bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Transcutaneous Electrical Acupuncture Point Stimulation at Different Frequencies in a Rat Model of Neuropathic Pain
Authors: Yu Xiangdi , Zhang Fangxiang , Chen Bingning
Published: October 2016

Background

Acupuncture and related techniques are used worldwide to alleviate pain; however, their mechanisms of action are still not fully understood. In the present study, we investigated the effect of transcutaneous electrical acupuncture point stimulation (TEAS) at different frequencies in a chronic constriction injury (CCI) model of neuropathic pain in rats.

Methods

CCI was induced by ligating the common sciatic nerve, which produced neuropathic pain. 18 male Sprague–Dawley rats with CCI were randomly divided into three groups (n=6 each) that remained untreated (CCI group) or received TEAS at high frequency (CCI+TEAS-H group) or TEAS at low frequency (CCI+TEAS-L group). Rats in the CCI+TEAS-H group received high frequency stimulation (6–9 mA, 100 Hz) at GB34/GV26/ST36; those in the CCI+TEAS-L group received low frequency stimulation (6–9 mA, 2 Hz) at the same points. Rats in the control group had the same electrodes applied but received no stimulation. All three groups were subjected to behavioural studies after treatment. Expression of μ opioid receptors (MORs) in the L3–L5 dorsal root ganglion (DRG) was determined by immunofluorescence staining and Western blotting after treatment.

Results

Compared with the untreated CCI group, both mechanical allodynia and thermal hypergesia were significantly attenuated, and MOR expression in the DRG was significantly increased by low frequency TEAS treatment at GB34/GV26/ST36 (p<0.05). In contrast, no significant differences were observed between the CCI and CCI+TEAS-H groups.

Conclusions

The use of low frequency TEAS significantly mitigated neuropathic pain in this rat model, and its analgesic effect is likely mediated by upregulation of MOR expression in the DRG.
Infantile wheeze: rethinking dogma
Authors: de Benedictis Fernando Maria , Bush Andrew
Published: October 2016

Wheeze is a common symptom in young children and is usually associated with viral illnesses. It is a major source of morbidity and is responsible for a high consumption of healthcare and economic resources worldwide. A few children have a condition resembling classical asthma. Rarer specific conditions may have a wheezy component and should be considered in the differential diagnosis. Over the last half century, there have been many circular discussions about the best way of managing preschool wheeze. In general, intermittent wheezing should be treated with intermittent bronchodilator therapy, and a controller therapy should be prescribed for a young child with recurrent wheezing only if positively indicated, and only then if carefully monitored for efficacy. Good multidisciplinary support, attention to environmental exposition and education are essential in managing this common condition. This article analyses the pathophysiological basis of wheezing in infancy and critically discusses the evolution of the scientific progress over time in this unique field of respiratory medicine.
Severe hypercalcaemia in a child secondary to use of alternative therapies
Authors: Boyd Catriona , Moodambail Abdul
Published: October 2016

We describe a case of a 4-year-old boy who presented with acute vomiting, weight loss, loss of appetite, polyuria and polydipsia. Initial investigations revealed a very elevated corrected calcium level which peaked at 4.46 mmol/L. He had a prior diagnosis of autism and his mother had consulted an alternative therapist who had recommended many supplements, including calcium and vitamin D. He required treatment with hyperhydration, calcitonin, furosemide and several doses of pamindronate before his calcium level returned to the normal range 2 weeks later.
Multimodality approach in the diagnosis and management of bilateral giant juvenile breast fibroadenoma
Authors: Rafeek Noora , Rangasami Rajeswaran , Dhanraj Kamakshi , Joseph Santhosh
Published: October 2016

Juvenile giant fibroadenoma is a very rare breast disease affecting young girls of premenarche and adolescent ages. It is a benign fibroepithelial tumour characterised by stromal and epithelial proliferation that causes rapidly growing breast mass. Bilateral symmetrical involvement is extremely rare. In this article, we describe this entity in a girl aged 13 years who presented with bilateral gigantically enlarged breasts. Ultrasonography and MRI showed large, multilobulated masses involving both breasts entirely. Endovascular embolisation of bilateral internal mammary arteries and lateral thoracic arteries supplying the masses was performed prior to surgery to reduce their vascularity. The patient subsequently underwent excision of bilateral breast masses and reduction mammoplasty. Histopathologically, bilateral breast masses were confirmed to be juvenile fibroadenomas.
Consensus on Exercise Reporting Template (CERT): Explanation and Elaboration Statement
Authors: Slade Susan C , Dionne Clermont E , Underwood Martin , Buchbinder Rachelle
Published: October 2016

Exercise is effective for prevention and management of acute and chronic health conditions. However, trial descriptions of exercise interventions are often suboptimal, leaving readers unclear about the content of effective programmes. To address this, the 16-item internationally endorsed Consensus on Exercise Reporting Template (CERT) was developed. The aim is to present the final template and provide an Explanation and Elaboration Statement to operationalise the CERT. Development of the CERT was based on the EQUATOR Network methodological framework for developing reporting guidelines. We used a modified Delphi technique to gain consensus of international exercise experts and conducted 3 sequential rounds of anonymous online questionnaires and a Delphi workshop. The 16-item CERT is the minimum data set considered necessary to report exercise interventions. The contents may be included in online supplementary material, published as a protocol or located on websites and other electronic repositories. The Explanation and Elaboration Statement is intended to enhance the use, understanding and dissemination of the CERT and presents the meaning and rationale for each item, together with examples of good reporting. The CERT is designed specifically for the reporting of exercise programmes across all evaluative study designs for exercise research. The CERT can be used by authors to structure intervention reports, by reviewers and editors to assess completeness of exercise descriptions and by readers to facilitate the use of the published information. The CERT has the potential to increase clinical uptake of effective exercise programmes, enable research replication, reduce research waste and improve patient outcomes.
Strength Training for Adolescents with cerebral palsy (STAR): study protocol of a randomised controlled trial to determine the feasibility, acceptability and efficacy of resistance training for adolescents with cerebral palsy
Authors: Ryan Jennifer M , Theis Nicola , Kilbride Cherry , Baltzopoulos Vasilios , Waugh Charlie , Shortland Adam , Lavelle Grace , Noorkoiv Marika , Levin Wendy , Korff Thomas
Published: October 2016

Introduction

Gait is inefficient in children with cerebral palsy, particularly as they transition to adolescence. Gait inefficiency may be associated with declines in gross motor function and participation among adolescents with cerebral palsy. Resistance training may improve gait efficiency through a number of biomechanical and neural mechanisms. The aim of the Strength Training for Adolescents with cerebral palsy (STAR) trial is to evaluate the effect of resistance training on gait efficiency, activity and participation in adolescents with cerebral palsy. We also aim to determine the biomechanical and neural adaptations that occur following resistance training and evaluate the feasibility and acceptability of such an intervention for adolescents with cerebral palsy.

Methods and analysis

60 adolescents (Gross Motor Function Classification System level I–III) will be randomised to a 10-week resistance training group or a usual care control group according to a computer-generated random schedule. The primary outcome is gait efficiency. Secondary outcomes are habitual physical activity, participation, muscle–tendon mechanics and gross motor function. General linear models will be used to evaluate differences in continuous data between the resistance training and usual care groups at 10 and 22 weeks, respectively. A process evaluation will be conducted alongside the intervention. Fidelity of the resistance training programme to trial protocol will be quantified by observations of exercise sessions. Semistructured interviews will be conducted with participants and physiotherapists following the resistance training programme to determine feasibility and acceptability of the programme.

Ethics and dissemination

This trial has ethical approval from Brunel University London's Department of Clinical Sciences' Research Ethics Committee and the National Research Ethics Service (NRES) Committee London—Surrey Borders. The results of the trial will be submitted for publication in academic journals, presented at conferences and distributed to adolescents, families and healthcare professionals through the media with the assistance of the STAR advisory group.

Trial registration number

ISRCTN90378161; Pre-results.
A work observation study of nuclear medicine technologists: interruptions, resilience and implications for patient safety
Authors: Larcos George , Prgomet Mirela , Georgiou Andrew , Westbrook Johanna
Published: October 2016

Background

Errors by nuclear medicine technologists during the preparation of radiopharmaceuticals or at other times can cause patient harm and may reflect the impact of interruptions, busy work environments and deficient systems or processes. We aimed to: (a) characterise the rate and nature of interruptions technologists experience and (b) identify strategies that support safety.

Methods

We performed 100 hours of observation of 11 technologists at a major public hospital and measured the proportions of time spent in eight categories of work tasks, location of task, interruption rate and type and multitasking (tasks conducted in parallel). We catalogued specific safety-oriented strategies used by technologists.

Results

Technologists completed 5227 tasks and experienced 569 interruptions (mean, 4.5 times per hour; 95% CI 4.1 to 4.9). The highest interruption rate occurred when technologists were in transit between rooms (10.3 per hour (95% CI 8.3 to 12.5)). Interruptions during radiopharmaceutical preparation occurred a mean of 4.4 times per hour (95% CI 3.3 to 5.6). Most (n=426) tasks were interrupted once only and all tasks were resumed after interruption. Multitasking occurred 16.6% of the time. At least some interruptions were initiated by other technologists to convey important information and/or to render assistance. Technologists employed a variety of verbal and non-verbal strategies in all work areas (notably in the hot-lab) to minimise the impact of interruptions and optimise the safe conduct of procedures. Although most were due to individual choices, some strategies reflected overt or subliminal departmental policy.

Conclusions

Some interruptions appear beneficial. Technologists' self-initiated strategies to support safe work practices appear to be an important element in supporting a resilient work environment in nuclear medicine.
Image-based teleconsultation using smartphones or tablets: qualitative assessment of medical experts
Authors: Boissin Constance , Blom Lisa , Wallis Lee , Laflamme Lucie
Published: October 2016

Background

Mobile health has promising potential in improving healthcare delivery by facilitating access to expert advice. Enabling experts to review images on their smartphone or tablet may save valuable time. This study aims at assessing whether images viewed by medical specialists on handheld devices such as smartphones and tablets are perceived to be of comparable quality as when viewed on a computer screen.

Methods

This was a prospective study comparing the perceived quality of 18 images on three different display devices (smartphone, tablet and computer) by 27 participants (4 burn surgeons and 23 emergency medicine specialists). The images, presented in random order, covered clinical (dermatological conditions, burns, ECGs and X-rays) and non-clinical subjects and their perceived quality was assessed using a 7-point Likert scale. Differences in devices' quality ratings were analysed using linear regression models for clustered data adjusting for image type and participants’ characteristics (age, gender and medical specialty).

Results

Overall, the images were rated good or very good in most instances and more so for the smartphone (83.1%, mean score 5.7) and tablet (78.2%, mean 5.5) than for a standard computer (70.6%, mean 5.2). Both handheld devices had significantly higher ratings than the computer screen, even after controlling for image type and participants' characteristics. Nearly all experts expressed that they would be comfortable using smartphones (n=25) or tablets (n=26) for image-based teleconsultation.

Conclusion

This study suggests that handheld devices could be a substitute for computer screens for teleconsultation by physicians working in emergency settings.
Employing imaginative rationality: using metaphor when discussing death
Authors: Llewellyn Rebecca , Jaye Chrystal , Egan Richard , Cunningham Wayne , Young Jessica , Radue Peter
Published: October 2016

The prevalence of metaphors in medicine is widely acknowledged. In a qualitative study exploring expectations of longevity, we observed repeated recourse to the imaginative rationality provided by metaphors to express perspectives on longevity and death. Bafflement, acceptance, uncertainty and distress were conveyed through metaphors, providing valuable insight into the internal healthcare frameworks of participants. Skilful use of imaginative rationality in the healthcare setting may illuminate the elusive and often eschewed topic of death in a way that fosters clarity and new understandings, and pave the way towards a better life, and death for patients. By becoming aware of the nuances contained within patients'—as well as their own—metaphors, clinicians may enhance patients’ overall healthcare experience and avert unintended miscommunication.
Leadership and the medical registrar: how can organisations support these unsung heroes?
Authors: Blake Tim , Whallett Andrew
Published: October 2016

Medical registrars have been described as the ‘workhorses’ of National Health Service hospitals, being at the interface of acute and chronic health services. They are expected to demonstrate effective leadership skills. There are concerns from the Royal College of Physicians that medical registrars are being overwhelmed and unsupported by organisations, and are struggling in their ability to provide safe, high-quality patient care. Junior colleagues are also being deterred by general medical specialties by the prospect of becoming the ‘Med Reg’. There is a growing need to support medical registrars in several key aspects of training, not least medical leadership. Thus far, there has been a distinct disparity in the provision of medical leadership training for junior doctors in the UK that has adversely affected the standard of care given to patients. Recent landmark reviews and initiatives, principally the Medical Leadership Competency Framework, have raised awareness of leadership competencies for all doctors and the need for their incorporation into undergraduate and postgraduate curricula. It is hoped that interactive strategies to engage medical registrars in leadership training will lead to positive results including improvements in interdisciplinary communication, patient outcomes and fulfilment of curriculum competencies. Organisations have a duty to improve the quality of medical leadership training so that doctors feel equipped to influence change throughout their careers and be tomorrow's leaders. This review outlines the deficiencies in training, the importance of developing leadership skills in medical registrars and educational strategies that could be implemented by organisations in a cost-effective manner.
An evidence-based review of recent advances in therapy for heart failure with reduced ejection fraction (HFrEF)
Authors: Raj Leah , Adhyaru Bhavin
Published: October 2016

An estimated 5.1 million Americans have chronic heart failure and this is expected to increase 25% by 2030. Heart failure is a clinical syndrome that evolves from either functional or structural changes to the ventricles that lead to filling or ejection abnormalities. Thus far, pharmacotherapy has been show to be beneficial in patients only with reduced ejection fraction; however, new therapies have been developed in hopes of reducing the burden of heart failure. In this review, we will discuss current pharmacotherapies recommended in American College of Cardiology/American Heart Association guidelines, the evidence behind these recommendations as well as new and emerging therapies that have been developed.
Really mixed practice – a career in conservation medicine
Authors: Chatterton James
Published: October 2016

James Chatterton is veterinary services manager at Auckland Zoo. Part of his role involves providing veterinary care for the kakapo, one of the most endangered birds in New Zealand. He regularly provides onsite help on two protected islands off the South Island of New Zealand as part of his role as veterinary coordinator to the Kakapo Recovery Group
Structure and kinematic evolution of the Duke River fault, southwestern Yukon
Authors: Cobbett Rosie , Israel Steve , Mortensen Jim , Joyce Nancy , Crowley James
Published: October 2016

In southwest Yukon, the boundary between the Alexander terrane and Wrangellia corresponds with the Duke River fault. In this paper, we report on observations of the Duke River fault from four localities in southwest Yukon, and provide new constraints on (1) Permian regional metamorphism within the Alexander terrane, (2) Cretaceous ductile deformation along the Duke River fault, and (3) post-Miocene brittle deformation along the fault. Within these areas, the Duke River fault juxtaposes imbricated, pervasively foliated and folded greenschist-facies rocks of the Alexander terrane southwest of the fault against sub-greenschist-facies, less deformed rocks of Wrangellia. Multiple lines of evidence from this region indicate the Alexander terrane has been juxtaposed against Wrangellia along a southwest-dipping thrust fault. 40Ar/39Ar dates from muscovite, which grew during faulting or have been reset by motion along the Duke River fault, range from 79 to 105 Ma, suggesting that ductile movement along the fault is at least as old as Cretaceous (Albian to Cenomanian). This phase of faulting is interpreted as the local expression of Cretaceous shortening, which has been documented along the length and width of the Cordillera. Cretaceous structures along the Duke River fault are overprinted by brittle deformation that affects rocks as young as Miocene (or Pliocene?). The Duke River fault appears to be accommodating present-day transpression through uplift and reactivation of the thrust fault.
Reactive oxygen species and Ca2+ are involved in cadmium-induced cell killing in yeast cells
Authors: Wang Xinghua , Yi Min , Liu Hui , Han Yansha , Yi Huilan
Published: October 2016

Cadmium (Cd) is one of the most toxic heavy metals. It is of great environmental concern and its toxicity has been investigated in a variety of cells. In this study, we elucidated the toxic effects of Cd in cells of yeast (Saccharomyces cerevisiae). Our results showed that Cd2+ (0.05–5.0 mmol·L−1) significantly inhibited yeast cell growth, and the inhibitory effect was positively correlated with Cd2+ concentrations. Cd2+ caused loss of yeast cell viability in a concentration- and duration-dependent manner. Intracellular reactive oxygen species (ROS) and Ca2+ levels increased in yeast cells after exposure to 5.0 mmol·L−1 Cd for 6 h. Cd2+-caused cell viability loss was blocked by antioxidants (0.5 mmol·L−1 ascorbic acid or 500 U·mL−1 catalase) or Ca2+ antagonists (0.5 mmol·L−1 ethylene glycol tetraacetic acid or 0.5 mmol·L−1 LaCl3). Moreover, a collapse of mitochondrial membrane potential (ΔΨm) was observed in Cd2+-treated yeast cells. These results indicate that Cd-induced yeast cell killing was associated with the elevation of intracellular ROS and Ca2+ levels and also the loss of ΔΨm.
The effect of the laser polarization direction on the detached electron flux of H− in external field near surface
Authors: Tang T.T. , Zhu Z.L. , Yao J.G. , Wang D.H.
Published: October 2016

By using the semi-classical open orbit theory, the effect of the laser polarization direction on the detached electron flux of H− in electric field near metal surface has been studied. The result suggests that the azimuth angle [Formula: see text] has little effect on the electron flux distribution. We find that the influence of polarization angle θL on electron flux distribution is more obvious than the influence of the azimuth angle [Formula: see text]. In other words, the effect of the polarization angle θL on electron flux distribution is more important. We hope that our study will provide a new understanding of the electron flux distribution of negative ion in external field and surfaces, and can be used to guide the future experiment research on the negative ion photo-detachment microscopy.
Comparative thermal biology and depth distribution of largemouth bass (Micropterus salmoides) and northern pike (Esox lucius) in an urban harbour of the Laurentian Great Lakes
Authors: Peat Tyler B. , Gutowsky Lee F.G. , Doka Susan E. , Midwood Jonathan D. , Lapointe Nicholas W.R. , Hlevca Bogdan , Wells Mathew G. , Portiss Rick , Cooke Steven J.
Published: October 2016

Understanding how individuals are distributed in space and time, as well as how they interact with dynamic environmental conditions, represent fundamental knowledge gaps for many fish species. Using acoustic telemetry tags, we monitored the temperatures and depths used by northern pike (Esox lucius L., 1758) and largemouth bass (Micropterus salmoides (Lacepède, 1802)) in Toronto Harbour (Lake Ontario). Northern pike and largemouth bass had similar thermal experiences throughout the year, except during summer, when northern pike were observed in cooler waters than largemouth bass. Both species used different depths throughout the year, with northern pike occupying deeper depths. Statistical modelling indicated that depth usage was influenced by all variables (season, species, and body size) and interactions between them, whereas thermal preferences were influenced by the main effects and interactions between species:season and species : body size. Both species were observed at temperatures warmer than those in the vicinity of nearby telemetry stations, but as station temperatures exceeded 20 °C, northern pike moved into cooler water, indicating active thermoregulation. These data will be useful for refining our understanding of the spatial ecology of fish and for informing fisheries and habitat management in this and other urban harbours of the Laurentian Great Lakes.
Association equilibria for proteins interacted with crowders of short-range attraction in crowded environment
Authors: Wei Jiachen , Song Fan
Published: October 2016

Based on a very simple coarse-grained colloidal model, here we implement an effective hard-sphere theory and numerical simulation to capture the general features of the association equilibria for globular proteins in crowded environment. We measure the activity coefficient, i.e., the deviation from ideal behavior of protein solution, and the crowding factor, i.e., the contribution of crowders to the association equilibria, for proteins in macromolecular crowding. The results show that the association balance in macromolecular crowding depends sensitively on the magnitude of protein–crowder attraction and the relative size of reactant to crowding agent. Since our coarse-grained model is irrelevant to the microscopic details of the molecules, it can be applied to the control of the association equilibria of many globular proteins such as bovine serum albumin, crystallin and lysozyme.
“No One Knows What’s Gonna Happen Tomorrow”: Mistress Arrangement and the Emotional Dislocation of Rural Women in Urban China
Authors: XIAO SUOWEI
Published: October 2016

Studies on urban to rural migration in China over the past three decades have paid little attention to the emotional strains of migrants, either overlooking the impotency of migrant social networks in providing consistent emotional and spiritual support or overestimating the affective connection between individual migrants and their rural families. This study, which draws upon 12 months of ethnographic fieldwork in southern China, explores in-depth the intimate worlds of an array of migrant women who entered into long-term relationships with married men in their urban destination. I argue that some migrant women engage in the mistress arrangement as a means to navigate through social and emotional dislocation in the process of rural to urban migration. The relationship, socially stigmatized though, serves as a temporary shield that allows for care and ease in the city and an excuse to postpone an undesirable marital life back home. It, however, tends to place these women in a situation of isolation and dependency.
Local behavior of Iwasawa’s invariants
Authors: Kleine Sören
Published: October 2016

Let [Formula: see text] be a number field, let [Formula: see text] denote a fixed rational prime. We study the local behavior of Iwasawa’s invariants as functions on the set [Formula: see text] of all [Formula: see text]-extensions of [Formula: see text]. With respect to a certain topology on [Formula: see text] that takes care of ramification, we prove that for each [Formula: see text] the [Formula: see text]-invariant of [Formula: see text] is locally maximal among the [Formula: see text]-invariants, and we give sufficient conditions for the [Formula: see text]-invariant to be locally maximal (e.g., a vanishing [Formula: see text]-invariant). This concerns a question raised by R. Greenberg in 1973. Our main result also provides information about [Formula: see text]- (and even [Formula: see text]-) invariants in the case of a nonvanishing [Formula: see text]-invariant. The main tool used in the proof is a new result based on the stabilization of certain ranks, which considerably generalizes a theorem of T. Fukuda.
Ion-Exchange Synthesis and Enhanced Visible-Light Photoactivity of Graphene/Hexagonal CuS/Ag2S Nanocomposites
Authors: Zeng Bin , Zeng Wujun
Published: October 2016

Graphene loaded hexagonal CuS/Ag2S nanoplates have been successfully synthesized. Scanning electron microscopy and transmission electron microscopy observations show that hexagonal CuS/Ag2S nanoplates are tightly anchored onto graphene. The experimental results show that these nanocomposites have a highly visible-light photocatalytic performance. The high visible photocatalytic activities can be attributed to direct photoinduced interfacial charge transfer in the hexagonal CuS/Ag2S nanoplates and the further electrons transfer from CuS/Ag2S to graphene.
Differences and similarities between emplacement models of kimberlite and basaltic maar-diatreme volcanoes
Authors: Kurszlaukis Stephan , Lorenz Volker
Published: October 2016

Most kimberlite maar-diatreme volcanoes erupted during the Tertiary or earlier and therefore their tephra rings and, less often, their near-surface diatreme-filling deposits have usually been eliminated by erosion. Poorly eroded Quaternary non-kimberlite maar-diatreme volcanoes, especially those of mafic and ultramafic magma types, have the same diatreme size range (diameter and depth) as kimberlite pipes and show similar internal volcaniclastic diatreme lithofacies. In addition, these young volcanoes often have a more or less preserved tephra ring consisting of hundreds to perhaps a few thousand thin tephra beds. Volcanological analyses of the xenolith-rich primary volcaniclastic deposits both within these diatremes and in the tephra ring beds reflect phases of explosive pipe growth and are of convincingly phreatomagmatic origin.

The similarities between non-kimberlite pipes and kimberlite pipes suggest to some researchers that phreatomagmatic processes were also responsible for pipe excavation processes in kimberlite maar-diatreme volcanoes. In contrast, other researchers have suggested that kimberlite maar-diatreme volcanoes were emplaced largely by magmatic processes as a consequence of exsolution and the explosive expansion of juvenile volatiles. We therefore analysed and compared some key geological features of kimberlite and ultrabasic to basic ‘basaltic’ maar-diatreme volcanoes to determine similarities and differences with respect to their emplacement behaviour.
Caveolin-3 plays a critical role in autophagy after ischemia-reperfusion
Authors: Kassan Adam , Pham Uyen , Nguyen Quynhmy , Reichelt Melissa E. , Cho Eunbyul , Patel Piyush M. , Roth David M. , Head Brian P. , Patel Hemal H.
Published: October 2016

Autophagy is a dynamic recycling process responsible for the breakdown of misfolded proteins and damaged organelles, providing nutrients and energy for cellular renovation and homeostasis. Loss of autophagy is associated with cardiovascular diseases. Caveolin-3 (Cav-3), a muscle-specific isoform, is a structural protein within caveolae and is critical to stress adaptation in the heart. Whether Cav-3 plays a role in regulating autophagy to modulate cardiac stress responses remains unknown. In the present study, we used HL-1 cells, a cardiac muscle cell line, with stable Cav-3 knockdown (Cav-3 KD) and Cav-3 overexpression (Cav-3 OE) to study the impact of Cav-3 in regulation of autophagy. We show that traditional stimulators of autophagy (i.e., rapamycin and starvation) result in upregulation of the process in Cav-3 OE cells while Cav-3 KD cells have a blunted response. Cav-3 coimmunoprecipitated with beclin-1 and Atg12, showing an interaction of caveolin with autophagy-related proteins. In the heart, autophagy may be a major regulator of protection from ischemic stress. We found that Cav-3 KD cells have a decreased expression of autophagy markers [beclin-1, light chain (LC3-II)] after simulated ischemia and ischemia-reperfusion (I/R) compared with WT, whereas OE cells showed increased expression. Moreover, Cav-3 KD cells showed increased cell death and higher level of apoptotic proteins (cleaved caspase-3 and cytochrome c) with suppressed mitochondrial function in response to simulated ischemia and I/R, whereas Cav-3 OE cells were protected and had preserved mitochondrial function. Taken together, these results indicate that autophagy regulates adaptation to cardiac stress in a Cav-3-dependent manner.
Developmental plasticity of mitochondrial function in American alligators,Alligator mississippiensis
Authors: Galli Gina L. J. , Crossley Janna , Elsey Ruth M. , Dzialowski Edward M. , Shiels Holly A. , Crossley Dane A.
Published: October 2016

The effect of hypoxia on cellular metabolism is well documented in adult vertebrates, but information is entirely lacking for embryonic organisms. The effect of hypoxia on embryonic physiology is particularly interesting, as metabolic responses during development may have life-long consequences, due to developmental plasticity. To this end, we investigated the effects of chronic developmental hypoxia on cardiac mitochondrial function in embryonic and juvenile American alligators ( Alligator mississippiensis). Alligator eggs were incubated in 21% or 10% oxygen from 20 to 90% of embryonic development. Embryos were either harvested at 90% development or allowed to hatch and then reared in 21% oxygen for 3 yr. Ventricular mitochondria were isolated from embryonic/juvenile alligator hearts. Mitochondrial respiration and enzymatic activities of electron transport chain complexes were measured with a microrespirometer and spectrophotometer, respectively. Developmental hypoxia induced growth restriction and increased relative heart mass, and this phenotype persisted into juvenile life. Embryonic mitochondrial function was not affected by developmental hypoxia, but at the juvenile life stage, animals from hypoxic incubations had lower levels of Leak respiration and higher respiratory control ratios, which is indicative of enhanced mitochondrial efficiency. Our results suggest developmental hypoxia can have life-long consequences for alligator morphology and metabolic function. Further investigations are necessary to reveal the adaptive significance of the enhanced mitochondrial efficiency in the hypoxic phenotype.
Acetaminophen study yields new insights into neurobiological underpinnings of empathy
Authors: Tully John , Petrinovic Marija M.
Published: October 2016

Empathy is a cornerstone of social behavior, impairments of which are characteristic of neuropsychiatric disorders such as autism and psychopathy. According to the “shared representations” theory, empathy relies on neural processes similar to those underpinning the first-hand experience of a given emotion. A recent study by Mischkowski, Crocker, and Way ( Soc Cogn Affect Neurosci 11: 1345–1353, 2016) provides novel insights into neurobiological underpinnings of empathy by demonstrating that acetaminophen, a widely used painkiller, reduces empathy for other's physical and social pain.
Small-Molecule Disruption of the Myb/p300 Cooperation Targets Acute Myeloid Leukemia Cells
Authors: Uttarkar Sagar , Piontek Therese , Dukare Sandeep , Schomburg Caroline , Schlenke Peter , Berdel Wolfgang E. , Müller-Tidow Carsten , Schmidt Thomas J. , Klempnauer Karl-Heinz
Published: October 2016

The transcription factor c-Myb is essential for the proliferation of hematopoietic cells and has been implicated in the development of leukemia and other human cancers. Pharmacologic inhibition of Myb is therefore emerging as a potential therapeutic strategy for these diseases. By using a Myb reporter cell line, we have identified plumbagin and several naphthoquinones as potent low-molecular weight Myb inhibitors. We demonstrate that these compounds inhibit c-Myb by binding to the c-Myb transactivation domain and disrupting the cooperation of c-Myb with the coactivator p300, a major driver of Myb activity. Naphthoquinone-induced inhibition of c-Myb suppresses Myb target gene expression and induces the differentiation of the myeloid leukemia cell line HL60. We demonstrate that murine and human primary acute myeloid leukemia cells are more sensitive to naphthoquinone-induced inhibition of clonogenic proliferation than normal hematopoietic progenitor cells. Overall, our work demonstrates for the first time the potential of naphthoquinones as small-molecule Myb inhibitors that may have therapeutic potential for the treatment of leukemia and other tumors driven by deregulated Myb. Mol Cancer Ther; 15(12); 2905–15. ©2016 AACR.
Stress Effects in Vowel Perception as a Function of Language-Specific Vocabulary Patterns
Authors: Warner Natasha , Cutler Anne
Published: October 2016

Background/Aims: Evidence from spoken word recognition suggests that for English listeners, distinguishing full versus reduced vowels is important, but discerning stress differences involving the same full vowel (as in mu- from music or museum) is not. In Dutch, in contrast, the latter distinction is important. This difference arises from the relative frequency of unstressed full vowels in the two vocabularies. The goal of this paper is to determine how this difference in the lexicon influences the perception of stressed versus unstressed vowels. Methods: All possible sequences of two segments (diphones) in Dutch and in English were presented to native listeners in gated fragments. We recorded identification performance over time throughout the speech signal. The data were here analysed specifically for patterns in perception of stressed versus unstressed vowels. Results: The data reveal significantly larger stress effects (whereby unstressed vowels are harder to identify than stressed vowels) in English than in Dutch. Both language-specific and shared patterns appear regarding which vowels show stress effects. Conclusion: We explain the larger stress effect in English as reflecting the processing demands caused by the difference in use of unstressed vowels in the lexicon. The larger stress effect in English is due to relative inexperience with processing unstressed full vowels.
Voltage-Gated Potassium Channel Antibodies in Slow-Progression Motor Neuron Disease
Authors: Godani Massimiliano , Zoccarato Marco , Beronio Alessandro , Zuliani Luigi , Benedetti Luana , Giometto Bruno , Del Sette Massimo , Raggio Elisa , Baldi Roberta , Vincent Angela
Published: October 2016

Background: The spectrum of autoimmune neurological diseases associated with voltage-gated potassium channel (VGKC)-complex antibodies (Abs) ranges from peripheral nerve disorders to limbic encephalitis. Recently, low titers of VGKC-complex Abs have also been reported in neurodegenerative disorders, but their clinical relevance is unknown. Objective: The aim of the study was to explore the prevalence of VGKC-complex Abs in slow-progression motor neuron disease (MND). Methods: We compared 11 patients affected by slow-progression MND with 9 patients presenting typical progression illness. Sera were tested for VGKC-complex Abs by radioimmunoassay. The distribution of VGKC-complex Abs was analyzed with the Mann-Whitney U test. Results: The statistical analysis showed a significant difference between the mean values in the study and control groups. A case with long-survival MND harboring VGKC-complex Abs and treated with intravenous immunoglobulins is described. Conclusion: Although VGKC-complex Abs are not likely to be pathogenic, these results could reflect the coexistence of an immunological activation in patients with slow disease progression.
Paraneoplastic Necrotizing Autoimmune Myopathy in a Patient Undergoing Laparoscopic Pancreatoduodenectomy for Distal Cholangiocarcinoma
Authors: van Dijk Stefan , van der Kooi Anneke J. , Aronica Eleonora , van Gulik Thomas M. , Busch Olivier R. , Besselink Marc G.
Published: October 2016

A 73-year-old male presented with jaundice and severe muscle weakness. He was diagnosed with distal cholangiocarcinoma and paraneoplastic necrotizing autoimmune myopathy (NAM). Treatment of NAM consisted of dexamethasone pulse therapy, prednisone, and single-dose intravenous immunoglobulin. The distal cholangiocarcinoma was resected through a total laparoscopic pancreatoduodenectomy. After hospital discharge, muscle strength initially increased postoperatively; however, pneumonia resulted in the deterioration of his general condition and death 5 months after the diagnosis of paraneoplastic NAM.
Kcne4 Deletion Sex-Dependently Alters Vascular Reactivity
Authors: Abbott Geoffrey W. , Jepps Thomas A.
Published: October 2016

Voltage-gated potassium (Kv) channels formed by Kv7 (KCNQ) α-subunits are recognized as crucial for vascular smooth muscle function, in addition to their established roles in the heart (Kv7.1) and the brain (Kv7.2-5). In vivo, Kv7 α-subunits are often regulated by KCNE subfamily ancillary (β) subunits. We investigated the effects of targeted germline Kcne4 deletion on mesenteric artery reactivity in adult male and female mice. Kcne4 deletion increased mesenteric artery contractility in response to α-adrenoceptor agonist methoxamine, and decreased responses to Kv7.2-7.5 channel activator ML213, in male but not female mice. In contrast, Kcne4 deletion markedly decreased vasorelaxation in response to isoprenaline in both male and female mice. Kcne4 expression was 2-fold lower in the female versus the male mouse mesenteric artery, and Kcne4 deletion elicited only moderate changes of other Kcne transcripts, with no striking sex-specific differences. However, Kv7.4 protein expression in females was twice that in males, and was reduced in both sexes by Kcne4 deletion. Our findings confirm a crucial role for KCNE4 in regulation of Kv7 channel activity to modulate vascular tone, and provide the first known molecular mechanism for sex-specificity of this modulation that has important implications for vascular reactivity and may underlie sex-specific susceptibility to cardiovascular diseases.
Metabolic Syndrome in Children and Adolescents
Authors: Graf Christine , Ferrari Nina
Published: October 2016

Background: Juvenile obesity is associated with multiple cardiometabolic comorbidities, which may culminate in the metabolic syndrome (MetS). Methods: Based on a narrative review, the current knowledge of prevalence and the underlying metabolic principles regarding juvenile obesity and MetS are summarized to compile up-to-date information. In addition, the role of lifestyle as well as positive and negative influencing factors are focused on. Results: The prevalence of MetS occurs between 1 and up to 23% in the total pediatric population and in up to 60% amongst the obese and overweight. It can be considered as the consequence of multiple processes in terms of lifestyle, perinatal programming, and (epi-)genetic pathways; however, the complex underlying mechanisms and their interplay are not completely understood. Conclusion: Besides preventive approaches, the growing number of obese children and youth as well as its consequences call for effective and lasting therapeutic measures.
Are CSF Biomarkers Useful as Prognostic Indicators in Diagnostically Unresolved Cognitively Impaired Patients in a Normal Clinical Setting
Authors: Schjønning Nielsen Malene , Simonsen Anja Hviid , Siersma Volkert , Hasselbalch Steen Gregers , Høgh Peter
Published: October 2016

Background: Despite an extensive evaluation program, patients may remain diagnostically unresolved with regard to the etiology of their cognitive dysfunction. Cerebrospinal fluid neuroinflammation and Alzheimer disease (AD) biomarkers may act as indicators of neurodegenerative disorders in diagnostically unresolved patients. Methods: Data on 348 patients were retrospectively evaluated. All participants had a standardized diagnostic workup and follow-up in a memory clinic. Results: Aβ42 levels and Aβ42/p-tau ratios were reduced and levels of t-tau and p-tau as well as the t-tau × p-tau/Aβ42 ratio were elevated in diagnostically unresolved patients who clinically progressed, compared to a stable group. No differences in neuroinflammatory parameters were found. Conclusion: AD biomarkers - in particular the Aβ42/p-tau ratio, but not neuroinflammatory parameters - predicted clinical progression, regardless of etiology.
Defining Subpopulations of Arcuate Nucleus GABA Neurons in Male, Female, and Prenatally Androgenized Female Mice
Authors: Marshall Christopher J. , Desroziers Elodie , McLennan Timothy , Campbell Rebecca E.
Published: October 2016

Background/Aims: Arcuate nucleus (ARN) γ-aminobutyric acid (GABA) neurons are implicated in many critical homeostatic mechanisms, from food intake to fertility. To determine the functional relevance of ARN GABA neurons, it is essential to define the neurotransmitters co-expressed with and potentially co-released from ARN GABA neurons. Methods: The present study investigated the expression of markers of specific signaling molecules by ARN GABA neurons in brain sections from male, female, and, in some cases, prenatally androgen-treated (PNA) female, vesicular GABA transporter (VGaT)-ires-Cre/tdTomato reporter mice. Immunofluorescence for kisspeptin, β-endorphin, neuropeptide Y (NPY), tyrosine hydroxylase (TH) and neuronal nitric oxide synthase (nNOS) was detected by confocal microscopy, and co-localization with tdTomato VGaT reporter expression throughout the ARN was quantified. Results: GABA neurons rarely co-localized with kisspeptin (<2%) or β-endorphin (<1%), and only a small proportion of kisspeptin (∼10%) or β-endorphin (∼3%) neurons co-localized with VGaT in male and female mice. In contrast, one-third of ARN GABA neurons co-localized with NPY, and nearly all NPY neurons (>95%) co-localized with VGaT across groups. Both TH and nNOS labeling was co-localized with ∼10% of ARN GABA neurons. The proportion of TH neurons co-localized with VGaT was significantly greater in males than either control or PNA females, and the proportion of nNOS neurons co-localizing VGaT was higher in control and PNA females compared with males. Conclusion: These data highlight NPY as a significant subpopulation of ARN GABA neurons, demonstrate no significant impact of PNA on signal co-expression, and, for the first time, show sexually dimorphic co-expression patterns of TH and nNOS with ARN GABA neurons.
Epidemiology of first and recurrent venous thromboembolism in patients with active cancer
Authors: Katholing Anja , Rietbrock Stephan , Bamber Luke , Martinez Carlos , Cohen Alexander T.
Published: October 2016

Population studies on the incidence of venous thromboembolism (VTE) in patients with active cancer are limited. An observational cohort study was undertaken to estimate the incidence of first and recurrent VTE. The source population consisted of all patients in the UK Clinical Practice Research Datalink, with additional information on hospitalisation and cause of death, between 2001 and 2011. A cancer-related clinical diagnosis or therapy within the 90 days before or after a VTE constituted an active-cancer-associated VTE. Incidence rates of first VTE among patients with active cancer and incidence rates of recurrent VTE during the 10-year observational period after a first VTE event were estimated. Incidence rates of all-cause mortality and age- and gender-specific mortality were also calculated. There were 6,592 active-cancer-associated VTEs with a total of 112,738 cancer-associated person-years of observation. The incidence rate of first VTE in patients with active cancer was 5.8 (95 % confidence interval 5.7–6.0) per 100 person-years. A first VTE recurrence was observed in 591 patients. The overall incidence rate for recurrence was 9.6 (95 % confidence interval 8.8–10.4) per 100 person-years, with a peak at 22.1 in the first six months. Recurrence rates were similar after initial pulmonary embolism and after initial deep-vein thrombosis. The mortality risk after VTE was considerable, with 64.5 % mortality after one year and 88.1 % after 10 years. VTE in patients with active cancer is common and associated with high recurrence and mortality rates. Efforts are needed to prevent VTE and reduce recurrence, especially in the first year after VTE diagnosis.

Supplementary Material to this article is available online at www.thrombosis-online.com.
Powerful Men and Boyhood Sexuality in K. Sello Duiker’s Thirteen Cents
Authors: Nabutanyi Edgar
Published: October 2016

In Southern African postcolonial discourses, sexual violation is often deployed as an allegory for either patriarchal control or racial domination. This perhaps explains the huge archive of narratives of sexual violence in the Southern African literary canon. While this archive and its scholarship mainly concentrates on the experiences of women and girls, a substantial number of texts portraying the sexual abuse of boys from the region demand that scholarly attention is paid to this phenomenon. Does contemporary South African fiction’s privileging of the sexual violation of boys suggest that boys are as vulnerable to this form of violence in moments of national crisis as are girls and women? Reading K. Sello Duiker’s Thirteen Cents1 as a portrayal of the precarious intersection of post-apartheid familial dystopia on children’s bodies—articulated through under-age prostitution—I explore how fiction intervenes successfully to spotlight the susceptibility of boys to pederasty in moments of societal crisis. Additionally, I examine how homosexual prostitution is portrayed as a tool for survival for helpless boys, on the one hand, and exhibition of patriarchal power for the men that pay to have sex with these boys, on the other. I argue that the depiction of underage sex work of some boys in South African cities can help rescue these victims from being perceived as mere statistical footnotes to Southern African inequities and patriarchal power.