bluuebunny/crossref_metadata_2025 huggingface dataset:
Introduction
Authors: Youngner Stuart J. , Arnold Robert M.
Published: December 2015

This volume explores the topic of death and dying from the late twentieth to the early twenty-first centuries, with particular emphasis on the United States. The book comprises six sections. Section I examines how the law has helped shape clinical practice, emphasizing the roles of rights and patient autonomy. Section II focuses on specific clinical issues, including death and dying in children, continuous sedation as a way to relieve suffering at the end of life, and the problem of prognostication in patients who are thought to be dying. Section III considers psychosocial and cultural issues, Section IV discusses death and dying among various vulnerable populations such as the elderly and persons with disabilities, and Section V deals with physician-assisted suicide and active euthanasia (lethal injection). Finally, Section VI looks at hospice and palliative care as a way to address the psychosocial and ethical problems of death and dying.
γ-Aminobutyric Acid Type A Receptor Modulation by Etomidate Analogs
Authors: Pejo Ervin , Santer Peter , Wang Lei , Dershwitz Philip , Husain S. Shaukat , Raines Douglas E.
Published: December 2015

AbstractAbstract

By using both in vitro and in vivo assays of etomidate action, γ-aminobutyric acid type A receptor and hypnotic potencies of etomidate and 22 etomidate analogs were significantly correlated, supporting a direct role for receptor activation in etomidate-induced hypnosis. Molecular modeling computational techniques were used to build pharmacophore models that revealed multiple structural elements associated with high-potency binding-site interactions of etomidate.

Background

Etomidate is a highly potent anesthetic agent that is believed to produce hypnosis by enhancing γ-aminobutyric acid type A (GABAA) receptor function. The authors characterized the GABAA receptor and hypnotic potencies of etomidate analogs. The authors then used computational techniques to build statistical and graphical models that relate the potencies of these etomidate analogs to their structures to identify the specific molecular determinants of potency.

Methods

GABAA receptor potencies were defined with voltage clamp electrophysiology using α1β3γ2 receptors harboring a channel mutation (α1[L264T]) that enhances anesthetic sensitivity (n = 36 to 60 measurements per concentration–response curve). The hypnotic potencies of etomidate analogs were defined using a loss of righting reflexes assay in Sprague Dawley rats (n = 9 to 21 measurements per dose–response curve). Three-dimensional quantitative structure–activity relationships were determined in silico using comparative molecular field analysis.

Results

The GABAA receptor and hypnotic potencies of etomidate and the etomidate analogs ranged by 91- and 53-fold, respectively. These potency measurements were significantly correlated (r2 = 0.72), but neither measurement correlated with drug hydrophobicity (r2 = 0.019 and 0.005, respectively). Statistically significant and predictive comparative molecular field analysis models were generated, and a pharmacophore model was built that revealed both the structural elements in etomidate analogs associated with high potency and the interactions that these elements make with the etomidate-binding site.

Conclusions

There are multiple specific structural elements in etomidate and etomidate analogs that mediate GABAA receptor modulation. Modifying any one element can alter receptor potency by an order of magnitude or more.
Quadruple ESIN (Elastic Stable Intramedullary Nailing): Modified Treatment in Pediatric Distal Tibial Fractures
Authors: Bauer Jan , Hirzinger Corinna , Metzger Roman
Published: December 2015

Purpose:

Nailing of the tibial shaft with 2 Prevot nails is the gold standard for tibial shaft fractures in children. This technical report aims to show a simple way to stabilize pediatric distal tibial fractures without changing of the operation method.

Methods:

A retrospective chart review of all distal tibial fractures treated with the modified elastic stable intramedullary nailing (ESIN) method during a 6-year period was conducted. The modified ESIN technique hardly differs from the classic method, other than the addition of 2 other Prevot nails inserted using the same entry point.

Results:

Eight children were treated with the modified ESIN. The mean operation duration was 57 minutes (range, 33 to 88 min). In all cases 2 to 4 mm titanium nails were used. None of our patients required a postoperative cast.

Within an average of 14.5 days all of the patients could fully bear their weight (2 to 30 d) and full range of motion was reached.

Conclusions:

The modified ESIN technique achieves good results regarding stability and early weight-bearing. Therefore, this technique could be applied in unstable distal tibial fractures. Nevertheless, a prospective and biomechanical study is needed to verify our experience.

Level of Evidence:

Level IV—therapeutic studies.
Osteomyelitis is Commonly Associated With Septic Arthritis of the Shoulder in Children
Authors: Ernat Justin , Riccio Anthony I. , Fitzpatrick Kelly , Jo ChanHee , Wimberly Robert L.
Published: December 2015

Purpose:

To describe the clinical presentation, management, and outcomes of surgically treated septic arthritis of the shoulder in a pediatric population.

Methods:

A retrospective chart review over 5 years of children with operatively managed septic arthritis of the shoulder was completed. Demographics, clinical presentation, symptoms duration, antibiotic regimen and duration, number of surgical procedures, and evaluation of laboratory value improvements were collected. Pretreatment and final radiographs were assessed. Causative organisms were reviewed. Patients were stratified in age groups to determine clinical variability based upon patient age.

Results:

A total of 22 children, ages 15 days to 14 years (average 37.3 mo), were treated for septic arthritis of the shoulder from 2006 to 2010 at a single pediatric institution. All patients were managed with open anterior arthrotomy at an average of 1.95 days after initial orthopaedic consultation (range, 0 to 15 d). Multiple presenting signs were noted; the most common was decreased use (59%). Average admission laboratory values include C-reactive protein 10.6 (range, 0.3 to 41.6), erythrocyte sedimentation rate 62.8 (range, 11 to 107), and white blood cell count 14.9 (range, 5.9 to 31.7). Initial radiographs were read as normal in 12 patients, concern for osteomyelitis in 5, cortical irregularity in 4, effusion in 3, and neoplasm in a single child. Nineteen patients had a preoperative magnetic resonance imaging and 15 demonstrated an effusion, 15 had evidence of humeral osteomyelitis, 5 had a subperisoteal abscess, and 4 had soft tissue abscesses. Eight patients remained culture negative. The most commonly identified organism was methcillin-resistant Staphylococcus aureus (MRSA) (22.7%). The patients under 12 months of age revealed more diverse organisms at culture and were less likely to have MRSA. All patients averaged 1.55 (range, 1 to 5) surgical procedures and had an average hospital stay of 13.5 days. Intravenous antibiotics averaged 16.3 days followed by an average of 34 days of oral treatment. MRSA patients were significantly more likely to require multiple operations to eradicate the infection (P<0.02) and had a longer duration of intravenous antibiotic use (P<0.003). MRSA patients were more likely to have abnormal radiographs at final follow-up (P<0.03).

Conclusions:

Septic arthritis of the shoulder in children is commonly associated with adjacent osteomyelitis. Pediatric septic arthritis of the shoulder due to MRSA bacteria can have a more virulent course than other bacterial causes, but is a less commonly identified organism in the youngest patients.

Significance:

To our knowledge, this is one of the largest series published concerning the treatment, course, and outcomes of pediatric septic arthritis of the shoulder.

Level of Evidence:

Level III—therapeutic.
The genomic basis of electrotaxis inDictyostelium discoideum: Electric field sensitive amino acids are dynamically encoded en masse for the streaming-stage proteome
Authors: Erives Albert J.
Published: December 2015

Electrotaxis plays a critical role in developmental cell migration, axon growth cone guidance, epithelial wound healing, tissue regeneration, and the degree of invasiveness characterizing different cancer cell lines. During electrotaxis in a direct current electric field (EF), a cell migrates preferentially either towards the anode or cathode depending on the cell-type. However, the types and ranges of mechanisms coupling trans-cellular electric fields to cellular EF-sensitive signaling systems are largely unknown. To address this cell biological phenomenon, I use transcriptomic data from a developmental genetic model in which multicellular social aggregation is induced by starvation of amoeboid cells. I find that the developmental proteome expressed during the streaming aggregation stage is measurably and substantially enriched in charged and highly polar amino acids relative to the proteomes of either the unicellular amoeboid or the multicellular fruiting body. This large-scale coding augmentation of EF-sensitive amino acid residues in thousands of streaming-specific proteins is accompanied by a proportional coding decrease in the number of small, uncharged amino acid residues. I also confirm an expected coding increase of biosynthetically costly amino acids in the proteome of the satiated feeding-stage amoeboid. These findings suggest that electrotactic capability is encoded broadly in the genetically regulated deployment of a developmental proteome with augmented EF-sensitivity. These results signify that extreme, nonuniform, evolutionary constraints can be exerted on the amino acid composition of an organism’s proteome.
Host-pathogen coevolution and the emergence of broadly neutralizing antibodies in chronic infections
Authors: Nourmohammad Armita , Otwinowski Jakub , Plotkin Joshua B
Published: December 2015

The vertebrate adaptive immune system provides a flexible and diverse set of molecules to neutralize pathogens. Yet, viruses such as HIV can cause chronic infections by evolving as quickly as the adaptive immune system, forming an evolutionary arms race. Here we introduce a mathematical framework to study the coevolutionary dynamics of antibodies with antigens within a host. We focus on changes in the binding interactions between the antibody and antigen populations, which result from the underlying stochastic evolution of genotype frequencies driven by mutation, selection, and drift. We identify the critical viral and immune parameters that determine the distribution of antibody-antigen binding affinities. We also identify definitive signatures of coevolution that measure the reciprocal response between antibodies and viruses, and we introduce experimentally measurable quantities that quantify the extent of adaptation during continual coevolution of the two opposing populations. Using this analytical framework, we infer rates of viral and immune adaptation based on time-shifted neutralization assays in two HIV-infected patients. Finally, we analyze competition between clonal lineages of antibodies and characterize the fate of a given lineage in terms of the state of the antibody and viral populations. In particular, we derive the conditions that favor the emergence of broadly neutralizing antibodies, which may be useful in designing a vaccine against HIV.
Refining the Y chromosome phylogeny with southern African sequences
Authors: Barbieri Chiara , Hübner Alexander , Macholdt Enrico , Ni Shengyu , Lippold Sebastian , Schröder Roland , Mpoloka Sununguko Wata , Purps Josephine , Roewer Lutz , Stoneking Mark , Pakendorf Brigitte
Published: December 2015

The recent availability of large-scale sequence data for the human Y chromosome has revolutionized analyses of and insights gained from this non-recombining, paternally inherited chromosome. However, the studies to date focus on Eurasian variation, and hence the diversity of early-diverging branches found in Africa has not been adequately documented. Here we analyze over 900 kb of Y chromosome sequence obtained from 547 individuals from southern African Khoisan and Bantuspeaking populations, identifying 232 new sequences from basal haplogroups A and B. We find new branches within haplogroups A2 and A3b1 and suggest that the prehistory of haplogroup B2a is more complex than previously suspected; this haplogroup is likely to have existed in Khoisan groups before the arrival of Bantu-speakers, who brought additional B2a lineages to southern Africa. Furthermore, we estimate older dates than obtained previously for both the A2-T node within the human Y chromosome phylogeny and for some individual haplogroups. Finally, there is pronounced variation in branch length between major haplogroups; haplogroups associated with Bantu-speakers have significantly longer branches. This likely reflects a combination of biases in the SNP calling process and demographic factors, such as an older average paternal age (hence a higher mutation rate), a higher effective population size, and/or a stronger effect of population expansion for Bantu-speakers than for Khoisan groups.
Retroviruses integrate into a shared, non-palindromic motif
Authors: Kirk Paul D. W. , Huvet Maxime , Melamed Anat , Maertens Goedele N. , Bangham Charles R. M.
Published: December 2015

Palindromic consensus nucleotide sequences are found at the genomic integration sites of retroviruses and other transposable elements. It has been suggested that the palindromic consensus arises as a consequence of structural symmetry in the integrase complex, but the precise mechanism has yet to be elucidated. Here we perform a statistical analysis of large datasets of HTLV-1 and HIV-1 integration sites. The results show that the palindromic consensus sequence is not present in individual integration sites, but appears to arise in the population average as a consequence of the existence of a non-palindromic nucleotide motif that occurs in approximately equal proportions on the plus-strand and the minus-strand of the host genome. We demonstrate that palindromic probability position matrices are characteristic of such situations. We develop a generally applicable algorithm to sort the individual integration site sequences into plus-strand and minus-strand subpopulations. We apply this algorithm to identify the respective integration site nucleotide motifs of five retroviruses of different genera: HTLV-1, HIV-1, MLV, ASLV, and PFV. The results reveal a non-palindromic motif that is shared between these retroviruses.
External drivers of entry mode decisions of a higher education institution
Authors: Goi Mei Teh
Published: December 2015

Purpose

– The purpose of this paper is to examine the impact of cultural distance, governance quality, and market attractiveness on attachment of agents with a university.

Design/methodology/approach

– A single university was chosen as a case study and secondary data were collected. The focus of this paper is on education agents who market higher education institution (HEI) in international market and recruit international students.

Findings

– Multiple regression was performed and the finding indicated that governance quality and market attractiveness are significantly related with a number of agents attached to the marketing department of the university. However, cultural distance showed no significant relationship with agent attachment.

Research limitations/implications

– The availability of data was most challenging in gathering data for this study because the culture of a country may change across time and the sample was based on only one case study, a minimal amount of information was obtained.

Practical implications

– This study addresses the external factors that needed to be considered in selecting new agents.

Originality/value

– This study contributes to the international marketing literature by a focus on HEI and focus on agency approach.
Evaluating specific service quality aspects which impact on customers’ behavioural loyalty in high-tech internet services
Authors: Thaichon Paramaporn , Jebarajakirthy Charles
Published: December 2015

Purpose

– The purpose of this paper is to examine the influence of quality perception on customers’ repurchase behaviour in home internet services. Specifically, it was found that information quality, and privacy affected customers’ commitment and perceived value which were directly related to customer behavioural loyalty.

Design/methodology/approach

– In order to achieve the research objectives, a model is proposed. The literature review and formulation of hypotheses related to each construct are then discussed. An online survey was conducted. The final usable sample size was 2,059.

Findings

– Information quality was a stronger determinant of commitment and value when compared with privacy. The positive indirect effects of information quality and privacy on behavioural loyalty were also confirmed.

Originality/value

– The research provides practical implications which can be used to design effective marketing strategies to retain customers in the residential internet market. Moreover, current issues of high-customer churn rate can be resolved. In general, the study confirms that putting customers’ privacy in the heart of company operations is critical for an internet service provider’s success and long-term sustainability.
Apparel firms’ corporate social responsibility communications
Authors: Woo Hongjoo , Jin Byoungho
Published: December 2015

Purpose

– Corporate social responsibility (CSR) communication is a strategy to address companies’ goodwill to the society. Based on the institutional theory suggesting the influence of environmental factors of companies’ country-of-origins on their marketing practices, the purpose of this paper is to explore and compare the CSR communication practices of apparel firms from different countries.

Design/methodology/approach

– As a case study approach, this study investigates six apparel firms’ CSR communication disclosures on the official websites using a content analysis method and the Global Reporting Initiative’s categorial CSR reporting guidelines.

Findings

– Findings revealed that the six firms’ CSR communication adoption levels and focusses varied; the USA firms largely focussed on labor issues, while the European firms focussed on environmental issues and the Asian firms centered on social issues.

Research limitations/implications

– Although this study has limitations that pertain to case studies in general, this study provides academic contributions to the literature and managerial implications about different CSR focusses and communication activities across countries.

Originality/value

– CSR is especially important for the apparel business that highly involves social issues such as labor-intensive production. However, limited research showed how apparel firms are actually communicating CSR. This study was one of the early attempts on this topic.
Principal leadership and school capacity effects on teacher learning in Hong Kong
Authors: Li Lijuan , Hallinger Philip , Ko James
Published: December 2015

Purpose

– Over the past decade, studies of school leadership effects have increasingly aimed at identifying and validating the paths through which principal leadership impacts key teaching and learning processes in schools. A recent meta-analysis by Robinson and colleagues identified principal practices that shape teacher professional development experiences in schools as the highest impact path used by instructional leaders. The purpose of this paper is to examine relationships between principal leadership, dimensions of school capacity, and teacher professional learning in 32 Hong Kong primary schools.

Design/methodology/approach

– The study employed a cross-sectional research design and quantitative methods to analyze teacher perceptions of principal leadership and key school conditions. The research employed hierarchical linear regression analysis to explore survey data collected from a sample of 970 teachers. The surveys covered a range of principal leadership and school capacity dimensions, as well as a measure of teacher professional learning.

Findings

– Results indicated that multiple dimensions of principal leadership made significant contributions to both school capacity and teacher professional learning. The presence of cooperation, trust, communication, support for students, and alignment, coherence, and structure in schools also affected teacher professional learning.

Research limitations/implications

– These findings contribute to the global discourse on leadership for learning. The study addresses the need established by multiple scholars (e.g. Leithwood, Hallinger, Heck, Robinson, Witziers) for research that further illuminates “paths” and “intermediate targets” through which leadership impacts teaching and learning. The findings elaborate on the means by which leadership can enhance school capacities that directly impact teacher classroom practice and student learning. Consistent with other scholarly research (e.g. Bryk and Schneider, Louis and colleagues, Sahphier and King) the findings also point toward the importance of establishing selected workplace conditions (e.g. trust, cooperation, communication) as a foundation for fostering teacher professional learning.

Practical implications

– The study reinforces the finding from other studies that it is productive for principals to foster an environment aimed at enhancing teacher professionalism. The study also highlights the potentially dysfunctional consequences that can arise from competing system-level initiatives aimed at increasing monitoring and teacher accountability and fostering teacher professionalism.

Originality/value

– The study contributes to a small but growing body of leadership effects research conducted in non-Western societies. As such the study offers insights with relevance for understanding leadership processes in other Asian and non-Western cultures.
Factors affecting teachers’ motivation
Authors: Rasheed Muhammad Imran , Humayon Asad Afzal , Awan Usama , Ahmed Affan ud Din
Published: December 2015

Purpose

– The purpose of this paper is to explore/investigate various issues of teachers
'
motivation in public sector Higher Educational Institutions of Pakistan.

Design/methodology/approach

– This is an exploratory research where surveys have been conducted in the well known public sector Universities of Pakistan; primary data have been collected through questionnaire and in depth face to face interviews.

Findings

– Findings of the research have shown that although compensation packages and financial incentives are important factors for employees in the competitive market environment of the higher education sector but some other factors like job design and working environment, performance management system, and training and development are also significant. The research has also explored various issues being faced by teachers in public sector HEIs related to the above mentioned factors.

Originality/value

– This study can play a vital role in compelling the higher education authorities to ponder over the motivational issues of teachers in universities. The research can prove to be an effectual document for other worldwide universities where teachers are facing similar issues.
Estimating nutrition-income elasticities in sub-Saharan Africa: implications on health
Authors: Ogundari Kolawole , Ito Shoichi , Okoruwa Victor O
Published: December 2015

Purpose

– The purpose of this paper is to examine how the intakes of calories, proteins, and fats vary with income in sub-Saharan Africa (SSA).

Design/methodology/approach

– Annual time series data for 43 countries covering 1975-2009 that yields a balanced panel was employed for analysis. Nutrient-income elasticities are estimated based on the aggregate Engel Curve framework, using a feasible generalized least squares (FGLS) technique that is robust to autocorrelation.

Findings

– The estimated nutrient-income elasticities are small: a 10 percent increase in income will lead, respectively, to rises of about 0.73, 0.87, and 0.90 percent in calories, proteins, and fats intake; showing that policies that are aimed at eliminating malnutrition through only the growth of per capita income will have positive but limited impacts. The estimated aggregate Engel Curve and the non-parametric plots show that at higher income levels the relationship between income and nutrient intake is non-linear and diminished, suggesting a low likelihood for the manifestation of an obesity epidemic in SSA.

Originality/value

– This is the very study that attempts to look at the nutrition-income elasticities at cross-country level in SSA.
Financial integration via panel cointegration approaches in ASEAN+5
Authors: Shafighi Najla , Shaari Abu Hassan , Gharleghi Behrooz , Sarmidi Tamat , Omar Khairuddin
Published: December 2015

Purpose

– The purpose of this paper is to identify whether any financial integration exists among ASEAN+5 members and some East Asian countries, including China, Japan, Korea, Hong Kong, and Taiwan, through interest rate, exchange rate, level of prices, and real output.

Design/methodology/approach

– Therefore, the authors intend to identify any long-term relationship among these variables utilizing the data in the most efficient manner via panel cointegration and panel unit root tests. The study likewise uses a panel-based vector error correction (panel-vec) model for comparison and also short-run relationship analysis. The long-run relationship is estimated using dynamic ordinary least square technique and a panel multi-layer perceptron (MLP) neural network.

Findings

– For the ten countries under consideration, the empirical result supports the long-run equilibrium relationship among real output, exchange rate, interest rate, and level of prices, and that the cointegration relationship implies unidirectional causality from exchange rate to real output. This result is favorable to a model that contains real output as a dependent variable and exchange rate, interest rate, and level of prices as explanatory variables. Panel-vec results indicate no evidence of short-run causality from exchange rate to real output. Furthermore, the comparison result of long-run equation estimation shows the superiority of neural networks over econometric models.

Originality/value

– This paper adds to the literature by examining the financial cointegration using a panel model that contains real exchange rate, interest rate, real output, and inflation rate in ASEAN+5. Additionally this paper applied the MLP neural network to yield a robust estimation of the long-run equation obtained among the variables.
Utility of flexion–extension radiography for the detection of ligamentous cervical spine injury and its current role in the clearance of the cervical spine
Authors: Oh Jason Jaeseong , Asha Stephen Edward
Published: December 2015

Detecting the presence of injuries to the cervical spine is an important component of the initial assessment of patients sustaining blunt trauma. A small proportion of cervical spine injuries consists of ligamentous disruption. Accurate detection of ligamentous injury is essential as it may result in sequelae including radiculopathy, quadriplegia and death. Flexion–extension (FE) radiography has traditionally been utilised for the detection of ligamentous injury in patients who have been cleared of bony injury. There are controversies surrounding the use of FE for alert patients with neck pain. There are studies that call into question the diagnostic accuracy of FE, the high proportion of inadequate FE images due to muscle spasm and the adverse effects of prolonged cervical collar immobilisation while awaiting FE. Other literature indicates that FE provides no additional diagnostic information following a multi‐detector helical computed tomography. This review evaluates the literature on the utility of FE for the detection of ligamentous injury and explores alternate strategies for clearing the cervical spine of ligamentous injury.
RANZCR Celebrates 80 Years
Authors: Milross Chris
Published: December 2015

2015 marks the 80th anniversary of the formation of the Australian and New Zealand Association of Radiology (ANZAR) in 1935. The association underwent several name changes over the following decades, finally becoming The Royal Australian and New Zealand College of Radiologists (RANZCR) in 1998. The following is the text from the speech given by the President of the College, A/Prof Chris Milross, at the 2015 RANZCR Annual Scientific Meeting to mark the anniversary.
A simple method for isocapnic hyperventilation evaluated in a lung model
Authors: Hallén K. , Stenqvist O. , Ricksten S.‐E. , Lindgren S.
Published: December 2015

Background

Isocapnic hyperventilation (IHV) has the potential to increase the elimination rate of anaesthetic gases and has been shown to shorten time to wake‐up and post‐operative recovery time after inhalation anaesthesia. In this bench test, we describe a technique to achieve isocapnia during hyperventilation (HV) by adding carbon dioxide (CO2) directly to the breathing circuit of a standard anaesthesia apparatus with standard monitoring equipment.

Methods

Into a mechanical lung model, carbon dioxide was added to simulate a CO2 production (Vco2) of 175, 200 and 225 ml/min. Dead space (VD) volume could be set at 44, 92 and 134 ml. From baseline ventilation (BLV), HV was achieved by doubling the minute ventilation and fresh gas flow for each level of Vco2, and dead space. During HV, CO2 was delivered (Dco2) by a precision flow meter via a mixing box to the inspiratory limb of the anaesthesia circuit to achieve isocapnia.

Results

During HV, the alveolar ventilation increased by 113 ± 6%. Tidal volume increased by 20 ± 0.1% during IHV irrespective of VD and Vco2 level. Dco2 varied between 147 ± 8 and 325 ± 13 ml/min. Low Vco2 and large VD demanded a greater Dco2 administration to achieve isocapnia. The FICO2 level during IHV varied between 2.3% and 3.3%.

Conclusion

It is possible to maintain isocapnia during HV by delivering carbon dioxide through a standard anaesthesia circuit equipped with modern monitoring capacities. From alveolar ventilation, CO2 production and dead space, the amount of carbon dioxide that is needed to achieve IHV can be estimated.
Global genome splicing analysis reveals an increased number of alternatively spliced genes with aging
Authors: Rodríguez Sofía A. , Grochová Diana , McKenna Tomás , Borate Bhavesh , Trivedi Niraj S. , Erdos Michael R. , Eriksson Maria
Published: December 2015

Alternative splicing (AS) is a key regulatory mechanism for the development of different tissues; however, not much is known about changes to alternative splicing during aging. Splicing events may become more frequent and widespread genome‐wide as tissues age and the splicing machinery stringency decreases. Using skin, skeletal muscle, bone, thymus, and white adipose tissue from wild‐type C57BL6/J male mice (4 and 18 months old), we examined the effect of age on splicing by AS analysis of the differential exon usage of the genome. The results identified a considerable number of AS genes in skeletal muscle, thymus, bone, and white adipose tissue between the different age groups (ranging from 27 to 246 AS genes corresponding to 0.3–3.2% of the total number of genes analyzed). For skin, skeletal muscle, and bone, we included a later age group (28 months old) that showed that the number of alternatively spliced genes increased with age in all three tissues (P < 0.01). Analysis of alternatively spliced genes across all tissues by gene ontology and pathway analysis identified 158 genes involved in RNA processing. Additional analysis of AS in a mouse model for the premature aging disease Hutchinson–Gilford progeria syndrome was performed. The results show that expression of the mutant protein, progerin, is associated with an impaired developmental splicing. As progerin accumulates, the number of genes with AS increases compared to in wild‐type skin. Our results indicate the existence of a mechanism for increased AS during aging in several tissues, emphasizing that AS has a more important role in the aging process than previously known.
Diagnosing Acute Heart Failure in the Emergency Department: A Systematic Review and Meta‐analysis
Authors: Martindale Jennifer L. , Wakai Abel , Collins Sean P. , Levy Phillip D. , Diercks Deborah , Hiestand Brian C. , Fermann Gregory J. , deSouza Ian , Sinert Richard
Published: December 2015

Background

Acute heart failure (AHF) is one of the most common diagnoses assigned to emergency department (ED) patients who are hospitalized. Despite its high prevalence in the emergency setting, the diagnosis of AHF in ED patients with undifferentiated dyspnea can be challenging.

Objectives

The primary objective of this study was to perform a systematic review and meta‐analysis of the operating characteristics of diagnostic elements available to the emergency physician for diagnosing AHF. Secondary objectives were to develop a test–treatment threshold model and to calculate interval likelihood ratios (LRs) for natriuretic peptides (NPs) by pooling patient‐level results.

Methods

PubMed, EMBASE, and selected bibliographies were searched from January 1965 to March 2015 using MeSH terms to address the ability of the following index tests to predict AHF as a cause of dyspnea in adult patients in the ED: history and physical examination, electrocardiogram, chest radiograph (CXR), B‐type natriuretic peptide (BNP), N‐terminal proB‐type natriuretic peptide (NT‐proBNP), lung ultrasound (US), bedside echocardiography, and bioimpedance. A diagnosis of AHF based on clinical data combined with objective test results served as the criterion standard diagnosis. Data were analyzed using Meta‐DiSc software. Authors of all NP studies were contacted to obtain patient‐level data. The Quality Assessment Tool for Diagnostic Accuracy Studies‐2 (QUADAS‐2) for systematic reviews was utilized to evaluate the quality and applicability of the studies included.

Results

Based on the included studies, the prevalence of AHF ranged from 29% to 79%. Index tests with pooled positive LRs ≥ 4 were the auscultation of S3 on physical examination (4.0, 95% confidence interval [CI] = 2.7 to 5.9), pulmonary edema on both CXR (4.8, 95% CI = 3.6 to 6.4) and lung US (7.4, 95% CI = 4.2 to 12.8), and reduced ejection fraction observed on bedside echocardiogram (4.1, 95% CI = 2.4 to 7.2). Tests with low negative LRs were BNP < 100 pg/mL (0.11, 95% CI = 0.07 to 0.16), NT‐proBNP < 300 pg/mL (0.09, 95% CI = 0.03 to 0.34), and B‐line pattern on lung US LR (0.16, 95% CI = 0.05 to 0.51). Interval LRs of BNP concentrations at the low end of “positive” results as defined by a cutoff of 100 pg/mL were substantially lower (100 to 200 pg/mL; 0.29, 95% CI = 0.23 to 0.38) than those associated with higher BNP concentrations (1000 to 1500 pg/mL; 7.12, 95% CI = 4.53 to 11.18). The interval LR of NT‐proBNP concentrations even at very high values (30,000 to 200,000 pg/mL) was 3.30 (95% CI = 2.05 to 5.31).

Conclusions

Bedside lung US and echocardiography appear to the most useful tests for affirming the presence of AHF while NPs are valuable in excluding the diagnosis.
Chronic EtOH effects on putative measures of compulsive behavior in mice
Authors: Radke Anna K. , Jury Nicholas J. , Kocharian Adrina , Marcinkiewcz Catherine A. , Lowery‐Gionta Emily G. , Pleil Kristen E. , McElligott Zoe A. , McKlveen Jessica M. , Kash Thomas L. , Holmes Andrew
Published: December 2015

Addictions, including alcohol use disorders, are characterized by the loss of control over drug seeking and consumption, but the neural circuits and signaling mechanisms responsible for the transition from controlled use to uncontrolled abuse remain incompletely understood. Prior studies have shown that ‘compulsive‐like’ behaviors in rodents, for example, persistent responding for ethanol (EtOH) despite punishment, are increased after chronic exposure to EtOH. The main goal of the current study was to assess the effects of chronic intermittent EtOH (CIE) exposure on multiple, putative measures of compulsive‐like EtOH seeking in C57BL/6 J mice. Mice were exposed to two or four weekly cycles of CIE and then, post‐withdrawal, tested for progressive ratio responding for EtOH, sustained responding during signaled EtOH unavailability and (footshock) punished suppression of responding for EtOH. Results showed that mice exposed to CIE exhibited attenuated suppression of EtOH seeking during punishment, as compared with air‐exposed controls. By contrast, CIE exposure affected neither punished food reward‐seeking behavior, nor other putative measures of compulsive‐like EtOH seeking. Ex vivo reverse transcription polymerase chain reaction analysis of brain tissue found reduced sensitivity to punished EtOH seeking after CIE exposure was accompanied by a significant increase in gene expression of the GluN1 and GluN2A subunits of the N‐methyl‐d‐aspartate receptor, specifically in the medial orbitofrontal cortex. Moreover, slice electrophysiological analysis revealed increased N‐methyl‐d‐aspartate receptor‐mediated currents in the orbitofrontal cortex after CIE exposure in test‐naïve mice. Collectively, the current findings add to the growing body of evidence demonstrating that chronic exposure to EtOH fosters resistance to punished EtOH seeking in association with adaptations in cortical glutamatergic transmission.
Prefrontal functional connectivity measured with near‐infrared spectroscopy during smoking cue exposure
Authors: Kroczek Agnes M. , Haeussinger Florian B. , Fallgatter Andreas J. , Batra Anil , Ehlis Ann‐Christine
Published: December 2015

Cue reactivity (CR) is an important concept for relapse in substance use disorders (SUD). Although cue exposure (CE) therapy is discussed as relapse prevention, current approaches still need improvement considering its efficacy. From a neurobiological perspective, CR is related to an over‐activation in sensitized subcortical structures, their projections to motivationally relevant cortical structures (e.g. orbitofrontal cortex, OFC) and deficient prefrontal inhibitory control. Therefore, we analyzed prefrontal cortical activation and its relation to craving during smoking CE. We focused on the OFC—as a projection area of sensitized subcortical structures—due its importance in the processing of reinforcement value and the dorsolateral prefrontal cortex (dlPFC) based on its importance for behavioral inhibition. Functional near‐infrared spectroscopy (fNIRS) was used to assess hemodynamics in prefrontal regions during smoking CE in 24 subjects (n = 12 occasional smokers, n = 12 controls). Subjective craving intensity (minimum craving as marker of baseline inhibition, range as marker of inhibition time course) was additionally assessed. Craving ratings indicated that CR was elicited solely in smokers, not controls. Those subjective ratings correlated with hemodynamic activity in OFC (craving range) and dlPFC (minimum craving). OFC activation was found earlier throughout the CE in smokers compared to controls. Connectivity (seed‐based correlation) between OFC and dlPFC was increased in smokers. fNIRS can capture prefrontal hemodynamic activity involved in CR elicited during CE and is therefore a promising method to investigate CR and its implications for relapse prevention in SUD.
Oropharyngeal cancer and human papilloma virus: evolving diagnostic and management paradigms
Authors: Buckley Lisa , Gupta Ruta , Ashford Bruce , Jabbour Joe , Clark Jonathan R.
Published: December 2015

The significant increase in human papilloma virus (HPV)‐associated oropharyngeal carcinoma (OPC) over recent years has lead to a surge in research and an improved understanding of the disease. Most patients with HPV‐associated OPC present with cystic nodal metastases with a small primary tumour, and respond well to all treatment modalities including primary surgery and primary chemoradiotherapy. Current research is evaluating treatment de‐escalation to reduce long‐term treatment‐associated morbidities. Transoral robotic surgery (TORS) is particularly relevant as the transoral approach allows small primary tumours to be removed with lower morbidity than traditional surgical approaches. The current American Joint Committee on Cancer staging system for oropharyngeal cancer does not appropriately stratify HPV‐associated OPC; hence, alternative risk stratification and staging classifications are being proposed.
Baseline quality of life predicts pelvic exenteration outcome
Authors: Choy Ian , Young Jane M. , Badgery‐Parker Tim , Masya Lindy M. , Shepherd Heather L. , Koh Cherry , Heriot Alexander G. , Solomon Michael J.
Published: December 2015

Background

Recurrent rectal cancer affects a significant group of patients with no current consensus on management. This study investigated patients' quality of life (QoL) in the 12 months after pelvic exenteration.

Method

Prospective cohort study with clinical and QoL data collected at baseline and 1, 3, 6, 9 and 12 months. QoL trajectories were modelled over 12 months from date of discharge using linear mixed models.

Results

Of 117 patients, 93 underwent pelvic exenteration surgery, 24 did not. Thirty‐day mortality was nil for both groups. For patients who had surgery, 15 (16%) died within 12 months of surgery compared with nine (38%) of the non‐surgery group. Baseline QoL scores were highly variable. The non‐exenteration patients' QoL gradually declined over 12 months while exenteration patients declined then recovered. Patients with high baseline QoL scores remained high, and those with low baseline QoL remained low. Baseline QoL score, gender and bony resection were significant predictors of QoL score at 12 months.

Conclusion

Baseline QoL is a significant, independent predictor of patients' QoL after pelvic exenteration for recurrent rectal cancer.
Coats’ disease and retrobulbar haemodynamics
Authors: Zhao Qi , Peng Xiao‐Yan , Yang Wen‐Li , Li Dong‐Jun , You Qi‐Sheng , Jonas Jost B.
Published: December 2015

Purpose

To study the retrobulbar haemodynamics in patients with Coats’ disease.

Methods

The clinical study included 43 patients with Coats’ disease. Using colour Doppler imaging, we measured the blood flow velocity in the ophthalmic artery (OA), central retinal artery (CRA) and posterior ciliary arteries (PCA), and recorded the peak systolic velocity (PSV), end diastolic velocity (EDV), time averaged maximum velocity (TAMX), pulsatility index (PI) and resistance indexes (RI). The unaffected contralateral eyes served as control group. The disease was graded into four stages.

Results

Compared to the contralateral eyes, the Coats’ disease affected eyes showed for the CRA a significant decrease in PSV (7.08 ± 1.38 cm/s versus 8.64 ± 1.45 cm/s; p < 0.001), EDV (2.03 ± 0.41 cm/s versus 2.52 ± 0.62 cm/s; p < 0.001) and TAMX (3.67 ± 0.96 cm/s versus 4.40 ± 1.22 cm/s; p = 0.003) and for the PCA a significant decrease in PSV (9.15 ± 1.87 cm/s versus 10.14 ± 1.61 cm/s; p = 0.01). Subgroup analysis revealed that the decrease in haemodynamic parameters existed mainly in patients with stage 3A2 and stage 3B of Coats' disease.

Conclusions

As measured by colour Doppler imaging, the retrobulbar blood vessels showed decreased haemodynamic parameters in patients with Coats’ disease on the affected side as compared to the contralateral unaffected side, in particular in advanced stages of the disease. Future studies may address the causes and effects of these haemodynamic changes.
Assessment of calpain and caspase systems activities during ageing of two bovine muscles by degradation patterns of αII spectrin and PARP‐1
Authors: Saccà Elena , Pizzutti Nicoletta , Corazzin Mirco , Lippe Giovanna , Piasentier Edi
Published: December 2015

The activities of calpain and caspase systems during ageing in Longissimus lumborum (LL) and Infraspinatus (IS) muscles of Italian Simmental young bulls (Bos taurus) were assessed. Samples from 10 animals were collected within 20 min of exsanguination (T0), after 48 h (T1) and 7 days (T2) post mortem. Calpain and caspase activity were evaluated based on the formation of αII spectrin cleavage products of 145 kDa (SBDP145) and 120 kDa (SBDP120), respectively. Caspase activity was also assessed by the presence of poly (adenosine diphosphate‐ribose) polymerase‐1 (PARP‐1) cleavage product. At T0, LL showed higher levels of SBDP145 than IS (P < 0.01), while SBDP120 and PARP‐1 degradation products were similar between muscles. At T1, no difference was found in the level of SBDP145 between muscles, while SBDP120 and PARP‐1 cleavage products were not detected. At T2 neither αII spectrin nor PARP‐1 cleavage products were found. LL and IS showed different proteolysis after slaughter that was influenced more by calpain than caspase activity, which was detectable only in the early post mortem period.
Exploration of steroidogenesis‐related genes in testes, ovaries, adrenals, liver and adipose tissue in pigs
Authors: Robic Annie , Feve Katia , Louveau Isabelle , Riquet Juliette , Prunier Armelle
Published: December 2015

To explore the metabolism of steroids in the pig species, a qualitative PCR analysis was performed for the main transcript of 27 genes involved in steroid metabolism. We compared samples of testes, adipose tissue and liver from immature and peripubertal males, adrenal cortex from peripubertal males, ovaries from cyclic females and adipose tissue from peripubertal females. Some genes were shown to have a tissue‐specific expression. Two of them were expressed only in testes, ovaries and adrenals: CYP11A1 and CYP11B. The CYP21 and HSD17B3 genes, were expressed respectively only in adrenals and only in testes. Very few differences were observed between transcriptional patterns of peripubertal testes and adrenal glands as well as between male and female fat tissues. However, the expression of genes involved in the sulfonation of steroids was higher in testes than in adrenals from males. Main differences between ovaries and testes were observed for HSD17B1/2/3, AKR1C‐pig6 and sulfotransferase genes (SULT2A1/SULT2B1). The present study shows that the SRD5A2 and CYP21 genes were not involved in the testicular biosynthesis of androstenone. It also shows that porcine adrenal glands produce essentially corticosteroids and that fat tissue is unable to produce de novo steroids.
Synbiotics suppress the release of lactate dehydrogenase, promote non‐specific immunity and integrity of jejunum mucosa in piglets
Authors: Andrejčáková Zuzana , Sopková Drahomíra , Vlčková Radoslava , Kulichová Lucia , Gancarčíková Soňa , Almášiová Viera , Holovská Katarína , Petrilla Vladimír , Krešáková Lenka
Published: December 2015

The aim of our experiment was to study how synbiotics are able to deal with the problems of post‐weaning piglets. Lactobacillus plantarum – BiocenolTM LP96 (CCM 7512), Lactobacillus fermentum – BiocenolTM LF99 (CCM 7514) and flaxseed (rich in n‐3 polyunsaturated fatty acids) were administered to 36 conventional piglets from a problematic breed with confirmed presence of enterotoxigenic Escherichia coli and Coronavirus. The experimental piglets were supplied with probiotic cheeses and crushed flax‐seed in the period starting 10 days before weaning and lasting up to 14 days post‐weaning. Piglets in the control group were supplied only control cheese. The impact of such additives on the release of lactate dehydrogenase (LDH; spectroscopic and electrophoretic assay), alteration of immunity (index of metabolic activity), jejunum histology (light microscopy), and health of conventional piglets from a problematic breed (monitoring of hematology, consistency and moisture of feces and body temperature) were examined. We found significant decrease in LDH leakage in the blood serum and tissue extracts, indicating better cell membrane integrity in the individual organs of animals. Probiotics and flaxseed applied together seem to be a good source of nutrients to improve the immune status and the integrity of jejunum mucosa during infection. © 2015 Japanese Society of Animal Science