bluuebunny/crossref_metadata_2025 huggingface dataset:
Craniosynostosis
Authors: Samandouras George
Published: August 2014

Chapter 13.2 covers craniosynostosis, including basic concepts, pathogenesis, diagnosis and treatment, syndromiccraniosynostosis, and non-syndromiccraniosynostosis.
Introduction to epilepsy
Authors: Samandouras George
Published: August 2014

Chapter 14.1 provides an introduction to epilepsy, including basic concepts, epidemiology, aetiology, initial diagnostic approach to seizures, and anti-epileptic drugs.
Inflammatory spinal disease
Authors: Samandouras George
Published: August 2014

Chapter 16.4 covers inflammatory spinal disease, including rheumatoid arthritis (RA) and ankylosing spondylitis (AS).
Ossified posterior longitudinal ligament (OPLL)
Authors: Samandouras George
Published: August 2014

Chapter 16.7 covers ossified posterior longitudinal ligament (OPLL), including basic concepts, pathogenesis, clinical features, diagnosis, and treatment.
Lumbar canal stenosis
Authors: Samandouras George
Published: August 2014

Chapter 16.12 covers lumbar canal stenosis, including pathogenesis, clinical presentation, investigations, management, and surgical technique of laminectomy.
Cauda equina syndrome
Authors: Samandouras George
Published: August 2014

Chapter 16.13 covers caudaequina syndrome, including basic concepts, pathophysiology, imaging, and treatment.
Complications of inflammatory bowel disease
Authors: Marks Daniel , Harbord Marcus
Published: August 2014

Description of ulcerative colitis and Crohn’s disease

Initial assessment of the patient with suspected IBD

Assessing disease severity

Management of ulcerative colitis

Management of Crohn’s disease

Special situations

Complications of medical therapy

Ulcerative colitis (UC) causes chronic inflammation of the rectum (proctitis) and colon (colitis). Caused by environmental triggers (possibly NSAIDs, infections, stress) in genetically susceptible hosts. Lifetime risk ~0.1% (1–2% if affected first-degree relative). Onset at any age, with bimodal distribution (15–30y and 50–70y). Presents with diarrhoea and rectal bleeding, followed by periods of remission and relapse. At any time, ~25% of patients are well (taking no medication), while two-thirds have mild disease requiring simple therapies (...
Drug-induced liver injury
Authors: Marks Daniel , Harbord Marcus
Published: August 2014

Drug-induced liver injury

Paracetamol

Statins

NSAIDs and aspirin

Anticonvulsants

Antidepressants

Amiodarone

Anti-tuberculosis drugs

Co-amoxiclav

Minocycline

Oral contraceptive pill

Khat

Herbal remedies

Drug-induced liver injury (DILI) accounts for ~1% of general medical admissions, 〈5% of all cases of jaundice, but up to 30% of acute liver failure. It is associated with 〉1,000 medications and herbal products. The following principles apply:
...
Prevalence and distribution of pain in children
Authors: Stevens Bonnie J. , Zempsky William T.
Published: August 2014

There has been a paucity of studies that have attempted to determine the prevalence and distribution of pain (acute or chronic) in large groups of infants and children across multiple settings. Rather, there is a preponderance of single-site studies that report local prevalence and distribution of paediatric pain data. Although one could extrapolate these results to gain a broader sense of pain in children, this approach would garner only a general estimate at best. Furthermore, studies of pain prevalence vary as to the pain and prevalence definitions used, the reporting period (i.e. point prevalence, period prevalence), and stratification by duration of involvement, which makes comparison of findings challenging. In this chapter, definitions of prevalence and acute and chronic pain will be clarified and used to explore the prevalence and distribution of pain in hospitals and in community health care settings for infants and children. Recommendations for clinical practice and future research will be proposed.
Long-term effects of pain in children
Authors: Grunau Ruth E.
Published: August 2014

Major advances in high-technology medical care have led to greatly increased survival of medically fragile infants born extremely preterm, or with major congenital anomalies or other life-threatening conditions. These infants are exposed to procedural, surgical, and post-surgical pain. For millennia human infancy was a prolonged period of adult protection, with pain rarely encountered early in life. While the biological mechanisms for perception of pain develop during the fetal period, endogenous capacities to dampen pain mature later. Until relatively recently, this biological substrate was a good fit, matching the environment of infancy. However, the revolution in medical care has led to unforeseen challenges to understand and manage infant pain. In full-term infants, the primary concern is whether early pain alters later pain sensitivity. In contrast, due to the immaturity of the developing nervous system, the greatest impact of pain is likely to occur in the least maturely born infants. Therefore, in infants born very preterm who undergo lengthy hospitalization, pain may affect multiple aspects of development. This chapter focuses on long-term effects of early pain on subsequent pain perception, neurodevelopment, brain development, and programming of stress systems in the context of clinical studies, and whether caregiving factors may ameliorate potential long-term adverse effects.
Nociceptive signalling in the periphery and spinal cord
Authors: Walker Suellen M. , Baccei Mark L.
Published: August 2014

Responses to painful or noxious stimuli are functional at birth. However, postnatal changes in the transmitters, receptors, and pathways involved in nociceptive signalling result in significant age-related changes in the nature and degree of response.
Noxious mechanical, thermal, and chemical stimuli are detected by peripheral nociceptors, transduced into electrical stimuli, and transmitted to the spinal cord. Within the spinal cord, there are significant postnatal changes in the balance of inhibitory and excitatory signalling, that not only influence the acute response to afferent input, but can also underlie long-term alterations in sensory processing following tissue injury in early life.
Evaluating age-related changes in nociceptive signalling is essential not only for understanding acute behavioural responses to noxious stimuli, but also for identifying the most appropriate and effective pain management interventions at different developmental ages.
Neuroimmune interactions and pain during postnatal development
Authors: Vega-Avelaira David , Beggs Simon
Published: August 2014

The immune system is essential for identifying and mounting defensive responses to tissue damage and infection. In addition, it is increasingly recognized that interactions between immune cells and nociceptive pathways can modulate pain sensitivity. The role and function of immune cells in the central nervous system changes during postnatal development, and as a result, the impact of neuroimmune interactions on pain signalling varies with both age and the type of injury.
Procedural sedation
Authors: Cravero Joseph P.
Published: August 2014

Paediatric patients undergoing procedures often require sedation to provide the appropriate combination of anxiolysis, analgesia, and motionlessness. Due to the behavioural and developmental issues involved with this population, children actually require sedation to accomplish procedures much more often than adults. Paediatric sedation is a dynamic area of practice. Requests for this care continue to rise. The variety of providers involved in this care has also increased significantly. This chapter reviews the basic concepts involved in sedation delivery and then addresses the various considerations involved in sedation cases from the point of view of patient factors, procedure factors, and provider factors. Various drugs available for sedation are also reviewed with comments on appropriate strategies for a variety of common diagnostic and therapeutic procedures.
Non-inflammatory musculoskeletal pain
Authors: Clinch Jacqui
Published: August 2014

Non-inflammatory musculoskeletal pain is common in children and adolescents, and when persistent or widespread, can have a negative impact on physical and psychological well-being. Diagnostic labels and criteria are not uniform in the current literature, but musculoskeletal pain may present as widespread pain or juvenile fibromyalgia, complex regional pain syndrome, or in association with joint hypermobility. Chronic musculoskeletal pain, irrespective of its trigger, can bring persistent and recurrent distress, disability, and widespread family disruption. Once serious medical causes have been excluded by history, examination, and relevant investigations, the focus should be on rehabilitation. Multidisciplinary team management to facilitate cohesive working and the introduction of psychological and physical therapies can improve outcome. Further research is required to define the role of pharmacological interventions.
Self-report: the primary source in assessment after infancy
Authors: von Baeyer Carl L.
Published: August 2014

Self-report is the primary source of information for assessment of pain and measurement of its intensity in children age 3 years and older. This chapter provides an overview of the variables addressed in assessment, specific tools used to obtain self-reports, and interpretation of pain scores. Challenges include establishing whether children are able to understand and use self-report scales and interpreting self-reported pain scores when they conflict with clinicians’ observation. New developments in self-report assessment are introduced, such as new support for the use of numerical rating scales and development of computer and smartphone self-report tools. Recommendations are provided supporting integration of self-report of pain in pain management.
Biomarkers of pain: physiological indices of pain reactivity in infants and children
Authors: Brummelte Susanne , Oberlander Tim F. , Craig Kenneth D.
Published: August 2014

Biomarkers are common in all areas of clinical work, health research, and are critical indicators of diseases and physiological states. Preferably, a biomarker should be non-invasively accessible, low in cost, highly specific, sensitive, and easy to interpret. Due to the complexity of the pain system, no unidimensional reliable biomarker for pain has been identified to date. Developmental changes and delayed maturation of the involved physiological systems add another layer of complexity to the use of biomarkers in the paediatric population. Nevertheless, readily available and reliable biomarkers of pain would greatly enhance timely and appropriate treatment of pain, especially in infants and verbally or cognitively challenged children. This chapter examines currently available markers, their use, and limitations.
Sensory processing and neurophysiological evaluation in children
Authors: Hermann Christiane
Published: August 2014

Traditionally, pain in children is assessed by behavioural observation and by self-report with a focus on perceived pain intensity. In this chapter, more recently developed standardized psychophysical procedures to assess abnormalities in sensory and pain processing and non-invasive neurophysiological methods to unravel the neuronal mechanisms underlying the experience of pain are described and how they have been used for investigating paediatric pain. For both sensory and neurophysiological assessment methods, the underlying assumptions and theoretical underpinnings are outlined. Following a brief overview of commonly used measures and methods, methodological issues are addressed that need to be considered when planning to use such methods and when interpreting the obtained findings. Finally, empirical examples are reviewed that highlight the use of these techniques for addressing major research questions such as the development of pain processing and changes in sensory and pain processing associated with chronic paediatric pain.
Principles of pain pharmacology in paediatrics
Authors: Chau Kim , Koren Gideon
Published: August 2014

Changes during growth and development may profoundly alter the pharmacokinetic and pharmacodynamics profile of medications in children of different ages, and in comparison to adults. Genetic factors can also influence the disposition and action of a drug, and contribute to interindividual differences in clinical response. Safe and effective pharmacological management of pain in neonates, infants, and children requires a thorough understanding of the principles of analgesic pharmacology in paediatric patients. Analgesic dosing regimens should take into account the severity of pain, the age or developmental state of the infant, and the therapeutic window of the drug.
Complementary drugs—herbs, vitamins, and dietary supplements for pain and symptom management
Authors: Weydert Joy A.
Published: August 2014

Because of the interest of patients and physicians, there has been increasing research into the use of botanical agents, nutritional supplements, and diet as a means to manage pain. Pharmacological agents typically are chosen as first-line therapy for pain and symptom management; however, for some patients these agents may not work well long term or have side effects that are not tolerated. Other patients may prefer non-pharmacological therapies. Most clinicians are not trained or may not be comfortable recommending these complementary agents.
Theory-informed approaches to translating pain evidence into practice
Authors: Yamada Janet , Hutchinson Alison M.
Published: August 2014

Despite great strides in evidence-based pain assessment and management strategies, infants and children still experience acute pain (including multiple painful procedures) and chronic pain during hospitalization. Translating best evidence on pain assessment and management into clinical practice remains a challenge. The knowledge- or evidence-to-practice gap in pain in children can be addressed by implementing strategies, underpinned by knowledge translation theories, frameworks, and models, to promote and sustain practice change. A range of factors related to the organizational context and individual behaviour play a role in the adoption of new pain assessment and management practices.
Organizational systems in paediatric pain
Authors: Embrett Mark , Buckley Norman
Published: August 2014

This chapter first focuses on an overview of the similar elements to approaches of chronic pain, acute pain, and palliative care, concluding with a description of the ideal multidisciplinary pain management approach (MPMA). The chapter then proceeds to review the specific organization and operations of acute pain and chronic pain services, respectively. Finally, research about the expectation of parents when they enter a clinic and importance of accommodating and promoting positive expectations is presented. The patient flow process in acute pain differs from the chronic pain model and is described. The emphasis remains on consistent clear communication among providers and between providers and patient/family.
Integrative Nursing Management of Stress
Authors: Lindquist Ruth , Witt Dawn R. , Crane Lynette
Published: August 2014

Stress is ubiquitous in the modern world. Recognition and understanding of the complex system-specific aspects of the “stress response,” as well as the manifestations of stress and adaptation in the integrated whole are essential to for integrative nursing management of symptoms of stress. A wide-variety of interventions can be selected and implemented by the nurse in collaboration with the individual, family or community to address acute or chronic stress; single or multi-faceted approaches to intervention are applied from options from “tiers” of increasing intensity/invasiveness, while being mindful of principles of integrative nursing, to achieve desired mutually planned and desired outcomes.
Integrative Nursing in Mental Health
Authors: Kaas Merrie J. , Peterson Barbara , Kristofersson Gisli
Published: August 2014

Given recent U.S. health care policy changes which encourage integrated models for mental health care, this chapter compares three exemplars of integrative mental health care using a conceptual framework of team-oriented practice and identify some of the issues in developing future integrated, integrative team approaches to mental health care.
Integrative Nursing of Older Adults Across the Continuum
Authors: Halcón Linda L. , Schein Constance , Cheung Corjena
Published: August 2014

The use of integrative therapies continues to grow and a large percent (69%) of seniors do not discuss their use of integrative approaches with their primary care providers. Understanding the developmental tasks of older adulthood is necessary to provide holistic and integrative care. This includes understanding their journey, their understanding of health and their desired trajectory and relationships. Innovative care models are emerging that incorporate integrative approaches into the full continuum of care from home, to assisted living to long-term care.
Graduate Nursing Education for Integrative Nursing
Authors: Fenton Mary V. , Halcón Linda L. , Napolitano Marie
Published: August 2014

The term integrative nursing embodies many terms and concepts that nurses have historically used to describe whole person/whole systems approaches to health care. This chapter focuses on the current status of incorporating concepts and principles of integrative nursing in graduate nursing programs with examples of both master’s and doctor of nursing practice education models. Two of the American Association of Colleges of Nursing Essentials of Doctoral Education for Advanced Nursing Practice Essentials, Organization and Systems Leadership and Advanced Nursing Practice are provided as examples of teaching integrative nursing in doctoral programs to prepare nurses to model and lead transformative change in our health care system.
Esophagus
Authors: Johnson C. Daniel
Published: August 2014

Cases are presented related to inflammatory and ulcerative diseases, strictures, masses and filling defects, diverticula, and miscellaneous conditions of the esophagus. Each case contains a relevant image or images, imaging findings, a differential diagnosis, the actual diagnosis, and a discussion. Supplementary materials provided with each chapter include differential diagnoses, anatomical illustrations, and a question and answer section.
Improved artificial origins for phage Φ29 terminal protein-primed replication. Insights into early replication events
Authors: Gella Pablo , Salas Margarita , Mencía Mario
Published: August 2014

The replication machinery of bacteriophage Φ29 is a paradigm for protein-primed replication and it holds great potential for applied purposes. To better understand the early replication events and to find improved origins for DNA amplification based on the Φ29 system, we have studied the end-structure of a double-stranded DNA replication origin. We have observed that the strength of the origin is determined by a combination of factors. The strongest origin (30-fold respect to wt) has the sequence CCC at the 3′ end of the template strand, AAA at the 5′ end of the non-template strand and 6 nucleotides as optimal unpairing at the end of the origin. We also show that the presence of a correctly positioned displaced strand is important because origins with 5′ or 3′ ssDNA regions have very low activity. Most of the effect of the improved origins takes place at the passage between the terminal protein-primed and the DNA-primed modes of replication by the DNA polymerase suggesting the existence of a thermodynamic barrier at that point. We suggest that the template and non-template strands of the origin and the TP/DNA polymerase complex form series of interactions that control the critical start of terminal protein-primed replication.
ELP3 Is Involved in Sexual and Asexual Development, Virulence, and the Oxidative Stress Response in Fusarium graminearum
Authors: Lee Yoonji , Min Kyunghun , Son Hokyoung , Park Ae Ran , Kim Jin-Cheol , Choi Gyung Ja , Lee Yin-Won
Published: August 2014

Fusarium graminearum is an important fungal plant pathogen that causes serious losses in cereal crop yields and mycotoxicoses in humans and livestock. In this study, we characterized an insertion mutant, Z39R9282, with pleiotropic defects in sexual development and virulence. We determined that the insertion occurred in a gene encoding an ortholog of yeast elongator complex protein 3 (ELP3). Deletion of elp3 led to significant defects in sexual and asexual development in F. graminearum. In the elp3 deletion mutant, the number of perithecia formed was reduced and maturation of perithecia was delayed. This mutant also produced morphologically abnormal ascospores and conidia. Histone acetylation in the elp3 deletion mutant was reduced compared with the wild type, which likely caused the developmental defects. Trichothecenes were not produced at detectable levels, and expression of trichothecene biosynthesis genes were significantly reduced in the elp3 deletion mutant. Infection of wheat heads revealed that the elp3 deletion mutant was unable to spread from inoculated florets to neighboring spikelets. Furthermore, the elp3 deletion mutant was more sensitive to oxidative stress than the wild type, and the expression of putative catalase genes was reduced. We demonstrate that elp3 functions in sexual and asexual development, virulence, and the oxidative stress response of F. graminearum by regulating the expression of genes involved in these various developmental processes.
Molecular Polymorphism and Phenotypic Diversity in the Eutypa Dieback PathogenEutypa lata
Authors: Travadon Renaud , Baumgartner Kendra
Published: August 2014

Pathogen adaptation to different hosts can lead to specialization and, when coupled with reproductive isolation, genome-wide differentiation and ecological speciation. We tested the hypothesis of host specialization among California populations of Eutypa lata (causal fungus of Eutypa dieback of grapevine and apricot), which is reported from >90 species. Genetic analyses of nine microsatellite loci in 182 isolates from three hosts (grapevine, apricot, and willow) at three locations were complemented by cross-inoculations on cultivated hosts grapevine and apricot to reveal patterns of host specialization. The cultivated hosts are likely more important sources of inoculum than the wild host willow, based on our findings of higher pathogen prevalence and allelic richness in grapevine and apricot. High levels of gene flow among all three hosts and locations, and no grouping by clustering analyses, suggest neither host nor geographic differentiation. Cross-inoculations revealed diversified phenotypes harboring various performance levels in grapevine and apricot, with no apparent correlation with their host of origin. Such phenotypic diversity may enable this pathogen to persist and reproduce as a generalist. Regular genetic reshuffling through sexual recombination, frequent immigration among hosts, and the lack of habitat choice in this passively dispersed fungus may prevent fixation of alleles controlling host specialization.
Identification of the determinants of tRNA function and susceptibility to rapid tRNA decay by high-throughput in vivo analysis
Authors: Guy Michael P. , Young David L. , Payea Matthew J. , Zhang Xiaoju , Kon Yoshiko , Dean Kimberly M. , Grayhack Elizabeth J. , Mathews David H. , Fields Stanley , Phizicky Eric M.
Published: August 2014

Sequence variation in tRNA genes influences the structure, modification, and stability of tRNA; affects translation fidelity; impacts the activity of numerous isodecoders in metazoans; and leads to human diseases. To comprehensively define the effects of sequence variation on tRNA function, we developed a high-throughput in vivo screen to quantify the activity of a model tRNA, the nonsense suppressor SUP4oc of Saccharomyces cerevisiae. Using a highly sensitive fluorescent reporter gene with an ochre mutation, fluorescence-activated cell sorting of a library of SUP4oc mutant yeast strains, and deep sequencing, we scored 25,491 variants. Unexpectedly, SUP4oc tolerates numerous sequence variations, accommodates slippage in tertiary and secondary interactions, and exhibits genetic interactions that suggest an alternative functional tRNA conformation. Furthermore, we used this methodology to define tRNA variants subject to rapid tRNA decay (RTD). Even though RTD normally degrades tRNAs with exposed 5′ ends, mutations that sensitize SUP4oc to RTD were found to be located throughout the sequence, including the anti-codon stem. Thus, the integrity of the entire tRNA molecule is under surveillance by cellular quality control machinery. This approach to assess activity at high throughput is widely applicable to many problems in tRNA biology.
Proteins with High Turnover Rate in Barley Leaves Estimated by Proteome Analysis Combined with in Planta Isotope Labeling
Authors: Nelson Clark J. , Alexova Ralitza , Jacoby Richard P. , Millar A. Harvey
Published: August 2014

Protein turnover is a key component in cellular homeostasis; however, there is little quantitative information on degradation kinetics for individual plant proteins. We have used 15N labeling of barley (Hordeum vulgare) plants and gas chromatography-mass spectrometry analysis of free amino acids and liquid chromatography-mass spectrometry analysis of proteins to track the enrichment of 15N into the amino acid pools in barley leaves and then into tryptic peptides derived from newly synthesized proteins. Using information on the rate of growth of barley leaves combined with the rate of degradation of 14N-labeled proteins, we calculate the turnover rates of 508 different proteins in barley and show that they vary by more than 100-fold. There was approximately a 9-h lag from label application until 15N incorporation could be reliably quantified in extracted peptides. Using this information and assuming constant translation rates for proteins during the time course, we were able to quantify degradation rates for several proteins that exhibit half-lives on the order of hours. Our workflow, involving a stringent series of mass spectrometry filtering steps, demonstrates that 15N labeling can be used for large-scale liquid chromatography-mass spectrometry studies of protein turnover in plants. We identify a series of abundant proteins in photosynthesis, photorespiration, and specific subunits of chlorophyll biosynthesis that turn over significantly more rapidly than the average protein involved in these processes. We also highlight a series of proteins that turn over as rapidly as the well-known D1 subunit of photosystem II. While these proteins need further verification for rapid degradation in vivo, they cluster in chlorophyll and thiamine biosynthesis.
Technical quality assurance during the TROG 03.04 RADAR prostate radiotherapy trial: Are the results reflected in observed toxicity rates?
Authors: Ebert Martin A , Bulsara Max , Haworth Annette , Kearvell Rachel , Richardson Sharon , Kennedy Angel , Spry Nigel A , Bydder Sean A , Joseph David J , Denham James W
Published: August 2014

Introduction

Multicentre radiotherapy clinical trials can incorporate quality assurance (QA) procedures for ensuring consistent application of the trial protocol in the planning, delivery and reporting of participant treatments. Subsequently detected variations from trial protocol have previously been shown to reduce treatment efficacy, although little has been shown for toxicity rates. The purpose of this study was to investigate the association of QA measures and protocol variations on toxicity incidence in the context of a prostate radiotherapy trial.

Methods

Using QA records from the TROG 03.04 RADAR trial, the impact of variations on gastrointestinal (GI) and genito‐urinary (GU) toxicities was investigated.

Results

Protocol variation rates were lower than reported in previous studies, and showed little correlation with GI toxicity outcomes. Variations classified as ‘major’ showed a non‐significant trend for increased toxicity relative to those classified as ‘minor’. Results from a Level III phantom‐based dosimetry study showed some correlation with GI toxicity, whereas ranking on a set‐up accuracy study did not impact on toxicity. Toxicity in general increased with the number of participants accrued per centre, at odds with previous reports relating to disease progression, with a potential link to increases in low–mid‐range rectal doses in the cohort from higher‐accruing centres. No QA‐related variables correlated with GU toxicities.

Conclusions

Besides non‐significant trends, minimal association was observed between QA variables and toxicity rates for the RADAR trial. The intention of the trial's QA programme was to reduce treatment variations and minimise toxicity in the context of a relevantly advanced treatment approach.
Analysis of the coincidence rate between imaging and pathological findings of pulmonary metastasis in 45 cases with invasive bone and soft tissue sarcoma
Authors: Huang Zhen , Chen Keneng , Kang Xiaozheng , Zhang Qing , Hao Lin , Li Yuan , Niu Xiaohui
Published: August 2014

Background

It is not uncommon for imaging examinations of invasive bone and soft tissue sarcoma patients during initial treatment or postoperative follow‐up to detect pulmonary nodules. This has important significance in determining the nature of nodules either for tumor staging and therapeutic regimen selection or for prognosis evaluation.

Methods

A review was carried out of invasive bone and soft tissue sarcoma patients diagnosed and treated in the department of orthopedic oncology of Beijing Jishuitan Hospital from June 2002 to June 2012. Data from patients who developed pulmonary metastases, diagnosed by imaging and treated surgically, were analyzed for consistency between imaging and postoperative pathological diagnoses.

Results

A total of 45 patients with pulmonary metastasis diagnosed by imaging and treated with resection of pulmonary lesions were included in the study. Thirty‐eight cases with pulmonary metastases (84.4%) and seven cases without pulmonary metastases (15.6%) were confirmed by postoperative pathological examination. The most common pathological type in the latter patients was tuberculosis, with a total of four cases (57.1%).

Conclusion

There is a certain degree of misdiagnosis when using imaging for diagnosis of pulmonary metastasis, and attention should be paid to the pathological diagnosis of pulmonary metastasis in order to avoid overtreatment. Tuberculosis is most common in invasive bone and soft tissue sarcoma patients with pulmonary benign lesions, and it should be distinguished.
Novel retinoblastoma mutation abrogating the interaction to E2F2/3, but not E2F1, led to selective suppression of thyroid tumors
Authors: Toki Hideaki , Inoue Maki , Minowa Osamu , Motegi Hiromi , Saiki Yuriko , Wakana Shigeharu , Masuya Hiroshi , Gondo Yoichi , Shiroishi Toshihiko , Yao Ryoji , Noda Tetsuo
Published: August 2014

Mutant mouse models are indispensable tools for clarifying gene functions and elucidating the pathogenic mechanisms of human diseases. Here, we describe novel cancer models bearing point mutations in the retinoblastoma gene (Rb1) generated by N‐ethyl‐N‐nitrosourea mutagenesis. Two mutations in splice sites reduced Rb1 expression and led to a tumor spectrum and incidence similar to those observed in the conventional Rb1 knockout mice. The missense mutant, Rb1D326V/+, developed pituitary tumors, but thyroid tumors were completely suppressed. Immunohistochemical analyses of thyroid tissue revealed that E2F1, but not E2F2/3, was selectively inactivated, indicating that the mutant Rb protein (pRb) suppressed thyroid tumors by inactivating E2F1. Interestingly, Rb1D326V/+ mice developed pituitary tumors that originated from the intermediate lobe of the pituitary, despite selective inactivation of E2F1. Furthermore, in the anterior lobe of the pituitary, other E2F were also inactivated. These observations show that pRb mediates the inactivation of E2F function and its contribution to tumorigenesis is highly dependent on the cell type. Last, by using a reconstitution assay of synthesized proteins, we showed that the D326V missense pRb bound to E2F1 but failed to interact with E2F2/3. These results reveal the effect of the pRb N‐terminal domain on E2F function and the impact of the protein on tumorigenesis. Thus, this mutant mouse model can be used to investigate human Rb family‐bearing mutations at the N‐terminal region.
Strong Inhibition of Beta‐Amyloid Peptide Aggregation Realized by Two‐Steps Evolved Peptides
Authors: Ghimire Gautam Sunita , Komatsu Masayuki , Nishigaki Koichi
Published: August 2014

Several decades of cumulated research evidence have proven that aggregation of beta‐amyloid 42 (Aβ42) is the main cause of neuronal death in the brains of patients with Alzheimer's disease. Therefore, inhibition of Aβ42 aggregation holds great promise for the prevention and treatment of Alzheimer's disease. To this end, we used a systematic in vitro evolution including a paired peptide library method. We identified two peptides with high binding affinity (with Kd in the nm range) for Aβ42. Functionally, these peptides strongly inhibited the aggregation of Aβ42 as shown by the thioflavin T assay and atomic force microscopy. Moreover, these peptides rescued PC12 cells from the cytotoxic effect of aggregated Aβ42 in vitro. Our results suggest that these novel peptides may be potential therapeutic seeds for the treatment of Alzheimer's disease.
Re‐Presentations of Space in Hollywood Movies: An Event‐Indexing Analysis
Authors: Cutting James , Iricinschi Catalina
Published: August 2014

Popular movies present chunk‐like events (scenes and subscenes) that promote episodic, serial updating of viewers’ representations of the ongoing narrative. Event‐indexing theory would suggest that the beginnings of new scenes trigger these updates, which in turn require more cognitive processing. Typically, a new movie event is signaled by an establishing shot, one providing more background information and a longer look than the average shot. Our analysis of 24 films reconfirms this. More important, we show that, when returning to a previously shown location, the re‐establishing shot reduces both context and duration while remaining greater than the average shot. In general, location shifts dominate character and time shifts in event segmentation of movies. In addition, over the last 70 years re‐establishing shots have become more like the noninitial shots of a scene. Establishing shots have also approached noninitial shot scales, but not their durations. Such results suggest that film form is evolving, perhaps to suit more rapid encoding of narrative events.
B‐cell receptor signalling and its crosstalk with other pathways in normal and malignant cells
Authors: Seda Vaclav , Mraz Marek
Published: August 2014

The physiology of B cells is intimately connected with the function of their B‐cell receptor (BCR). B‐cell lymphomas frequently (dys)regulate BCR signalling and thus take advantage of this pre‐existing pathway for B‐cell proliferation and survival. This has recently been underscored by clinical trials demonstrating that small molecules (fosfamatinib, ibrutinib, idelalisib) inhibiting BCR‐associated kinases (SYK, BTK, PI3K) have an encouraging clinical effect. Here we describe the current knowledge of the specific aspects of BCR signalling in diffuse large B‐cell lymphoma (DLBCL), follicular lymphoma, chronic lymphocytic leukaemia (CLL) and normal B cells. Multiple factors can contribute to BCR pathway (dys)regulation in these malignancies and the activation of ‘chronic’ or ‘tonic’ BCR signalling. In lymphoma B cells, the balance of initiation, amplitude and duration of BCR activation can be influenced by a specific immunoglobulin structure, the expression and mutations of adaptor molecules (like GAB1, BLNK, GRB2, CARD11), the activity of kinases (like LYN, SYK, PI3K) or phosphatases (like SHIP‐1, SHP‐1 and PTEN) and levels of microRNAs. We also discuss the crosstalk of BCR with other signalling pathways (NF‐κB, adhesion through integrins, migration and chemokine signalling) to emphasise that the ‘BCR inhibitors’ target multiple pathways interconnected with BCR, which might explain some of their clinical activity.
Pathogenic role of antibodies against monomeric C‐reactive protein in tubulointerstitial nephritis and uveitis syndrome
Authors: Jakuszko K. , Krajewska M. , Hałoń A. , Kościelska–Kasprzak K. , Myszka M. , Żabińska M. , Augustyniak‐Bartosik H. , Rukasz D. , Weyde W. , Klinger M.
Published: August 2014

Antibodies against monomeric C‐reactive protein, which is a target antigen expressed both in kidney tubules and uveal cells, have been recently detected in patients with active tubulointerstitial nephritis and uveitis syndrome. We report the case of an 65‐year‐old woman with acute renal failure caused by biopsy‐proven tubulointerstitial nephritis and the onset of uveitis 21 months later. The expression of monomeric C‐reactive protein in kidney oligobiopsy was confirmed by immunohistochemical staining using mouse monoclonal antibody against human monomeric C‐reactive protein. The levels of antibodies against monomeric C‐reactive protein were 117% of the reference during the flare and 22% during the remission of the disease. The difference in the levels of antibodies against monomeric C‐reactive protein during flare and remission, and above all positive biopsy staining, supports their pathogenic role in this disease.
Factors associated with birth weight inequalities in Jordan
Authors: Mohammad K. , Kassab M. , Gamble J. , Creedy D.K. , Foster J.
Published: August 2014

Background

Birth weight is a good indicator of mothers' and neonates' nutritional status, and it contributes to the newborn baby's survival, health, growth and development.

Aim

This study identified social factors associated with differences in the mean birth weight of newborn babies in Jordan.

Methods

This retrospective study analysed medical records to determine possible risk factors associated with differences in newborn BW in the Irbid governorate of Jordan. All full‐term singleton births during the year 2010 were reviewed. Abstracted data included mother's age, educational level, and monthly family income. Newborn information included birth weight, gender and birth order.

Results

A total of 5414 full‐term singleton births were included. Of these, 15.1% were low birth weight, 73.6% were normal birth weight, and 11.3% were high birth weight. Bivariate analysis of variance revealed that low mean birth weight was associated with female gender, first‐born babies, higher maternal age (>35 years), lower educational level and lower income (<500 JD). Multivariate analysis of variance revealed that mean birth weight was lower in female infants, first‐born infants, infants of less educated mothers, higher age and low monthly income.

Limitations

The findings can be generalized to full‐term singleton pregnancies in countries who share similar cultural and traditional values.

Conclusion

Education of mothers is a modifiable variable that can positively influence birth weight, particularly in the case of female and first‐born infants.

Implication for Nursing and Health Policy

The findings inform our understanding of some social factors affecting birth weights of neonates in Jordan and development of effective public health interventions that could reduce the adverse effects of such factors on newborn birth weight. Preconception and antenatal care is also important for early detection of such possible risk and targeting mothers who require early interventions and support.
Are male tokens bad for females? The effect of social dominance orientation on high‐status tokens' evaluations of low‐status members
Authors: Simmons Aneika L. , Watkins Marla Baskerville , Umphress Elizabeth E.
Published: August 2014

Prior research has not given much attention to understanding how those in the numeric minority (i.e., tokens) with high social status (e.g., males) react to those with low social status (e.g., females). We draw from social dominance orientation (SDO) to better understand how male tokens' beliefs about group‐based hierarchies affect their evaluation of a highly qualified female candidate. We conducted a laboratory study in which participants were placed in a selection situation and were asked to evaluate a highly qualified female candidate. We discovered a significant interaction between token status and SDO such that male tokens who were high in SDO were more likely to evaluate negatively a highly qualified female.
Management Guidance Pre‐ and Post‐Restatement
Authors: Gordon Elizabeth A. , Henry Elaine , Li Xudong , Sun Lili
Published: August 2014

We examine whether the quality of restating firms’ management guidance differs in periods before and after restatement announcements. While characteristics of restating firms and the consequences of restatement have been a central topic in accounting and auditing research, the quality of management guidance around restatements is less well understood. We consider two competing characterizations of the link between management forecast accuracy and bias and restatement (an event that tends to signal poor financial controls): “Forecast–Opportunism Explanation” and “Forecast–Ability Explanation”. Under the Forecast–Opportunism Explanation, pre‐restatement weaknesses in financial controls enable managers to manipulate earnings toward forecasts and to meet or exceed opportunistically biased forecasts, and the post‐restatement strengthening of financial controls constrains opportunistic behavior. Under the Forecast–Ability Explanation, pre‐restatement weaknesses in financial controls impede managers’ ability to issue accurate forecasts, and post‐restatement improvements remove impediments so that the accuracy of forecasts improves; forecast bias remains unaffected. Evidence indicates that before a restatement, restating firms’ forecasts are more accurate and relatively more downwardly biased than control firms’ forecasts. Post‐restatement, restating firms have less accurate and less downwardly biased management guidance. Our overall results are consistent with the Forecast–Opportunism Explanation.
Atypical nodular astrocytosis in simian immunodeficiency virus‐infected rhesus macaques (Macaca mulatta)
Authors: Petrosky Keiko Y. , Knight Heather L. , Westmoreland Susan V. , Miller Andrew D.
Published: August 2014

Background

Simian immunodeficiency virus (SIV), a model for HIV pathogenesis, is associated with neuropathology.

Methods

Five SIV‐infected animals were selected following a database search of 1206 SIV‐infected animals for nodular or astrocytic lesions. Two of five had neurologic dysfunction, and 3 of 5 were incidental findings.

Results

Histologic examination revealed multifocal nodular foci in the gray and white matter formed by interlacing astrocytes with abundant cytoplasm and large, reactive nuclei. Nodules were often enmeshed with small capillaries. Immunohistochemistry revealed variable immunoreactivity for a panel of markers: GFAP (4/5), vimentin (5/5), Glut‐1 (1/5), CNPase (0/5), S100 (5/5), Iba1 (0/5), Ki67 (0/5), and p53 (4/4). In situ hybridization failed to detect any SIV RNA (0/5). Immunohistochemistry for simian virus 40, rhesus cytomegalovirus, and rhesus lymphocryptovirus failed to detect any antigen within the lesions.

Conclusion

The immunoreactivity of p53 in the lesions compared with adjacent tissue suggests a local derangement in astrocyte proliferation and function.
Electrocardiographic Difference between Ventricular Arrhythmias from the Right Ventricular Outflow Tract and Idiopathic Right Ventricular Arrhythmias
Authors: REN LAN , LIU ZHENG , JIA YUHE , FANG PIHUA , PU JIELIN , ZHANG SHU
Published: August 2014

Background

Ventricular arrhythmias (VA) arising from arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) and idiopathic right ventricular outflow tract ventricular arrhythmias (RVOT‐VA) share the pattern of left bundle branch block (LBBB)/inferior axis. The existence of QRS notching showed a discriminating effect of the two conditions in recent research; however, there are little data regarding the difference in the distribution of QRS notching. The aim of this study was to compare the VA morphology between the two conditions, especially evaluating the diagnostic role of QRS notching.

Methods

Electrocardiographic (ECG) recordings of VA episode with LBBB/inferior axis of 16 ARVD/C and 45 idiopathic RVOT‐VA patients (30 originated from the septum, 15 from the free‐wall) were gathered and compared.

Results

ARVD/C had longer mean QRS duration in all 12 leads, and significant differences existed in leads Ⅰ,Ⅱ,Ⅲ, aVL, aVF, and V1 (P < 0.05). Lead Ⅰ had the largest mean difference of 25.1 ± 5.8 ms. In addition, ARVD/C had more R‐wave transition in lead V5 or later (37.5% vs 8.9%, P < 0.01).The presence of QRS notching (15/16 [93.8%] vs 36/45 [80.0%], P = 0.20) and the total number of leads expressing notching (2.88 ± 2.0 vs 2.80 ± 2.0, P = 0.90) were not different between ARVD/C and idiopathic RVOT‐VA. However, QRS notching existing simultaneously in leads I and aVL was more common in ARVD/C (43.8% vs13.3%, P = 0.011).

Conclusion

Longer QRS duration, later precordial R/S transition, and QRS notching in lateral leads (leads Ⅰ and aVL) are useful in discriminating ARVD/C from idiopathic RVOT‐VA.
The structure of motor programming: Evidence from reaction times and lateralized readiness potentials
Authors: Xu Lu , Sommer Werner , Masaki Hiroaki
Published: August 2014

There is a widely accepted notion that movement elements are assembled prior to movement execution in a central motor programming stage. However, it is not clear how this stage is structured—whether it is a unitary stage allowing different motor parameters to cross talk or whether there are several independent processes dealing with each motor parameter. We addressed this question by orthogonally manipulating two movement‐related factors: response sequence complexity and movement duration. Both factors yielded main effects on reaction time but no interaction. Additive effects of both factors on the onsets of response‐ but not stimulus‐synchronized lateralized readiness potentials suggest separable motoric loci of sequence complexity and duration. These findings are at variance with the notion of a unitary movement programming stage.
Estimating Benchmark Exposure for Air Particulate Matter Using Latent Class Models
Authors: Mbah Alfred K. , Hamisu Ibrahim , Naik Eknath , Salihu Hamisu M.
Published: August 2014

We performed benchmark exposure (BME) calculations for particulate matter when multiple dichotomous outcome variables are involved using latent class modeling techniques and generated separate results for both the extra risk and additional risk. The use of latent class models in this study is advantageous because it combined several outcomes into just two classes (namely, a high‐risk class and a low‐risk class) and compared these two classes to obtain the BME levels. This novel approach addresses a key problem in risk estimation—namely, the multiple comparisons problem, where separate regression models are fitted for each outcome variable and the reference exposure will rely on the results of the best‐fitting model. Because of the complex nature of the estimation process, the bootstrap approach was used to estimate the reference exposure level, thereby reducing uncertainty in the obtained values. The methodology developed in this article was applied to environmental data by identifying unmeasured class membership (e.g., morbidity vs. no morbidity class) among infants in utero using observed characteristics that included low birth weight, preterm birth, and small for gestational age.