bluuebunny/crossref_metadata_2025_split huggingface dataset:
Secretagogin is Expressed in Sensory CGRP Neurons and in Spinal Cord of Mouse and Complements other Calcium-Binding Proteins, with a Note on Rat and Human
Authors: Shi Tie-Jun Sten , Xiang Qiong , Zhang Ming-Dong , Tortoriello Giuseppe , Hammarberg Henrik , Mulder Jan , Fried Kaj , Wagner Ludwig , Josephson Anna , Uhlén Mathias , Harkany Tibor , Hökfelt Tomas 
Published: October 2012

Background: Secretagogin (Scgn), a member of the EF-hand calcium-binding protein (CaBP) superfamily, has recently been found in subsets of developing and adult neurons. Here, we have analyzed the expression of Scgn in dorsal root ganglia (DRGs) and trigeminal ganglia (TGs), and in spinal cord of mouse at the mRNA and protein levels, and in comparison to the well-known CaBPs, calbindin D-28k, parvalbumin and calretinin. Rat DRGs, TGs and spinal cord, as well as human DRGs and spinal cord were used to reveal phylogenetic variations. Results: We found Scgn mRNA expressed in mouse and human DRGs and in mouse ventral spinal cord. Our immunohistochemical data showed a complementary distribution of Scgn and the three CaBPs in mouse DRG neurons and spinal cord. Scgn was expressed in ∼7% of all mouse DRG neuron profiles, mainly small ones and almost exclusively co-localized with calcitonin gene-related peptide (CGRP). This co-localization was also seen in human, but not in rat DRGs. Scgn could be detected in the mouse sciatic nerve and accumulated proximal to its constriction. In mouse spinal cord, Scgn-positive neuronal cell bodies and fibers were found in gray matter, especially in the dorsal horn, with particularly high concentrations of fibers in the superficial laminae, as well as in cell bodies in inner lamina II and in some other laminae. A dense Scgn-positive fiber network and some small cell bodies were also found in the superficial dorsal horn of humans. In the ventral horn, a small number of neurons were Scgn-positive in mouse but not rat, confirming mRNA distribution. Both in mouse and rat, a subset of TG neurons contained Scgn. Dorsal rhizotomy strongly reduced Scgn fiber staining in the dorsal horn. Peripheral axotomy did not clearly affect Scgn expression in DRGs, dorsal horn or ventral horn neurons in mouse. Conclusions: Scgn is a CaBP expressed in a subpopulation of nociceptive DRG neurons and their processes in the dorsal horn of mouse, human and rat, the former two co-expressing CGRP, as well as in dorsal horn neurons in all three species. Functional implications of these findings include the cellular refinement of sensory information, in particular during the processing of pain.
Integrative analysis of neuroblastoma and pheochromocytoma genomics data
Authors: Szabó Peter M , Pintér Miklós , Szabó Diana Rita , Zsippai Adrienn , Patócs Attila , Falus András , Rácz Károly , Igaz Peter 
Published: October 2012

AbstractBackgroundPheochromocytoma and neuroblastoma are the most common neural crest-derived tumors in adults and children, respectively. We have performed a large-scale in silico analysis of altogether 1784 neuroblastoma and 531 pheochromocytoma samples to establish similarities and differences using analysis of mRNA and microRNA expression, chromosome aberrations and a novel bioinformatics analysis based on cooperative game theory.MethodsDatasets obtained from Gene Expression Omnibus and ArrayExpress have been subjected to a complex bioinformatics analysis using GeneSpring, Gene Set Enrichment Analysis, Ingenuity Pathway Analysis and own software.ResultsComparison of neuroblastoma and pheochromocytoma with other tumors revealed the overexpression of genes involved in development of noradrenergic cells. Among these, the significance of paired-like homeobox 2b in pheochromocytoma has not been reported previously. The analysis of similar expression patterns in neuroblastoma and pheochromocytoma revealed the same anti-apoptotic strategies in these tumors. Cancer regulation by stathmin turned out to be the major difference between pheochromocytoma and neuroblastoma. Underexpression of genes involved in neuronal cell-cell interactions was observed in unfavorable neuroblastoma. By the comparison of hypoxia- and Ras-associated pheochromocytoma, we have found that enhanced insulin like growth factor 1 signaling may be responsible for the activation of Src homology 2 domain containing transforming protein 1, the main co-factor of RET. Hypoxia induced factor 1α and vascular endothelial growth factor signaling included the most prominent gene expression changes between von Hippel-Lindau- and multiple endocrine neoplasia type 2A-associated pheochromocytoma.ConclusionsThese pathways include previously undescribed pathomechanisms of neuroblastoma and pheochromocytoma and associated gene products may serve as diagnostic markers and therapeutic targets.
Network insights on oxaliplatin anti‐cancer mechanisms
Authors: Alian Osama M , Azmi Asfar S , Mohammad Ramzi M 
Published: October 2012

AbstractOxaliplatin has been a crucial component of combination therapies since admission into the clinic causing modest gains in survival across multiple malignancies. However, oxaliplatin functions in a non‐targeted manner, posing a difficulty in ascertaining precise efficacy mechanisms. While previously thought to only affect DNA repair mechanisms, Platinum‐protein adducts (Pt‐Protein) far outnumber Pt‐DNA adducts leaving a big part of oxaliplatin function unknown. Through preliminary network modeling of high throughput data, this article critically reviews the efficacy of oxaliplatin as well as proposes a better model for enhanced efficacy based on a network approach. In our study, not only oxaliplatin's function in interrupting DNA‐replication was confirmed, but also its role in initiating or intensifying tumorigenesis pathways was uncovered. From our data we present a novel picture of competing signaling networks that collectively provide a plausible explanation of chemotherapeutic resistance, cancer stem cell survival, as well as invasiveness and metastases. Here we highlight oxaliplatin signaling networks, their significance and the clinical implications of these interactions that verifies the importance of network modeling in rational drug design.
Muscle-fiber transdifferentiation in an experimental model of respiratory chain myopathy
Authors: Venhoff Nils , Lebrecht Dirk , Pfeifer Dietmar , Venhoff Ana C , Bissé Emmanuel , Kirschner Janbernd , Walker Ulrich A 
Published: October 2012

Abstract
Introduction
Skeletal muscle fiber composition and muscle energetics are not static and change in muscle disease. This study was performed to determine whether a mitochondrial myopathy is associated with adjustments in skeletal muscle fiber-type composition.

Methods
Ten rats were treated with zidovudine, an antiretroviral nucleoside reverse transcriptase inhibitor that induces a myopathy by interfering with mitochondrial functions. Soleus muscles were examined after 21 weeks of treatment. Ten untreated rats served as controls.

Results
Zidovudine induced a myopathy with mitochondrial DNA depletion, abnormalities in mitochondrial ultrastructure, and reduced cytochrome c oxidase activity. Mitochondrial DNA was disproportionally more diminished in type I compared with type II fibers, whereas atrophy predominated in type II fibers. Compared with those of controls, zidovudine-exposed soleus muscles contained an increased proportion (256%) of type II fibers, whereas neonatal myosin heavy chains remained repressed, indicating fiber-type transformation in the absence of regeneration. Microarray gene-expression analysis confirmed enhanced fast-fiber isoforms, repressed slow-fiber transcripts, and reduced neonatal fiber transcripts in the mitochondrial myopathy. Respiratory chain transcripts were diminished, whereas the enzymes of glycolysis and glycogenolysis were enhanced, indicating a metabolic adjustment from oxidative to glycolytic capacities. A coordinated regulation was found of transcription factors known to orchestrate type II fiber formation (upregulation of MyoD, Six1, Six2, Eya1, and Sox6, and downregulation of myogenin and ERRγ).

Conclusions
The type I to type II fiber transformation in mitochondrial myopathy implicates mitochondrial function as a new regulator of skeletal muscle fiber type.
Medical emergency teams are associated with reduced mortality across a major metropolitan health network after two years service: a retrospective study using government administrative data
Authors: Tobin Antony E , Santamaria John D 
Published: October 2012

Abstract
Introduction
Medical emergency teams (MET) are implemented to ensure prompt clinical review of patients with deteriorating physiology with the intention of averting further deterioration, cardiac arrest and death. We sought to determine if MET implementation has led to reductions in hospital mortality across a large metropolitan health network utilising routine administrative data submitted by hospitals to the Department of Health Victoria.

Methods
The Victorian admissions episodes data set (VAED) contains data on all individual hospital separations in the State of Victoria, Australia. After gaining institutional ethics approval, we extracted data on all acute admissions to metropolitan hospitals for which we had information on the presence and timing of a MET system. Using logistic regression we determined whether there was an effect of MET implementation on mortality controlling for age, gender, Charlson comorbidity diagnostic groupings, emergency admission, same day admission, ICU admission, mechanical ventilation, year, indigenous ethnicity, liaison nurse service and hospital designation.

Results
5911533 individual admissions and 73,599 associated deaths from July 1999 to June 2010 were included in the analysis. 52.2% were male and median age was 57(42-72 IQR). Mortality rates for MET and non-MET periods were 3.92 (3.88-3.95 95%CI) and 4.56 (4.51-4.61 95%CI) deaths per 1000 patient days with a rate ratio after adjustment for year of 0.88 (0.86-0.89 95%CI) P < 0.001. In a multivariable logistic regression, mortality was associated with a MET team being active in the hospital for more than 2 years. The odds ratio for mortality in hospitals where a MET system had been in place for greater than 4 years duration was 0.90 (0.88-0.92). Mortality during the first 2 years of a MET system being in place was not statistically different from pre-MET periods.

Conclusions
Utilising routinely collected administrative data we demonstrated that the presence of a hospital MET system for greater than 2 years was associated with an independent reduction in hospital mortality across a major metropolitan health network. Mortality benefits after the introduction of a MET system take time to become apparent.
Polymorphic variants in exon 8 at the 3' UTR of the HLA-G gene are associated with septic shock in critically ill patients
Authors: Graebin Pietra , Veit Tiago D , Alho Clarice S , Dias Fernando S , Chies José AB 
Published: October 2012

Abstract
Introduction
Critically ill patients are characterized as individuals hospitalized in the Intensive Care Unit (ICU) and can evolve to sepsis, septic shock or even death. Among others, genetic factors can influence the outcome of critically ill patients. HLA-G is a non-classical class Ib molecule that has limited protein variability, presenting seven isoforms generated by alternative splicing, and presents immunomodulatory properties. Polymorphisms at the 3'UTR are thought to influence HLA-G gene expression. It was previously observed that increased sHLA-G5 levels were predictive of survival among septic shock patients. We assessed the frequencies of 7 polymorphisms in exon 8 at the 3' UTR of HLA-G and associated these variants with different clinical outcomes in critically ill patients.

Methods
Exon 8 at the 3' UTR of the HLA-G gene from 638 critically ill subjects was amplified by PCR and sequenced. Genotypes were identified using FinchTV software v.1.4.0 and the most probable haplotype constitution of each sample was determined by PHASE software v.2.1. Haplotype frequencies, linkage disequilibrium, heterozygosity test and Hardy-Weinberg Equilibrium were estimated using ARLEQUIN software v.3.5.

Results
Among all critically ill patients, an association between carriers of the +2960IN_+3142 G_+3187A haplotype and septic shock (P = 0.047) was observed. Septic patients who carried the +2960IN_+3142G_+3187A haplotype presented an increased risk for septic shock (P = 0.031).

Conclusions
The present study showed, for the first time, an association between polymorphisms in exon 8 at the 3 'UTR of HLA-G gene and outcomes of critically ill patients. These results may be important for understanding the mechanisms involved in evolution to septic shock in critically ill patients.
The estimation of cardiac output by the Nexfin device is of poor reliability for tracking the effects of a fluid challenge
Authors: Monnet Xavier , Picard Fabien , Lidzborski Elsa , Mesnil Malcie , Duranteau Jacques , Richard Christian , Teboul Jean-Louis 
Published: October 2012

Abstract
Introduction
The Nexfin device estimates arterial pressure by the volume clamp method through a finger pneumatic cuff. It also allows to estimate cardiac index (CInoninv) by pulse contour analysis of the non-invasive arterial pressure curve. We evaluated the ability of the device to track changes in cardiac index induced by a fluid challenge.

Methods
We included 45 patients for whom a volume expansion (500 mL of saline infused over 30 min) was planned. The volume expansion-induced changes in cardiac index measured by transpulmonary thermodilution (CIinv, PiCCO device) and in CInoninv were recorded.

Results
In seven patients, the Nexfin could not record the arterial curve due to finger hypoperfusion. Considering both the values obtained before and after volume expansion (n = 76 pairs of measurements), the bias (lower and upper limits of agreement) between CIinv and CInoninv was 0.2 (-1.8 to 2.2) L/min/m2. The mean change in CInoninv was 10 ± 11%. The percentage error of CInoninv was 57%. The correlation between the changes in CIinv and CInoninv observed during volume expansion was significant (P = 0.0002) with an r2 = 0.31.

Conclusions
The estimation of CI by the Nexfin device in critically ill patients is not reliable, neither for estimating absolute values of CI nor for tracking its changes during volume expansion.
Diagnostics of septic arthritis in the sternoclavicular region: 10 consecutive patients and literature review
Authors: Bodker Tina , Tøttrup Mikkel , Petersen Klaus Kjær , Jurik Anne Grethe 
Published: October 2012

Background Septic arthritis in the sternoclavicular (SC) region is rare and may be difficult to diagnose clinically and radiologically. It mainly affects immunocompromised persons, and can clinically be misinterpreted as tumor and rheumatic disorders. Lacking radiological reference standard, a multimodality approach may contribute to a prolonged diagnostic process. Purpose To describe the diagnostics of septic arthritis in the SC region. Material and Methods Between 2001 and 2011 10 patients with Staphylococcus infection in the SC region were investigated in our institution. Clinical, biochemical, radiological, and microbiological findings were studied retrospectively; all CT and MR examinations were re-evaluated. Results Initial radiography in nine patients and ultrasonography in six patients were inconclusive resulting in supplementary MRI and/or CT. Five patients examined by MRI were immediately diagnosed with septic arthritis whereas CT in five patients led to the diagnosis in only one. Three were subsequently diagnosed by MRI, but delayed more than 2.5 weeks, and one was diagnosed by surgery. The median time to diagnosis was 1.5 weeks. The delay caused by imaging was 0 days to 11.5 weeks (median 0 days). By re-evaluation overlooked complications included mediastinitis in seven patients (three diffuse, four localized), and abscesses and pleuritis each in four patients. Conclusion Awareness of infection in the SC region is important to avoid diagnostic delay. MRI is proposed as the initial imaging procedure.
Malleolar fractures and their ligamentous injury equivalents have similar outcomes in supination-external rotation type IV fractures of the ankle treated by anatomical internal fixation
Authors: Berkes M. B. , Little M. T. M. , Lazaro L. E. , Sculco P. K. , Cymerman R. M. , Daigl M. , Helfet D. L. , Lorich D. G. 
Published: October 2012

It has previously been suggested that among unstable ankle fractures, the presence of a malleolar fracture is associated with a worse outcome than a corresponding ligamentous injury. However, previous studies have included heterogeneous groups of injury. The purpose of this study was to determine whether any specific pattern of bony and/or ligamentous injury among a series of supination-external rotation type IV (SER IV) ankle fractures treated with anatomical fixation was associated with a worse outcome. We analysed a prospective cohort of 108 SER IV ankle fractures with a follow-up of one year. Pre-operative radiographs and MRIs were undertaken to characterise precisely the pattern of injury. Operative treatment included fixation of all malleolar fractures. Post-operative CT was used to assess reduction. The primary and secondary outcome measures were the Foot and Ankle Outcome Score (FAOS) and the range of movement of the ankle. There were no clinically relevant differences between the four possible SER IV fracture pattern groups with regard to the FAOS or range of movement. In this population of strictly defined SER IV ankle injuries, the presence of a malleolar fracture was not associated with a significantly worse clinical outcome than its ligamentous injury counterpart. Other factors inherent to the injury and treatment may play a more important role in predicting outcome.
The effects of rivaroxaban on the complications of surgery after total hip or knee replacement
Authors: Lassen M. R. , Gent M. , Kakkar A. K. , Eriksson B. I. , Homering M. , Berkowitz S. D. , Turpie A. G. G. 
Published: October 2012

Post-operative complications after total hip or knee replacement can delay recovery, prolong hospitalisation, increase rates of re-admission and, in the most severe cases, lead to long-term disability or even death. In this analysis of pooled data from four large, randomised, phase III clinical trials that compared the oral, direct Factor Xa inhibitor rivaroxaban with subcutaneous enoxaparin for the prevention of venous thromboembolism after total hip or knee replacement (n = 12 729), the incidence of complications, including bleeding and adverse events related to surgery (such as wound infection, wound dehiscence and haemarthrosis) are reported. Interventions and procedures relating to surgery are also compared between the groups. Bleeding events, including excessive wound haematoma and surgical-site bleeding, occurred at similar rates in the rivaroxaban and enoxaparin groups. Over the total study duration, adverse surgical events occurred at a similar rate in the rivaroxaban group compared with the enoxaparin group after total knee replacement (2.26% vs 2.69%, respectively) and total hip replacement (1.48% vs 1.65%, respectively). Blood loss, wound drainage and transfusion requirements were also similar between the two groups. This analysis shows that the incidence of adverse surgical events with rivaroxaban was similar to enoxaparin.
Using a calliper to restore the centre of the femoral head during total hip replacement
Authors: Hill J. C. , Archbold H. A. P. , Diamond O. J. , Orr J. F. , Jaramaz B. , Beverland D. E. 
Published: October 2012

Restoration of leg length and offset is an important goal in total hip replacement. This paper reports a calliper-based technique to help achieve these goals by restoring the location of the centre of the femoral head. This was validated first by using a co-ordinate measuring machine to see how closely the calliper technique could record and restore the centre of the femoral head when simulating hip replacement on Sawbone femur, and secondly by using CT in patients undergoing hip replacement.Results from the co-ordinate measuring machine showed that the centre of the femoral head was predicted by the calliper to within 4.3 mm for offset (mean 1.6 (95% confidence interval (CI) 0.4 to 2.8)) and 2.4 mm for vertical height (mean -0.6 (95% CI -1.4 to 0.2)). The CT scans showed that offset and vertical height were restored to within 8 mm (mean -1 (95% CI -2.1 to 0.6)) and -14 mm (mean 4 (95% CI 1.8 to 4.3)), respectively.Accurate assessment and restoration of the centre of the femoral head is feasible with a calliper. It is quick, inexpensive, simple to use and can be applied to any design of femoral component.
A prospective, randomised controlled trial comparing ceramic-on-metal and metal-on-metal bearing surfaces in total hip replacement
Authors: Schouten R. , Malone A. A. , Tiffen C. , Frampton C. M. , Hooper G. 
Published: October 2012

In a double-blinded randomised controlled trial, 83 patients with primary osteoarthritis of the hip received either a ceramic-on-metal (CoM) or metal-on-metal (MoM) total hip replacement (THR). The implants differed only in the bearing surfaces used. The serum levels of cobalt and chromium and functional outcome scores were compared pre-operatively and at six and 12 months post-operatively. Data were available for 41 CoM and 36 MoM THRs (four patients were lost to follow-up, two received incorrect implants). The baseline characteristics of both cohorts were similar. Femoral head size measured 36 mm in all but two patients who had 28 mm heads. The mean serum cobalt and chromium levels increased in both groups, with no difference noted between groups at six months (cobalt p = 0.67, chromium p = 0.87) and 12 months (cobalt p = 0.76, chromium p = 0.76) post-operatively. Similarly, the mean Oxford hip scores, Western Ontario and McMaster Universities Osteoarthritis index and University of California, Los Angeles activity scores showed comparable improvement at 12 months. Our findings indicate that CoM and MoM couplings are associated with an equivalent increase in serum cobalt and chromium levels, and comparable functional outcome scores at six and 12-months follow-up.
A review of rapid prototyped surgical guides for patient-specific total knee replacement
Authors: Krishnan S. P. , Dawood A. , Richards R. , Henckel J. , Hart A. J. 
Published: October 2012

Improvements in the surgical technique of total knee replacement (TKR) are continually being sought. There has recently been interest in three-dimensional (3D) pre-operative planning using magnetic resonance imaging (MRI) and CT. The 3D images are increasingly used for the production of patient-specific models, surgical guides and custom-made implants for TKR. The users of patient-specific instrumentation (PSI) claim that they allow the optimum balance of technology and conventional surgery by reducing the complexity of conventional alignment and sizing tools. In this way the advantages of accuracy and precision claimed by computer navigation techniques are achieved without the disadvantages of additional intra-operative inventory, new skills or surgical time. This review describes the terminology used in this area and debates the advantages and disadvantages of PSI.