bluuebunny/crossref_metadata_2025_split huggingface dataset:
Apoptosis, mastocytosis, and diminished adipocytokine gene expression accompany reduced epididymal fat mass in long-standing diet-induced obese mice
Authors: Altintas Mehmet M , Rossetti Maria A , Nayer Behzad , Puig Alvaro , Zagallo Patricia , Ortega Luis M , Johnson Kevin B , McNamara George , Reiser Jochen , Mendez Armando J , Nayer Ali 
Published: November 2011

Abstract

Background
Obesity is characterized by increased cell death and inflammatory reactions in the adipose tissue. Here, we explored pathophysiological alterations taking place in the adipose tissue in long-standing obesity. In the epididymal fat of C57BL/6 mice fed a high-fat diet for 20 weeks, the prevalence and distribution of dead adipocytes (crown-like structures), mast cells (toluidine blue, mMCP6), macrophages (F4/80), and apoptotic cells (cleaved caspase-3) were measured. Moreover, gene and/or protein expression of several adipocytokines (leptin, adiponectin, TNF-α, IL-10, IL-6, MCP-1), F4/80, mMCP6, cleaved caspase-3 were determined.

Results
We observed that the epididymal fat mass was lower in obese than in lean mice. In obese mice, the epididymal fat mass correlated inversely with body weight and liver mass. Dead adipocytes, mast cells, macrophages, and apoptotic cells were abundant in the epididymal fat of obese mice, especially in the rostral vs. caudal zone. Accordingly, mMCP6, F4/80, and cleaved caspase-3 gene and/or protein expression was increased. Conversely, adiponectin, leptin, IL-6, and MCP-1 gene expression levels were lower in the epididymal fat of obese than lean mice. Although TNF-α and IL-10 gene expression was higher in the epididymal fat of obese mice, their expression relative to F4/80 and mMCP6 expression were lower in the heavily infiltrated rostral than caudal zone.

Conclusions
This study demonstrates that in mice with long-standing obesity diminished gene expression of several adipocytokines accompany apoptosis and reduced mass of the epididymal fat. Our findings suggest that this is due to both increased prevalence of dead adipocytes and altered immune cell activity. Differential distribution of metabolically challenged adipocytes is indicative of the presence of biologically diverse zones within the epididymal fat.
Embryotoxicity assays for leached components from dental restorative materials
Authors: Libonati Antonio , Marzo Giuseppe , Klinger Francesca G , Farini Donatella , Gallusi Gianni , Tecco Simona , Mummolo Stefano , De Felici Massimo , Campanella Vincenzo 
Published: November 2011

Abstract

Background
Currently, there are no suitable assays available to evaluate the embryotoxicity of leached components from restorative dental materials.

Methods
The effect of the medium conditioned by composites and amalgam on mouse blastocysts in vitro was tested. The materials were also subcutaneously implanted, and the effect of the medium supplemented with serum from the host blood was evaluated in the embryotoxicity assay. The embryo implantation rate in the material-transplanted mothers was also evaluated.

Results
The results show that while the culture in media conditioned by amalgams did not affect blastocyst development, the medium conditioned by composites caused blastocyst degeneration and apoptosis. The development of blastocysts in a medium containing serum obtained from animals after transplantation was, however, without effect. Finally, inconsistent reduction in the implantation rate in transplanted mothers was observed.

Conclusions
In this study, we provide examples of in vitro and in vivo tests that may be used to evaluate embryotoxicity for dental materials. Our results show that leached components from our composite-material induced embryotoxicity in vitro, however, no toxicity was observed when subcutaneously implanted in vivo. This highlights the necessity of integrated in vitro and in vivo tests for valuable predictive estimation of embryotoxicity for complex materials.
Gold-silver alloy nanoshells: a new candidate for nanotherapeutics and diagnostics
Authors: Gheorghe Dana E , Cui Lili , Karmonik Christof , Brazdeikis Audrius , Penaloza Jose M , Young Joseph K , Drezek Rebekah A , Bikram Malavosklish 
Published: November 2011

AbstractWe have developed novel gold-silver alloy nanoshells as magnetic resonance imaging (MRI) dual T1 (positive) and T2 (negative) contrast agents as an alternative to typical gadolinium (Gd)-based contrast agents. Specifically, we have doped iron oxide nanoparticles with Gd ions and sequestered the ions within the core by coating the nanoparticles with an alloy of gold and silver. Thus, these nanoparticles are very innovative and have the potential to overcome toxicities related to renal clearance of contrast agents such as nephrogenic systemic fibrosis. The morphology of the attained nanoparticles was characterized by XRD which demonstrated the successful incorporation of Gd(III) ions into the structure of the magnetite, with no major alterations of the spinel structure, as well as the growth of the gold-silver alloy shells. This was supported by TEM, ICP-AES, and SEM/EDS data. The nanoshells showed a saturation magnetization of 38 emu/g because of the presence of Gd ions within the crystalline structure with r1 and r2 values of 0.0119 and 0.9229 mL mg-1 s-1, respectively (Au:Ag alloy = 1:1). T1- and T2-weighted images of the nanoshells showed that these agents can both increase the surrounding water proton signals in the T1-weighted image and reduce the signal in T2-weighted images. The as-synthesized nanoparticles exhibited strong absorption in the range of 600-800 nm, their optical properties being strongly dependent upon the thickness of the gold-silver alloy shell. Thus, these nanoshells have the potential to be utilized for tumor cell ablation because of their absorption as well as an imaging agent.
Naturally occurring genotype 2b/1a hepatitis C virus in the United States
Authors: Bhattacharya Dipankar , Accola Molly A , Ansari Israr H , Striker Rob , Rehrauer William M 
Published: November 2011

Abstract

Background
Hepatitis C Virus (HCV) infected patients are frequently repeatedly exposed to the virus, but very few recombinants between two genotypes have been reported.

Findings
We describe the discovery of an HCV recombinant using a method developed in a United States clinical lab for HCV genotyping that employs sequencing of both 5' and 3' portions of the HCV genome. Over twelve months, 133 consecutive isolates were analyzed, and a virus from one patient was found with discordant 5' and 3' sequences suggesting it was a genotype 2b/1a recombinant. We ruled out a mixed infection and mapped a recombination point near the NS2/3 cleavage site.

Conclusions
This unique HCV recombinant virus described shares some features with other recombinant viruses although it is the only reported recombinant of a genotype 2 with a subtype 1a. This recombinant represents a conundrum for current clinical treatment guidelines, including treatment with protease inhibitors. This recombinant is also challenging to detect by the most commonly employed methods of genotyping that are directed primarily at the 5' structural portion of the HCV genome.
DnaJ homolog Hdj2 Facilitates Japanese Encephalitis Virus Replication
Authors: Wang Robert Yung-Liang , Huang Yu-Ru , Chong Ka-Man , Hung Chun-Yu , Ke Zhi-Long , Chang Ruey-Yi 
Published: November 2011

Abstract

Background
Japanese encephalitis virus (JEV) is a member of the mosquito-borne Flaviviridae family of viruses that causes human encephalitis. Upon infection of a new host, replication of viral RNA involves not only the viral RNA-dependent RNA polymerase (RdRp), but also host proteins. Host factors involved in JEV replication are not well characterized.

Results
We identified Hdj2, a heat-shock protein 40 (Hsp40)/DnaJ homolog, from a mouse brain cDNA library interacting with JEV nonstructural protein 5 (NS5) encoding viral RdRp using yeast two-hybrid system. Specific interaction of Hdj2 with NS5 was confirmed by coimmunoprecipitation and colocalization in JEV-infected cells. Overexpression of Hdj2 in JEV-infected cells led to an increase of RNA synthesis, and the virus titer was elevated approximately 4.5- to 10-fold. Knocking down of Hdj2 by siRNA reduced the virus production significantly.

Conclusions
We conclude that Hdj2 directly associates with JEV NS5 and facilitates viral replication. This study is the first to demonstrate Hdj2 involved in JEV replication, providing insight into a potential therapeutic target and cell-based vaccine development of JEV infection.
Cough management: a practical approach
Authors: De Blasio Francesco , Virchow Johann C , Polverino Mario , Zanasi Alessandro , Behrakis Panagiotis K , Kilinç Gunsely , Balsamo Rossella , De Danieli Gianluca , Lanata Luigi 
Published: November 2011

Abstract
Cough is one of the most common symptoms for which patients seek medical attention from primary care physicians and pulmonologists. Cough is an important defensive reflex that enhances the clearance of secretions and particles from the airways and protects the lower airways from the aspiration of foreign materials. Therapeutic suppression of cough may be either disease-specific or symptom related. The potential benefits of an early treatment of cough could include the prevention of the vicious cycle of cough. There has been a long tradition in acute cough, which is frequently due to upper respiratory tract infections, to use symptom-related anti-tussives. Suppression of cough (during chronic cough) may be achieved by disease-specific therapies, but in many patients it is often necessary to use symptomatic anti-tussives, too. According to the current guidelines of the American College of Chest Physician on "Cough Suppressants and Pharmacologic Protussive Therapy" and additional clinical trials on the most frequent anti-tussive drugs, it should be possible to diagnose and treat cough successfully in a majority of cases. Among drugs used for the symptomatic treatment of cough, peripherally acting anti-tussives such as levodropropizine and moguisteine show the highest level of benefit and should be recommended especially in children. By improving our understanding of the specific effects of these anti-tussive agents, the therapeutic use of these drugs may be refined. The present review provides a summary of the most clinically relevant anti-tussive drugs in addition to their potential mechanism of action.
The genome diversity and karyotype evolution of mammals
Authors: Graphodatsky Alexander S , Trifonov Vladimir A , Stanyon Roscoe 
Published: November 2011

AbstractThe past decade has witnessed an explosion of genome sequencing and mapping in evolutionary diverse species. While full genome sequencing of mammals is rapidly progressing, the ability to assemble and align orthologous whole chromosome regions from more than a few species is still not possible. The intense focus on building of comparative maps for companion (dog and cat), laboratory (mice and rat) and agricultural (cattle, pig, and horse) animals has traditionally been used as a means to understand the underlying basis of disease-related or economically important phenotypes. However, these maps also provide an unprecedented opportunity to use multispecies analysis as a tool for inferring karyotype evolution. Comparative chromosome painting and related techniques are now considered to be the most powerful approaches in comparative genome studies. Homologies can be identified with high accuracy using molecularly defined DNA probes for fluorescencein situhybridization (FISH) on chromosomes of different species. Chromosome painting data are now available for members of nearly all mammalian orders. In most orders, there are species with rates of chromosome evolution that can be considered as 'default' rates. The number of rearrangements that have become fixed in evolutionary history seems comparatively low, bearing in mind the 180 million years of the mammalian radiation. Comparative chromosome maps record the history of karyotype changes that have occurred during evolution. The aim of this review is to provide an overview of these recent advances in our endeavor to decipher the karyotype evolution of mammals by integrating the published results together with some of our latest unpublished results.
Passive leg raising can predict fluid responsiveness in patients placed on venovenous extracorporeal membrane oxygenation
Authors: Guinot Pierre-Grégoire , Zogheib Elie , Detave Mathieu , Moubarak Mona , Hubert Vincent , Badoux Louise , Bernard Eugénie , Besserve Patricia , Caus Thierry , Dupont Hervé 
Published: November 2011

Abstract
Introduction
In ICUs, fluid administration is frequently used to treat hypovolaemia. Because volume expansion (VE) can worsen acute respiratory distress syndrome (ARDS) and volume overload must be avoided, predictive indicators of fluid responsiveness are needed. The purpose of this study was to determine whether passive leg raising (PLR) can be used to predict fluid responsiveness in patients with ARDS treated with venovenous extracorporeal membrane oxygenation (ECMO).

Methods
We carried out a prospective study in a university hospital surgical ICU. All patients with ARDS treated with venovenous ECMO and exhibiting clinical and laboratory signs of hypovolaemia were enrolled. We measured PLR-induced changes in stroke volume (ΔPLRSV) and cardiac output (ΔPLRCO) using transthoracic echocardiography. We also assessed PLR-induced changes in ECMO pump flow (ΔPLRPO) and PLR-induced changes in ECMO pulse pressure (ΔPLRPP) as predictors of fluid responsiveness. Responders were defined by an increase in stroke volume (SV) > 15% after VE.

Results
Twenty-five measurements were obtained from seventeen patients. In 52% of the measurements (n = 13), SV increased by > 15% after VE (responders). The patients' clinical characteristics appeared to be similar between responders and nonresponders. In the responder group, PLR significantly increased SV, cardiac output and pump flow (P < 0.001). ΔPLRSV values were correlated with VE-induced SV variations (r2 = 0.72, P = 0.0001). A 10% increased ΔPLRSV predicted fluid responsiveness with an area under the receiver operating characteristic curve (AUC) of 0.88 ± 0.07 (95% confidence interval (CI95): 0.69 to 0.97; P < 0.0001), 62% sensitivity and 92% specificity. On the basis of AUCs of 0.62 ± 0.11 (CI95: 0.4 to 0.8; P = 0.31) and 0.53 ± 0.12 (CI95: 0.32 to 0.73, P = 0.79), respectively, ΔPLRPP and ΔPLRPO did not predict fluid responsiveness.

Conclusions
In patients treated with venovenous ECMO, a > 10% ΔPLRSV may predict fluid responsiveness. ΔPLRPP and ΔPLRPO cannot predict fluid responsiveness.
Payment by results for learning disability services: a model for the future?
Authors: Bhaumik Sabyasachi , Devapriam John , Gangadharan Satheesh , Hiremath Avinash , Roy Ashok 
Published: November 2011

SummaryPayment by results (PbR) for mental health services is currently being piloted with the aim of arriving at a national tariff for mental health by 2013/2014. The Department of Health has also established two pilot sites to consider applicability of PbR for learning disability services. This article outlines the concept of PbR in learning disability services and describes the progress of the pilot work being undertaken in this area.
Implementing legislative changes on young people's consent to treatment: a guide for trainers
Authors: Huline-Dickens Sarah 
Published: November 2011

SummaryThis article reviews the recent changes in the law in England and Wales relating to consent to treatment for young people, in particular the Mental Capacity Act 2005 and the 2007 amendments to the Mental Health Act 1983. Using a fictitious case study, it offers a structured approach to the application of these new items of legislation that could be useful to trainers and their trainees.
Early intervention in psychosis: strengths and limitations of services
Authors: Murphy Brendan P. , Brewer Warrick J. 
Published: November 2011

SummaryEarly intervention services were established on the basis of a number of fundamental principles, including the notions that intervening in the early stages of psychosis alters illness trajectory and prognosis, that multicomponent interventions promote psychosocial recovery and reduce iatrogenic damage, and that early targeting of non-responders reduces treatment resistance. There is growing evidence of the benefits of specialised early intervention services. These include improved clinical, social and vocational outcomes, reduced in-patient stays and better engagement. Early intervention services can also significantly reduce the risk of a second episode and are highly valued by service users and carers. Duration of treatment appears to determine long-term outcome and there remains uncertainty about how long such intensive intervention should last and whether all patients need the same length of care. Budgetary constraints are pervasive and are particularly likely to affect prodrome clinics and community awareness programmes.
Transference: keeping mum or mummified?
Authors: Johnston James 
Published: November 2011

SummaryTransference reveals the mental state of the other to us through our countertransference. Our emotional responses to the transference relationship are different depending on the degree of disturbance evoked in us. Reflecting on our countertransference can convey emotional insight into the nature and meaning of the transference as a way of understanding the emotional experiences of the other.
Low serotonergic tone and elevated risk for substance misuse
Authors: Nutt David 
Published: November 2011

SummaryCox et al's paper addresses an issue that has long been assumed to be a central aspect of brain function – the interplay of different neurotransmitters – but for which we have very little evidence so far. It is currently unclear whether these findings will have implications for the treatment of those with cocaine or other substance dependence.
Clinical and cognitive characteristics of children with attention-deficit hyperactivity disorder, with and without copy number variants
Authors: Langley Kate , Martin Joanna , Agha Sharifah Shameem , Davies Charlotte , Stergiakouli Evangelia , Holmans Peter , Williams Nigel , Owen Michael , O'Donovan Michael , Thapar Anita 
Published: November 2011

BackgroundSubmicroscopic, rare chromosomal copy number variants (CNVs) contribute to neurodevelopmental disorders but it is not known whether they define atypical clinical cases.AimsTo identify whether large, rare CNVs in attention-deficit hyperactivity disorder (ADHD) are confined to a distinct clinical subgroup.MethodA total of 567 children with ADHD aged 5–17 years were recruited from community clinics. Psychopathology was assessed using the Child and Adolescent Psychiatric Assessment. Large, rare CNVs (>500 kb, <1% frequency) were defined from single nucleotide polymorphism data.ResultsCopy number variant carriers (13.6%) showed no differences from non-carriers in ADHD symptom severity, symptom type, comorbidity, developmental features, family history or pre-/ perinatal markers. The only significant difference was a higher rate of intellectual disability (24% v. 9%, χ2 = 15.5, P = 0.001). Most CNV carriers did not have intellectual disability.ConclusionsLarge, rare CNVs are not restricted to an atypical form of ADHD but may be more highly enriched in children with cognitive problems.
Improving end-of-life care for people with dementia
Authors: Sampson Elizabeth L. , Burns Alistair , Richards Mike 
Published: November 2011

SummaryOne in three adults over the age of 60 years will die with dementia. Most will have complex physical and psychological needs. Despite this, many people with dementia receive poor-quality end-of-life care. Recent government strategies have highlighted the importance of improved coordination and provision of services.
Factors that discourage medical students from pursuing a career in psychiatry
Authors: Curtis-Barton Marie T. , Eagles John M. 
Published: November 2011

Aims and methodThis cross-sectional study investigated the evolution of intentions among medical students to pursue a career in psychiatry and the factors that might discourage them from becoming a psychiatrist. A questionnaire survey was sent to medical students in years 1–5 at Aberdeen University.ResultsFrom 918 students, 467 (51%) returned useable responses. Proportions of students across the 5-year groups who definitely or probably intended to become psychiatrists remained fairly stable at 4–7%. In their final year, psychiatry remained a possible career option for a further 17% of students. The most potent discouraging factor was the perception of poor prognoses among psychiatric patients. Perceptions of a lack of scientific/evidence base reduced enthusiasm for becoming a psychiatrist. Issues relating to the prestige of the specialty were also important.ImplicationsIf recruitment to the specialty is to improve, these negative perceptions among students should be addressed by their teachers and more widely within psychiatry.
Longer-Term Outcomes of Letrozole Versus Placebo After 5 Years of Tamoxifen in the NCIC CTG MA.17 Trial: Analyses Adjusting for Treatment Crossover
Authors: Jin Huan , Tu Dongsheng , Zhao Naiqing , Shepherd Lois E. , Goss Paul E. 
Published: November 2011

Purpose The interim analysis of the National Cancer Institute of Canada Clinical Trials Group MA.17 trial showed that letrozole was significantly better than placebo in disease-free survival (DFS) for postmenopausal women with hormone receptor–positive breast cancer following about 5 years of tamoxifen therapy. When patients were unblinded, those on placebo were offered letrozole. Longer-term efficacy of letrozole, especially survival, was of particular interest because the median follow-up of the first interim analysis was only 2.5 years. Efficacy was difficult to assess because more than 60% of placebo patients crossed over to letrozole after being unblinded. Patients and Methods Two statistical approaches were used to adjust for the potential effects of treatment crossover: one was based on the inverse probability of censoring weighted (IPCW) Cox model and the other on a Cox model with time-dependent covariates. Results With a median follow-up of 64 months, the hazard ratios (HRs) of letrozole and placebo from the IPCW analyses were HR of 0.52 (95% CI, 0.45 to 0.61; P < .001) for DFS, HR of 0.51 (95% CI, 0.42 to 0.61; P < .001) for distant disease-free survival (DDFS), and HR of 0.61 (95% CI, 0.52 to 0.71; P < .001) for overall survival (OS). The results from the analyses based on the Cox model with time-dependent covariates were similar for letrozole and placebo: HR of 0.58 (95% CI, 0.47 to 0.72; P < .001) for DFS, HR of 0.68 (95% CI, 0.52 to 0.88; P = .004) for DDFS, and HR of 0.76 (95% CI, 0.60 to 0.96; P = .02) for OS. Conclusion Exploratory analyses based on longer follow-up and adjusting for treatment crossover suggest that extended adjuvant letrozole was superior to placebo in DFS, DDFS, and OS.