bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effect of Aggressive Rosuvastatin Treatment on Steroid Hormone Production in Men with Coronary Artery Disease
Authors: Krysiak Robert , Okopien Boguslaw 
Published: November 2013

AbstractMost steroid hormones are produced from cholesterol contained in low‐density lipoproteins, which is uptaken by the gonads and adrenal cortex, and used as a substrate for steroidogenesis. Theoretically, in states associated with very low‐density lipoprotein (LDL) cholesterol levels, cholesterol conversion to steroid hormones may be impaired. The study included 15 men with coronary artery disease, in whom initial statin treatment had been unsuccessful and therefore was replaced with rosuvastatin (20–40 mg daily). Although in 11 patients, rosuvastatin decreased plasma LDL cholesterol levels to below 70 mg/dL, the drug only moderately reduced testosterone levels and increased gonadotropin levels, as well as insignificantly increased plasma ACTH levels. Aggressive rosuvastatin treatment did not affect plasma cortisol and dehydroepiandrosterone sulphate levels, and urine free cortisol. Our results suggest that intensive rosuvastatin treatment is associated with only small changes in adrenal and testicular steroidogenesis.
Assisted Reproduction and Distributive Justice
Authors: Panitch Vida 
Published: November 2013

AbstractThe Canadian province of Quebec recently amended its Health Insurance Act to cover the costs of In Vitro Fertilization (IVF). The province of Ontario recently de‐insured IVF. Both provinces cited cost‐effectiveness as their grounds, but the question as to whether a public health insurance system ought to cover IVF raises the deeper question of how we should understand reproduction at the social level, and whether its costs should be a matter of individual or collective responsibility. In this article I examine three strategies for justifying collective provisions in a liberal society and assess whether public reproductive assistance can be defended on any of these accounts. I begin by considering, and rejecting, rights‐based and needs‐based approaches. I go on to argue that instead we ought to address assisted reproduction from the perspective of the contractarian insurance‐based model for public health coverage, according to which we select items for inclusion based on their unpredictability in nature and cost. I argue that infertility qualifies as an unpredictable incident against which rational agents would choose to insure under ideal conditions and that assisted reproduction is thereby a matter of collective responsibility, but only in cases of medical necessity or inability to pay. The policy I endorse by appeal to this approach is a means‐tested system of coverage resembling neither Ontario nor Quebec's, and I conclude that it constitutes a promising alternative worthy of serious consideration by bioethicists, political philosophers, and policy‐makers alike.
Policy on Synthetic Biology: Deliberation, Probability, and the Precautionary Paradox
Authors: Wareham Christopher , Nardini Cecilia 
Published: November 2013

AbstractSynthetic biology is a cutting‐edge area of research that holds the promise of unprecedented health benefits. However, in tandem with these large prospective benefits, synthetic biology projects entail a risk of catastrophic consequences whose severity may exceed that of most ordinary human undertakings. This is due to the peculiar nature of synthetic biology as a ‘threshold technology’ which opens doors to opportunities and applications that are essentially unpredictable. Fears about these potentially unstoppable consequences have led to declarations from civil society groups calling for the use of a precautionary principle to regulate the field. Moreover, the principle is prevalent in law and international agreements. Despite widespread political recognition of a need for caution, the precautionary principle has been extensively criticized as a guide for regulatory policy. We examine a central objection to the principle: that its application entails crippling inaction and incoherence, since whatever action one takes there is always a chance that some highly improbable cataclysm will occur. In response to this difficulty, which we call the ‘precautionary paradox,’ we outline a deliberative means for arriving at threshold of probability below which potential dangers can be disregarded. In addition, we describe a Bayesian mechanism with which to assign probabilities to harmful outcomes. We argue that these steps resolve the paradox. The rehabilitated PP can thus provide a viable policy option to confront the uncharted waters of synthetic biology research.
The Melbourne Consensus Statement on the early detection of prostate cancer
Authors: Murphy Declan G. , Ahlering Thomas , Catalona William J. , Crowe Helen , Crowe Jane , Clarke Noel , Cooperberg Matthew , Gillatt David , Gleave Martin , Loeb Stacy , Roobol Monique , Sartor Oliver , Pickles Tom , Wootten Addie , Walsh Patrick C. , Costello Anthony J. 
Published: November 2013

Various conflicting guidelines and recommendations about prostate cancer screening and early detection have left both clinicians and their patients quite confused. At the Prostate Cancer World Congress held in Melbourne in August 2013, a multidisciplinary group of the world's leading experts in this area gathered together and generated this set of consensus statements to bring some clarity to this confusion.
The five consensus statements provide clear guidance for clinicians counselling their patients about the early detection of prostate cancer.
Culturing muscle fibres in hanging drop: A novel approach to solve an old problem
Authors: Archacka Karolina , Pozzobon Michela , Repele Andrea , Rossi Carlo Alberto , Campanella Michelangelo , De Coppi Paolo 
Published: November 2013

Background InformationThe satellite cells (SCs) associated with muscle fibres play a key role in postnatal growth and regeneration of skeletal muscle. Commonly used methods of isolation and in vitro culture of SCs lead to the mixture of their subpopulations that exist within muscle. To solve this problem, we used the well established technique, the hanging drop system, to culture SCs in a three‐dimensional environment and thus, to monitor them in their original niche.ResultsUsing hanging drop technique, we were able to culture SCs associated with the fibre at least for 9 days with one transfer of fibres to the fresh drops. In comparison, in the classical method of myofibres culture, that is, on the dishes coated with Matrigel, SCs leave the fibres within 3 days after the isolation. Cells cultured in both systems differed in expression of Pax7 and MyoD. While almost all cells cultured in adhesion system expressed MyoD before the fifth day of the culture, the majority of SCs cultured in hanging drop still maintained expression of Pax7 and were not characterised by the presence of MyoD. Among the cells cultured with single myofibre for up to 9 days, we identified two different subclones of SCs: low proliferative clone and high proliferative clone, which differed in proliferation rate and membrane potential.ConclusionsThe hanging drop enables the myofibres to be kept in suspension for at least 9 days, and thus, allows SCs and their niche to interact each other for prolonged time. In a consequence, SCs cultured in hanging drop maintain expression of Pax7 while those cultured in a traditional adhesion culture, that is, devoid of signals from the original niche, activate and preferentially undergo differentiation as manifested by expression of MyoD. Thus, the innovative method of SCs culturing in the hanging drop system may serve as a useful tool to study the fate of different subpopulations of these cells in their anatomical location and to determine reciprocal interactions between them and their niche.
European Treatment and Outcome Study score does not predict imatinib treatment response and outcome in chronic myeloid leukemia patients
Authors: Yamamoto Eri , Fujisawa Shin , Hagihara Maki , Tanaka Masatsugu , Fujimaki Katsumichi , Kishimoto Kumiko , Hashimoto Chizuko , Itabashi Megumi , Ishibashi Daisuke , Nakajima Yuki , Tachibana Takayoshi , Kawasaki Rika , Kuwabara Hideyuki , Koharazawa Hideyuki , Yamazaki Etsuko , Tomita Naoto , Sakai Rika , Fujita Hiroyuki , Kanamori Heiwa , Ishigatsubo Yoshiaki 
Published: November 2013

The Sokal and Hasford scores were developed in the chemotherapy and interferon era and are widely used as prognostic indicators in patients with chronic myeloid leukemia (CML). Recently, a new European Treatment and Outcome Study (EUTOS) scoring system was developed. We performed a multicenter retrospective study to validate the effectiveness of each of the three scoring systems. The study cohort included 145 patients diagnosed with CML in chronic phase who were treated with imatinib. In the EUTOS low‐ and high‐risk groups, the cumulative incidence of complete cytogenetic response (CCyR) at 18 months was 86.9% and 87.5% (P = 0.797) and the 5‐year overall survival rate was 92.6% and 93.3% (P = 0.871), respectively. The cumulative incidence of CCyR at 12 months, 5‐year event‐free survival and 5‐year progression‐free survival were not predicted using the EUTOS scoring system. However, there were significant differences in both the Sokal score and Hasford score risk groups. In our retrospective validation study, the EUTOS score did not predict the prognosis of patients with CML in chronic phase treated with imatinib.
Rituximab is associated with improved survival in cardiac allograft patients with antibody‐mediated rejection: a single center review
Authors: Ravichandran Ashwin K. , Schilling Joel D. , Novak Eric , Pfeifer John , Ewald Gregory A. , Joseph Susan M. 
Published: November 2013

AbstractAntibody‐mediated rejection (AMR) after cardiac transplantation is associated with significant mortality, and the optimal treatment of this condition is poorly defined. Rituximab has been used successfully for the treatment for antibody‐mediated diseases; however, its role in AMR is unclear. We review our experience with rituximab in patients with cardiac allograft AMR. We conducted a retrospective analysis of cardiac transplant patients with a diagnosis of AMR from 2001 to 2011. Inclusion criteria were clinical suspicion of rejection with the presence of C4d complement staining on endomyocardial biopsy and the absence of cellular rejection of grade 2R or greater. Patients were divided into Rituximab and NoRituximab groups. The primary endpoint was all‐cause mortality. Secondary endpoints were infection, change in ejection fraction (EF), and rehospitalization. Thirty‐three patients met inclusion criteria, of whom 13 received rituximab and 20 did not. Baseline characteristics were similar between groups. Kaplan–Meier curves for a three‐yr follow‐up period demonstrate improved survival in the Rituximab group (p = 0.0089). There were no differences in secondary endpoints. We found that rituximab therapy was associated with improved survival in cardiac allograft AMR. Further prospective, randomized studies in larger patient populations are needed to confirm this finding and to define ideal timing for rituximab administration.
The law of diminishing returns: woodland birds respond to native vegetation cover at multiple spatial scales and over time
Authors: Cunningham Ross B. , Lindenmayer David B. , Crane Mason , Michael Damian R. , Barton Philip S. , Gibbons Philip , Okada Sachiko , Ikin Karen , Stein John A. R. 
Published: November 2013

AbstractAimTo quantify at multiple spatial scales: (1) spatial dependence in several measures of aggregate bird biodiversity, (2) the role of native vegetation cover in explaining variation in aggregate bird biodiversity and (3) relationships between change over 8 years in bird diversity and changes in native vegetation.LocationSouth‐easternAustralia.MethodsWe gathered data on birds between 2002 and 2010 on 184 (2 ha) sites nested within 46 (1000 ha) farms nested within 23 (10,000 ha) landscapes. We statistically estimated spatial and temporal components of variation at the landscape, farm and site scale for several composite indices of bird diversity. Second, we modelled the relationships between aggregate bird biodiversity and log % of native vegetation cover at each spatial scale and over time.ResultsVariation in bird biodiversity at the landscape, farm and site scale exhibited significant, intrinsic scale‐specific effects. This dependence was largely accounted for by native vegetation cover with aggregate biodiversity increasing with increasing native vegetation cover at each spatial scale and over time. Every doubling of % cover resulted in an increase of 3.1, 2.3 and 0.7 species per landscape, farm and site, respectively. Similar statistically significant positive relationship between proxy abundance and richness of species of conservation concern and % cover of vegetation were also found. Species richness at the site scale also was related to vegetation cover in the surrounding landscape. Over the period of study, relationships between changes in bird biodiversity and changes in vegetation cover were not statistically significant.Main conclusionsWe used ‘diminishing returns’ response curves to model relationships between measures of bird biodiversity and vegetation cover at all spatial scales. Absolute gains in biodiversity per unit increase in vegetation cover were greatest at relatively low amounts of vegetation cover. These results can help prioritize investment strategies such as replanting native vegetation under agri‐environment schemes.
Considerations for a Human Rights Impact Assessment of a Population Wide Treatment for HIV Prevention Intervention
Authors: Hanefeld Johanna , Bond Virginia , Seeley Janet , Lees Shelley , Desmond Nicola 
Published: November 2013

AbstractIncreasing attention is being paid to the potential of anti‐retroviral treatment (ART) for HIV prevention. The possibility of eliminating HIV from a population through a universal test and treat intervention, where all people within a population are tested for HIV and all positive people immediately initiated on ART, as part of a wider prevention intervention, was first proposed in 2009. Several clinical trials testing this idea are now in inception phase. An intervention which relies on universally testing the entire population for HIV will pose challenges to human rights, including obtaining genuine consent to testing and treatment. It also requires a context in which people can live free from fear of stigma, discrimination and violence, and can access services they require. These challenges are distinct from the field of medical ethics which has traditionally governed clinical trials and focuses primarily on patient researcher relationship. This paper sets out the potential impact of a population wide treatment as prevention intervention on human rights. It identifies five human right principles of particular relevance: participation, accountability, the right to health, non‐discrimination and equality, and consent and confidentiality. The paper proposes that explicit attention to human rights can strengthen a treatment as prevention intervention, contribute to mediating likely health systems challenges and offer insights on how to reach all sections of the population.
An Australian population study of factors associated with MRI patterns in cerebral palsy
Authors: Reid Susan M , Dagia Charuta D , Ditchfield Michael R , Carlin John B , Meehan Elaine M , Reddihough Dinah S 
Published: November 2013

AimThe aim of this study was to describe the distribution of magnetic resonance imaging (MRI) patterns in a large population sample of children with cerebral palsy (CP) and to examine associations between MRI patterns, and antenatal and perinatal variables.MethodData were retrieved from the Victorian CP Register for 884 children (527 males, 357 females) born between 1999 and 2006. Postneonatal MRI was classified for 594 children. For 563 children (329 males, 234 females) for whom classification was to a single MRI pattern, the frequency of each variable was compared between patterns and with the population frequency.ResultsWhite matter injury was the most common MRI pattern (45%), followed by grey matter injury (14%), normal imaging (13%), malformations (10%), focal vascular insults (9%), and miscellaneous patterns (7%). Parity, birth gestation, level of neonatal care, Apgar score, and time to established respiration varied between MRI patterns (p<0.01). Nulliparity was most strongly associated with focal vascular insults, whereas multiparity was associated only with malformations. Grey matter injury was not associated with birth in a tertiary unit, but was strongly associated with severe perinatal compromise. The frequency of neonatal seizures and of nursery admissions was lowest among children with malformations.InterpretationAs known risk factors for CP are differentially associated with specific MRI patterns, future exploration of causal pathways might be facilitated when performed in pathogenically defined groups.
Efficacy and safety of teneligliptin added to glimepiride in Japanese patients with type 2 diabetes mellitus: a randomized, double‐blind, placebo‐controlled study with an open‐label, long‐term extension
Authors: Kadowaki T. , Kondo K. 
Published: November 2013

AimsTo assess the efficacy and safety of teneligliptin in combination with glimepiride in Japanese patients with type 2 diabetes mellitus (T2DM) inadequately controlled with glimepiride monotherapy.MethodsIn the initial 12‐week, double‐blind, placebo‐controlled, parallel‐group period, 194 patients [haemoglobin A1c (HbA1c): 8.4 ± 0.8%; fasting plasma glucose (FPG): 164.2 ± 28.1 mg/dl] were randomized to either teneligliptin 20 mg or placebo once daily while continuing stable glimepiride therapy. This randomized period was then followed by a 40‐week, open‐label period, where all patients received teneligliptin once daily. The primary endpoint was the change in HbA1c from baseline to week 12.ResultsTeneligliptin reduced HbA1c significantly compared with placebo at week 12. The placebo‐subtracted change in HbA1c was −1.0 ± 0.1% [least‐squares (LS) mean ± s.e., p < 0.001]. Teneligliptin also significantly reduced FPG and 2‐h postprandial glucose (PPG) as compared with placebo at week 12; the placebo‐subtracted changes were −27.1 ± 3.2 and −49.1 ± 6.2 mg/dl (LS mean ± s.e., both p < 0.001), respectively. The blood glucose‐lowering effects were sustained throughout the 40‐week open‐label period. The incidence rates of adverse events and adverse drug reactions, including hypoglycaemia, during the double‐blind randomized period were similar in both groups. Therefore, teneligliptin was generally well tolerated when used in combination with glimepiride.ConclusionsThe addition of teneligliptin was effective and generally well tolerated in Japanese patients with T2DM inadequately controlled with glimepiride monotherapy. The improvements in glycaemic control were maintained for up to 52 weeks.
Cyclooxygenase‐2 in epilepsy
Authors: Rojas Asheebo , Jiang Jianxiong , Ganesh Thota , Yang Myung‐Soon , Lelutiu Nadia , Gueorguieva Paoula , Dingledine Raymond 
Published: November 2013

SummaryEpilepsy is one of the more prevalent neurologic disorders in the world, affecting approximately 50 million people of different ages and backgrounds. Epileptic seizures propagating through both lobes of the forebrain can have permanent debilitating effects on a patient's cognitive and somatosensory brain functions. Epilepsy, defined by the sporadic occurrence of spontaneous recurrent seizures (SRS), is often accompanied by inflammation of the brain. Pronounced increases in the expression of key inflammatory mediators (e.g., interleukin ‐1β [IL‐1β], tumor necrosis factor alpha [TNFα], cyclooxygenase‐2 [COX‐2], and C‐X‐C motif chemokine 10 [CXCL10]) after seizures may cause secondary damage in the brain and increase the likelihood of repetitive seizures. The COX‐2 enzyme is induced rapidly during seizures. The increased level of COX‐2 in specific areas of the epileptic brain can help to identify regions of seizure‐induced brain inflammation. A good deal of effort has been expended to determine whether COX‐2 inhibition might be neuroprotective and represent an adjunct therapeutic strategy along with antiepileptic drugs used to treat epilepsy. However, the effectiveness of COX‐2 inhibitors on epilepsy animal models appears to depend on the timing of administration. With all of the effort placed on making use of COX‐2 inhibitors as therapeutic agents for the treatment of epilepsy, inflammation, and neurodegenerative diseases there has yet to be a selective and potent COX‐2 inhibitor that has shown a clear therapeutic outcome with acceptable side effects.
Evaluation of all non‐synonymous single nucleotide polymorphisms (SNPs) in the genes encoding human deoxyribonuclease I and I‐like 3 as a functional SNP potentially implicated in autoimmunity
Authors: Ueki Misuzu , Kimura‐Kataoka Kaori , Takeshita Haruo , Fujihara Junko , Iida Reiko , Sano Rie , Nakajima Tamiko , Kominato Yoshihiko , Kawai Yasuyuki , Yasuda Toshihiro 
Published: November 2013

The objectives of this study were to evaluate all the non‐synonymous single nucleotide polymorphisms (SNPs) in the DNase I and DNase I‐like 3 (1L3) genes potentially implicated in autoimmune diseases as a functional SNP in terms of alteration of the activity levels. We examined the genotype distributions of the 32 and 20 non‐synonymous SNPs in DNASE1 and DNASE1L3, respectively, in three ethnic groups, and the effect of these SNPs on the DNase activities. Among a total of 44 and 25 SNPs including those characterized in our previous studies [Yasuda et al., Int J Biochem Cell Biol42 (2010) 1216–1225; Ueki et al. Electrophoresis32 (2012) 1465–1472], only four and one, respectively, exhibited genetic heterozygosity in one or all of the ethnic groups examined. On the basis of alterations in the activity levels resulting from the corresponding amino acid substitutions, 11 activity‐abolishing and 11 activity‐reducing SNPs in DNASE1 and two activity‐abolishing and five activity‐reducing SNPs in DNASE1L3 were confirmed as a functional SNP. Phylogenetic analysis showed that all of the amino acid residues in activity‐abolishing SNPs were completely or well conserved in animal DNase I and 1L3 proteins. Although almost all non‐synonymous SNPs in both genes that affected the catalytic activity showed extremely low genetic heterogeneity, it seems plausible that a minor allele of 13 activity‐abolishing SNPs producing a loss‐of‐function variant in both the DNase genes would be a direct genetic risk factor for autoimmune diseases. These findings may have clinical implications in relation to the prevalence of autoimmune diseases.