bluuebunny/crossref_metadata_2025 huggingface dataset:
Absence of Po2 change in fetal brain despite Po2 increase in placenta in response to maternal oxygen challenge
Authors: Huen I , Morris DM , Wright C , Sibley CP , Naish JH , Johnstone ED
Published: May 2014

Objective

Magnetic resonance imaging allows the noninvasive observation of Po2 changes between air breathing and oxygen breathing through quantification of the magnetic longitudinal relaxation time T1. Changes in Po2 are proportional to changes in the longitudinal relaxation rate ΔR1 (where ΔR1 = 1/T1oxygen − 1/T1air). Knowledge of this response could inform clinical interventions using maternal oxygen administration antenatally to treat fetal growth restriction. We present in vivo measurements of the response of the fetal–placental unit to maternal hyperoxia.

Design

Prospective cohort.

Setting

Large tertiary maternity hospital.

Sample

Nine women undergoing low‐risk pregnancy (21–33 weeks of gestation) and five nonpregnant adults.

Methods

During imaging the air supply to mothers was changed from medical air (21% oxygen) to medical oxygen (100% oxygen) and T1 was monitored over time in both the placenta and fetal brain using a periodically repeated magnetic resonance imaging sequence. To demonstrate that the method could detect a brain response, brain responses from five normal adult volunteers were measured using a similar imaging protocol.

Main outcome measure

Changes in T1 following oxygen challenge.

Results

No significant ΔR1 (P = 0.42, paired t‐test) was observed in fetal brains. A significant placental ΔR1 (P = 0.0002, paired t‐test) of 0.02 ± 0.01/s (mean ± SD) was simultaneously observed in the same participants. In the brains of the nonpregnant adults, a significant ΔR1 (P = 0.01, paired t‐test) of 0.005 ± 0.002/s was observed.

Conclusion

Short‐term maternal oxygen administration does not improve fetal brain oxygenation, in contrast to the response observed in the adult brain.
Beef Credence Attributes: Implications of Substitution Effects on Consumers’ WTP
Authors: Viegas Inês , Nunes Luís Catela , Madureira Lívia , Fontes Magda Aguiar , Santos José Lima
Published: May 2014

Consumers’ food choices are influenced by a wide variety of credence attributes, but the food industry faces problems assessing whether the price premiums that consumers are willing to pay for these attributes will be sufficient to offset higher production costs. In this context, consumers’ willingness to pay (WTP) for safer, cleaner and animal friendlier beef was investigated through a choice experiment. The relative importance of WTP for these attributes shows that consumers place the highest values on food safety, followed by animal welfare and finally environmental protection. WTP for different combinations of the three attributes cannot be obtained by independent valuation and summation due to the presence of significant substitution relationships. However, some suggestions for the relationships between these attributes can be proposed through an after‐survey analytical solution. The bias involved in separately valuing closely related attributes can potentially jeopardise the success of a differentiation strategy.
Chemotherapy mediates intestinal injury via p53/p53 upregulated modulator of apoptosis (PUMA) signaling pathway
Authors: Zhan Ya Shi , Tan Si Wei , Mao Wei , Jiang Jie , Liu Hui Ling , Wu Bin
Published: May 2014

Objective

The aim of this study was to investigate the potential mechanism and signaling pathway involved in chemotherapy‐induced intestinal mucosal injury (CIMI), which is a common physiopathological problem in patients with cancer.

Methods

For the in vivo experiment, mice received intraperitoneal injection of 5‐fluorouracil (5‐FU) at a dose of 75 mg/kg/day for 1, 3 or 5 days. Villus height and crypt depth of the small intestine, cell apoptosis and proliferation were then examined to determine the extent of CIMI. The expressions of Akt, p53, PUMA and p21 were evaluated both in vivo in mice models and in vitro in the IEC‐6 and HCT116 cell lines.

Results

After 5‐FU therapy both the intestinal villus height (275.93 μm vs 164.52 μm, P < 0.001) and crypt depth (64.13 μm vs 42.48 μm, P < 0.001) were decreased. The apoptotic index was greatly increased from 0.32% to 15.84% (P < 0.001) and proliferation was suppressed (63.58% vs 39.15%, P < 0.001). Additionally, p53 expression was significantly increased in the intestinal crypt along with the expressions of PUMA and p21. Western blot showed that the administration of 5‐FU induced p53/PUMA‐mediated apoptosis and upregulated p21 expression to suppress cell proliferation.

Conclusion

Chemotherapy might mediate intestinal injury via p53/PUMA‐mediated apoptotic signaling and the suppression of proliferation in response to p21.
‘Direct PCR’ optimization yields a rapid, cost‐effective, nondestructive and efficient method for obtaining DNA barcodes without DNA extraction
Authors: Wong Wing Hing , Tay Ywee Chieh , Puniamoorthy Jayanthi , Balke Michael , Cranston Peter S. , Meier Rudolf
Published: May 2014

Macroinvertebrates that are collected in large numbers pose major problems in basic and applied biodiversity research: identification to species via morphology is often difficult, slow and/or expensive. DNA barcodes are an attractive alternative or complementary source of information. Unfortunately, obtaining DNA barcodes from specimens requires many steps and thus time and money. Here, we promote a short cut to DNA barcoding, that is, a nondestructive PCR method that skips DNA extraction (‘direct PCR’) and that can be used for a broad range of invertebrate taxa. We demonstrate how direct PCR can be optimized for the larvae and adults of nonbiting midges (Diptera: Chironomidae), a typical invertebrate group that is abundant, contains important bioindicator species, but is difficult to identify based on morphological features. After optimization, direct PCR yields high PCR success rates (>90%), preserves delicate morphological features (e.g. details of genitalia, and larval head capsules) while allowing for the recovery of genomic DNA. We also document that direct PCR can be successfully optimized for a wide range of other invertebrate taxa that need routine barcoding (flies: Culicidae, Drosophilidae, Dolichopodidae, Sepsidae; sea stars: Oreasteridae). Key for obtaining high PCR success rates is optimizing (i) tissue quantity, (ii) body part, (iii) primer pair and (iv) type of Taq polymerase. Unfortunately, not all invertebrates appear suitable because direct PCR has low success rates for other taxa that were tested (e.g. Coleoptera: Dytiscidae, Copepoda, Hymenoptera: Formicidae and Odonata). It appears that the technique is less successful for heavily sclerotized insects and/or those with many exocrine glands.
Challenges to barcoding an entire flora
Authors: Elliott Tammy L. , Jonathan Davies T.
Published: May 2014

DNA barcodes are species‐specific genetic markers that allow taxonomic identification of biological samples. The promise of DNA barcoding as a rapid molecular tool for conducting biodiversity inventories has catalysed renewed efforts to document and catalogue the diversity of life, parallel to the large‐scale sampling conducted by Victorian naturalists. The unique contribution of DNA barcode data is in its ability to identify biotic material that would be impossible to classify using traditional taxonomic keys. However, the utility of DNA barcoding relies upon the construction of accurate barcode libraries that provide a reference database to match to unidentified samples. Whilst there has been much debate in the literature over the choice and efficacy of barcode markers, there has been little consideration of the practicalities of generating comprehensive barcode reference libraries for species‐rich floras. Here, we discuss several challenges to the generation of such libraries and present a case study from a regional biodiversity hotspot in southern Quebec. We suggest that the key challenges include (i) collection of specimens for rare or ephemeral species, (ii) limited access to taxonomic expertise necessary for reliable identification of reference specimens and (iii) molecular challenges in amplifying and matching barcode data. To be most effective, we recommend that sampling must be both flexible and opportunistic and conducted across the entire growing season by expert taxonomists. We emphasize that the success of the global barcoding initiative will depend upon the close collaboration of taxonomists, plant collectors, and molecular biologists.
Psychometric examination of the Persian version of Osteoarthritis Knee and Hip Quality of Life questionnaire
Authors: Saffari Mohsen , Emami Meybodi Mohammad Kazem , Koenig Harold G. , Pakpour Amir H. , Rshidi Jahan Hojat
Published: May 2014

Aim

Osteoarthritis is a serious and prevalent health problem that creates considerable disability when it involves the knee or hip joints. The aim of the study was to adapt and validate the Osteoarthritis Knee and Hip Quality of Life (OAKHQOL) questionnaire for use in a Persian‐speaking population.

Methods

A total of 434 patients were recruited. The forward‐backward translation process was used to develop the Persian version. Participants were asked to complete the Short Form 12 Health Survey, EuroQoL, visual analog scale for pain and the OAKHQOL questionnaire. Reliability was assessed using Cronbach's alpha and the test‐retest method. The structure of the questionnaire was evaluated by exploratory factor analysis. The OAKHQOL was correlated with related measures to establish construct validity. Convergent and discriminant validity were examined with demographic and clinical variables. Comparisons were performed between patients with different severity grades of osteoarthritis.

Results

The mean age of participants was 61.9 (SD 12.1) and the majority were female (91.2%). Principal component analysis demonstrated a five‐factor solution that explained 58.4% of the variance. Cronbach's alpha coefficients ranged between 0.74 and 0.89 for all domains of the questionnaire with the exception of the social activities domain. The kappa for test‐retest reliability was 0.85. The OAKHQOL demonstrated good discriminative and convergent validity. Construct validity was established by determining significant relationships between related measures. The results of known‐groups validity indicated different scores on most domains (P < 0.001) across different levels of disease severity.

Conclusion

The questionnaire may be used as a valid and reliable measure for assessing quality of life among Iranian patients with lower limb osteoarthritis.
Spatial targeting of infectious disease control: identifying multiple, unknown sources
Authors: Verity Robert , Stevenson Mark D. , Rossmo D. Kim , Nichols Richard A. , Le Comber Steven C.
Published: May 2014

Geographic profiling (GP) was originally developed as an analytical tool in criminology, where it uses the spatial locations of linked crimes (for example murder, rape or arson) to identify areas that are most likely to include the offender's residence. The technique has been extremely successful in this field and is now widely used by police forces and investigative agencies around the world. More recently, the same method has been applied to biological data, notably in spatial epidemiology, where it uses the locations of disease cases to identify infection sources: the identification of these sources is critical to control efforts of diseases such as malaria, since targeted intervention is more efficient and cost‐effective than untargeted intervention.

Here, we solve the problem of identifying multiple sources, even when the number of sources is unknown – a requirement for many biological studies. We present a new, rigorous mathematical and computational method and show why previous Bayesian methods were often outperformed by the empirically developed criminal geographic targeting (CGT) algorithm used in criminology.

We use simulations and real‐world examples to compare our model to both the CGT algorithm and to an existing Bayesian model. We demonstrate that our method combines the advantages of both previous methods, particularly in cases featuring large data sets and multiple sources.

Our approach provides an increase in search efficiency over other methods and is likely to lead to improved targeting of interventions and more efficient use of resources. We suggest that the Dirichlet process mixture (DPM) model provides a useful and practical tool for conservation biologists and epidemiologists that can be used to inform management decisions and public health policy.
Aging impairs peritoneal but not bone marrow‐derived macrophage phagocytosis
Authors: Linehan Eimear , Dombrowski Yvonne , Snoddy Rachel , Fallon Padraic G. , Kissenpfennig Adrien , Fitzgerald Denise C.
Published: May 2014

Aging results in deterioration of the immune system, which is associated with increased susceptibility to infection and impaired wound healing in the elderly. Phagocytosis is an essential process in both wound healing and immune defence. As such, age‐related impairments in phagocytosis impact on the health of the elderly population. Phagocytic efficiency in peritoneal macrophages, bone marrow‐derived macrophages and bone marrow monocytes from young and old mice was investigated. Aging significantly impaired phagocytosis by peritoneal macrophages, both in vitro and in vivo. However, bone marrow‐derived macrophages and bone marrow monocytes did not exhibit age‐related impairments in phagocytosis, suggesting no intrinsic defect in these cells. We sought to investigate underlying mechanisms in age‐related impairments in phagocytosis by peritoneal macrophages. We hypothesized that microenvironmental factors in the peritoneum of old mice impaired macrophage phagocytosis. Indeed, macrophages from young mice injected into the peritoneum of old mice exhibited impaired phagocytosis. Proportions of peritoneal immune cells were characterized, and striking increases in numbers of T cells, B1 and B2 cells were observed in the peritoneum of old mice compared with young mice. In addition, B cell‐derived IL‐10 was increased in resting and LPS‐activated peritoneal cell cultures from old mice. These data demonstrate that aging impairs phagocytosis by tissue‐resident peritoneal macrophages, but not by bone marrow‐derived macrophages/monocytes, and suggest that age‐related defects in macrophage phagocytosis may be due to extrinsic factors in the tissue microenvironment. As such, defects may be reversible and macrophages could be targeted therapeutically in order to boost immune function in the elderly.
Electoral Competition through Issue Selection
Authors: Aragonès Enriqueta , Castanheira Micael , Giani Marco
Published: May 2014

Politics must address multiple problems simultaneously. In an ideal world, political competition would force parties to adopt priorities that reflect the voters' true concerns. In reality, parties can run their campaigns in such a way as to manipulate voters' priorities. This phenomenon, known as priming, may allow parties to underinvest in solving the issues that they intend to mute. We develop a model of endogenous issue ownership in which two vote‐seeking parties (a) invest in policy quality to increase the value of their platform and (b) choose a communication strategy to prime voters. We identify novel feedback between communication and investment. In particular, we find that stronger priming effects can constrain parties to invest more resources in all issues. We also identify the conditions under which parties prefer to focus on their “historical issues” or to engage in “issue stealing.”
A nomogram for calculating the maximum dose of local anaesthetic
Authors: Williams D. J. , Walker J. D.
Published: May 2014

Toxic dose limits (mg.kg−1) for local anaesthetics based on body weight are well‐established, but calculation of the maximum safe volume (ml) of a given agent and formulation is complex, and frequently results in errors. We therefore developed a nomogram to perform this calculation. We compared the performance of the nomogram with a spreadsheet and a general purpose calculator using simulated clinical data. Bland‐Altman analysis showed close agreement between the nomogram and spreadsheet, with bias of −0.07 ml and limits of agreement of −0.38 to +0.24 ml (correlation coefficient r2 = 0.9980; p < 0.001). The nomogram produced fewer and smaller errors compared with the calculator. Our nomogram calculates the maximum safe volume (ml) of local anaesthetic to a clinically acceptable degree of accuracy. It facilitates rapid cross‐checking of dosage calculations performed by electronic or other means at negligible cost, and can potentially reduce the incidence of local anaesthetic toxicity.
Comparison of the duration of neuromuscular blockade following a single bolus dose of rocuronium during laparoscopic gynaecological surgery vs conventional open surgery
Authors: Wang T. , Huang S. , Geng G.
Published: May 2014

We investigated whether laparoscopic vs open surgical approaches affected the duration of neuromuscular blockade following a single bolus dose of rocuronium. Fifty‐three female patients underwent either laparoscopic or open gynaecological surgery. Rocuronium 0.6 mg.kg−1 was administered to achieve neuromuscular blockade in all subjects, and adductor pollicis train‐of‐four responses following ulnar nerve stimulation were monitored with mechanomyography. The mean (SD) time from injection of rocuronium until spontaneous recovery of the first twitch, and to 5% and 25% of baseline, was significantly prolonged in the laparoscopic group (27.2 (8.3) min, 31.3 (9.1) min and 38.1 (10.6) min, respectively) compared with the open surgery group (21.1 (5.8) min, 25.6 (6.3) min and 31.2 (6.7) min, respectively). Changes in liver function both before surgery and at 24 h postoperatively were similar between the two groups (p > 0.05). Our findings suggest that neuromuscular blockade may be prolonged following a single bolus dose of rocuronium given during laparoscopic procedures.
Edge effects shape the spatial distribution of lianas and epiphytic ferns in Australian tropical rain forest fragments
Authors: Magrach Ainhoa , Rodríguez‐Pérez Javier , Campbell Mason , Laurance William F.
Published: May 2014

Question

In fragmented forests, edge effects lead to changes in the distribution of plant species. In particular, tropical forest edges are increasingly dominated by lianas. Will this increase in lianas lead to changes in their interactions with other plant morphological groups? If so, will this alter the local distributions and abundance of other species?

Location

Plots located at increasing distances from the nearest forest edge and in remnant fragments of rain forest in the Atherton Tablelands, far northeast Queensland, Australia.

Methods

We mapped the distribution of trees, lianas and epiphytic ferns to better understand the role of forest disturbance in shaping their competitive and facilitative interactions. We then used specific spatial point‐process analyses to examine the effects of the spatial distribution of trees on the presence and abundance of lianas and epiphytic ferns.

Results

Tree aggregation near forest edges was lower than that in the interior. The higher abundance of lianas near edges was associated with increased spatial segregation between lianas and epiphytic ferns. This segregation suggests there is competition between these two functional groups, and that lianas, being much more abundant, probably outcompete epiphytic ferns.

Conclusions

The ability of lianas to thrive in disturbed tropical rain forests appears to reduce the abundance of epiphytic ferns, probably via direct competition for space. Epiphytic ferns provide unique microclimates and harbour much biodiversity, and their decline could negatively affect many animals and plants that rely upon them.
From lists of behaviour change techniques (BCTs) to structured hierarchies: Comparison of two methods of developing a hierarchy of BCTs
Authors: Cane James , Richardson Michelle , Johnston Marie , Ladha Ruhina , Michie Susan
Published: May 2014

Objectives

Behaviour change technique (BCT) Taxonomy v1 is a hierarchically grouped, consensus‐based taxonomy of 93 BCTs for reporting intervention content. To enhance the use and understanding of BCTs, the aims of the present study were to (1) quantitatively examine the ‘bottom‐up’ hierarchical structure of Taxonomy v1, (2) identify whether BCTs can be reliably mapped to theoretical domains using a ‘top‐down’ theoretically driven approach, and (3) identify any overlap between the ‘bottom‐up’ and ‘top‐down’ groupings.

Methods and design

The ‘bottom‐up’ structure was examined for higher‐order groupings using a dendrogram derived from hierarchical cluster analysis. For the theory‐based ‘top‐down’ structure, 18 experts sorted BCTs into 14 theoretical domains. Discriminant Content Validity was used to identify groupings, and chi‐square tests and Pearson's residuals were used to examine the overlap between groupings.

Results

Behaviour change techniques relating to ‘Reward and Punishment’ and ‘Cues and Cue Responses’ were perceived as markedly different to other BCTs. Fifty‐nine of the BCTs were reliably allocated to 12 of the 14 theoretical domains; 47 were significant and 12 were of borderline significance. Thirty‐four of 208 ‘bottom‐up’ × ‘top‐down’ pairings showed greater overlap than expected by chance. However, only six combinations achieved satisfactory evidence of similarity.

Conclusions

The moderate overlap between the groupings indicates some tendency to implicitly conceptualize BCTs in terms of the same theoretical domains. Understanding the nature of the overlap will aid the conceptualization of BCTs in terms of theory and application. Further research into different methods of developing a hierarchical taxonomic structure of BCTs for international, interdisciplinary work is now required.

Statement of contribution

What is already known on this subject?

Behaviour change interventions are effective in improving health care and health outcomes.

The ‘active’ components of these interventions are behaviour change techniques and over 93 have been identified.

Taxonomies of behaviour change techniques require structure to enable potential applications.

What does this study add?

This study identifies groups of BCTs to aid the recall of BCTs for intervention coding and design.

It compares two methods of grouping – ‘bottom‐up’ and theory‐based ‘top‐down’ – and finds a moderate overlap.

Building on identified BCT groups, it examines relationships between theoretical domains and BCTs.
The Link Between Middle School Mathematics Course Placement and Achievement
Authors: Domina Thurston
Published: May 2014

The proportion of eighth graders in United States public schools enrolled in algebra or a more advanced mathematics course doubled between 1990 and 2011. This article uses Early Childhood Longitudinal Study's Kindergarten Cohort data to consider the selection process into advanced middle school mathematics courses and estimate the effects of advanced courses on students’ mathematics achievement (n = 6,425; mean age at eighth grade = 13.7). Eighth‐grade algebra and geometry course placements are academically selective, but considerable between‐school variation exists in students’ odds of taking these advanced courses. While analyses indicate that advanced middle school mathematics courses boost student achievement, these effects are most pronounced in content areas closely related to class content and may be contingent on student academic readiness.
Interleukin (IL)-17A, F and AF in inflammation: a study in collagen-induced arthritis and rheumatoid arthritis
Authors: Sarkar S , Justa S , Brucks M , Endres J , Fox D A , Zhou X , Alnaimat F , Whitaker B , Wheeler J C , Jones B H , Bommireddy S R
Published: May 2014

Interleukin (IL)-17 plays a critical role in inflammation. Most studies to date have elucidated the inflammatory role of IL-17A, often referred to as IL-17. IL-17F is a member of the IL-17 family bearing 50% homology to IL-17A and can also be present as heterodimer IL-17AF. This study elucidates the distribution and contribution of IL-17A, F and AF in inflammatory arthritis. Neutralizing antibody to IL-17A alone or IL-17F alone or in combination was utilized in the mouse collagen-induced arthritis (CIA) model to elucidate the contribution of each subtype in mediating inflammation. IL-17A, F and AF were all increased during inflammatory arthritis. Neutralization of IL-17A reduced the severity of arthritis, neutralization of IL-17A+IL-17F had the same effect as neutralizing IL-17A, while neutralization of IL-17F had no effect. Moreover, significantly higher levels of IL-17A and IL-17F were detected in peripheral blood mononuclear cells (PBMC) from patients with rheumatoid arthritis (RA) in comparison to patients with osteoarthritis (OA). IL-17A and AF were detected in synovial fluid mononuclear cells (SFMC) in RA and OA, with IL-17A being significantly higher in RA patients. Enriched CD3+ T cells from RA PBMCs produced singnificantly high levels of IL-17A and IL-17AF in comparison to OA peripheral blood CD3+ T cells. IL-17A, F and AF were undetectable in T cells from SFMCs from RA and OA. While IL-17A, F, and AF were all induced during CIA, IL-17A played a dominant role. Furthermore, production of IL-17A, and not IL-17F or IL-17AF, was elevated in PBMCs, SFMCs and enriched peripheral blood CD3+ T in RA.
Methylmalonic aciduria cblB type: characterization of two novel mutations and mitochondrial dysfunction studies
Authors: Brasil S. , Richard E. , Jorge‐Finnigan A. , Leal F. , Merinero B. , Banerjee R. , Desviat L.R. , Ugarte M. , Pérez B.
Published: May 2014

Methylmalonic aciduria (MMA) cblB type is caused by mutations in the MMAB gene, which codes for the enzyme adenosine triphosphate (ATP): cobalamin adenosyltransferase (ATR). This study reports differences in the metabolic and disease outcomes of two pairs of siblings with MMA cblB type, respectively harbouring the novel changes p.His183Leu/p.Arg190dup (P1 and P2) and the previously described mutations p.Ile96Thr/p.Ser174fs (P3 and P4). Expression analysis showed p.His183Leu and p.Arg190dup to be destabilizing mutations. Both were associated with reduced ATR stability and a shorter half‐life than wild‐type ATR. Analysis of several parameters related to oxidative stress and mitochondrial function showed an increase in reactive oxygen species (ROS) content, a decrease in mitochondrial respiration and changes in mitochondria morphology and structure in patient‐derived fibroblasts compared to control cells. The impairment in energy production and the presence of oxidative stress and fission of the mitochondrial reticulum suggested mitochondrial dysfunction in cblB patients' fibroblasts. The recovery of mitochondrial function should be a goal in efforts to improve the clinical outcome of MMA cblB type.
BRCA2 gene: a candidate for clinical testing in familial colorectal cancer type X
Authors: Garre P. , Martín L. , Sanz J. , Romero A. , Tosar A. , Bando I. , Llovet P. , Diaque P. , García‐Paredes B. , Díaz‐Rubio E. , de la Hoya M. , Caldés T.
Published: May 2014

Familial colorectal cancer type X (FCCX) encompasses a group of families with dominant inheritance pattern of colorectal cancer (CRC) but no alteration in any known CRC susceptibility gene. Therefore, the explanation of their susceptibility is a priority to offer an accurate genetic counseling. We screened the 27 coding exons and exon–intron boundaries of BRCA2 in 48 FCCX probands. We identified 29 variants including a frameshift mutation. Deleterious variant c.3847_3848delGT p.(Val1283Lysfs*2) showed cosegregation with disease as well as loss of heterozygosity (LOH) in CRC tumor DNA. This is the first evidence of germline BRCA2 pathogenic mutation associated with CRC risk. Furthermore, missense variants c.502C>A p.(Pro168Thr), c.5744C>T p.(Thr1915Met) and c.7759C>T p.(Leu2587Phe) were proposed as candidate risk alleles based on cosegregation, LOH tumor analysis and in silico testing.
Monoallelic ABCC8 mutations are a common cause of diazoxide‐unresponsive diffuse form of congenital hyperinsulinism
Authors: Saint‐Martin C. , Zhou Q. , Martin G.M. , Vaury C. , Leroy G. , Arnoux J.‐B. , de Lonlay P. , Shyng S.‐L. , Bellanné‐Chantelot C.
Published: May 2014

ABCC8 encodes a subunit of the β‐cell potassium channel (KATP) whose loss of function is responsible for congenital hyperinsulinism (CHI). Patients with two recessive mutations of ABCC8 typically have severe diffuse forms of CHI unresponsive to diazoxide. Some dominant ABCC8 mutations are responsible for a subset of diffuse diazoxide‐unresponsive forms of CHI. We report the analysis of 21 different ABCC8 mutations identified in 25 probands with diazoxide‐unresponsive diffuse CHI and carrying a single mutation in ABCC8. Nine missense ABCC8 mutations were subjected to in vitro expression studies testing traffic efficiency and responses of mutant channels to activation by MgADP and diazoxide. Eight of the 9 missense mutations exhibited normal trafficking. Seven of the 8 mutants reaching the plasma membrane had dramatically reduced response to MgADP or to diazoxide (<10% of wild‐type response). In our cohort, dominant KATP mutations account for 22% of the children with diffuse unresponsive‐diazoxide CHI. Their clinical phenotype being indistinguishable from that of children with focal CHI and diffuse CHI forms due to two recessive KATP mutations, we show that functional testing is essential to make the most reliable diagnosis and offer appropriate genetic counseling.
Linking Indices for Biodiversity Monitoring to Extinction Risk Theory
Authors: MCCARTHY MICHAEL A. , MOORE ALANA L. , KRAUSS JOCHEN , MORGAN JOHN W. , CLEMENTS CHRISTOPHER F.
Published: May 2014

Biodiversity indices often combine data from different species when used in monitoring programs. Heuristic properties can suggest preferred indices, but we lack objective ways to discriminate between indices with similar heuristics. Biodiversity indices can be evaluated by determining how well they reflect management objectives that a monitoring program aims to support. For example, the Convention on Biological Diversity requires reporting about extinction rates, so simple indices that reflect extinction risk would be valuable. We developed 3 biodiversity indices that are based on simple models of population viability that relate extinction risk to abundance. We based the first index on the geometric mean abundance of species and the second on a more general power mean. In a third index, we integrated the geometric mean abundance and trend. These indices require the same data as previous indices, but they also relate directly to extinction risk. Field data for butterflies and woodland plants and experimental studies of protozoan communities show that the indices correlate with local extinction rates. Applying the index based on the geometric mean to global data on changes in avian abundance suggested that the average extinction probability of birds has increased approximately 1% from 1970 to 2009.

Conectando Índices para el Monitoreo de la Biodiversidad con la Teoría de Riesgo de Extinción
The dramatic increase in the rate of methylisothiazolinone contact allergy in Belgium: a multicentre study
Authors: Aerts Olivier , Baeck Marie , Constandt Lieve , Dezfoulian Bita , Jacobs Marie‐Claude , Kerre Stefan , Lapeere Hilde , Pierret Lauranne , Wouters Kristien , Goossens An
Published: May 2014

Background

The rate of contact allergy and allergic contact dermatitis caused by methylisothiazolinone (MI) is dramatically increasing throughout Europe.

Objectives

To report on methylchloroisothiazolinone (MCI)/MI and MI allergy in Belgium.

Patients and methods

Between January 2010 and December 2012, the medical charts of 6599 patients of the Belgian Contact and Environmental Dermatitis Group were retrospectively reviewed for MCI/MI and MI sensitization by use of a standardized questionnaire. Available data on sensitization in 2081 patients tested in 2013 were also included.

Results

In 2012, the sensitization rate for MCI/MI had increased to 4.5% and that for MI to 6.0%; the latter showed a further increase to 7.2% in 2013. The people mainly affected were women with a median age of 49 years with hand and/or facial dermatitis, most often resulting from the use of cosmetics. Simultaneous reactions to octylisothiazolinone were observed.

Conclusion

A dramatic increase in the rate of contact allergy caused by MI in cosmetics is occurring in Belgium. Notwithstanding the recent recommendation to discontinue the use of MI in leave‐on cosmetics, safer use concentrations should also be determined for rinse‐off products. Close monitoring of MI sensitization in the near future will be necessary, and the highest test concentrations reported for MI and MCI/MI should be included in the baseline series.
HOUSING MARKETS AND THE GLOBAL FINANCIAL CRISIS: THE COMPLEX DYNAMICS OF A CREDIT SHOCK
Authors: Grimes Arthur , Hyland Sean
Published: May 2014

We analyze the multiple channels of influence that global financial crisis‐induced credit restrictions had on New Zealand's subnational housing markets. The dynamics caused by the credit shock are compared to those caused by a migration shock, a more common form of housing shock in New Zealand. We focus on the impacts on two outcome variables, house prices and housing supply, within a structural time series model of regional housing markets. Both shocks cause substantial and prolonged cyclical adjustments in each variable. Similar cyclical dynamics could complicate the conduct of macroprudential policies designed to affect bank credit allocation. (JEL E32, E44, R21)
Integrin αvβ5 as a biomarker for the assessment of non‐small cell lung cancer metastasis and overall survival
Authors: Bai Sally Yan , Xu Nuo , Chen Cuicui , Song Yuan‐lin , Hu Jie , Bai Chun‐xue
Published: May 2014

Background and Aim

There is growing interest in how integrins play a role in cancer disease biology and what applications these may have in anti‐cancer therapeutic development. This study investigates integrin αvβ5 expression in non‐small cell lung carcinoma (NSCLC) and its correlations with clinical information.

Methods

Tumor human tissue microarrays of 147 radically operated Chinese NSCLC patients were retrieved from the pathology archive, and sections were autoimmune stained along with positive and negative controls. Integrin αvβ5 (P1F6) mouse monoclonal antibody were validated by both Western blotting and immunoreactivity on the same set of cell pellets, according to a precedent of expression levels in cell flow cytometry. The immunoreactivity of all patients’ cases against integrin αvβ5 antibody was graded in a semi‐quantitative manner by two pathologists blind to any patient data.

Results

Overall survival significantly correlated to integrin αvβ5 immunoreactivity by Cox regression analysis with P = 0.032. When applying Kaplan–Meier to analyze the comparison between positive and negative expression on lymph node metastasis patients, P = 0.082. Therefore, integrin αvβ5 expression emerges as a significant prognostic factor for NSCLC. In total, 39 of 147 (26.5%) showed an integrin αvβ5 immunoreactivity positive, as it ranged from 6.1% in squamous cell carcinoma to 19.7% in adenocarcinoma. This expression correlated significantly with histological subtypes (P = 0.007), tumor node metastasis classification of malignant tumors (P = 0.027) and lymph node metastases (P = 0.006).

Conclusion

This study support the hypothesis that integrin αvβ5 is a prognostic biomarker and correlates to metastasis with therapeutic development potential in NSCLC.
Large non‐functioning parathyroid cysts: our institutional experience of a rare entity and a possible pitfall in thyroid cytology
Authors: Rossi E. D. , Revelli L. , Giustozzi E. , Straccia P. , Stigliano E. , Lombardi C. P. , Pontecorvi A. , Fadda G.
Published: May 2014

Objective

Large non‐functioning parathyroid cysts represent a rare entity with a benign clinical course. They may be misdiagnosed as thyroid cystic neoplasms on fine needle aspiration cytology (FNAC), resulting in inappropriate surgical treatment. We evaluated our institutional experience in the diagnosis of large parathyroid cystic lesions underlining all the differential diagnoses and pitfalls.

Methods

In the period between 1998 and 2012, we reported the cytology of eight large (>2.5 cm) parathyroid cystic lesions (all female patients) with histological control. The aspirations were performed with a 25‐gauge needle with ultrasonographic guidance. The aspirated material was processed with liquid‐based cytology (LBC). All the patients had normal serum parathyroid hormone (PTH) and calcium.

Results

The cytological samples showed a fluid watery component without colloid and few or absent epithelial cells. The resulting negativity for thyroglobulin and positivity for PTH, carried out on the cystic fluids, suggested parathyroid lesions rather than either thyroid cystic lesions (including follicular thyroid neoplasm) or cystic malignant lesions. All the patients underwent surgery without complications.

Conclusions

To the best of our knowledge, this is one of the largest series with cytohistological evaluation of large parathyroid cysts. The incidence of large parathyroid cysts remains controversial as most patients are asymptomatic. FNAC may be performed with conclusive results in the majority of cystic cases. The detection of PTH and calcium on the cystic liquid is likely to achieve a correct cytological diagnosis, allowing adequate treatment and ruling out a more frequent thyroid lesion.
Modern wound care – practical aspects of non‐interventional topical treatment of patients with chronic wounds
Authors: Dissemond Joachim , Augustin Matthias , Eming Sabine A. , Goerge Tobias , Horn Thomas , Karrer Sigrid , Schumann Hauke , Stücker Markus
Published: May 2014

The treatment of patients with chronic wounds is becoming increasingly complex. It was therefore the aim of the members of the working group for wound healing (AGW) of the German Society of Dermatology (DDG) to report on the currently relevant aspects of non‐interventional, topical wound treatment for daily practice. ­Beside necessary procedures, such as wound cleansing and débridement, we describe commonly used wound dressings, their indications and practical use. Modern antiseptics, which are currently used in wound therapy, usually contain polyhexanide or octenidine. Physical methods, such as negative‐pressure treatment, are also interesting options. It is always important to objectify and adequately treat pain symptoms which often affect these patients. Modern moist wound therapy may promote healing, reduce complications, and improve the quality of life in patients with chronic wounds. Together with the improvement of the underlying causes, modern wound therapy is an important aspect in the overall treatment regime for patients with chronic wounds.
Non‐melanoma skin cancer is reduced after switch of immunosuppression to mTOR‐inhibitors in organ transplant recipients
Authors: Alter Mareike , Satzger Imke , Schrem Harald , Kaltenborn Alexander , Kapp Alexander , Gutzmer Ralf
Published: May 2014

Background

Organ transplant recipients are prone to the development of non‐melanoma skin cancer. Organ transplant recipients often develop multiple non‐melanoma skin cancers and the tumors show an aggressive growth pattern, therefore surgical therapy can be difficult. Switch of the immunosuppressive regimen to mTOR‐inhibitors such as everolimus or sirolimus can have an antitumor effect.

Patients and Methods

In a monocentric retrospective study we evaluated organ transplant recipients who presented with non‐melanoma skin cancer in the years 2008–2010. Experience with patients who were switched to an mTOR‐inhibitor due to non‐melanoma skin cancer are reported in detail, and recent clinical studies are reviewed.

Results

60 organ transplant recipients with non‐melanoma skin cancer were evaluated. Due to the development of multiple non‐melanoma skin cancer within a few years, the immunosuppressive regimen was switched to everolimus in 7 patients and to sirolimus in 5 patients. Eight patients were evaluable for the effect of mTOR‐inhibitors on the development of non‐melanoma skin cancer; 4 patients had to discontinue the medication with mTOR‐inhibitors early due to various side effects. In the year before the switch to mTOR‐inhibitors, 8 patients developed 16 squamous cell carcinomas, 3 Basal cell carcinomas and 22 cases of Bowen's disease. All tumors were histologically confirmed. In the year after switch of immunosuppression, the rate of squamous cell carcinomas (n = 2) and Bowen's disease (n = 3), but not of basal cell carcinomas (n = 2) was significantly reduced. Moreover, 5 prospective randomized trials recently have demonstrated a reduced number of non‐melanoma skin cancers in organ transplant recipients after switch of the immunosuppressive regimen to mTOR‐inhibitors.

Conclusion

Switch of the immunosuppressive regimen to mTOR‐inhibitors should be considered for organ transplant recipients suffering from multiple non‐melanoma skin cancers.
The Right to Health and Medicines: The Case of Recent Multilateral Negotiations on Public Health, Innovation and Intellectual Property
Authors: Velasquez German
Published: May 2014

The negotiations of the intergovernmental group known as the ‘IGWG’, undertaken by the Member States of the WHO, were the result of a deadlock in the World Health Assembly held in 2006 where the Member States of the WHO were unable to reach an agreement on what to do with the 60 recommendations in the report on ‘Public Health, Innovation and Intellectual Property Rights submitted to the Assembly in the same year by a group of experts designated by the Director General of the WHO. The result of these negotiations was the ‘Global strategy and plan of action on public health, innovation and intellectual property’ which was approved by the World Health Assembly in 2008. The intention of the Global Strategy and Plan of Action (GSPOA) which was produced by the IGWG was to substantially reform the pharmaceuticals' research and development system in view of the findings that this system, whose purpose is to produce medicines for diseases which affect the greater part of the world population which lives in developing countries, had failed. The intellectual property rights imposed by the Agreement on Trade‐Related Aspects of Intellectual Property Rights (TRIPS) and the recent trade agreements could become one of the main obstacles to access to medicines. The GSPOA makes a critical analysis of this reality, and opens the door to searching for new solutions to this problem.
Association between skeletal muscle fat content and very‐low‐density lipoprotein‐apolipoprotein B‐100 transport in obesity: effect of weight loss
Authors: Chan D. C. , Gan S. K. , Wong A. T. Y. , Barrett P. H. R. , Watts G. F.
Published: May 2014

Aims

Ectopic deposition of fat in skeletal muscle is a feature of metabolic syndrome, but its specific association with very‐low‐density lipoprotein (VLDL)‐apolipoprotein (apo) B‐100 metabolism remains unclear.

Methods

We examined the association between skeletal muscle fat content and VLDL‐apoB‐100 kinetics in 25 obese subjects, and the responses of these variables to weight loss. The fat contents of liver, abdomen and skeletal muscle were determined by magnetic resonance imaging, and VLDL‐apoB‐100 kinetics were assessed using stable isotope tracers.

Results

In obese subjects who were insulin sensitive (homeostasis model assessment, HOMA, score ≤ 2.6, n = 12), skeletal muscle fat content was significantly associated with hepatic fat content (r = 0.636), energy intake (r = 0.694), plasma triglyceride (r = 0.644), apoB‐100 (r = 0.529), glucose (r = 0.622), VLDL‐apoB‐100 concentrations (r = 0.860), VLDL‐apoB‐100 fractional catabolic rate (FCR; r = −0.581) and VLDL‐apoB‐100 secretion rate (r = 0.607). These associations were not found in obese subjects who were insulin resistant (HOMA score >2.6, n = 13). Of these 25 subjects, 10 obese subjects underwent a 16‐week weight loss program. The low‐fat diet achieved significant reduction (p < 0.05) in body weight, visceral and subcutaneous fat areas, liver and skeletal muscle fat, energy intake, triglyceride, insulin, HOMA score, VLDL‐apoB100 concentrations and VLDL‐apoB100 secretion rate. The percentage reduction of skeletal muscle fat with weight loss was significantly associated with the corresponding changes in VLDL‐apoB100 concentration (r = 0.770, p = 0.009) and VLDL‐apoB‐100 secretion (r = 0.682, p = 0.030).

Conclusions

Skeletal muscle fat content is associated with VLDL‐apoB‐100 transport. Weight loss lowers skeletal muscle fat and VLDL‐apoB‐100 secretion.
Real Time Three‐Dimensional Transthoracic Echocardiography of a Supracristal Ventricular Septal Defect Associated with a Bicuspid Aortic Valve
Authors: Théron Alexis , Obadia Benjamin , Bonnet Guillaume , Pinto Johan , Mace Loïc , Collart Frederic
Published: May 2014

Mini‐Abstract

A 21‐year‐old man was referred to our department for surgical treatment of a nonrestrictive supracristal ventricular septal defect (VSD) associated with a Sievers' type 0 bicuspid aortic valve (type 0, ap, I) (BAV). Cardiac catheterization revealed a significant left‐to‐right ventricular shunt (Qp/Qs 3:1) with pulmonary hypertension. Surgical intervention was performed to close the VSD through the pulmonary artery trunk using a Gore‐Tex patch. Live 3D transthoracic echocardiography (TTE) was performed before and after the intervention. We compared the live 3DTTE features with the surgical findings.
Relation of Epicardial Fat Thickness to Subclinical Right Ventricular Dysfunction Assessed by Strain and Strain Rate Imaging in Subjects with Metabolic Syndrome: A Two‐Dimensional Speckle Tracking Echocardiography Study
Authors: Gökdeniz Tayyar , Erkol Ayhan , Kalaycıoğlu Ezgi , Çağrı Aykan Ahmet , Gül İlker , Boyacı Faruk , Turan Burak , Ozkan Mehmet
Published: May 2014

Background

Right ventricular (RV) function is known to be impaired in the presence of metabolic syndrome (MetS). Epicardial adipose tissue is a metabolically active organ that generates various bioactive molecules, which might affect cardiac function and morphology. Thus, we hypothesized that RV dysfunction in patients with MetS may be related to increased epicardial fat thickness (EFT) in these patients. In patients with MetS, we aimed to assess the relation of EFT with RV function using two‐dimensional speckle tracking echocardiography (2DSTE)‐derived strain and strain rate imaging.

Methods

The study involved 76 subjects with MetS and 61 subjects without MetS. Biventricular structure and function together with EFT were evaluated by conventional echocardiography. RV free and septal walls strain (RVFW‐S & RVSW‐S), systolic and early diastolic strain rates (RVSRs & RVSRe) were evaluated by 2DSTE.

Results

Epicardial fat thickness was significantly higher in subjects with MetS (6.45 ± 1.48 mm vs. 5.49 ± 1.05 mm, P < 0.001). RVFW‐S (−22.95 ± 4.97% vs. −24.96 ± 3.63%; P = 0.007), RVSRs (1.53 ± 0.33/sec vs. −1.70 ± 0.33/sec; P = 0.002), and RVSRe (1.40 ± 0.44/sec vs. 1.75 ± 0.49/sec; P < 0.001) were all lower in subjects with MetS, while RVSW‐S did not differ. Multiple regression analysis showed that EFT was independently associated with RVFW‐S (β = −0.547, P < 0.001), RVSRs (β = −0.332, P = 0.001), and RVSRe (β = −0.187, P = 0.019) in subjects with MetS.

Conclusions

Metabolic syndrome is associated with subclinical RV systolic and diastolic dysfunction. In subjects with MetS, increased EFT is independently related to RV systolic and diastolic dysfunction.