bluuebunny/crossref_metadata_2025 huggingface dataset:
Cytokine gene expression at the maternal–fetal interface after somatic cell nuclear transfer pregnancies in small ruminants
Authors: Rutigliano Heloisa M. , Wilhelm Amanda , Hall Justin , Shi Bi , Meng Qinggang , Stott Rusty , Bunch Thomas D. , White Kenneth L. , Davies Christopher J. , Polejaeva Irina A.
Published: October 2015

The present retrospective study investigated pregnancy rates, the incidence of pregnancy loss and large offspring syndrome (LOS) and immune-related gene expression of sheep and goat somatic cell nuclear transfer (SCNT) pregnancies. We hypothesised that significantly higher pregnancy losses observed in sheep compared with goat SCNT pregnancies are due to the increased amounts of T-helper 1 cytokines and proinflammatory mediators at the maternal–fetal interface. Sheep and goat SCNT pregnancies were generated using the same procedure. Control pregnancies were established by natural breeding. Although SCNT pregnancy rates at 45 days were similar in both species, pregnancy losses between 45 and 60 days of gestation and the incidence of LOS were significantly greater in sheep than in goats. At term, the expression of proinflammatory genes in sheep SCNT placentas was increased, whereas that in goats was similar to that in control animals. Genes with altered expression in sheep SCNT placentas included cytotoxic T-lymphocyte-associated protein 4 (CTLA4), interleukin 2 receptor alpha (IL2RA), cluster of differentiation 28 (CD28), interferon gamma (IFNG), interleukin 6 (IL6), interleukin 10 (IL10), transforming growth factor beta 1 (TGFB1), tumor necrosis factor alpha (TNF-α), interleukin 1 alpha (IL1A) and chemokine (C-X-C motif) ligand 8 (CXCL8). Major histocompatibility complex-I protein expression was greater in sheep and goat SCNT placentas at term than in control pregnancies. An unfavourable immune environment is present at the maternal–fetal interface in sheep SCNT pregnancies.
Peri-ovulatory endocrine regulation of the prostanoid pathways in the bovine uterus at early dioestrus
Authors: Oliveira Milena Lopes , D'Alexandri Fabio Luiz , Pugliesi Guilherme , Van Hoeck Veerle , Mesquita Fernando Silveira , Membrive Claudia M. B. , Negrão João Alberto , Wheelock Craig E. , Binelli Mario
Published: October 2015

We hypothesised that different endocrine profiles associated with pre-ovulatory follicle (POF) size would impact on uterine prostanoid pathways and thereby modulate the histotroph composition. Beef cows (n = 15 per group) were hormonally manipulated to have small (SF-SCL group) or large (LF-LCL group) pre-ovulatory follicles (POF) and corpora lutea (CL). Seven days after induction of ovulation, animals were slaughtered and uterine tissues and flushings were collected for quantification of prostanoids. The POF and CL size and the circulating progesterone concentrations at Day 7 were greater (P < 0.05) in the LF-LCL cows than in the SF-SCL group, as expected. The abundance of 5 out of 19 genes involved in prostanoid regulation was different between groups. Transcript abundance of prostaglandin F2α, E2 and I2 synthases was upregulated (P < 0.05) and phospholipase A2 was downregulated (P < 0.05) in endometrium of the LF-LCL group. No difference (P > 0.1) in prostanoid concentrations in the endometrium or in uterine flushings was detected between groups. However, prostaglandin F2α and E2 concentrations in the uterine flushings were positively correlated with the abundance of transcripts for prostaglandin endoperoxide synthase 2 (0.779 and 0.865, respectively; P < 0.002). We conclude that endometrial gene expression related to prostanoid synthesis is modulated by the peri-ovulatory endocrine profile associated with POF size, but at early dioestrus differences in transcript abundance were not reflected in changes in prostanoid concentrations in the uterine tissue and fluid.
The Research on Medical Education Outcomes (ROMEO) Registry: Addressing Ethical and Practical Challenges of Using “Bigger,” Longitudinal Educational Data
Authors: Gillespie Colleen , Zabar Sondra , Altshuler Lisa , Fox Jaclyn , Pusic Martin , Xu Junchuan , Kalet Adina
Published: October 2015

Problem

Efforts to evaluate and optimize the effectiveness of medical education have been limited by the difficulty of designing medical education research. Longitudinal, epidemiological views of educational outcomes can help overcome limitations, but these approaches require “bigger data”—more learners, sources, and time points. The rich data institutions collect on students and residents can be mined, however, ethical and practical barriers to using these data must first be overcome.

Approach

In 2008, the authors established the Research on Medical Education Outcomes (ROMEO) Registry, an educational data registry modeled after patient registries. New York University School of Medicine students, residents, and fellows provide consent for routinely collected educational, performance, quality improvement, and clinical practice data to be compiled into a deidentified, longitudinal database. As of January 2015, this registry included 1,225 residents and fellows across 12 programs (71% consent rate) and 841 medical students (86% consent rate). Procedures ensuring voluntary informed consent are essential to ethical enrollment and data use. Substantial resources are required to provide access to and manage the data.

Outcomes

The registry supports educational scholarship. Seventy-two studies using registry data have been presented or published. These focus on evaluating the curriculum, quality of care, and measurement quality and on assessing needs, competencies, skills development, transfer of skills to practice, remediation patterns, and links between education and patient outcomes.

Next Steps

The authors are working to integrate assessment of relevant outcomes into the curriculum, maximize both the quantity and quality of the data, and expand the registry across institutions.
Is a Drain Tip Culture Required After Spinal Surgery?
Authors: Kobayashi Kazuyoshi , Imagama Shiro , Ito Zenya , Ando Kei , Yagi Hideki , Hida Tetsuro , Ito Kenyu , Ishikawa Yoshimoto , Tsushima Mikito , Ishiguro Naoki
Published: October 2015

Study Design:

The efficacy of use of a drain tip culture for early detection of surgical-site infection (SSI) was investigated in 329 patients after spinal surgery.

Objective:

To examine the efficacy of a wound drain tip culture for detection of SSI in spinal surgery.

Summary of Background Data:

A complication of SSI after spinal surgery has high associated morbidity and mortality, and is often difficult to treat.

Materials and Methods:

The subjects were patients who underwent spinal surgery at our institution between January 2010 and March 2013. All subjects were treated with antimicrobial prophylaxis based on evidence-based guidelines and were followed for at least 6 months after surgery. Data from culture studies using the distal tip of the wound drain were used for analysis.

Results:

Drain tip cultures were positive in 34 cases and there were 19 SSIs. Ten of the 34-tip culture-positive wounds developed SSI. Drain tip cultures had a sensitivity of 52%, specificity of 92%, positive predictive value (PPV) of 29%, and negative predictive value of 97% for predicting a wound infection. The association between a positive suction tip culture and wound infection was significant (P<0.05). The PPV for SSI was 60% in cases in which methicillin-resistant bacteria were detected in a drain tip, and the SSI rate in these cases differed significantly compared with those with non–methicillin-resistant bacteria (P=0.01).

Conclusions:

A drain tip culture is useful for early detection of SSI caused by methicillin-resistant bacteria.
Nutritional Intake, Energy Expenditure, and Growth of Infants Following Congenital Diaphragmatic Hernia Repair
Authors: Haliburton Beth , Chiang Monping , Marcon Margaret , Moraes Theo J. , Chiu Priscilla P. , Mouzaki Marialena
Published: October 2015

Background/Objectives:

The pathophysiology of failure to thrive in congenital diaphragmatic hernia (CDH) has not been fully elucidated, and the nutritional care of these infants is hindered by paucity of data on the optimal calorie requirements for growth. The primary objective of this study was to investigate the energy intake required for infants with CDH to grow optimally at the time of first hospital discharge. The secondary objectives were to assess their measured resting energy expenditure in infancy, and their long‐term growth outcomes.

Methods:

Nutritional intake, anthropometrics, indirect calorimetry results, and respiratory status of infants with CDH from 2011 to 2014 were collected retrospectively. Data on confounders (gastroesophageal reflux disease and feeding intolerance, respiratory rate and pulmonary hypertension) were also collected. Analyses were performed using Stata (College Station, TX).

Results:

Of the 72 infants diagnosed with CDH during that period of time, 43 met the inclusion criteria. A caloric intake of 125.0 ± 20 kcal · kg−1 · day−1 was required to meet discharge weight gain criteria (25–35 g · kg−1 · day−1). In a subset of 17 patients, measured resting energy expenditure was higher than predicted resting energy expenditure (58.0 ± 18 vs 46.6 ± 3 kcal · kg−1 · day−1, P < 0.05), and 59% of infants were hypermetabolic (measured resting energy expenditure >110% of predicted resting energy expenditure) in early infancy. Failure to thrive prevalence at discharge was 16.2% compared to 3.6% and 4.2% at 12‐ and 24‐months of age, respectively (P = 0.03; P = 0.005, respectively).

Conclusions:

Optimal weight gain can be achieved with higher than predicted calorie provision. Most infants with CDH are hypermetabolic. Despite this, failure to thrive prevalence can improve during the first year of life.
Choline Supplementation With a Structured Lipid in Children With Cystic Fibrosis
Authors: Schall Joan I. , Mascarenhas Maria R. , Maqbool Asim , Dougherty Kelly A. , Elci Okan , Wang Dah‐Jyuu , Altes Talissa A. , Hommel Kevin A. , Shaw Walter , Moore Jeff , Stallings Virginia A.
Published: October 2015

Background:

Choline depletion is seen in cystic fibrosis (CF) and pancreatic insufficiency in spite of enzyme treatment and may result in liver, fatty acid, and muscle abnormalities. This study evaluated the efficacy and safety of an easily absorbed choline‐rich structured lipid (LYM‐X‐SORB™ [LXS]) to improve choline status.

Methods:

Children with CF and pancreatic insufficiency were randomized to LXS or placebo in a 12‐month double blind trial. Dietary choline intake, plasma cholines, plasma and fecal phospholipids, coefficient of fat absorption, pulmonary function, growth status, body composition, and safety measures were assessed. Magnetic resonance spectroscopy for calf muscle choline and liver fat were assessed in a subgroup and compared with a healthy comparison group matched for age, sex, and body size.

Results:

A total of 110 subjects were enrolled (age 10.4 ± 3.0 years). Baseline dietary choline, 88% recommended, increased 3‐fold in the LXS group. Plasma choline, betaine, and dimethylglycine increased in the LXS but not placebo (P = 0.007). Plasma lysophosphatidylcholine and phosphatidylcholine increased, and fecal phosphatidylcholine/phosphatidylethanolamine ratio decreased (P ≤ 0.05) in LXS only, accompanied by a 6% coefficient of fat absorption increase (P = 0.001). Children with CF had higher liver fat than healthy children and depleted calf muscle choline at baseline. Muscle choline concentration increased in LXS and was associated with improvement in plasma choline status. No relevant changes in safety measures were evident.

Conclusions:

LXS had improved choline intake, plasma choline status, and muscle choline stores compared with placebo group. The choline‐rich supplement was safe, accepted by participants, and improved choline status in children with CF.
Reduced birth intervals following the birth of children with long-term illness: evidence supporting a conditional evolved response
Authors: Waynforth David
Published: October 2015

Human birth interval length is indicative of the level of parental investment that a child will receive: a short interval following birth means that parental resources must be split with a younger sibling during a period when the older sibling remains highly dependent on their parents. From a life-history theoretical perspective, it is likely that there are evolved mechanisms that serve to maximize fitness depending on context. One context that would be expected to result in short birth intervals, and lowered parental investment, is after a child with low expected fitness is born. Here, data drawn from a longitudinal British birth cohort study were used to test whether birth intervals were shorter following the birth of a child with a long-term health problem. Data on the timing of 4543 births were analysed using discrete-time event history analysis. The results were consistent with the hypothesis: birth intervals were shorter following the birth of a child diagnosed by a medical professional with a severe but non-fatal medical condition. Covariates in the analysis were also significantly associated with birth interval length: births of twins or multiple births, and relationship break-up were associated with significantly longer birth intervals.
International funding agencies: potential leaders of impact evaluation in protected areas?
Authors: Craigie Ian D. , Barnes Megan D. , Geldmann Jonas , Woodley Stephen
Published: October 2015

Globally, protected areas are the most commonly used tools to halt biodiversity loss. Yet, some are failing to adequately conserve the biodiversity they contain. There is an urgent need for knowledge on how to make them function more effectively. Impact evaluation methods provide a set of tools that could yield this knowledge. However, rigorous outcome-focused impact evaluation is not yet used as extensively as it could be in protected area management. We examine the role of international protected area funding agencies in facilitating the use of impact evaluation. These agencies are influential stakeholders as they allocate hundreds of millions of dollars annually to support protected areas, creating a unique opportunity to shape how the conservation funds are spent globally. We identify key barriers to the use of impact evaluation, detail how large funders are uniquely placed to overcome many of these, and highlight the potential benefits if impact evaluation is used more extensively.
Nucleotide excision repair is impaired by binding of transcription factors to DNA
Authors: Sabarinathan Radhakrishnan , Mularoni Loris , Deu-Pons Jordi , Gonzalez-Perez Abel , Lopez-Bigas Nuria
Published: October 2015

Somatic mutations are the driving force of cancer genome evolution. The rate of somatic mutations appears in great variability across the genome due to chromatin organization, DNA accessibility and replication timing. However, other variables that may influence the mutation rate locally, such as DNA-binding proteins, are unknown. Here we demonstrate that the rate of somatic mutations in melanoma tumors is highly increased at active Transcription Factor binding sites (TFBS) and nucleosome embedded DNA, compared to their flanking regions. Using recently available excision-repair sequencing (XR-seq) data, we show that the higher mutation rate at these sites is caused by a decrease of the levels of nucleotide excision repair (NER) activity. Therefore, our work demonstrates that DNA-bound proteins interfere with the NER machinery, which results in an increased rate of mutations at their binding sites. This finding has important implications in our understanding of mutational and DNA repair processes and in the identification of cancer driver mutations.
Effects of workaholism on satisfaction among US managerial and professional women
Authors: Levy Daniele V
Published: October 2015

Purpose

– The purpose of this paper is to evaluate relationships between workaholism and satisfaction outcomes with job, career and life overall among managerial and professional women and explore the moderating role of social support in these associations.

Design/methodology/approach

– Self-report measures collected online from 350 alumnae from top-ranked business schools currently in the US labor force were analyzed through hierarchical multiple regression analyses.

Findings

– Workaholism components explained significant amounts of variance in job, career and life satisfaction. Specifically, lower levels of work enjoyment were consistently associated with detrimental outcomes and high drive impacted both job and life satisfaction negatively. Social support moderated the relationship between job satisfaction and workaholism through work enjoyment, with women with greater social support demonstrating higher job satisfaction at equivalent work enjoyment levels versus those with low social support.

Research limitations/implications

– This paper shares methodological weaknesses involving the nature of the sample and self-report methods of measurement common to workaholism research.

Practical implications

– In the context of today’s competitive workplaces, results provide a cautionary message of the harmful effects of workaholic dispositions for a certain segment of professional women. It emphasizes the importance of work enjoyment and positive intrinsic motivation, while suggesting that job designs that reflect the work involvement predispositions of each woman can be beneficial.

Originality/value

– This paper extends the understanding of workaholism correlates to female MBA graduates from top management schools in the USA and investigates, for the first time, the role of social support in those relationships.
Personalisation in children’s social work: from family support to “the child’s budget”
Authors: Whitaker Emilie Morwenna
Published: October 2015

Purpose

– The purpose of this paper is to explore the changing meaning of personalisation from the New Labour era of bespoke, integrated family support to the more recent implementation of personal budgets for disabled children to deliver “choice and control”. The paper explores the discursive change from early help to “intervention”, the shifting conceptualisation of parents and the turn away from family support towards a focus upon individualised commissioning to meet needs.

Design/methodology/approach

– In addition to a literature review of policy shifts, findings presented are taken from an ethnographic case study of one team of children’s disability social workers. Observations were undertaken of the team in the office space and at meetings, in addition interviews were conducted with all team members and with seven families. An interpretivist and qualitative approach was adopted throughout.

Findings

– Findings reveal the frontline and familial challenges of delivering choice and control in a climate of austerity and child-centricism. Salient points for integration around families and between organisations as personalisation narrows in scope are also considered.

Research limitations/implications

– Findings are taken from one case study site; further research in different sites is required to consider the array of understandings and experiences across the social care landscape and to provide a strong empirical baseline.

Originality/value

– The paper reports on one of the first ethnographic studies of personalisation in children’s services. The paper is of value to practitioners and managers in social care and the NHS. It is also of value to academics exploring the conceptual and practical issues of individualised care.
Investigation of Microbial Communities of Chinese Sourdoughs Using Culture‐Dependent and DGGE Approaches
Authors: Zhang Guohua , Sadiq Faizan A. , Zhu Liying , Liu Tongjie , Yang Huanyi , Wang Xin , He Guoqing
Published: October 2015

Sourdough is typically characterized by the complex microbial communities mainly comprising of yeasts and lactic acid bacteria (LAB). The objective of this study was to explore the microbiota of Chinese traditional sourdoughs collected from different areas of China using culture‐dependent and denaturing gradient gel electrophoresis (DGGE) methods. A total of 131 yeasts, 2 molds, and 106 LAB strains were isolated and identified. Based on the culture‐dependent analysis, the populations of yeasts and LAB were at the level of 105 to 107 and 106 to 107 cfu/g, respectively. Similarly, the results of RT‐qPCR showed that the values of total yeasts and LAB populations were in the range of 106 to 107 and 107 to 108 copies/g, respectively. Using culture‐dependent method, a total of 7 yeasts, 2 molds and 7 LAB species were identified. Results showed that Saccharomyces cerevisiae and Lactobacillus plantarum were the predominant species among the yeasts and LAB microflora. Similarly, using PCR‐DGGE approach, 7 yeasts, 1 mold and 9 LAB species were detected. The yeast, S. cerevisiae, represented the predominant, while the yeast Candida tropicalis represented the subdominant species of the yeast community. Among the LAB community, Lactobacillus sanfranciscensis was the predominant species, while Lactococcus qarvieae, Enterococcus faecium, Lactobacillus delbrueckii and Enterococcus cecorum were among the less dominant species.
Early Onset Alcohol Use and Self‐Harm: A Discordant Twin Analysis
Authors: Few Lauren R. , Werner Kimberly B. , Sartor Carolyn E. , Grant Julia D. , Trull Timothy J. , Nock Matthew K. , Bucholz Kathleen K. , Deitz Sarah K. , Glowinski Anne L. , Martin Nicholas G. , Nelson Elliot C. , Statham Dixie J. , Madden Pamela A. F. , Heath Andrew C. , Lynskey Michael T. , Agrawal Arpana
Published: October 2015

Background

Self‐harm has considerable societal and economic costs and has been extensively studied in relation to alcohol involvement. Although early onset alcohol use (EAU) has been causally linked to maladaptive clinical outcomes, its association with self‐harm is less well characterized. This study aimed to further examine the link between EAU and both nonsuicidal self‐injury (NSSI) and suicide attempt (SA), and elucidate shared familial and causal/individual‐specific pathways that explain this co‐occurrence.

Methods

Using data from 6,082 Australian same‐sex twin pairs (1,732 monozygotic [MZ] and 1,309 dizygotic [DZ]), ages 23 to 40, we examined prevalence rates of NSSI and SA among twin pairs concordant and discordant for EAU. Conditional logistic regression, controlling for early clinical covariates and the influence of zygosity on EAU, was used to examine the odds ratio (OR) of self‐harm within twin pairs discordant for EAU.

Results

Prevalence rates of both NSSI and SA were highest among twin pairs concordant for EAU and for twins who reported EAU within discordant twin pairs. Results from discordant twin analyses revealed nearly 4‐fold increased odds of SA for the twin who endorsed EAU, and this OR was equal across MZ and DZ twins. EAU also was associated with elevated odds of NSSI (OR = 7.62), although this was only the case for DZ twins in discordant pairs.

Conclusions

The equivalent increase in odds of SA for both MZ and DZ twins suggests that causal or individual‐specific influences explain the link between EAU and SA. For NSSI, elevated odds for DZ twins and nonsignificant findings for MZ twins implicate correlated genetic factors in the association between EAU and NSSI. Future studies should test mechanisms through which EAU may causally influence SA, as well as examine whether genetic risk for third variables (e.g., negative urgency, stress reactivity) may explain the genetic overlap between EAU and NSSI.
Prevalence and reversibility of lung hyperinflation in adult asthmatics with poorly controlled disease or significant dyspnea
Authors: Perez T. , Chanez P. , Dusser D. , Devillier P.
Published: October 2015

Background

In asthma, inflammation affects both the proximal and distal airways and may induce significant hyperinflation (HI). This study sought to evaluate the prevalence of HI in asthmatic patients with poorly controlled disease and/or dyspnea.

Methods

Poor asthma control was defined by an Asthma Control Test (ACT) score <20 (n = 287), and dyspnea was defined as a modified Medical Research Council score ≥1 (n = 18). HI was defined as either a residual volume/total lung capacity (RV/TLC) above the upper limit of normal (RV‐HI) or a functional residual capacity (FRC) >120% predicted (FRC‐HI). HI reversibility after administration of salbutamol (400 μg) was defined as a decrease in RV >20% or a reduction in FRC >10%. Changes in dyspnea and chest tightness were evaluated on a visual analogue scale.

Results

Both RV‐HI and FRC‐HI were observed in 48% of the 305 patients (mean ± SD age: 49 ± 17; FEV1: 75 ± 18% predicted) included in the study. The prevalence of HI was higher in patients with a FEV1 <60% predicted (93% for RV‐HI and 71% for FRC‐HI, vs 21% and 41% in patients with a FEV1 > 80%). In patients with HI, the ACT score was lower and chest tightness higher. HI reversibility was obtained in 38% of the asthmatics with FRC‐HI and 29% of the asthmatics with RV‐HI, whereas FEV1 reversibility was obtained in half of these patients.

Conclusions

HI is highly prevalent in poorly controlled asthmatics suggesting small airway dysfunction and may represent an additional criteria for evaluating responsiveness to bronchodilators.
Organizational form and output quality
Authors: Dubrovinsky Mati , Winter Ralph A.
Published: October 2015

This paper re‐examines the relationship between a firm's organizational form, not‐for‐profit versus for‐profit, and its output quality. The Arrow‐Hansmann theory of hidden action on the part of providers predicts higher quality for not‐for‐profit suppliers. This prediction has a puzzling lack of support in the empirical literature. We propose a theory that resolves the empirical puzzle and generates additional testable implications. The theory starts with the traditional assumptions of hidden action and supplier altruism. It then incorporates two additional features of real‐world markets: hidden information on supplier ability to provide high quality and a variation across buyers in the degree of informational asymmetry. The central prediction of the theory is that quality has a higher variance across for‐profits than across not‐for‐profits. Preliminary evidence from the US market for hospital care is consistent with this prediction.
The Impact of Maternal Gestational Stress on Motor Development in Late Childhood and Adolescence: A Longitudinal Study
Authors: Grace Tegan , Bulsara Max , Robinson Monique , Hands Beth
Published: October 2015

The number and timing of stressors experienced during pregnancy were investigated using longitudinal data from the Western Australian Pregnancy (Raine) Study cohort (N = 2,900). Motor development data were collected at 10 (n = 1,622), 14 (n = 1,584), and 17 (n = 1,222) years using the McCarron Assessment of Neuromuscular Development. Linear mixed models were used to examine the effect of stress on motor development, accounting for repeated measures. Number of stressful events and mean Neuromuscular Development Index were negatively related (β = −1.197, p = .001). Stressful events experienced in late pregnancy were negatively related with offspring motor development (β = −0.0541, p = .050), while earlier stressful events had no significant impact.
The mother of all sudden stops: capital flows and reversals in Europe, 1919–32
Authors: Accominotti Olivier , Eichengreen Barry
Published: October 2015

New data documenting European bond issues in major financial centres from 1919 to 1932 show that conditions in international capital markets and not just in borrowing countries are important for explaining the surge and reversal in capital flows. In particular, the sharp increase in stock market volatility in the major financial centres at the end of the 1920s figured importantly in the decline in foreign lending. This article draws parallels with Europe after 2008.
Inactivation of Fam20B in the dental epithelium of mice leads to supernumerary incisors
Authors: Tian Ye , Ma Pan , Liu Chao , Yang Xiudong , Crawford Derrick M. , Yan Wenjuan , Bai Ding , Qin Chunlin , Wang Xiaofang
Published: October 2015

Tooth formation is tightly regulated by epithelial‐mesenchymal interactions via hierarchic cascades of signaling molecules. The glycosaminoglycan (GAG) chains covalently attached to the core protein of proteoglycans (PGs) provide docking sites for signaling molecules and their receptors during the morphogenesis of tissues and organs. Although PGs are believed to play important roles in tooth formation, little is known about their exact functions in this developmental process and the relevant molecular basis. Family with sequence similarity member 20‐B (FAM20B) is a newly identified kinase that phosphorylates the xylose in the common linkage region connecting the GAG with the protein core of PGs. The phosphorylation of xylose is essential for elongation of the common linkage region and the subsequent GAG assembly. In this study, we generated a Fam20B‐floxed allele in mice and found that inactivating Fam20B in the dental epithelium leads to supernumerary maxillary and mandibular incisors. This finding highlights the pivotal role of PGs in tooth morphogenesis and opens a new window for understanding the regulatory mechanism of PG‐mediated signaling cascades during tooth formation.
Drought tolerance and growth in populations of a wide‐ranging tree species indicate climate change risks for the boreal north
Authors: Montwé David , Isaac‐Renton Miriam , Hamann Andreas , Spiecker Heinrich
Published: October 2015

Choosing drought‐tolerant planting stock in reforestation programs may help adapt forests to climate change. To inform such reforestation strategies, we test lodgepole pine (Pinus contorta Doug. ex Loud. var latifolia Englm.) population response to drought and infer potential benefits of a northward transfer of seeds from drier, southern environments. The objective is addressed by combining dendroecological growth analysis with long‐term genetic field trials. Over 500 trees originating from 23 populations across western North America were destructively sampled in three experimental sites in southern British Columbia, representing a climate warming scenario. Growth after 32 years from provenances transferred southward or northward over long distances was significantly lower than growth of local populations. All populations were affected by a severe natural drought event in 2002. The provenances from the most southern locations showed the highest drought tolerance but low productivity. Local provenances were productive and drought tolerant. Provenances from the boreal north showed lower productivity and less drought tolerance on southern test sites than all other sources, implying that maladaptation to drought may prevent boreal populations from taking full advantage of more favorable growing conditions under projected climate change.
Different glucose tolerance status and incident cardiovascular disease and all‐cause mortality among elderly Iranians
Authors: Mirbolouk Mohammadhassan , Hajebrahimi Mohammad Ali , Akbarpour Samaneh , Tohidi Maryam , Azizi Fereidoun , Hadaegh Farzad
Published: October 2015

Aims

To determine the effect of different glucose categories on incident cardiovascular disease (CVD) and all‐cause mortality in a population‐based cohort.

Methods

A total of 834 individuals aged 65 years and older without a history of CVD at baseline were stratified according to 2‐h post‐load glucose fasting glucose test into six categories including: (i) normal fasting glucose/normal glucose tolerance; (ii) prediabetes, (iii) isolated fasting hyperglycemia (IFH); (iv) isolated post‐challenge hyperglycemia (IPH); (v) IPH and IFH; and (vi) known diabetes mellitus. The prognostic significance of these groups on CVD and total mortality were examined by Cox proportional hazard ratios in a multivariate adjusted model.

Results

Over 9 years of follow up, 186 incidents of CVD and 218 deaths occurred (72 CVD mortality).Of the population, 45.2%, 30.7%, 1.2%, 6.1% 4.7%, and 11.9% were normal fasting glucose/normal glucose tolerance, prediabetes IFH, IPH, IFH and IPH, and known diabetes mellitus, respectively. Multivariate adjusted hazard ratios for CVD were 1.13 (95% CI 0.78–1.64), 1.03 (95% CI 0.25–4.22), 1.17 (95% CI 0.65–2.11), 2.52 (95% CI 1.43–4.42) and 2.39 (95% CI 1.55–3.69), and for CVD mortality were 0.59 (95% CI 0.27–1.30), 2.02 (95% CI 0.27–15.15), 1.26 (95% CI 0.51–3.16), 3.57 (95% CI 1.64–7.75), and 4.70 (95% CI 2.54–8.69) for prediabetes, IFH, IPH, IFH and IPH, and known diabetes mellitus phenotypes, respectively. Corresponding hazard ratios for all‐cause mortality in multivariate model adjusted for prevalent CVD were 1.07 (95% CI 0.73–1.57), 0.59 (95% CI 0.08–4.30), 0.92 (95% CI 0.5–1.70), 2.31 (95% CI 1.33–4.01) and 3.88 (95% CI 2.70–5.55), respectively.

Conclusion

Among the elderly population with newly diagnosed diabetes, only the combined IFH and IPH phenotype, but not IFH or IPH alone, was a significant predictor of CVD and mortality events. Prediabetes was not associated with any risk. Geriatr Gerontol Int 2016; 16: 1263–1271.
Focal But Not Diffuse Myocardial Fibrosis Burden Quantification Using Cardiac Magnetic Resonance Imaging Predicts Left Ventricular Reverse Modeling Following Cardiac Resynchronization Therapy
Authors: CHEN ZHONG , SOHAL MANAV , SAMMUT EVA , CHILD NICK , JACKSON TOM , CLARIDGE SIMON , COOKLIN MICHAEL , O'NEILL MARK , WRIGHT MATTHEW , GILL JASWINDER , CHIRIBIRI AMEDEO , SCHAEFFTER TOBIAS , CARR‐WHITE GERRY , RAZAVI REZA , RINALDI C. ALDO
Published: October 2015

Focal But Not Diffuse Fibrosis Burden Predicts CRT Remodeling Response

Introduction

Many heart failure patients with dyssynchrony do not reverse remodel (RR) in response to cardiac resynchronization therapy (CRT). The presence of focal and diffuse interstitial myocardial fibrosis may explain this high nonresponse rate. T1 mapping is a new cardiac magnetic resonance imaging (CMR) technique that overcomes the limitations of conventional contrast CMR and provides reliable quantitative assessment of diffuse myocardial fibrosis. The study tested the hypothesis that focal and diffuse fibrosis quantification would correlate with a lack of left ventricular (LV) RR to CRT.

Methods and Results

In a prospective study of 48 consecutive patients (27 ischemic cardiomyopathy, 21 dilated cardiomyopathy) LV scar burdens were quantified (scar core and gray zone using late gadolinium enhancement LGE CMR; interstitial fibrosis using T1 mapping) before CRT implant. LV RR was defined by a ≥ 15% reduction in LV end‐systolic volume 6 months postimplant. Twenty‐seven (56%) patients were responders with RR. Association between scar quantification and LV RR was assessed using the Poisson regression model. Univariate analysis showed that QRS duration/morphology, scar core, and gray zone volumes expressed as % of LV mass and extracellular volume index (ECV) (a measure of interstitial fibrosis from T1 mapping) to be significant predictors of LV RR. Multivariable‐adjusted analyses demonstrated scar core quantification (≥13.7% LV mass) to be the only independent predictor of LV RR (prevalence ratio 0.40, P = 0.038).

Conclusions

Focal scar burden detected by LGE CMR is associated with a poor response to CRT. Diffuse interstitial fibrosis assessment by T1 mapping, however, is not independently predictive of CRT response.
Apixaban, Rivaroxaban, and Dabigatran in Patients Undergoing Atrial Fibrillation Ablation
Authors: RILLIG ANDREAS , LIN TINA , PLESMAN JOAQUINA , HEEGER CHRISTIAN‐H. , LEMES CHRISTINE , METZNER ANDREAS , MATHEW SHIBU , WISSNER ERIK , WOHLMUTH PETER , OUYANG FEIFAN , KUCK KARL‐HEINZ , TILZ ROLAND RICHARD
Published: October 2015

Periprocedural Anticoagulation in AF Ablation

Introduction

Data on the novel oral anticoagulants (NOACS) during catheter ablation (CA) of atrial fibrillation (AF) are still limited. This study evaluated the periprocedural major complications (MC) of CA of AF, and compared Apixaban, Dabigatran, and Rivaroxaban with continuous phenoprocoumon.

Methods and Results

A total of 444 patients (mean age = 65.1 ± 9.4 years; 283 [64%] male) with paroxysmal (n = 180 [41%]), persistent (n = 256 [58%]), or longstanding‐persistent AF were enrolled. CA was performed in all patients using radiofrequency energy in conjunction with a 3D‐mapping system. MCs were defined according to the current guidelines. Continuous phenprocoumon‐therapy was administered in 120/444 (27%) patients (group 1) and 324/444 (73%) patients were treated with NOACs (group 2; Dabigatran: n = 51 [15.7%]; Rivaroxaban: n = 193 [59.6%]; Apixaban: n = 80 [24.7%]). Procedure times were comparable between groups 1 and 2 (128.2 ± 39.7 minutes vs. 129.7 ± 51.2 minutes; P = 0.77). CHA2DS2‐Vasc (3.0 [2.0, 4.0)] vs. 2.0 [1.0, 3.0]; P < 0.01) and HASBLED scores (2.0 [2.0, 2.5] vs. 2.0 [1.0, 2.0]; P = 0.002) were higher in group 1 patients. The incidence of MCs in the overall group was 8/444 (2%) and was equally distributed between groups 1 and 2 (2/120 [2%] vs. 6/324 [2%], P = 0.90). The incidence of MCs was comparable between the three different NOACs. There were no significant differences between patients with and without MCs with regard to age, CHA2DS2‐Vasc‐score or HASBLED‐score.

Conclusions

The major complication rate between all three NOACs currently available and continuous phenprocoumon during AF ablation seem to be comparable. Complication rates were similar between patients treated with the three different available NOACs.
Unravelling risks for child psychopathologies – general lessons from eating disorder research
Authors: Maughan Barbara
Published: October 2015

Clarifying risks for childhood disorders is one of the core aims of research in developmental psychopathology; disseminating findings from the most robust and clinically relevant of that risk research is a core aim of JCPP. This issue exemplifies that tradition, including articles that use a range of research designs and strategies to confirm – or in some instances disconfirm – the roles of hypothesized risks. It begins with one of our occasional series of reviews of risk research: Culbert, Racine and Klump's lucid synthesis of recent findings on the causes of eating disorders, and the accompanying Commentary by Smith and Davis. These will, of course, be of special interest to those who work in the eating disorders field, but – like all good reviews – their underlying messages have a wider resonance and relevance for the field. We highlight just three issues of particular interest in this Editorial.
Physiologic Breastfeeding: A Contemporary Approach to Breastfeeding Initiation
Authors: Schafer Robyn , Genna Catherine Watson
Published: October 2015

Early initiation of breastfeeding has numerous benefits for maternal‐child health. Maternity care providers have been shown to play a significant role in establishing breastfeeding, yet there is limited research about clinical approaches that support breastfeeding initiation in the immediate postpartum. Traditional methods that focused on position and attachment have not demonstrated consistent, positive effects on breastfeeding outcomes. Contemporary approaches to breastfeeding initiation emphasize innate maternal and neonatal breastfeeding abilities and the importance of breastfeeding self‐efficacy, dyad‐centered care, and a supportive breastfeeding environment free from unnecessary interventions. Recommendations for clinical practice for physiologic breastfeeding initiation are provided.
Labor Dystocia: A Common Approach to Diagnosis
Authors: Neal Jeremy L. , Lowe Nancy K. , Schorn Mavis N. , Holley Sharon L. , Ryan Sharon L. , Buxton Margaret , Wilson‐Liverman Angela M.
Published: October 2015

Contemporary labor and birth population norms should be the basis for evaluating labor progression and determining slow progress that may benefit from intervention. The aim of this article is to present guidelines for a common, evidence‐based approach for determination of active labor onset and diagnosis of labor dystocia based on a synthesis of existing professional guidelines and relevant contemporary publications. A 3‐point approach for diagnosing active labor onset and classifying labor dystocia‐related labor aberrations into well‐defined, mutually exclusive categories that can be used clinically and validated by researchers is proposed. The approach comprises identification of 1) an objective point that strictly defines active labor onset (point of active labor determination); 2) an objective point that identifies when labor progress becomes atypical, beyond which interventions aimed at correcting labor dystocia may be justified (point of protraction diagnosis); and 3) an objective point that identifies when interventions aimed at correcting labor dystocia, if used, can first be determined to be unsuccessful, beyond which assisted vaginal or cesarean birth may be justified (earliest point of arrest diagnosis). Widespread adoption of a common approach for diagnosing labor dystocia will facilitate consistent evaluation of labor progress, improve communications between clinicians and laboring women, indicate when intervention aimed at speeding labor progress or facilitating birth may be appropriate, and allow for more efficient translation of safe and effective management strategies into clinical practice. Correct application of the diagnosis of labor dystocia may lead to a decrease in the rate of cesarean birth, decreased health care costs, and improved health of childbearing women and neonates.
Regulation of Prescriptive Authority for Certified Nurse‐Midwives and Certified Midwives: 2015 National Overview
Authors: Osborne Kathryn
Published: October 2015

Precis

Statutory restrictions regarding the regulation of prescriptive authority for midwives continue to create barriers to practice in many states.
Antiretrovirals inhibit arginase in human microglia
Authors: Lisi Lucia , Laudati Emilia , Miscioscia Teresa F. , Dello Russo Cinzia , Topai Alessandra , Navarra Pierluigi
Published: October 2015

Preliminary evidence in an animal model, that is, primary cultures of rat microglia cells, suggested that some antiretroviral drugs (ARVs), namely darunavir, atazanavir, efavirenz, and nevirapine, increase NO production through a mechanism involving the inhibition of arginase (ARG) activity. This study was conceived to investigate the effects of ARVs on ARG activity in a human experimental model. We compared CHME‐5 human microglial immortalized cells under basal conditions with cells exposed to either IL‐4, a mix of inflammatory cytokines, or both stimuli given together. We also tested the effects of ARVs on CHME‐5 cell lysates after exposure to the above stimuli. Moreover, the interaction between the ARVs and ARG was investigated via computational chemistry. We found that ARVs consistently inhibit ARG activity both in intact and lysed cells. In docking studies, darunavir and atazanavir showed similar scores compared with both l‐arginine and the ARG antagonist nor‐NOHA. Efavirenz and nevirapine, which are less potent in inhibiting ARG in the biochemical assay, also had lower scores. In conclusion, the present findings in a human model support the notion that ARG pathway can present a new, additional molecular target for different ARVs in HIV treatments.

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We found that antiretroviral drugs (ARVs) consistently inhibit arginase (ARG)‐I activity both in intact and lysed cells. In docking studies, darunavir (DRV) and atazanavir (ATV) showed similar scores compared to both l‐arginine and the ARG antagonist, Nω‐hydroxy‐nor‐arginine (nor‐NOHA). Efavirenz (EFV) and nevirapine (NVP), which are less potent in inhibiting ARG in the biochemical assay, also had lower scores. In conclusion, the present findings in a human model support the notion that ARG pathway can be envisioned as an additional and new molecular target of different ARVs in HIV treatments.
Presynaptic G Protein‐Coupled Receptors Differentially Modulate Spontaneous Glutamate Release in the Supraoptic Nucleus
Authors: Muram S. , Rowe T. M. , Hirasawa M.
Published: October 2015

Spontaneous glutamate release in the supraoptic nucleus is modulated by a number of inhibitory G protein coupled receptors (GPCR), including GABAB, adenosine A1 and group III metabotropic glutamate receptors (mGluR). It remains unclear whether they have distinct roles or are redundant mechanisms that protect from hyperexcitation. To address this question, we facilitated spontaneous glutamate release using nifedipine or forskolin, which act in a protein kinase A (PKA)‐independent and ‐dependent manner, respectively, and tested the effects of inhibitory GPCR agonists. We found that a GABAB receptor (GABABR) agonist specifically inhibited forskolin‐induced miniature excitatory postsynaptic currents (mEPSC), in contrast to an adenosine A1 receptor (A1R) agonist, which specifically inhibited nifedipine‐induced mEPSCs. This suggests that GABABRs and A1Rs modulate independent mechanisms activated by forskolin and nifedipine, respectively. However, the inhibitory effects of GABABR and A1R agonists on basal mEPSCs occluded each other, suggesting that these receptors also have an overlapping role. Group III mGluRs appear to have a greater control over glutamate release because agonists to these receptors inhibited both nifedipine‐ and forskolin‐induced mEPSCs. mEPSCs induced by norepinephrine had the same characteristics as those induced by forskolin [i.e. PKA‐dependence and sensitivity to GABABR and group III mGluR agonists, but not an A1R agonist]. In summary, the present study highlights the differential effects of GABABR, A1R and mGluR agonists on glutamate release stimulated by different secretagogues, including the endogenous neuromodulator norepinephrine. These results suggest that the roles of these inhibitory GPCRs are not completely redundant, and also indicate the physiological implications of having different excitatory and inhibitory GPCRs on the same synapse.
The patient's experience of temporary paralysis from spinal anaesthesia, a part of total knee replacement
Authors: Bager Louise , Konradsen Hanne , Dreyer Pia Sander
Published: October 2015

Aims and objectives

The aim of this study was to describe the meaning of being temporary paralysed from spinal anaesthesia when undergoing total knee replacement.

Background

Total knee arthroplasty is a common procedure, and regional anaesthesia is used as a method for anaesthetising the patient. The experience is highly individual in substance and duration, and it can extend far beyond care settings as intraoperative care and the postanaesthesia care unit that have been investigated so far.

Design

A qualitative phenomenological hermeneutic design was chosen to gain a deeper understanding of the experience of spinal anaesthesia, as a part of having a total knee replacement.

Methods

Twelve patients were interviewed in March 2014 after undergoing an elective total knee arthroplasty under spinal anaesthesia. The interviews were analysed with a Ricoeur‐inspired interpretation method.

Results

Three themes were derived from the interviews: ‘anaesthesia – an unavoidable necessity’, ‘an unrecognisable and incomprehensible body’ and ‘the body returns – joy and agony’.

Conclusion

The results reveal that trust in the health care personnel and knowledge of the course of events play a key role in the experience. The trust can be breached by unforeseen events, or if the patient's experiences were not taken into account. The ability of the health care personnel to be in contact, share relevant knowledge with‐ and compensate for the patient is crucial in the prevention of negative experiences.

Relevance to clinical practice

The results of this study contribute to insights and deeper knowledge that can enhance staff's ability to provide care for patients undergoing total knee arthroplasty in spinal anaesthesia. The results provide perspectives that argue for care in accordance to individual needs.