bluuebunny/crossref_metadata_2025 huggingface dataset:
Meta-analysis of microarray data using a pathway-based approach identifies a 37-gene expression signature for systemic lupus erythematosus in human peripheral blood mononuclear cells
Authors: Arasappan Dhivya , Tong Weida , Mummaneni Padmaja , Fang Hong , Amur Shashi
Published: May 2011

Background

A number of publications have reported the use of microarray technology to identify gene expression signatures to infer mechanisms and pathways associated with systemic lupus erythematosus (SLE) in human peripheral blood mononuclear cells. However, meta-analysis approaches with microarray data have not been well-explored in SLE.

Methods

In this study, a pathway-based meta-analysis was applied to four independent gene expression oligonucleotide microarray data sets to identify gene expression signatures for SLE, and these data sets were confirmed by a fifth independent data set.

Results

Differentially expressed genes (DEGs) were identified in each data set by comparing expression microarray data from control samples and SLE samples. Using Ingenuity Pathway Analysis software, pathways associated with the DEGs were identified in each of the four data sets. Using the leave one data set out pathway-based meta-analysis approach, a 37-gene metasignature was identified. This SLE metasignature clearly distinguished SLE patients from controls as observed by unsupervised learning methods. The final confirmation of the metasignature was achieved by applying the metasignature to a fifth independent data set.

Conclusions

The novel pathway-based meta-analysis approach proved to be a useful technique for grouping disparate microarray data sets. This technique allowed for validated conclusions to be drawn across four different data sets and confirmed by an independent fifth data set. The metasignature and pathways identified by using this approach may serve as a source for identifying therapeutic targets for SLE and may possibly be used for diagnostic and monitoring purposes. Moreover, the meta-analysis approach provides a simple, intuitive solution for combining disparate microarray data sets to identify a strong metasignature.

Please see Research Highlight: http://genomemedicine.com/content/3/5/30
Bone regeneration: current concepts and future directions
Authors: Dimitriou Rozalia , Jones Elena , McGonagle Dennis , Giannoudis Peter V
Published: May 2011

Bone regeneration is a complex, well-orchestrated physiological process of bone formation, which can be seen during normal fracture healing, and is involved in continuous remodelling throughout adult life. However, there are complex clinical conditions in which bone regeneration is required in large quantity, such as for skeletal reconstruction of large bone defects created by trauma, infection, tumour resection and skeletal abnormalities, or cases in which the regenerative process is compromised, including avascular necrosis, atrophic non-unions and osteoporosis. Currently, there is a plethora of different strategies to augment the impaired or 'insufficient' bone-regeneration process, including the 'gold standard' autologous bone graft, free fibula vascularised graft, allograft implantation, and use of growth factors, osteoconductive scaffolds, osteoprogenitor cells and distraction osteogenesis. Improved 'local' strategies in terms of tissue engineering and gene therapy, or even 'systemic' enhancement of bone repair, are under intense investigation, in an effort to overcome the limitations of the current methods, to produce bone-graft substitutes with biomechanical properties that are as identical to normal bone as possible, to accelerate the overall regeneration process, or even to address systemic conditions, such as skeletal disorders and osteoporosis.
Alteration of T cell cytokine production in PLPp-139-151-induced EAE in SJL mice by an immunostimulatory CpG Oligonucleotide
Authors: Smolianov Vsevolod , Dehmel Thomas , Vollmar Patrick , Mausberg Anne K , Kieseier Bernd C , Hemmer Bernhard , Hartung Hans P , Hofstetter Harald H
Published: May 2011

Experimental autoimmune encephalomyelitis (EAE) is - in certain aspects - regarded as an animal model of the human CNS autoimmune disease multiple sclerosis (MS). While in EAE CNS-autoantigen-specific immunity is induced in a defined way, the initial processes leading to CNS autoimmunity in humans are so far unknown. Despite essential restrictions, which exist regarding the interpretation of EAE data towards MS, EAE might be a useful model to study certain basic aspects of CNS autoimmunity. Studies in MS have demonstrated that established autoimmune pathology can be critically influenced by environmental factors, in particular viral and bacterial infections. To investigate this interaction, EAE as an instrument to study CNS autoimmunity under defined conditions appears to be a suitable experimental tool. For this reason, we here investigated the influence of the Toll-like-receptor (TLR) ligand CpG oligonucleotide (CpG) on already established CNS autoimmunity in murine proteolipid protein (PLP)-induced EAE in SJL mice. CpG were found to co-stimulate PLPp-specific IFN-γ production in the peripheral immune system and in the CNS. However, CpG induced Interleukin (IL)-17 production in the inflamed CNS both alone and in combination with additional PLPp stimulation. These findings might indicate a mechanism by which systemic infections and the microbial stimuli associated with them may influence already existing CNS autoimmune pathology.
Identification of CD8+ cytotoxic T lymphocyte epitopes from porcine reproductive and respiratory syndrome virus matrix protein in BALB/c mice
Authors: Zhang Weijun , Lin Yan , Bai Yu , Tong Tiegang , Wang Qun , Liu Nihong , Liu Guangliang , Xiao Yihong , Yang Tao , Bu Zhigao , Tong Guangzhi , Wu Donglai
Published: May 2011

Twenty-seven nanopeptides derived from the matrix (M) protein of porcine reproductive and respiratory syndrome virus (PRRSV) were screened for their ability to elicit a recall interferon-γ (IFN-γ) response from the splenocytes of BALB/c mice following DNA vaccination and a booster vaccination with recombinant vaccinia virus rWR-PRRSV-M. We identified two peptides (amino acid residues K93FITSRCRL and F57GYMTFVHF) as CD8+cytotoxic T lymphocyte (CTL) epitopes. These peptides elicited significant numbers of IFN-γ secreting cells, compared with other M nonapeptides and one irrelevant nonapeptide. Bioinformatics analysis showed that the former is an H-2Kd-restricted CTL epitope, and the latter is an H-2Dd-restricted CTL epitope. Multiple amino acid sequence alignment among different PRRSV M sequences submitted to GenBank indicated that these two CTL epitopes are strongly conserved, and they should therefore be considered for further research on the mechanisms of cellular immune responses to PRRSV.
A novel candidate HIV vaccine vector based on the replication deficient Capripoxvirus, Lumpy skin disease virus (LSDV)
Authors: Shen Yen-Ju , Shephard Enid , Douglass Nicola , Johnston Nicolette , Adams Craig , Williamson Carolyn , Williamson Anna-Lise
Published: May 2011

Background

The Capripoxvirus, Lumpy skin disease virus (LSDV) has a restricted host-range and is being investigated as a novel HIV-1 vaccine vector. LSDV does not complete its replication cycle in non-ruminant hosts.

Methods

The safety of LSDV was tested at doses of 104 and 106 plaque forming units in two strains of immunocompromised mice, namely RAG mice and CD4 T cell knockout mice. LSDV expressing HIV-1 subtype C Gag, reverse transcriptase (RT), Tat and Nef as a polyprotein (Grttn), (rLSDV-grttn), was constructed. The immunogenicity of rLSDV-grttn was tested in homologous prime-boost regimens as well as heterologous prime-boost regimes in combination with a DNA vaccine (pVRC-grttn) or modified vaccinia Ankara vaccine (rMVA-grttn) both expressing Grttn.

Results

Safety was demonstrated in two strains of immunocompromised mice.

In the immunogenicity experiments mice developed high magnitudes of HIV-specific cells producing IFN-gamma and IL-2. A comparison of rLSDV-grttn and rMVA-grttn to boost a DNA vaccine (pVRC-grttn) indicated a DNA prime and rLSDV-grttn boost induced a 2 fold (p < 0.01) lower cumulative frequency of Gag- and RT-specific IFN-γ CD8 and CD4 cells than a boost with rMVA-grttn. However, the HIV-specific cells induced by the DNA vaccine prime rLSDV-grttn boost produced greater than 3 fold (p < 0.01) more IFN- gamma than the HIV-specific cells induced by the DNA vaccine prime rMVA-grttn boost. A boost of HIV-specific CD4 cells producing IL-2 was only achieved with the DNA vaccine prime and rLSDV-grttn boost. Heterologous prime-boost combinations of rLSDV-grttn and rMVA-grttn induced similar cumulative frequencies of IFN- gamma producing Gag- and RT-specific CD8 and CD4 cells. A significant difference (p < 0.01) between the regimens was the higher capacity (2.1 fold) of Gag-and RT-specific CD4 cells to produce IFN-γ with a rMVA-grttn prime - rLSDV-grttn boost. This regimen also induced a 1.5 fold higher (p < 0.05) frequency of Gag- and RT-specific CD4 cells producing IL-2.

Conclusions

LSDV was demonstrated to be non-pathogenic in immunocompromised mice. The rLSDV-grttn vaccine was immunogenic in mice particularly in prime-boost regimens. The data suggests that this novel vaccine may be useful for enhancing, in particular, HIV-specific CD4 IFN- gamma and IL-2 responses induced by a priming vaccine.
Brazil nuts intake improves lipid profile, oxidative stress and microvascular function in obese adolescents: a randomized controlled trial
Authors: Maranhão Priscila A , Kraemer-Aguiar Luiz G , de Oliveira Cecilia L , Kuschnir Maria CC , Vieira Yasmine R , Souza Maria GC , Koury Josely C , Bouskela Eliete
Published: May 2011

Background

Obesity is a chronic disease associated to an inflammatory process resulting in oxidative stress that leads to morpho-functional microvascular damage that could be improved by some dietary interventions. In this study, the intake of Brazil nuts (Bertholletia excelsa), composed of bioactive substances like selenium, α- e γ- tocopherol, folate and polyunsaturated fatty acids, have been investigated on antioxidant capacity, lipid and metabolic profiles and nutritive skin microcirculation in obese adolescents.

Methods

Obese female adolescents (n = 17), 15.4 ± 2.0 years and BMI of 35.6 ± 3.3 kg/m2, were randomized 1:1 in two groups with the diet supplemented either with Brazil nuts [BNG, n = 08, 15-25 g/day (equivalent to 3 to 5 units/day)] or placebo [PG (lactose), n = 09, one capsule/day] and followed for 16 weeks. Anthropometry, metabolic-lipid profiles, oxidative stress and morphological (capillary diameters) and functional [functional capillary density, red blood cell velocity (RBCV) at baseline and peak (RBCVmax) and time (TRBCVmax) to reach it during post-occlusive reactive hyperemia, after 1 min arterial occlusion] microvascular variables were assessed by nailfold videocapillaroscopy at baseline (T0) and after intervention (T1).

Results

T0 characteristics were similar between groups. At T1, BNG (intra-group variation) had increased selenium levels (p = 0.02), RBCV (p = 0.03) and RBCVmax (p = 0.03) and reduced total (TC) (p = 0.02) and LDL-cholesterol (p = 0.02). Compared to PG, Brazil nuts intake reduced TC (p = 0.003), triglycerides (p = 0.05) and LDL-ox (p = 0.02) and increased RBCV (p = 0.03).

Conclusion

Brazil nuts intake improved the lipid profile and microvascular function in obese adolescents, possibly due to its high level of unsaturated fatty acids and bioactive substances.

Trial Registration

Clinical Trials.gov
NCT00937599
Costunolide causes mitotic arrest and enhances radiosensitivity in human hepatocellular carcinoma cells
Authors: Liu Chia-Yuan , Chang Hsun-Shuo , Chen Ih-Sheng , Chen Chih-Jen , Hsu Ming-Ling , Fu Shu-Ling , Chen Yu-Jen
Published: May 2011

Purpose

This work aimed to investigate the effect of costunolide, a sesquiterpene lactone isolated from Michelia compressa, on cell cycle distribution and radiosensitivity of human hepatocellular carcinoma (HCC) cells.

Methods

The assessment used in this study included: cell viability assay, cell cycle analysis by DNA histogram, expression of phosphorylated histone H3 (Ser 10) by flow cytometer, mitotic index by Liu's stain and morphological observation, mitotic spindle alignment by immunofluorescence of alpha-tubulin, expression of cell cycle-related proteins by Western blotting, and radiation survival by clonogenic assay.

Results

Our results show that costunolide reduced the viability of HA22T/VGH cells. It caused a rapid G2/M arrest at 4 hours shown by DNA histogram. The increase in phosphorylated histone H3 (Ser 10)-positive cells and mitotic index indicates costunolide-treated cells are arrested at mitosis, not G2, phase. Immunofluorescence of alpha-tubulin for spindle formation further demonstrated these cells are halted at metaphase. Costunolide up-regulated the expression of phosphorylated Chk2 (Thr 68), phosphorylated Cdc25c (Ser 216), phosphorylated Cdk1 (Tyr 15) and cyclin B1 in HA22T/VGH cells. At optimal condition causing mitotic arrest, costunolide sensitized HA22T/VGH HCC cells to ionizing radiation with sensitizer enhancement ratio up to 1.9.

Conclusions

Costunolide could reduce the viability and arrest cell cycling at mitosis in hepatoma cells. Logical exploration of this mitosis-arresting activity for cancer therapeutics shows costunolide enhanced the killing effect of radiotherapy against human HCC cells.
A robust approach based on Weibull distribution for clustering gene expression data
Authors: Wang Huakun , Wang Zhenzhen , Li Xia , Gong Binsheng , Feng Lixin , Zhou Ying
Published: May 2011

Background

Clustering is a widely used technique for analysis of gene expression data. Most clustering methods group genes based on the distances, while few methods group genes according to the similarities of the distributions of the gene expression levels. Furthermore, as the biological annotation resources accumulated, an increasing number of genes have been annotated into functional categories. As a result, evaluating the performance of clustering methods in terms of the functional consistency of the resulting clusters is of great interest.

Results

In this paper, we proposed the WDCM (Weibull Distribution-based Clustering Method), a robust approach for clustering gene expression data, in which the gene expressions of individual genes are considered as the random variables following unique Weibull distributions. Our WDCM is based on the concept that the genes with similar expression profiles have similar distribution parameters, and thus the genes are clustered via the Weibull distribution parameters. We used the WDCM to cluster three cancer gene expression data sets from the lung cancer, B-cell follicular lymphoma and bladder carcinoma and obtained well-clustered results. We compared the performance of WDCM with k-means and Self Organizing Map (SOM) using functional annotation information given by the Gene Ontology (GO). The results showed that the functional annotation ratios of WDCM are higher than those of the other methods. We also utilized the external measure Adjusted Rand Index to validate the performance of the WDCM. The comparative results demonstrate that the WDCM provides the better clustering performance compared to k-means and SOM algorithms. The merit of the proposed WDCM is that it can be applied to cluster incomplete gene expression data without imputing the missing values. Moreover, the robustness of WDCM is also evaluated on the incomplete data sets.

Conclusions

The results demonstrate that our WDCM produces clusters with more consistent functional annotations than the other methods. The WDCM is also verified to be robust and is capable of clustering gene expression data containing a small quantity of missing values.
Parasites in pet reptiles
Authors: Rataj Aleksandra Vergles , Lindtner-Knific Renata , Vlahović Ksenija , Mavri Urška , Dovč Alenka
Published: May 2011

Exotic reptiles originating from the wild can be carriers of many different pathogens and some of them can infect humans. Reptiles imported into Slovenia from 2000 to 2005, specimens of native species taken from the wild and captive bred species were investigated. A total of 949 reptiles (55 snakes, 331 lizards and 563 turtles), belonging to 68 different species, were examined for the presence of endoparasites and ectoparasites. Twelve different groups (Nematoda (5), Trematoda (1), Acanthocephala (1), Pentastomida (1) and Protozoa (4)) of endoparasites were determined in 26 (47.3%) of 55 examined snakes. In snakes two different species of ectoparasites were also found. Among the tested lizards eighteen different groups (Nematoda (8), Cestoda (1), Trematoda (1), Acanthocephala (1), Pentastomida (1) and Protozoa (6)) of endoparasites in 252 (76.1%) of 331 examined animals were found. One Trombiculid ectoparasite was determined. In 563 of examined turtles eight different groups (Nematoda (4), Cestoda (1), Trematoda (1) and Protozoa (2)) of endoparasites were determined in 498 (88.5%) animals. In examined turtles three different species of ectoparasites were seen. The established prevalence of various parasites in reptiles used as pet animals indicates the need for examination on specific pathogens prior to introduction to owners.
Improvement of platelet dysfunction in chronic myelogenous leukemia following treatment with imatinib: a case report
Authors: Shimabukuro-Vornhagen Alexander , Rothe Achim , Nogova Lucia , Kochanek Matthias , Scheid Christoph , von Bergwelt-Baildon Michael
Published: May 2011

Introduction

In patients with chronic myeloid leukemia, tyrosine kinase inhibitors suppress the BCR-ABL
+ clone and often induce complete molecular remissions. Megakaryocytes in such patients have been shown to be derived from the BCR-ABL
+ clone, and abnormal platelet function is frequent in chronic myeloid leukemia. However, little is known about the influence of modern targeted therapy on chronic myeloid leukemia-associated platelet disorders.

Case presentation

We report the case of a massive hemorrhage in a 32-year-old Caucasian man caused by chronic myeloid leukemia-associated platelet dysfunction, which improved after treatment with imatinib.

Conclusion

This report demonstrates that platelet dysfunction and bleeding disorder in BCR-ABL
+ chronic myeloid leukemia can successfully be treated with imatinib. We suggest the monitoring of platelet function in future studies using imatinib to treat patients with chronic myeloid leukemia.
Evaluation of lymph node numbers for adequate staging of Stage II and III colon cancer
Authors: Shanmugam Chandrakumar , Hines Robert B , Jhala Nirag C , Katkoori Venkat R , Zhang Bin , Posey James A , Bumpers Harvey L , Grizzle William E , Eltoum Isam E , Siegal Gene P , Manne Upender
Published: May 2011

Background

Although evaluation of at least 12 lymph nodes (LNs) is recommended as the minimum number of nodes required for accurate staging of colon cancer patients, there is disagreement on what constitutes an adequate identification of such LNs.

Methods

To evaluate the minimum number of LNs for adequate staging of Stage II and III colon cancer, 490 patients were categorized into groups based on 1-6, 7-11, 12-19, and ≥ 20 LNs collected.

Results

For patients with Stage II or III disease, examination of 12 LNs was not significantly associated with recurrence or mortality. For Stage II (HR = 0.33; 95% CI, 0.12-0.91), but not for Stage III patients (HR = 1.59; 95% CI, 0.54-4.64), examination of ≥20 LNs was associated with a reduced risk of recurrence within 2 years. However, examination of ≥20 LNs had a 55% (Stage II, HR = 0.45; 95% CI, 0.23-0.87) and a 31% (Stage III, HR = 0.69; 95% CI, 0.38-1.26) decreased risk of mortality, respectively. For each six additional LNs examined from Stage III patients, there was a 19% increased probability of finding a positive LN (parameter estimate = 0.18510, p < 0.0001). For Stage II and III colon cancers, there was improved survival and a decreased risk of recurrence with an increased number of LNs examined, regardless of the cutoff-points. Examination of ≥7 or ≥12 LNs had similar outcomes, but there were significant outcome benefits at the ≥20 cutoff-point only for Stage II patients. For Stage III patients, examination of 6 additional LNs detected one additional positive LN.

Conclusions

Thus, the 12 LN cut-off point cannot be supported as requisite in determining adequate staging of colon cancer based on current data. However, a minimum of 6 LNs should be examined for adequate staging of Stage II and III colon cancer patients.
Lower limb biomechanics during running in individuals with achilles tendinopathy: a systematic review
Authors: Munteanu Shannon E , Barton Christian J
Published: May 2011

Background

Abnormal lower limb biomechanics is speculated to be a risk factor for Achilles tendinopathy. This study systematically reviewed the existing literature to identify, critique and summarise lower limb biomechanical factors associated with Achilles tendinopathy.

Methods

We searched electronic bibliographic databases (Medline, EMBASE, Current contents, CINAHL and SPORTDiscus) in November 2010. All prospective cohort and case‐control studies that evaluated biomechanical factors (temporospatial parameters, lower limb kinematics, dynamic plantar pressures, kinetics [ground reaction forces and joint moments] and muscle activity) associated with mid‐portion Achilles tendinopathy were included. Quality of included studies was evaluated using the Quality Index. The magnitude of differences (effect sizes) between cases and controls was calculated using Cohen's d (with 95% CIs).

Results

Nine studies were identified; two were prospective and the remaining seven case‐control study designs. The quality of 9 identified studies was varied, with Quality Index scores ranging from 4 to 15 out of 17. All studies analysed running biomechanics. Cases displayed increased eversion range of motion of the rearfoot (d = 0.92 and 0.67 in two studies), reduced maximum lower leg abduction (d = ‐1.16), reduced ankle joint dorsiflexion velocity (d = ‐0.62) and reduced knee flexion during gait (d = ‐0.90). Cases also demonstrated a number of differences in dynamic plantar pressures (primarily the distribution of the centre of force), ground reaction forces (large effects for timing variables) and also showed reduced peak tibial external rotation moment (d = ‐1.29). Cases also displayed differences in the timing and amplitude of a number of lower limb muscles but many differences were equivocal.

Conclusions

There are differences in lower limb biomechanics between those with and without Achilles tendinopathy that may have implications for the prevention and management of the condition. However, the findings need to be interpreted with caution due to the limited quality of a number of the included studies. Future well‐designed prospective studies are required to confirm these findings.
Multiplex single-nucleotide polymorphism typing of the human Y chromosome using TaqMan probes
Authors: Martínez-Cruz Begoña , Ziegle Janet , Sanz Paula , Sotelo Graciela , Anglada Roger , Plaza Stéphanie , Comas David ,   the Genographic Consortium
Published: May 2011

Background

The analysis of human Y-chromosome variation in the context of population genetics and forensics requires the genotyping of dozens to hundreds of selected single-nucleotide polymorphisms (SNPs). In the present study, we developed a 121-plex (121 SNPs in a single array) TaqMan array capable of distinguishing most haplogroups and subhaplogroups on the Y-chromosome human phylogeny in Europe.

Results

We present data from 264 samples from several European areas and ethnic groups. The array developed in this study shows >99% accuracy of assignation to the Y human phylogeny (with an average call rate of genotypes >96%).

Conclusions

We have created and evaluated a robust and accurate Y-chromosome multiplex which minimises the possible errors due to mixup when typing the same sample in several independent reactions.
Notochordal conditioned media from tissue increases proteoglycan accumulation and promotes a healthy nucleus pulposus phenotype in human mesenchymal stem cells
Authors: Purmessur Devina , Schek Rachel M , Abbott Rosalyn D , Ballif Bryan A , Godburn Karolyn E , Iatridis James C
Published: May 2011

Introduction

Notochordal cells (NCs) are influential in development of the intervertebral disc (IVD) and species that retain NCs do not degenerate. IVD repair using bone marrow derived mesenchymal stem cells (MSCs) is an attractive approach and the harsh microenvironment of the IVD suggests pre-differentiation is a necessary first step. The goal of this study was to use soluble factors from NCs in alginate and NCs in their native tissue to differentiate human MSCs to a young nucleus pulposus (NP) phenotype.

Methods

Human MSCs (cultured under micromass conditions for 21 days in hypoxia) were differentiated with conditioned medium derived from porcine notochordal cells in native tissue (NCT) or in alginate beads (NCA), and compared with chondrogenic (TGFβ-3) or basal medium. A PCR array of 42 genes was utilized to screen a large number of genes known to be associated with the healthy NP phenotype and pellet cultures were also evaluated for glycosaminoglycan content, histology and viability. Proteomic analysis was used to assess candidate soluble factors in NCA and NCT.

Results

Notochordal cell conditioned media had diverse effects on MSC phenotype. NCT resulted in the highest levels of glycosaminoglycan (GAG), as well as up-regulation of SOX9 and Collagen II gene expression. NCA demonstrated effects that were catabolic yet also anti-fibrotic and minimally hypertrophic with down-regulation of Collagens I and III and low levels of Collagen X, respectively. Micromass culture and hypoxic conditions were sufficient to promote chondrogenesis demonstrating that both basal and chondrogenic media produced similar phenotypes. Candidate matricellular proteins, clusterin and tenascin were identified by proteomics in the NCA group.

Conclusions

NCs secreted important soluble factors capable of differentiating MSCs to a NP phenotype synthesizing high levels of proteoglycan while also resisting collagen fiber expression and hypertrophy, yet results were sensitive to the conditions in which media was generated (cells in alginate versus cells in their native tissue) so that further mechanistic studies optimizing culture conditions and defining important NC secreted factors are required. Matricellular proteins, such as clusterin and tenascin, are likely to be important to optimize differentiation of MSCs for maximum GAG production and reduced collagen fiber expression.
Goal-directed haemodynamic therapy during elective total hip arthroplasty under regional anaesthesia
Authors: Cecconi Maurizio , Fasano Nicola , Langiano Nicola , Divella Michele , Costa Maria G , Rhodes Andrew , Rocca Giorgio Della
Published: May 2011

Introduction

Total hip replacement is one of the most commonly performed major orthopaedic operations. Goal-directed therapy (GDT) using haemodynamic monitoring has previously demonstrated outcome benefits in high-risk surgical patients under general anaesthesia. GDT has never been formally assessed during regional anaesthesia.

Methods

Patients undergoing total hip replacement while under regional anaesthesia were randomised to either the control group (CTRL) or the protocol group (GDT). Patients in the GDT group, in addition to standard monitoring, were connected to the FloTrac sensor/Vigileo monitor haemodynamic monitoring system, and a GDT protocol was used to maximise the stroke volume and target the oxygen delivery index to > 600 mL/minute/m2.

Results

Patients randomised to the GDT group were given a greater volume of intravenous fluids during the intraoperative period (means ± standard deviation (SD): 6,032 ± 1,388 mL vs. 2,635 ± 346 mL; P < 0.0001), and more of the GDT patients received dobutamine (0 of 20 CTRL patients vs. 11 of 20 GDT patients; P < 0.0003). The GDT patients also received more blood transfused during the intraoperative period (means ± SD: 595 ± 316 mL vs. 0 ± 0 mL; P < 0.0001), although the CTRL group received greater volumes of blood replacement postoperatively (CTRL patients 658 ± 68 mL vs. GDT patients 198 ± 292 mL; P < 0.001). Overall blood consumption (intraoperatively and postoperatively) was not different between the two groups. There were an increased number of complications in the CTRL group (20 of 20 CTRL patients (100%) vs. 16 of 20 GDT patients (80%); P = 0.05). These outcomes were predominantly due to a difference in minor complications (20 of 20 CTRL patients (100%) vs. 15 of 20 GDT patients (75%); P = 0.047).

Conclusions

GDT applied during regional anaesthesia in patients undergoing elective total hip replacement changes intraoperative fluid management and may improve patient outcomes by decreasing postoperative complications. Larger trials are required to confirm our findings.

Trial registration

SRCTN11616985
Complete Columbian mammoth mitogenome suggests interbreeding with woolly mammoths
Authors: Enk Jacob , Devault Alison , Debruyne Regis , King Christine E , Treangen Todd , O'Rourke Dennis , Salzberg Steven L , Fisher Daniel , MacPhee Ross , Poinar Hendrik
Published: May 2011

Background

Late Pleistocene North America hosted at least two divergent and ecologically distinct species of mammoth: the periglacial woolly mammoth (Mammuthus primigenius) and the subglacial Columbian mammoth (Mammuthus columbi). To date, mammoth genetic research has been entirely restricted to woolly mammoths, rendering their genetic evolution difficult to contextualize within broader Pleistocene paleoecology and biogeography. Here, we take an interspecific approach to clarifying mammoth phylogeny by targeting Columbian mammoth remains for mitogenomic sequencing.

Results

We sequenced the first complete mitochondrial genome of a classic Columbian mammoth, as well as the first complete mitochondrial genome of a North American woolly mammoth. Somewhat contrary to conventional paleontological models, which posit that the two species were highly divergent, the M. columbi mitogenome we obtained falls securely within a subclade of endemic North American M. primigenius.

Conclusions

Though limited, our data suggest that the two species interbred at some point in their evolutionary histories. One potential explanation is that woolly mammoth haplotypes entered Columbian mammoth populations via introgression at subglacial ecotones, a scenario with compelling parallels in extant elephants and consistent with certain regional paleontological observations. This highlights the need for multi-genomic data to sufficiently characterize mammoth evolutionary history. Our results demonstrate that the use of next-generation sequencing technologies holds promise in obtaining such data, even from non-cave, non-permafrost Pleistocene depositional contexts.
Editorial: Cytohesin-1, on the tail of two integrins
Authors: Hyduk Sharon J , Cybulsky Myron I
Published: May 2011

Bourgoin and colleagues report that cytohesin-1 functions to restrain fMLF-induced activation of the β2 integrin Mac-1 in polymorphonuclear leukocytes (PMNLs) which is in stark contrast to the role of cytohesin-1 in the activation of LFA-1, a different β2 integrin.
Revascularisation and mortality rates following acute coronary syndromes in people with severe mental illness: comparative meta-analysis
Authors: Mitchell Alex J. , Lawrence David
Published: May 2011

Background

High levels of comorbid physical illness and excess mortality rates have been previously documented in people with severe mental illness, but outcomes following myocardial infarction and other acute coronary syndromes are less clear.

Aims

To examine inequalities in the provision of invasive coronary procedures (revascularisation, angiography, angioplasty and bypass grafting) and subsequent mortality in people with mental illness and in those with schizophrenia, compared with those without mental ill health.

Method

Systematic search and random effects meta-analysis were used according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies of mental health and cardiovascular procedures following cardiac events were eligible but we required a minimum of three independent studies to warrant pooling by procedure type. We searched Medline/PubMed and EMBASE abstract databases and ScienceDirect, Ingenta Select, SpringerLink and Online Wiley Library full text databases.

Results

We identified 22 analyses of possible inequalities in coronary procedures in those with defined mental disorder, of which 10 also reported results in schizophrenia or related psychosis. All studies following acute coronary syndrome originated in the USA. The total sample size was 825 754 individuals. Those with mental disorders received 0.86 (relative risk, RR: 95% CI 0.80–0.92,P<0.0001) of comparable procedures with significantly lower receipt of coronary artery bypass graft (CABG; RR = 0.85, 95% CI 0.72–1.00), cardiac catheterisation (RR = 0.85, 95% CI 0.76–0.95) and percutaneous transluminal coronary angioplasty or percutaneous coronary intervention (PTCA/PCI; RR = 0.87, 95% CI 0.72–1.05). People with a diagnosis of schizophrenia received only 0.53 (95% CI 0.44–0.64,P<0.0001) of the usual procedure rate with significantly lower receipt of CABG (RR = 0.69, 95% CI 0.55–0.85) and PTCA/PCI (RR = 0.50, 95% CI 0.34–0.75). We identified 6 related studies examining mortality following cardiac events: for those with mental illness there was a 1.11 relative risk of mortality up to 1 year (95% CI 1.00–1.24,P= 0.05) but there was insufficient evidence to examine mortality rates in schizophrenia alone.

Conclusions

Following cardiac events, individuals with mental illness experience a 14% lower rate of invasive coronary interventions (47% in the case of schizophrenia) and they have an 11% increased mortality rate. Further work is required to explore whether these factors are causally linked and whether improvements in medical care might improve survival in those with mental ill health.
Grey matter and social functioning correlates of glutamatergic
metabolite loss in schizophrenia
Authors: Aoyama Naoko , Théberge Jean , Drost Dick J. , Manchanda Rahul , Northcott Sandra , Neufeld Richard W. J. , Menon Ravi S. , Rajakumar Nagalingam , Pavlosky William F. , Densmore Maria , Schaefer Betsy , Williamson Peter C.
Published: May 2011

Background

Thalamic glutamine loss and grey matter reduction suggest
neurodegeneration in first-episode schizophrenia, but the duration is
unknown.

Aims

To observe glutamine and glutamate levels, grey matter volumes and social
functioning in patients with schizophrenia followed to 80 months after
diagnosis.

Method

Grey matter volumes and proton magnetic resonance spectroscopy
metabolites in left anterior cingulate and left thalamus were measured in
17 patients with schizophrenia before medication and 10 and 80 months
after diagnosis. Social functioning was assessed with the Life Skills
Profile Rating Scale (LSPRS) at 80 months.

Results

The sum of thalamic glutamate and glutamine levels decreased over 80
months, and correlated inversely with the LSPRS. Thalamic glutamine and
grey matter loss were significantly correlated in frontal, parietal,
temporal and limbic regions.

Conclusions

Brain metabolite loss is correlated with deteriorated social functioning
and grey matter losses in schizophrenia, consistent with
neurodegeneration.
Dangerous and severe personality disorder
Authors: Duggan Conor
Published: May 2011

The Dangerous and Severe Personality Disorder (DSPD) initiative was introduced a decade ago against overwhelming opposition from psychiatrists and others concerned with the implications of extending the public protection agenda through the use of a questionable medical ‘diagnosis'. As this initiative is now being scaled down, it offers an opportunity to consider the positive and negative aspects of the initiative together with its longer-term legacy.
Mixed anxiety and depressive disorder outcomes: prospective
cohort study in primary care
Authors: Walters Kate , Buszewicz Marta , Weich Scott , King Michael
Published: May 2011

Background

Mixed anxiety and depressive disorder (MADD) is common yet ill-defined,
with little known about outcomes.

Aims

To determine MADD outcomes over 1 year.

Method

We recruited 250 adults attending seven London general practices with
mild–moderate distress. Three groups were defined using a diagnostic
interview: MADD, other ICD–10 psychiatric diagnosis, no psychiatric
diagnosis. We assessed symptoms of distress (General Health
Questionnaire–28), quality of life (12-item Short Form Health Survey),
general practitioner (GP) diagnosis and consultation rate at baseline, 3
months and 1 year.

Results

Two-thirds of participants with MADD had no significant psychological
distress at 3 months (61%) or 1 year (69%). However, compared with those
with no diagnosis, individuals had twice the risk of significant distress
(incidence rate ratio 2.39, 95% CI 1.29–4.42) at 3 months but not 1 year,
and persistently lower quality of life (mental health functioning). There
was no significant difference in GP consultation rate/diagnosis.

Conclusions

The majority with MADD improved, but individuals had an increased risk of
significant distress at 3 months and a lower quality of life. As we
cannot currently predict those with a poorer prognosis these patients
should be actively monitored in primary care.
Trends in rates of mental illness in homicide
perpetrators
Authors: Swinson Nicola , Flynn Sandra M. , While David , Roscoe Alison , Kapur Navneet , Appleby Louis , Shaw Jenny
Published: May 2011

Background

The rise in homicides by those with serious mental illness is of concern,
although this increase may not be continuing.

Aims

To examine rates of mental illness among homicide perpetrators.

Method

A national consecutive case series of homicide perpetrators in England
and Wales from 1997 to 2006. Rates of mental disorder were based on data
from psychiatric reports, contact with psychiatric services, diminished
responsibility verdict and hospital disposal.

Results

Of the 5884 homicides notified to the National Confidential Inquiry into
Suicide and Homicide by People with Mental Illness between 1997 and 2006,
the number of homicide perpetrators with schizophrenia increased at a
rate of 4% per year, those with psychotic symptoms at the time of the
offence increased by 6% per year. The number of verdicts of diminished
responsibility decreased but no change was found in the number of
perpetrators receiving a hospital order disposal. The likeliest
explanation for the rise in homicide by people with psychosis is the
misuse of drugs and/or alcohol, which our data show increased at a
similar magnitude to homicides by those with psychotic symptoms. However,
we are unable to demonstrate a causal association. Although the Poisson
regression provides evidence of an upward trend in homicide by people
with serious mental illness between 1997 and 2006, the number of
homicides fell in the final 2 years of data collection, so these findings
should be treated with caution.

Conclusions

There appears to be a concomitant increase in drug misuse over the
period, which may account for this rise in homicide. However, an increase
in the number of people in contact with mental health services may
suggest that access to mental health services is improving. Previous
studies have used court verdicts such as diminished responsibility as a
proxy measure of mental disorder. Our data indicate that this does not
reflect accurately the prevalence of mental disorder in this
population.
Preventive psychiatry: a paradigm to improve population mental
health and well-being
Authors: Bhui Kamaldeep , Dinos Sokratis
Published: May 2011

The government's Public Health White Paper for England sets out a utopian
vision of how to prevent and remedy mental health problems. The public
health approach relies on primary prevention, promoting individual
responsibilities and resilience, while also sustaining existing services and
tackling inequalities. These ambitions are consistent with the preventive
psychiatric paradigm, and with the best of evidence-based psychiatric
practice. Although the evidence on cost-effectiveness of public mental
health interventions is growing, the challenge is to ensure that specialist
knowledge informs policy, practice and research so that inequalities are not
compounded. Specialist mental health professionals are needed to inform and
lead public health reforms.
Forensic psychiatry and public protection
Authors: Buchanan Alec , Grounds Adrian
Published: May 2011

The prominence of risk in UK social and criminal justice policy creates
opportunities, challenges and dangers for forensic psychiatry. The future
standing of the specialty will depend not only on the practical utility of
its responses to those opportunities and challenges, but also the ethical
integrity of those responses.
Doctors' experience of a bespoke physician consultation service: cross-sectional investigation
Authors: Meerten Maja , Bland Julia , Gross Samantha R. , Garelick Antony I.
Published: May 2011

Aims and method

Our aim was to follow-up on a cohort of self-referred doctors who attended MedNet. We used a two-point cross-sectional design. Measures included three standardised self-report questionnaires administered before and after consultation. Doctors were also asked to complete a service user questionnaire, and data regarding engagement and onward referrals were gathered through case-note review.

Results

A statistically significant improvement in scores on all three questionnaires was found after intervention; however, scores on one subscale, the risk domain of the Clinical Outcomes in Routine Evaluation – Outcome Measure, did not change significantly. Of the doctors at no risk of suicide at intake, nearly two-thirds (n = 41/70, 59%) were sufficiently helped by the consultations provided to not need further treatment. Of the doctors at some risk of suicide at intake, two-thirds (n = 34/51, 67%) did need an onward referral. Only one doctor required hospital admission, an outcome that suggests the approach used is containing and clinically responsive.

Clinical implications

This paper highlights the efficacy, need and importance of specialist services for doctors in difficulty. We found that the bespoke consultation model provided at MedNet is valued highly by the doctors as service users.
Case-based discussion: a useful tool for revalidation
Authors: Mynors-Wallis Laurence , Cope Denise , Brittlebank Andrew , Palekar Fauzan
Published: May 2011

Aims and method

Revalidation is the process by which doctors demonstrate that they are up to date and fit to practise. Case-based discussion has been identified by both psychiatrists and service users and carers as a potentially useful tool for revalidation. The aim of this study was to examine the feasibility of case-based discussion for assessments to use in revalidation. A pilot using case-based discussion as an assessment/developmental technique for revalidation was undertaken in six trusts involving 86 consultant psychiatrists.

Results

The average time taken for each case-based discussion including preparation and reflection was 48 min. All but one of the doctors involved in the case-based discussion pilot described the process as useful or very useful in improving clinical practice. In total 87% of the assessed doctors and all of the assessors reported that they considered case-based discussion to be a useful part of the revalidation process assessed. The majority of doctors assessed believed that cases should be chosen at random (91%).

Clinical implications

Case-based discussions have the potential to be a useful quality improvement tool for revalidation.
General practitioners' attitudes on who should manage metabolic dysregulations associated with antipsychotics
Authors: Bainbridge Emma , Gallagher Anne , McDonald Gary , McDonald Colm , Ahmed Mohamed
Published: May 2011

Aims and method

To assess attitudes of general practitioners (GPs) on who should be responsible for managing metabolic dysregulations associated with the use of antipsychotics prescribed by psychiatrists. A total of 121 GPs in West Galway catchment area were surveyed using a simple questionnaire.

Results

A total of 104 GPs responded (86% response rate). The vast majority of responders (82%) believed that medical management should be provided within primary care. However, 46% indicated that initial screening and simple non-pharmacological management should be provided by mental health services.

Clinical implications

The vast majority of GPs appear willing to take over the medical management of metabolic dysregulations emerging from antipsychotic prescribing in secondary care. Clearly defined roles for mental health services and primary care in the management of metabolic complications are of paramount importance, and individual mental health services should implement protocols for screening, non-pharmacological management and referral to primary care.
Stability of the diagnosis of first-episode drug-induced psychosis
Authors: Komuravelli Aravind , Poole Rob , Higgo Robert
Published: May 2011

Aims and method

To assess the stability of the diagnosis of first-episode drug-induced psychosis over a follow-up period of at least 2 years. Patients with no psychiatric history who had been discharged from in-patient care between January 2002 and April 2006 with a firm diagnosis of drug-induced psychosis were identified. Follow-up information for at least the next 2 years or until discharge from mental health services was collected retrospectively from psychiatric records.

Results

Nearly all of the patients who remained under psychiatric follow-up had a change in diagnosis, most commonly to a schizophreniform disorder. Those who were retained in follow-up had significantly longer index admissions than those discharged to primary care (P = 0.05).

Clinical implications

This study suggests that many individuals diagnosed with drug-induced psychosis are further diagnosed as having a functional psychosis, usually schizophreniform in nature. This is compatible with the suggestion that individuals diagnosed with drug-induced psychosis are experiencing either the effects of drug intoxication or an ordinary functional psychosis complicated by incidental drug use.
Analysis of transition corner formation in hydroforming of rectangular-section tube
Authors: Yuan S , Song P , Wang X
Published: May 2011

The filling behaviour of a transition corner was investigated by theoretical analysis, experiment, and finite element method for a rectangular-section tube during the hydroforming process. The cracking mechanism of the transition region between the straight side and the corner was analysed. The expression of the limiting corner radius was given by way of mechanics analysis and the incremental strain theory. It has been shown that severe thinning deformation or cracking takes place first at the transition region because the effective stress increases gradually from the midpoint of the straight side to the transition point under the effect of friction on the straight side. The mechanism of limiting corner radius is that strain increment along the horizontal direction changes from a positive value to zero at a certain point along the straight side, near the transition point, and then no further material is fed into the corner. The forming pressure needed for the transition corner increases as the relative corner radius decreases during the corner filling process. Lubricant conditions have a significant influence on transition corner filling. The forming pressure needed for the transition corner is effectively reduced by improving lubrication conditions, so that a smaller limiting corner radius is achieved.