of immigrant background living in Denmark collected between 1999 and 2009, this article seeks to provide answers to this and related questions. As a social technology, do the regulations create changes in the practice field of the respondents which they gradually come to see as natural and reasonable, or do they leave them in a troubling subject position (Staunæs, 2005) based on a socially and legislatively regulated stigma?
Antigen‐specific B lymphocytes acquire proteoglycan aggrecan from cartilage extracellular matrix resulting in antigen presentation and CD4+T‐cell activation
Authors: Ciechomska Marzena , Wilson Caroline L. , Floudas Achilleas , Hui Wang , Rowan Andrew D. , van Eden Willem , Robinson John H. , Knight Andrew M.
Published: September 2013

The majority of studies examining antigen‐presenting cell (APC) function have focused on the capture and presentation of antigens released from pathogens or damaged cells. However, antigen‐specific B cells are also capable of efficiently extracting antigens that are either tethered to, or integrally part of the plasma membrane of various target cells. In this study we show that B cells are also highly efficient at extracting integral components of the extracellular matrix (ECM) for subsequent presentation. In particular we demonstrate that B cells specific for aggrecan, an integral component of cartilage ECM, acquire this rheumatoid arthritis candidate autoantigen in both a B‐cell‐receptor‐dependent and a contact‐dependent manner. We also demonstrate that the subsequent presentation of aggregan from ECM leads to CD4+ T‐cell activation and effector cell formation. Recent studies have identified B‐cell‐mediated antigen presentation as essential for the development of autoimmunity, but a unique role for B cells compared with other APC has yet to be defined. Our findings lead us to propose that the acquisition of ECM‐derived autoantigens represents a mechanism that defines the APC requirement for B cells in the development of autoimmunity.
MEET THE BUILDER
Authors: Crainer Stuart
Published: September 2013

Jimmy Maymann, builder of companies and CEO of the Huffington Post, profiled by Stuart Crainer.
THE ENTREPRENEURIAL JOURNEY
Authors: Crainer Stuart
Published: September 2013

For any entrepreneur, the route from idea to established business is a long and winding one. Stuart Crainer examines the starting points of the journey and some of the key stages along the way with London Business School's latest wave of founders.
REVIEW: BREAKING OUT EMERGING BRANDS GO GLOBAL
Authors: Peters Georgina
Published: September 2013

Brand Breakout, the latest book from Nirmalya Kumar (co‐authored with Jan‐Benedict Steenkamp) charts the rise of brands from emerging markets as they make the leap from local to global. Nirmalya Kumar talked to Georgina Peters about the book and its evolution.
VOICES: WHY CROSS‐COMPANY DIALOGUE DELIVERS
Authors: Kingl Adam
Published: September 2013

Adam Kingl examines the wisdom of diverse teams.
Uncertain Bequest Needs and Long‐Term Insurance Contracts
Authors: Fei Wenan , Fluet Claude , Schlesinger Harris
Published: September 2013

Abstract

We examine how long‐term life insurance contracts can be designed to incorporate uncertain future bequest needs. An individual who buys a life insurance contract early in life is often uncertain about the future financial needs of his or her family, in the event of an untimely death. Ideally, the individual would like to insure the risk of having high future bequest needs, but since bequest motives are typically unverifiable, a contract directly insuring these needs is not feasible. We derive a long‐term life insurance contract that is incentive compatible and achieves a higher welfare level than the naïve strategy of delaying the purchase of insurance until after one's bequest needs are known. We also examine the welfare effects of our contract and we show how third‐party financial products, although beneficial to the individual in the short run, can be detrimental to one's ex ante utility.
A Cognitive–Social Model of Fertility Intentions
Authors: Bachrach Christine A. , Morgan S. Philip
Published: September 2013

We examine the use and value of fertility intentions against the backdrop of theory and research in the cognitive and social sciences. First, we draw on recent brain and cognition research to contextualize fertility intentions within a broader set of conscious and unconscious mechanisms that contribute to mental function. Next, we integrate this research with social theory. Our conceptualizations suggest that people do not necessarily have fertility intentions; they form them only when prompted by specific situations. Intention formation draws on the current situation and on schemas of childbearing and parenthood learned through previous experience, imbued by affect, and organized by self‐representation. Using this conceptualization, we review apparently discordant knowledge about the value of fertility intentions in predicting fertility. Our analysis extends and deepens existing explanations for the weak predictive validity of fertility intentions at the individual level and provides a social‐cognitive explanation for why intentions predict as well as they do. When focusing on the predictive power of intentions at the aggregate level, our conceptualizations lead us to focus on how social structures frustrate or facilitate intentions and how the structural environment contributes to the formation of reported intentions in the first place. Our analysis suggests that existing measures of fertility intentions are useful but to varying extents and in many cases despite their failure to capture what they seek to measure.
Pepper‐spray and penguins
Authors: Tufekci Zeynep
Published: September 2013

Zeynep Tufekci reflects on the causes and consequences of Turkey's Gezi protests, a thoroughly modern movement sparked by social media but ultimately limited by a lack of organisation and infrastructure.
Modernisation that lasts
Authors: Riddell Mary
Published: September 2013

Amid more ‘brutalist’ options, Mary Riddell asks whether the real future for Tory modernisation lies in a kernel of David Cameron's past: the big society.
A Preliminary Investigation of Human Frontal Cortex Under Noxious Thermal Stimulation Over the Temporomandibular Joint Using Functional Near Infrared Spectroscopy
Authors: Yennu Amarnath , Tian Fenghua , Liu Hanli , Rawat Rohit , Manry Michael T. , Gatchel Robert
Published: September 2013

Functional near infrared spectroscopy (fNIRS) was used to explore hemodynamic responses in the human frontal cortex to noxious thermal stimulation over the right temporomandibular joint (TMJ). fNIRS experiments were performed on nine healthy volunteers under both low‐pain stimulation (LPS) and high‐pain stimulation (HPS), using a temperature‐controlled thermal stimulator. By analyzing the temporal profiles of changes in oxy‐hemoglobin concentration (HbO) using cluster‐based statistical tests, several regions of interest in the prefrontal cortex, such as the dorsolateral prefrontal cortex and the anterior prefrontal cortex, were identified, where significant differences (p < .05) between HbO responses to LPS and HPS were shown. In order to classify these two levels of pain, a neural network‐based classification algorithm was utilized. With leave‐one‐out cross‐validation, the two levels of pain were identified with 99% mean accuracy to high pain. Furthermore, the “internal mentation hypothesis” and the default‐mode network were introduced to explain our observations of the contrasting trend, as well as the rise and fall of HbO responses to HPS and LPS.
Private Equity and Investment in Innovation: Evidence from Patents
Authors: Lerner Josh , Sorensen Morten , Stromberg Per
Published: September 2013

The authors' analysis of the patenting activity of 472 companies that received private equity investments between 1986 and 2005 provides suggestive evidence of an increase in the effectiveness (though not necessarily the quantity) of their innovative activities. After such companies received private equity backing, the patents they applied for received more frequent citations than patents awarded before the involvement of PE firms. Companies acquired by private equity also show no sign of deterioration in patent “originality” and “generality,” which have been shown to be fairly reliable indicators of the fundamental nature of the research. And while there is no clear pattern of change in the level of patenting activity, corporate patent portfolios become more focused in the years after the private equity investments. The increases in our measure of patent “impact” are greatest in the areas that constitute the companies' historical core strengths. These findings are likely to prove increasingly important as private equity continues its incursions into growth areas of the economy.