bluuebunny/crossref_metadata_2025 huggingface dataset:
Aromatase and endometriosis: estrogens play a role
Authors: Ferrero Simone , Remorgida Valentino , Maganza Carlo , Venturini Pier Luigi , Salvatore Stefano , Papaleo Enrico , Candiani Massimo , Leone Roberti Maggiore Umberto
Published: April 2014

Endometriosis is an estrogen‐dependent inflammatory disease defined by the growth of endometrial stroma and glands outside of the uterus. Epidemiological and clinical studies show that estrogen is essential for the growth of endometriosis. There are several molecular links between estrogen production and inflammation in endometriosis. The enzyme aromatase P450 is expressed aberrantly in endometriosis and is stimulated by prostaglandin E2, resulting in production of estrogen that induces prostaglandin E2 expression within endometriotic lesions. Furthermore, estrogen promotes the secretion of several inflammatory cytokines and growth factors, which contribute to the progression of endometriosis and stimulate estrogen production. On the basis of the local estrogen biosynthesis in endometriotic implants, nonsteroidal aromatase inhibitors have been successfully used to treat pain symptoms caused by endometriosis. These agents do not cause the disappearance of endometriosis; they cannot be considered routine treatment and should only be administered in adequately controlled clinical studies.
Are glucocorticoids harmful to bone in early rheumatoid arthritis?
Authors: Lems Willem F.
Published: April 2014

In the past, patients with rheumatoid arthritis (RA) were treated with monotherapy with conventional drugs, such as sulfasalazine, methotrexate, and intramuscular gold, which often leads to persistent arthritis, loss of functional capacity, and decreased quality of life. Both active RA and the use of high‐dose glucocorticoids (GCs) are associated with generalized bone loss and fractures, but it is well known that GCs have a strong immunosuppressive effect. With the introduction of tumor necrosis factor (TNF‐α)‐blockers and other biologics, clinical remission is a realistic target in approximately half of the early RA patients; the same seems to be true for the use of methotrexate with chronic low‐dose or initially high‐dose GCs. With the use of a treat‐to‐target strategy focusing on clinical remission or low disease activity in early RA patients, the negative effects of systemic inflammation on bone can be arrested, and both local bone loss (in the joints) and generalized bone loss at the spine and hips can be prevented.
Processed foods and the nutrition transition: evidence from Asia
Authors: Baker P. , Friel S.
Published: April 2014

This paper elucidates the role of processed foods and beverages in the ‘nutrition transition’ underway in Asia. Processed foods tend to be high in nutrients associated with obesity and diet‐related non‐communicable diseases: refined sugar, salt, saturated and trans‐fats. This paper identifies the most significant ‘product vectors’ for these nutrients and describes changes in their consumption in a selection of Asian countries. Sugar, salt and fat consumption from processed foods has plateaued in high‐income countries, but has rapidly increased in the lower–middle and upper–middle‐income countries. Relative to sugar and salt, fat consumption in the upper–middle‐ and lower–middle‐income countries is converging most rapidly with that of high‐income countries. Carbonated soft drinks, baked goods, and oils and fats are the most significant vectors for sugar, salt and fat respectively. At the regional level there appears to be convergence in consumption patterns of processed foods, but country‐level divergences including high levels of consumption of oils and fats in Malaysia, and soft drinks in the Philippines and Thailand. This analysis suggests that more action is needed by policy‐makers to prevent or mitigate processed food consumption. Comprehensive policy and regulatory approaches are most likely to be effective in achieving these goals.
Basal dinosauriform and theropod dinosaurs from the mid–lateNorian (LateTriassic) ofPoland: implications forTriassic dinosaur evolution and distribution
Authors: Niedźwiedzki Grzegorz , Brusatte Stephen L. , Sulej Tomasz , Butler Richard J.
Published: April 2014

The rise of dinosaurs during theTriassic is a widely studied evolutionary radiation, but there are still many unanswered questions about early dinosaur evolution and biogeography that are hampered by an unevenly sampled Late Triassic fossil record. Although very common in westernNorthAmerica and parts ofSouthAmerica, dinosaur (and more basal dinosauriform) remains are relatively rare in the Upper Triassic deposits ofEurope, making any new discoveries critically important. One of the most diverse dinosauriform assemblages fromEurope comes from thePoręba site inPoland, a recently described locality with exposures of theZbąszynekBeds, which have a palynomorph assemblage characteristic for the mid–late Norian in the biostratigraphic schemes of theGermanicBasin. Using a synapomorphy‐based approach, we evaluate several isolated dinosauriform specimens fromPoręba. This assemblage includes a silesaurid, a herrerasaurid and remains of another type of theropod (potentially a neotheropod). ThePoręba herrerasaurid is the first record of this rare group of primitive dinosaurs fromEurope and one of the youngest records worldwide, whereas the silesaurid is the youngest record of a silesaurid fromEurope. These findings indicate that silesaurids persisted alongside true dinosaurs into the mid–lateNorian ofEurope and that silesaurid–herrerasaurid–neotheropod assemblages (which are also known from theNorian ofNorthAmerica, at low latitudes) were more widespread geographically and latitudinally than previously thought. Silesaurid–herrerasaurid–neotheropod assemblages may have been a common ecological structuring of dinosaurs during their early evolution, and their widespread distribution may indicate weak palaeolatitudinal controls on early dinosaur biogeography during the latestTriassic.
Ultrasound‐guided Prolotherapy with Polydeoxyribonucleotide Sodium in Ischiofemoral Impingement Syndrome
Authors: Kim Won‐Joong , Shin Hwa‐Yong , Koo Gill‐Hoi , Park Hae‐Gyun , Ha Yong‐Chan , Park Yong‐Hee
Published: April 2014

Ischiofemoral impingement syndrome is an uncommon disorder defined by hip pain caused by the narrowing of the space between the ischial tuberosity and lesser trochanter with associated entrapment of the quadratus femoris muscle. We effectively treated two male patients using ultrasound‐guided prolotherapy with polydeoxyribonucleotide sodium mixed with local anesthetics. A 24‐year‐old male patient with no history of trauma or surgery complained of bilateral hip and groin pain; magnetic resonance imaging demonstrated slight narrowing of the bilateral ischiofemoral spaces with mild enhancement of the left quadratus femoris muscle. A 23‐year‐old male patient with a history of iliotibial band release and iliopsoas tendon release complained of left hip and groin pain; magnetic resonance imaging revealed swelling of the left quadratus femoris muscle. After the fifth treatment session of prolotherapy, the pain severity score using the visual analog scale was found to be minimal (0–1/10), and follow‐up magnetic resonance imaging revealed a slightly decreased enhancement of the quadratus femoris muscle compared with that on previous images. Prolotherapy with polydeoxyribonucleotide sodium was an efficacious treatment for two patients with ischiofemoral impingement syndrome who were not candidates for surgery.
Safety assessment of genetically modified plants with deliberately altered composition
Authors: Halford Nigel G. , Hudson Elizabeth , Gimson Amy , Weightman Richard , Shewry Peter R. , Tompkins Steven
Published: April 2014

The development and marketing of ‘novel’ genetically modified (GM) crops in which composition has been deliberately altered poses a challenge to the European Union (EU)'s risk assessment processes, which are based on the concept of substantial equivalence with a non‐GM comparator. This article gives some examples of these novel GM crops and summarizes the conclusions of a report that was commissioned by the European Food Safety Authority on how the EU's risk assessment processes could be adapted to enable their safety to be assessed.
Tissue‐specific and light‐dependent regulation of phytochrome gene expression in rice
Authors: BABA‐KASAI AKIKO , HARA NAHO , TAKANO MAKOTO
Published: April 2014

Phytochromes are red‐ and far red light photoreceptors in higher plants. Rice (Oryza sativa L.) has three phytochromes (phyA, phyB and phyC), which play distinct as well as cooperative roles in light perception. To gain a better understanding of individual phytochrome functions in rice, expression patterns of three phytochrome genes were characterized using promoter‐GUS fusion constructs. The phytochrome genes PHYA and PHYB showed distinct patterns of tissue‐ and developmental stage‐specific expression in rice. The PHYA promoter‐GUS was expressed in all leaf tissues in etiolated seedlings, while its expression was restricted to vascular bundles in expanded leaves of light‐grown seedlings. These observations suggest that light represses the expression of the PHYA gene in all cells except vascular bundle cells in rice seedlings. Red light was effective, but far red light was ineffective in gene repression, and red light‐induced repression was not observed in phyB mutants. These results indicate that phyB is involved in light‐dependent and tissue‐specific repression of the PHYA gene in rice.
Neurofunctional maps of the ‘maternal brain’ and the effects of oxytocin: A multimodal voxel‐based meta‐analysis
Authors: Rocchetti Matteo , Radua Joaquim , Paloyelis Yannis , Xenaki Lida‐Alkisti , Frascarelli Marianna , Caverzasi Edgardo , Politi Pierluigi , Fusar‐Poli Paolo
Published: April 2014

Several studies have tried to understand the possible neurobiological basis of mothering. The putative involvement of oxytocin, in this regard, has been deeply investigated. Performing a voxel‐based meta‐analysis, we aimed at testing the hypothesis of overlapping brain activation in functional magnetic resonance imaging (fMRI) studies investigating the mother–infant interaction and the oxytocin modulation of emotional stimuli in humans. We performed two systematic literature searches: fMRI studies investigating the neurofunctional correlates of the ‘maternal brain’ by employing mother–infant paradigms; and fMRI studies employing oxytocin during emotional tasks. A unimodal voxel‐based meta‐analysis was performed on each database, whereas a multimodal voxel‐based meta‐analytical tool was adopted to assess the hypothesis that the neurofunctional effects of oxytocin are detected in brain areas implicated in the ‘maternal brain.’ We found greater activation in the bilateral insula extending to the inferior frontal gyrus, basal ganglia and thalamus during mother–infant interaction and greater left insular activation associated with oxytocin administration versus placebo. Left insula extending to basal ganglia and frontotemporal gyri as well as bilateral thalamus and amygdala showed consistent activation across the two paradigms. Right insula also showed activation across the two paradigms, and dorsomedial frontal cortex activation in mothers but deactivation with oxytocin. Significant activation in areas involved in empathy, emotion regulation, motivation, social cognition and theory of mind emerged from our multimodal meta‐analysis, supporting the need for further studies directly investigating the neurobiology of oxytocin in the mother–infant relationship.
Potential role of anticonvulsants in the treatment of obsessive–compulsive and related disorders
Authors: Wang Hee Ryung , Woo Young Sup , Bahk Won‐Myong
Published: April 2014

We reviewed the extant literature to evaluate the current evidence regarding the efficacy and safety of anticonvulsants in the treatment of obsessive–compulsive and related disorders. Relevant literature was accessed using the Cochrane database, embase and PubMed on 29 October 2013. Prospective studies examining the efficacy of anticonvulsants in obsessive–compulsive and related disorders were included. Case reports, case series, and retrospective studies were excluded. A total of 10 studies were included in this review. The studies of obsessive–compulsive disorder, except for two negative studies, showed favorable efficacy results of anticonvulsants. In one study on body dysmorphic disorder, levetiracetam showed favorable efficacy. In two lamotrigine studies for pathologic skin‐picking, the efficacy findings were inconsistent. In one trichotillomania study, topiramate had reduced hair‐pulling symptoms. Despite limited evidence, our review suggests that anticonvulsants have a potential role in the treatment of obsessive–compulsive and related disorders.
Microsatellite and mating type markers reveal unexpected patterns of genetic diversity in the pine root‐infecting fungusGrosmannia alacris
Authors: Duong T. A. , de Beer Z. W. , Wingfield B. D. , Eckhardt L. G. , Wingfield M. J.
Published: April 2014

Grosmannia alacrisis a fungus commonly associated with root‐infesting bark beetles occurring onPinusspp. The fungus has been recorded in South Africa, theUSA, France, Portugal and Spain and importantly, has been associated with pine root diseases in South Africa and theUSA. Nothing is known regarding the population genetics or origin ofG. alacris, although its association with root‐infesting beetles native to Europe suggests that it is an invasive alien in South Africa. In this study, microsatellite markers together with newly developed mating type markers were used to characterize a total of 170 isolates ofG. alacrisfrom South Africa and theUSA. The results showed that the genotypic diversity of the South African population ofG. alacriswas very high when compared to theUSApopulations. Two mating types were also present in South African isolates and theMAT1‐1/MAT1‐2ratio did not differ from 1:1 (χ2 = 1·39,P = 0·24). This suggests that sexual reproduction most probably occurs in the fungus in South Africa, although a sexual state has never been seen in nature. In contrast, the large collection ofUSAisolates harboured only a single mating type. The results suggest that multiple introductions, followed by random mating, have influenced the population structure in South Africa. In contrast, limited introductions of probably a single mating type (MAT1‐2) may best explain the clonality ofUSApopulations.
Metabolic profiling of the resurrection plant Haberlea rhodopensis during desiccation and recovery
Authors: Moyankova Daniela , Mladenov Petko , Berkov Strahil , Peshev Darin , Georgieva Desislava , Djilianov Dimitar
Published: April 2014

Desiccation tolerance is among the most important parameters for crop improvement under changing environments. Resurrection plants are useful models for both theoretical and practical studies. We performed metabolite profiling via gas chromatography coupled with mass spectrometry (GC‐MS) and high‐performance liquid chromatography (HPLC) and analyzed the antioxidant capacity of the endemic resurrection plant Haberlea rhodopensis at desiccation and recovery. More than 100 compounds were evaluated. Stress response included changes in both primary and secondary metabolic pathways. The high amounts of the specific glycoside myconoside and some phenolic acids – e.g. syringic and dihydrocaffeic acid under normal conditions tend to show their importance for the priming of H. rhodopensis to withstand severe desiccation and oxidative stress. The accumulation of sucrose (resulting from starch breakdown), total phenols, β‐aminoisobutyric acid, β‐sitosterol and α‐tocopherol increased up to several times at later stages of desiccation. Extracts of H. rhodopensis showed high antioxidant capacity at stress and normal conditions. Myconoside was with the highest antioxidant properties among tested phenolic compounds. Probably, the evolution of resurrection plants under various local environments has resulted in unique desiccation tolerance with specific metabolic background. In our case, it includes the accumulation of a relatively rare compound (myconoside) that contributes alone and together with other common metabolites. Further systems biology studies on the involvement of carbohydrates, phenolic acids and glycosides in the desiccation tolerance and antioxidant capacity of H. rhodopensis will definitely help in achieving the final goal – improving crop drought tolerance.
Complementary modulation of N2 and CRN by conflict frequency
Authors: Grützmann Rosa , Riesel Anja , Klawohn Julia , Kathmann Norbert , Endrass Tanja
Published: April 2014

The present study investigated the modulation of the N2 and the correct‐related negativity (CRN) by conflict frequency. Conflict costs, as measured by reaction times and error rate, were reduced with increasing conflict frequency, indicating improved conflict resolution. N2 amplitudes in incompatible trials increased with higher conflict frequency, while postresponse CRN amplitudes decreased. In concert with behavioral findings of reduced conflict costs and greater interference suppression, the increase of N2 might reflect enhanced conflict resolution during stimulus processing. The CRN, however, might reflect postresponse implementation of cognitive control, which is reduced when conflict is already adequately resolved during stimulus processing. Furthermore, N2 and CRN in incompatible trials were inversely related on the between‐ and within‐subject level, implying that the two modes of implementing cognitive control are applied complementarily.
A Case of Leucocyte Chimerism (78,XX/78,XY) in a Dog with a Disorder of Sexual Development
Authors: Szczerbal I , Nowacka‐Woszuk J , Nizanski W , Salamon S , Ochota M , Dzimira S , Atamaniuk W , Switonski M
Published: April 2014

Contents

A 1‐year‐old Shih Tzu dog was presented for examination because of abnormal external genitalia. A residual penis with a prepuce was located in a position typical of a male. The dog had no palpable testicles or scrotum. The ultrasound examination revealed the presence of the prostate, but the gonads remained undetectable. Cytogenetic analysis performed on chromosome preparations obtained from lymphocyte culture showed two cell lines – 78,XX and 78,XY. Molecular analysis of 14 polymorphic microsatellite markers allowed us to distinguish leucocyte chimerism from whole body chimerism. The presence of 3 or 4 alleles was confirmed in DNA isolated from blood, while in DNA isolated from hair follicles only 1 or 2 alleles were detected. The case was classified as leucocyte 78,XX/78,XY chimerism. Our study showed that XX/XY leucocyte chimerism might be associated with disorder of sexual development in dogs. Furthermore, it is emphasized that the use of cytogenetic study, in combination with analysis of polymorphic markers in DNA isolated from different somatic cells, facilitates distinguishing between leucocyte and whole body chimerism.
The Law of Transboundary Aquifers: Many Ways of Going Forward, but Only One Way of Standing Still
Authors: Eckstein Gabriel , Sindico Francesco
Published: April 2014

The international community has been considering international legal norms and policies for the management of transboundary aquifers for more than ten years. In 2008, the International Law Commission provided a framework with the adoption of the Draft Articles on the Law of Transboundary Aquifers, which are now formally annexed to a United Nations General Assembly (UNGA) Resolution. Since 2008, the topic of the law of transboundary aquifers has thrice been placed on the agenda of the UNGA Sixth Committee with a specific mandate to discuss the future form of the Draft Articles. This article explores the options before the international community regarding the future form of the Draft Articles and considers the possible advantages and disadvantages of each option. The article also discusses the extent to which the actual form of the Draft Articles matters in itself, or whether their impact ultimately will depend on other factors.
The Yin and Yang of International Water Law: China's Transboundary Water Practice and the Changing Contours of State Sovereignty
Authors: Wouters Patricia
Published: April 2014

International law, by its very nature, is dichotomous – at once anchored in tradition, and yet infused with future potential, inherently capable of transforming to address evolving contemporary challenges. This article explores the dynamic nature of international law in the context of transboundary freshwaters shared across Asia, with a focus on China. Soon to be the world's leading economy, China forges ahead with development on all fronts, placing increased pressures on its already diminishing qualities and quantities of freshwater. As an upper riparian State on close to 40 major transboundary watercourses shared with 14 neighbouring countries, China faces the ‘upstream dilemma’: how to meet domestic water‐related needs, while at the same time taking into account other nations' requirements. In short, how can China be the ‘good neighbour’ that it emphasizes is an integral part of its foreign policy strategy? A concise review of China's treaty and State practice related to its transboundary water resources reveals incremental but significant changes in that arena, which reflect new approaches to national sovereignty. The article suggests that the ancient Chinese concept of ‘yin and yang’ provides an apt metaphor for considering China's evolving transboundary water practice – an emerging ‘Chinese way’.
Can Two Global UN Water Conventions Effectively Co‐exist? Making the Case for a ‘Package Approach’ to Support Institutional Coordination
Authors: Rieu‐Clarke Alistair , Kinna Rémy
Published: April 2014

In the foreseeable future there will be two legal framework instruments covering transboundary water issues in force at the global level: the 1997 United Nations (UN) Watercourses Convention and the 1992 UN Economic Commission for Europe Water Convention. This development raises questions about the compatibility of both instruments, and how they might be implemented in a coordinated manner. A comparative analysis of the text of both instruments demonstrates that there are both similarities and differences between them, but that they are complementary. There is therefore significant benefit in promoting and implementing the conventions as a package. Three basic institutional options can be envisaged to support this ‘package approach’, each with their strengths and weaknesses. Ultimately, whichever option is chosen, the ‘package approach’ to the implementation of both conventions offers the best means by which to strengthen the law of international watercourses.
Association of group component genetic variations in COPD and COPD exacerbation in a Japanese population
Authors: Ishii Takeo , Motegi Takashi , Kamio Koichiro , Gemma Akihiko , Kida Kozui
Published: April 2014

Background and objective

Vitamin D supplementation can decrease the vulnerability to pulmonary infections. Therefore, it is speculated that the genes related to vitamin D metabolism are associated with an exacerbation‐prone phenotype in chronic obstructive pulmonary disease (COPD). Because genetic variations of group component (GC) affect immunological capacity and serum vitamin D concentration, they could also affect the susceptibility to COPD exacerbation and the disease progression. We investigated the association between GC genetic variations and COPD and its exacerbation frequency in a Japanese population.

Methods

We performed genotype analysis of 361 COPD patients and 219 controls to identify two coding single nucleotide polymorphisms of GC, rs4588 and rs7041. We examined whether these polymorphisms were associated with the frequency of COPD exacerbation and analysed the correlation between the genotypes, COPD, emphysema severity and COPD progression, namely, the annual decline in airflow obstruction and diffusing capacity.

Results

Subjects with a C allele at rs4588 exhibited a higher frequency of exacerbations (P = 0.0048), greater susceptibility to chronic obstructive pulmonary disease (P = 0.0003), and emphysema (P = 0.0029), and a tendency for rapid decline of airflow obstruction (P = 0.0927).

Conclusions

GC variations may affect exacerbation susceptibility, possibly leading to COPD worsening and its progression.
Type 1 diabetes – impact on children and parents at diagnosis and 1 year subsequent to the child's diagnosis
Authors: Jönsson Lisbeth , Lundqvist Pia , Tiberg Irén , Hallström Inger
Published: April 2014

Background and aim

When a child is diagnosed with type 1 diabetes, it is a complex and challenging situation for the whole family. The management of the disease places substantial demands on the family and they need to change their daily life. The short‐ and long‐term impact on the family has rarely been described; therefore, the aim of this study was to describe and compare the disease impact on parents and children in terms of health‐related quality of life (HRQOL) at diagnosis and 1 year subsequent to the child's diagnosis with type 1 diabetes. A further aim was to describe and compare the parents' satisfaction with the care received.

Method

Sixty‐nine children and their parents were included. Parents independently filled in the PedsQL™ Family Impact Module and the PedsQL™ Health Care Satisfaction Generic Module. The PedsQL™ 3.0 Diabetes Module was filled in by parents and children over the age of 5.

Results

Mothers reported a lower HRQOL than fathers both at the time of diagnosis (p = 0.003) and 1 year later (p = 0.041). For diabetes‐specific HRQOL, children aged 5–7 years and their parents reported more worry than children and parents in older age groups (p = 0.037). Children aged 8–12 and 13–18 years reported a higher treatment adherence than mothers (p = 0.011 and p = 0.039, respectively); no differences were found between children and fathers. Both parents expressed overall satisfaction with the child's health care.

Conclusion

The family is affected during the first year after their child is diagnosed with type 1 diabetes. Both parents and the youngest children estimated a high degree of worry. The diabetes team needs to be aware of this and to take it into consideration.
Instrument Assisted Regression for Errors in Variables Models with Binary Response
Authors: Xu Kun , Ma Yanyuan , Wang Liqun
Published: April 2014

We study errors‐in‐variables problems when the response is binary and instrumental variables are available. We construct consistent estimators through taking advantage of the prediction relation between the unobservable variables and the instruments. The asymptotic properties of the new estimator are established and illustrated through simulation studies. We also demonstrate that the method can be readily generalized to generalized linear models and beyond. The usefulness of the method is illustrated through a real data example.
Help‐seeking among Male Farmers: Connecting Masculinities and Mental Health
Authors: Roy Philippe , Tremblay Gilles , Robertson Steven
Published: April 2014

In many ways, male farmers can be considered to be a vulnerable group in relation to mental health, experiencing high rates of suicide, psychological distress and low use of health services. This study highlights important connections between rurality, farming and masculinities in the context of men's mental health. In‐depth interviews with 32 male farmers from Quebec, Canada were completed focusing on stress and coping strategies. Findings include informal and formal strategies. Many participants had previous positive experience of formal help and would be willing to use such help again and to recommend it to others in need. Those without such experience are sceptical about services but recognise the courage it requires to seek help. Pride and lack of knowledge about services are the main barriers to help‐seeking, but it can be legitimated in certain contexts, such as divorce or other psychosocial crisis, and by alignment with particular male ideals. Role models at national or local levels can also help farmers prioritise their own and their family's wellbeing over stigmas and rigid, traditional masculine ideals. Furthermore, gender‐based strengths and recommendations for practice are also discussed.
Identification of the novel HLA‐C*03:240 allele
Authors: Wang D. , Wu J. , Nie D. , Zhang H. , Zhen J. , Zou H.
Published: April 2014

HLA-C*03:240 differs from HLA-C*03:42 by a single nucleotide substitution that results in a missense mutation Tyr 99 Cys (TAT to TGT).
Identification of two novel HLA‐A*24 alleles, HLA‐A*24:02:69 and HLA‐A*24:247 by cloning and sequencing
Authors: Gao S.‐Q.
Published: April 2014

HLA‐A*24:02:69 differs from HLA‐A*24:02:01 at nt 501 C > T, HLA‐A*24:247 differs from A*24:02:01:01 at nt 395 G > T.
Randomized study of washing 40‐ to 42‐day‐stored red blood cells
Authors: Bennett‐Guerrero Elliott , Kirby Brett S. , Zhu Hongmei , Herman Annadele E. , Bandarenko Nicholas , McMahon Timothy J.
Published: April 2014

Background

Pretransfusion washing of red blood cells (RBCs) stored for a longer duration may have theoretical advantages but few data exist to support this practice. In many hospital settings, use of a point‐of‐care cell washer could conceivably be used to quickly wash allogeneic RBCs before transfusion. The purpose of this preliminary study was to compare a point‐of‐care device with a common blood bank device for washing longer‐stored RBCs.

Study Design and Methods

Forty RBC units stored for 40 to 42 days were randomized to washing with the COBE 2991 device (Terumo BCT; FDA‐cleared for washing stored RBCs) or the Cell Saver Elite (Haemonetics; FDA‐cleared point‐of‐care device for processing and washing fresh autologous shed whole blood). Supernatant and unit RBCs from unwashed (baseline) and washed blood were assayed for potassium, lactate, intracellular ATP, percentage of RBC recovery, cell‐free hemoglobin, RBC microparticles, and RBCs were examined for susceptibility to hemolysis by physical stress.

Results

Both devices recovered a high percentage of RBCs and efficiently removed extracelluar potassium. Washing with the Elite resulted in significant increases in cell‐free Hb, percent hemolysis, and RBC microparticle production, whereas washing with the COBE 2991 did not (fold Δ = 2.1 vs. 1.0, 4.6 vs. 1.2, 2.0 vs. 1.1, respectively; p < 0.05). Hemolysis induced by physical stress was not altered by washing.

Conclusion

Although point‐of‐care washing of longer‐stored RBCs is appealing, these preliminary data suggest that transfusion of washed, longer‐stored units could result in potentially greater exposure to plasma free Hb. More data are needed before this practice can be routinely recommended.
Treatment of hereditary angioedema: a review (CME)
Authors: Bhardwaj Neeti , Craig Timothy J.
Published: April 2014

Hereditary angioedema (HAE) is a rare autosomal dominant disorder characterized by recurrent attacks of self‐limiting tissue swelling. The management of HAE has transformed dramatically with recently approved therapies in the United States. However, there is lack of awareness among physicians about these new modalities. The aim of this review is to update the practicing physician about various therapeutic options available for HAE patients. An exhaustive literature search of PubMed and OVID was performed to develop this article. Management of HAE is traditionally classified into treatment of acute attacks or on‐demand therapy, short‐term (preprocedural) prophylaxis, and long‐term prophylaxis. Newer therapies include C1 esterase inhibitor (C1‐INH) and contact system modulators, namely, ecallantide and icatibant. Recombinant C1‐INH, which is available in Europe, is awaiting approval in the United States. C1‐INH concentrate is approved for prophylaxis as well as on‐demand therapy while ecallantide and icatibant are approved for acute treatment only. Effective HAE management further includes patient education, reliable access to specific medications, and regular follow‐up to monitor therapeutic response and safety.
Safety evaluation of combination CCNU and continuous toceranib phosphate (Palladia®) in tumour‐bearing dogs: a phase I dose‐finding study
Authors: Pan X. , Tsimbas K. , Kurzman I. D. , Vail D. M.
Published: April 2014

While maintaining a standard toceranib dosage [2.75 mg kg−1, PO, every other day (EOD)], three dose‐escalating CCNU cohorts up to and including 60 mg m−2, PO, q3wk, were completed. The dose‐limiting toxicities (DLT) for the combination were neutropenia and the maximum tolerated dose (MTD) for CCNU when given with continuous toceranib was determined to be 50 mg m−2, q3wk. While activity is not a primary objective of phase I trials, we observed one complete (lymphoma) and four partial responses (lymphoma, sarcoma, undifferentiated carcinoma and prostatic carcinoma) and two dogs experienced stable disease for >6 weeks [gastric adenocarcinoma and metastatic multilobulated osteochondrosarcoma (MLO)] for an objective response rate of 38.4% and a biological response rate of 53.8%. Concurrent continuous toceranib (2.75 mg kg−1, EOD) and pulse dose CCNU (50 mg m−2, q3wk) was well tolerated. Phase II effectiveness and phase III prospective randomized trials should further interrogate the potential activity of this combination.
Thromboelastographic evaluation of hemostatic function in dogs treated for crotalid snake envenomation
Authors: Armentano Robert A. , Bandt Carsten , Schaer Michael , Pritchett John , Shih Andre
Published: April 2014

Objective

To characterize the overall hemostatic changes in dogs envenomated by crotaline snakes via kaolin‐activated thromboelastography (TEG), and to determine any prognostic/monitoring value from a TEG tracing on presentation, as well as during treatment with antivenom therapy.

Design

Prospective observational, cohort study.

Setting

University teaching hospital and primary emergency hospital.

Animals

Thirty‐eight dogs envenomated by crotaline snakes.

Interventions

TEG tracings were evaluated on presentation to the hospital (pre) as well as immediately following (post) and 12 hours (12 h post) after antivenom treatment, if administered.

Measurements and Main Results

At presentation, data were available for 38 dogs envenomated by crotaline snakes. Twenty dogs were in Group 1 (Antivenin [Crotalidae] Polyvalent antivenom), 12 dogs were in Group 2 (Antivipmyn antivenom), and 6 dogs in Group 3 that were not treated with antivenom. The average number of vials administered to group 1 and 2 were equal at 2.2. On presentation, based on a G value < TEG reference range, 15/38 (39%) of the dogs had hypocoagulable TEG tracings. There was a significant increase in G and MA value from the pre and 12 hour post measurement (P = 0.0001 and 0.0003, respectively), as well as from the post to 12 hour post measurement (P = 0.003 and, 0.014, respectively). During the study, 5 of 38 dogs died (13%) and of the dogs that died, 4/5 (80%) had angle and MA equal to zero on presentation. A decreased G and MA were significantly associated with mortality (P = 0.02 and 0.04, respectively).

Conclusions

A hypocoagulable TEG tracing, particularly a decreased G value and MA, is associated with an increased mortality in crotaline snake envenomation. G and MA also demonstrate a significant increase over treatment time.
Decreased central venous oxygen saturation despite normalization of heart rate and blood pressure post shock resuscitation in sick dogs
Authors: Young Brian C. , Prittie Jennifer E. , Fox Philip , Barton Linda J.
Published: April 2014

Objective

To evaluate traditional and global perfusion parameters in clinical canine shock patients, and to evaluate for occult hypoperfusion as evidenced by low central venous oxygen saturation or high plasma lactate concentrations in clinical patients resuscitated to traditional endpoints.

Design

Clinical observational trial designed with a 1‐year data entry period and patient follow‐up of 28 days posthospital presentation.

Setting

Large, private urban teaching hospital, and emergency and critical care center.

Animals

Adult canine patients presenting to the emergency department with untreated shock.

Interventions

None.

Measurements and Main Results

Patients received fluid resuscitation to normalize perfusion parameters based on physical examination and arterial blood pressure (BP). Monitoring of central venous pressure (CVP) and central venous oxygen saturation (ScvO2) was feasible with current standard of care interventions in critically ill, client‐owned dogs. Decreased ScvO2was observed in 37.8% of patients resuscitated to normal traditional perfusion parameters. Hyperlactatemia was commonly recorded.

Conclusions

Decreased ScvO2exists in a significant proportion of critically ill dogs following standard fluid resuscitation for shock, providing a relevant target population for implementation of a more standardized early goal‐directed therapy bundle in veterinary patients. Normalization of heart rate, blood pressure, mentation, and perfusion parameters directed by physical examination may be attained despite the persistence of significant tissue hypoperfusion and oxygen debt.
Diagnostic accuracy of the SNAP and Spec canine pancreatic lipase tests for pancreatitis in dogs presenting with clinical signs of acute abdominal disease
Authors: Haworth Mark D. , Hosgood Giselle , Swindells Katrin L. , Mansfield Caroline S.
Published: April 2014

Objectives

To (i) assess the clinical diagnostic accuracy of SNAP canine pancreatic lipase (cPL) and specific canine pancreatic lipase (Spec cPL) and (ii) assess the agreement of an abnormal test result between SNAP cPL and Spec cPL in dogs presenting with acute abdominal disease.

Design

Prospective observational cohort study.

Setting

University teaching hospital emergency center.

Animals

Thirty‐eight client‐owned dogs that presented with acute abdominal disease, with a known final diagnosis between March 2009 and April 2010. Dogs were retrospectively assigned into 2 groups, dogs with acute pancreatitis (AP) (Group 1) and dogs without AP (Group 2).

Interventions

Paired serum samples obtained within 24 hours of presentation were analyzed using the SNAP cPL test and Spec cPL assay.

Measurements and Results

SNAP cPL clinical sensitivity and specificity was 82% (9/11 dogs of group 1) and 59% (16/27 dogs of group 2), respectively. Spec cPL clinical sensitivity and specificity was 70% (7/10 dogs of group 1) and 77% (20/26 dogs of group 2), respectively. Accuracy of the SNAP and Spec cPL for a clinical diagnosis of pancreatitis was found to be 66% and 75%, respectively. Agreement between a positive SNAP (cPL ≥ 200 μg/L) and a clinical diagnosis pancreatitis resulted in κ = 0.33. Agreement between an increased Spec (cPL ≥ 400 μg/L) and a clinical diagnosis of pancreatitis resulted in a κ = 0.43. The agreement between SNAP and Spec cPL (cPL ≥ 200 μg/L) for the entire cohort resulted in κ = 0.78.

Conclusion

SNAP cPL and Spec cPL results may provide a "false positive" diagnosis of pancreatitis in up to 40% of dogs presenting with acute abdominal disease. There is good overall agreement between SNAP cPL and Spec cPL; however, there were 4/38 dogs with positive SNAP cPL and "normal" Spec cPL.
Bounds for zeros of Meixner and Kravchuk polynomials
Authors: Jooste A. , Jordaan K.
Published: April 2014

The zeros of certain different sequences of orthogonal polynomials interlace in a well-defined way. The study of this phenomenon and the conditions under which it holds lead to a set of points that can be applied as bounds for the extreme zeros of the polynomials. We consider different sequences of the discrete orthogonal Meixner and Kravchuk polynomials and use mixed three-term recurrence relations, satisfied by the polynomials under consideration, to identify bounds for the extreme zeros of Meixner and Kravchuk polynomials.
Blazing Golf Trails in Wisconsin: Attracting Avid Golf Travelers to the State
Authors: Manion Michael T. , Knight Peter , Sheets Brenda Hayden , O’Reilly Norman
Published: April 2014

Chip Jahne loves the challenge of the game of golf and his career in the industry. A young executive at the Wisconsin Alliance for Golf (WAG), he has only two weeks to prepare and present well-reasoned arguments to the WAG Board for designing and implementing state golf trails. The great advantage to Wisconsin of a sponsored golf trail is that it attracts tourists to travel, to stay overnight while playing multiple days, and to spend not only on greens fees, but also on lodging, food, and beverage in the state. To prepare his case, he accesses secondary market research and conducts demographic and psychographic analyses. He realizes that extending the target market to nearby out-of-state population centers depends on funding from the state department of tourism. He preliminarily designs three golf trail options for the state and contemplates the use of social media as promotion tools. Wisconsin has three resources necessary for successful golf trails: 40 or more high-quality public access golf facilities, an excellent reputation as a state for outdoor recreation, and an interstate highway system connecting population centers to tourism destinations. The missing ingredient is a consensus by the interested stakeholders on how and when to take advantage of these resources for their mutual benefit. Chip recognizes that the economic benefits to golf trail participants will depend on his tourist projections and financial forecasts, so his design must seek to maximize them.
"Antigenomic" RNA as a Therapeutic Tool for Mitochondrial Diseases
Authors: Bhardwaj Anshu
Published: April 2014

Targeting point mutations in mtDNA with antigenomic RNA restores normal mitochondrial function.
Stopping Seizures After Brain Injury
Authors: Musiek Erik
Published: April 2014

The FDA-approved antihypertensive agent losartan prevents injury-induced epilepsy in rats by blocking pathogenic TGF-β signaling.
Vaccine-Induced Measles Virus-Specific T Cells Do Not Prevent Infection or Disease but Facilitate Subsequent Clearance of Viral RNA
Authors: Lin Wen-Hsuan W. , Pan Chien-Hsiung , Adams Robert J. , Laube Beth L. , Griffin Diane E.
Published: April 2014

Infection with wild-type measles virus (MeV) induces lifelong protection from reinfection, and parenteral delivery of the live attenuated measles vaccine (LAV) also provides protection from measles. The level of neutralizing antibody is a good indicator of protection, but the independent roles of MeV-specific antibody and T cells have not been identified. In this study, macaques immunized with LAV through a nebulizer and a mouthpiece developed MeV-specific T-cell responses but not neutralizing antibodies. Upon challenge with wild-type MeV, these animals developed rashes and viremias similar to those in naive animals but cleared viral RNA from blood 25 to 40 days faster. The nebulizer-immunized animals also had more robust MeV-specific CD4+and CD8+T-cell responses than the naive animals after challenge, characterized by a higher number and better durability of gamma interferon (IFN-γ)-producing cells. Induction of MeV-specific circulating CD4+and CD8+T cells capable of producing multiple cytokines correlated with clearance of viral RNA in the nebulizer-immunized macaques. These studies demonstrated that MeV-specific T-cell immunity alone did not prevent measles, but T-cell priming enhanced the magnitude, durability, and polyfunctionality of MeV-specific T cells after challenge infection and correlated with more rapid clearance of MeV RNA.

IMPORTANCEThe components of vaccine-induced immunity necessary for protection from infection and disease have not been clearly identified for most vaccines. Vaccine development usually focuses on induction of antibody, but T-cell-based vaccines are also under development. The live attenuated measles vaccine (LAV) given subcutaneously induces both T cells and neutralizing antibody and provides solid protection from infection. LAV delivered to the upper respiratory tract through a nebulizer and mouthpiece induced a T-cell response but no neutralizing antibody. These T-cell-primed macaques demonstrated no protection from rash or viremia when challenged with wild-type MeV, but viral RNA was cleared more rapidly than in unimmunized animals. Thus, T-cell immunity did not protect from infection or acute disease but facilitated virus clearance during recovery. These studies demonstrate the importance and independent roles of T cells and antibody in protection and recovery from measles.
Congenital disorders of glycosylation with neonatal presentation
Authors: Resende Catarina , Carvalho Carmen , Alegria Artur , Oliveira Dulce , Quelhas Dulce , Bandeira Anabela , Proença Elisa
Published: April 2014

Congenital disorders of glycosylation (CDG) are a group of hereditary diseases characterised by deficiency of enzymes involved in proteins glycosylation. We describe the clinical case of a neonate with CDG type 1a, nowadays designated phosphomannomutase 2 (PMM2)-CDG. Physical examination showed an abnormal facies, axial hypotonia, abnormal fat distribution, inverted nipples, non-palpable testicles and arachnodactyly. Progressive multiple system organ involvement and worsening of hypertrophic cardiomyopathy occurred. Metabolic study revealed a CDG disturbance, which was confirmed by genetic study. The following mutations were identified: c.193G>T; p.D65Y and c.470T>C; p.F157S. Clinical deterioration was inevitable with multisystemic failure and death. CDG represents a challenge for physicians due to multiple organ involvement, and heterogeneous clinical manifestations. The neonatal form is usually associated with the worst prognosis.
Aspergilloma and massive haemoptysis
Authors: Ding Wern Yew , Chan Tze , Yadavilli Rajesh Kumar , McWilliams Richard
Published: April 2014

A 40-year-old homeless woman who was a known intravenous drug user and heroin smoker, presented with massive haemoptysis. Initial CT-pulmonary angiogram (CT-PA) did not show active haemorrhage but found an opacity in a right upper lobe cavity likely to represent a mycetoma. She was started on antifungal therapy but haemoptysis persisted and bronchial angiography was performed. Again no active haemorrhage was identified but abnormal vasculature was seen supplying the right upper lobe. This was empirically embolised with particles which did not improve her symptoms. A subsequent CT-PA identified a pulmonary artery pseudoaneurysm in the cavity wall which was successfully embolised. There was no further haemoptysis and a repeat CT-PA 3 weeks later showed continuing occlusion of the pulmonary artery aneurysm. Investigations for tuberculosis were negative and she was discharged clinically well and on long-term antifungal therapy.
Haemoptysis in an intravenous drug user: injection needle impacted in the left main bronchus
Authors: Shah Asif R , Smyth Louise , Tolan Michael , Bartosik Waldemar
Published: April 2014

We report a case of a 35-year-old man who presented with 4-week history of haemoptysis, with a history of intravenous drug use. There was no other significant medical or surgical history and no recollection of any foreign body aspiration. Chest X-ray and CT scan showed 40 mm long needle in left main bronchus, partly lying outside the bronchus into the mediastinum. Flexible and rigid bronchoscopes proved to be unsuccessful in retrieving the needle. We proceeded with left posterolateral thoracotomy and the left main bronchus was explored to take out this 21-gauge (green) injection needle. The distal half of the needle with the sharp end was lying in the mediastinum piercing through the bronchial wall. Surgery was uneventful with good postoperative recovery and the patient was discharged 4 days later.