bluuebunny/crossref_metadata_2025 huggingface dataset:
Mycoplasma gallisepticum infection in the grey partridge Perdix perdix: outbreak description, histopathology, biochemistry and antioxidant parameters
Authors: Vitula Frantisek , Peckova Lucie , Bandouchova Hana , Pohanka Miroslav , Novotny Ladislav , Jira David , Kral Jiri , Ondracek Karel , Osickova Jitka , Zendulkova Dagmar , Rosenbergova Katerina , Treml Frantisek , Pikula Jiri
Published: July 2011

Background

The grey partridge is an important game bird in Europe that has declined considerably over the last decades. The production and release of farm-bred birds can be threatened by infectious agents. The objective of this study was to describe the outbreak, pathology, and blood and tissue biochemical responses in a flock of grey partridges naturally infected withMycoplasma gallisepticum.

Results

Morbidity and mortality rates were 100% and 60%, respectively. Necropsy revealed an accumulation of caseous exudate within the infraorbital sinuses, tracheitis, pneumonia and airsacculitis. There were significant increases in activities of lactate dehydrogenase, creatine kinase and amylase, and levels of total protein and glucose inMycoplasma-infected birds when compared to control. Catalase showed significantly lower activity in the heart, lungs, liver and gonads ofMycoplasma-infected birds. Glutathione-S-transferase activity was elevated in the eye and the associated infraorbital sinus and kidneys, and decreased in the liver. Decreased levels of reduced glutathione were found in the heart, kidneys, liver and gonads. The activity of glutathione reductase was lower only in the lungs. Compared to healthy birds, mycoplasmosis in the grey partridge caused significant differences in the level of lipid peroxidation in lungs and plasma (p < 0.05), while the ferric reducing antioxidant power was lower in the heart and kidneys (p < 0.01). Significant correlations among responses of the antioxidant parameters were found namely in the heart, lungs, spleen, liver and plasma. There were also numerous significant inter-tissue correlations of all the studied antioxidant parameters.

Conclusions

The present study demonstrates the high susceptibility of grey partridges to natural infection byM. gallisepticum, the severity of the disease based on histopathology, and the modulation of blood chemical profiles and oxidative stress-associated parameters in the avian hosts, thus enhancing the understanding of the pathogenesis of mycoplasmosis in birds. Moreover, the reported reference values can be useful for the evaluation of the state of health in grey partridges.
Patient Care Teams in treatment of diabetes and chronic heart failure in primary care: an observational networks study
Authors: Weenink Jan-Willem , van Lieshout Jan , Jung Hans Peter , Wensing Michel
Published: July 2011

Background

Patient care teams have an important role in providing medical care to patients with chronic disease, but insight into how to improve their performance is limited. Two potentially relevant determinants are the presence of a central care provider with a coordinating role and an active role of the patient in the network of care providers. In this study, we aimed to develop and test measures of these factors related to the network of care providers of an individual patient.

Methods

We performed an observational study in patients with type 2 diabetes or chronic heart failure, who were recruited from three primary care practices in The Netherlands. The study focused on medical treatment, advice on physical activity, and disease monitoring. We used patient questionnaires and chart review to measure connections between the patient and care providers, and a written survey among care providers to measure their connections. Data on clinical performance were extracted from the medical records. We used network analysis to compute degree centrality coefficients for the patient and to identify the most central health professional in each network. A range of other network characteristics were computed including network centralization, density, size, diversity of disciplines, and overlap among activity-specific networks. Differences across the two chronic conditions and associations with disease monitoring were explored.

Results

Approximately 50% of the invited patients participated. Participation rates of health professionals were close to 100%. We identified 63 networks of 25 patients: 22 for medical treatment, 16 for physical exercise advice, and 25 for disease monitoring. General practitioners (GPs) were the most central care providers for the three clinical activities in both chronic conditions. The GP's degree centrality coefficient varied substantially, and higher scores seemed to be associated with receiving more comprehensive disease monitoring. The degree centrality coefficient of patients also varied substantially but did not seem to be associated with disease monitoring.

Conclusions

Our method can be used to measure connections between care providers of an individual patient, and to examine the association between specific network parameters and healthcare received. Further research is needed to refine the measurement method and to test the association of specific network parameters with quality and outcomes of healthcare.
Midgut malrotation first presenting as acute bowel obstruction in adulthood: a case report and literature review
Authors: Emanuwa Okiemute F , Ayantunde Abraham A , Davies Tony W
Published: July 2011

Malrotation of the midgut is generally regarded as paediatric pathology with the majority of patients presenting in childhood. The diagnosis is rare in adults, which sometimes leads to delay in diagnosis and treatment. A high index of suspicion is therefore required when dealing with patients of any age group with abdominal symptoms. We present a case of a 55-year old man who presented with an acute abdomen with preoperative computed tomography scan and operative findings confirming midgut rotation. The duodenum, small bowel, caecum and appendix were abnormally located, with the presence of classical Ladd's bands. There was no evidence of intestinal volvulus. The patient underwent an emergency laparotomy with an uneventful postoperative recovery.

A review of the literature is presented to highlight the rarity of intestinal malrotation and the controversies surrounding its management in the adult population.
The reliability, validity and responsiveness of the Dutch version of the Oxford elbow score
Authors: de Haan Jeroen , Goei Harold , Schep Niels WL , Tuinebreijer Wim E , Patka Peter , den Hartog Dennis
Published: July 2011

Background

The Oxford elbow score (OES) is an English questionnaire that measures the patients' subjective experience of elbow surgery. The OES comprises three domains: elbow function, pain, and social-psychological effects. This questionnaire can be completed by the patient and used as an outcome measure after elbow surgery. The aim of this study was to develop and evaluate the Dutch version of the translated OES for reliability, validity and responsiveness with respect to patients after elbow trauma and surgery.

Methods

The 12 items of the English-language OES were translated into Dutch and then back-translated; the back-translated questionnaire was then compared to the original English version. The OES Dutch version was completed by 69 patients (group A), 60 of whom had an elbow luxation, four an elbow fracture and five an epicondylitis. Quick DASH, the visual analogue pain scale (VAS) and the Mayo Elbow Performance Index (MEPI) were also completed to examine the convergent validity of the OES in group A. To calculate the test-retest reliability and responsiveness of the OES, this questionnaire was completed three times by 43 different patients (group B). An average of 52 days elapsed between therapy and the administration of the third OES (SD = 24.1).

Results

The Cronbach's α coefficients for the function, pain and social-psychological domains were 0.90, 0.87 and 0.90, respectively. The intra-class correlation coefficients for the domains were 0.87 for function, 0.89 for pain and 0.87 for social-psychological. The standardised response means for the domains were 0.69, 0.46 and 0.60, respectively, and the minimal detectable changes were 27.6, 21.7 and 24.0, respectively. The convergent validity for the function, pain and social-psychological domains, which were measured as the Spearman's correlation of the OES domains with the MEPI, were 0.68, 0.77 and 0.77, respectively. The Spearman's correlations of the OES domains with Quick DASH were -0.43, -0.44 and -0.47, respectively, and the Spearman's correlations with the VAS were -0.33, -0.38 and -0.42, respectively.

Conclusions

The Dutch OES is a reliable and valid 12-item questionnaire that can be completed within several minutes by patients with elbow injuries. This Dutch questionnaire was useful as an outcome measure in patients with elbow trauma.
Comparing ambient, air-convection, and fluid-convection heating techniques in treating hypothermic burn patients, a clinical RCT
Authors: Kjellman Britt-Marie , Fredrikson Mats , Glad-Mattsson Gunilla , Sjöberg Folke , Huss Fredrik RM
Published: July 2011

Background

Hypothermia in burns is common and increases morbidity and mortality. Several methods are available to reach and maintain normal core body temperature, but have not yet been evaluated in critical care for burned patients. Our unit's ordinary technique for controlling body temperature (Bair Hugger®+ radiator ceiling + bed warmer + Hotline®) has many drawbacks e.g.; slow and the working environment is hampered.

The aim of this study was to compare our ordinary heating technique with newly-developed methods: the Allon™2001 Thermowrap (a temperature regulating water-mattress), and Warmcloud (a temperature regulating air-mattress).

Methods

Ten consecutive burned patients (> 20% total burned surface area and a core temperature < 36.0°C) were included in this prospective, randomised, comparative study. Patients were randomly exposed to 3 heating methods. Each treatment/measuring-cycle lasted for 6 hours. Each heating method was assessed for 2 hours according to a randomised timetable. Core temperature was measured using an indwelling (bladder) thermistor. Paired t-tests were used to assess the significance of differences between the treatments within the patients. ANOVA was used to assess the differences in temperature from the first to the last measurement among all treatments. Three-way ANOVA with the Tukey HSD post hoc test and a repeated measures ANOVA was used in the same manner, but included information about patients and treatment/measuring-cycles to control for potential confounding. Data are presented as mean (SD) and (range). Probabilities of less than 0.05 were accepted as significant.

Results

The mean increase, 1.4 (SD 0.6°C; range 0.6-2.6°C) in core temperature/treatment/measuring-cycle highly significantly favoured the Allon™2001 Thermowrap in contrast to the conventional method 0.2 (0.6)°C (range -1.2 to 1.5°C) and the Warmcloud 0.3 (0.4)°C (range -0.4 to 0.9°C). The procedures for using the Allon™2001 Thermowrap were experienced to be more comfortable and straightforward than the conventional method or the Warmcloud.

Conclusions

The Allon™2001 Thermowrap was more effective than the Warmcloud or the conventional method in controlling patients' temperatures.
Age-dependent decrease in glutamine synthetase expression in the hippocampal astroglia of the triple transgenic Alzheimer's disease mouse model: mechanism for deficient glutamatergic transmission?
Authors: Olabarria Markel , Noristani Harun N , Verkhratsky Alexei , Rodríguez José J
Published: July 2011

Astrocytes are fundamental for brain homeostasis and the progression and outcome of many neuropathologies including Alzheimer's disease (AD). In the triple transgenic mouse model of AD (3xTg-AD) generalised hippocampal astroglia atrophy precedes a restricted and specific β-amyloid (Aβ) plaque-related astrogliosis. Astrocytes are critical for CNS glutamatergic transmission being the principal elements of glutamate homeostasis through maintaining its synthesis, uptake and turnover via glutamate-glutamine shuttle. Glutamine synthetase (GS), which is specifically expressed in astrocytes, forms glutamine by an ATP-dependent amination of glutamate. Here, we report changes in GS astrocytic expression in two major cognitive areas of the hippocampus (the dentate gyrus, DG and the CA1) in 3xTg-AD animals aged between 9 and 18 months. We found a significant reduction in Nv(number of cell/mm3) of GS immunoreactive (GS-IR) astrocytes starting from 12 months (28.59%) of age in the DG, and sustained at 18 months (31.65%). CA1 decrease of GS-positive astrocytes Nv(33.26%) occurs at 18 months. This Nvreduction of GS-IR astrocytes is paralleled by a decrease in overall GS expression (determined by its optical density) that becomes significant at 18 months (21.61% and 19.68% in DG and CA1, respectively). GS-IR Nvchanges are directly associated with the presence of Aβ deposits showing a decrease of 47.92% as opposed to 23.47% in areas free of Aβ. These changes in GS containing astrocytes and GS-immunoreactivity indicate AD-related impairments of glutamate homeostatic system, at the advanced and late stages of the disease, which may affect the efficacy of glutamatergic transmission in the diseased brain that may contribute to the cognitive deficiency.
Mutant Prpf31 causes pre-mRNA splicing defects and rod photoreceptor cell degeneration in a zebrafish model for Retinitis pigmentosa
Authors: Yin Jun , Brocher Jan , Fischer Utz , Winkler Christoph
Published: July 2011

Background

Retinitis pigmentosa (RP) is an inherited eye disease characterized by the progressive degeneration of rod photoreceptor cells. Mutations in pre-mRNA splicing factors including PRPF31 have been identified as cause for RP, raising the question how mutations in general factors lead to tissue specific defects.

Results

We have recently shown that the zebrafish serves as an excellent model allowing the recapitulation of key events of RP. Here we use this model to investigate two pathogenic mutations in PRPF31, SP117 and AD5, causing the autosomal dominant form of RP. We show that SP117 leads to an unstable protein that is mislocalized to the rod cytoplasm. Importantly, its overexpression does not result in photoreceptor degeneration suggesting haploinsufficiency as the underlying cause in human RP patients carrying SP117. In contrast, overexpression of AD5 results in embryonic lethality, which can be rescued by wild-type Prpf31. Transgenic retina-specific expression of AD5 reveals that stable AD5 protein is initially localized in the nucleus but later found in the cytoplasm concurrent with progressing rod outer segment degeneration and apoptosis. Importantly, we show for the first time in vivo that retinal transcripts are wrongly spliced in adult transgenic retinas expressing AD5 and exhibiting increased apoptosis in rod photoreceptors.

Conclusion

Our data suggest that distinct mutations in Prpf31 can lead to photoreceptor degeneration through different mechanisms, by haploinsufficiency or dominant-negative effects. Analyzing the AD5 effects in our animal model in vivo, our data imply that aberrant splicing of distinct retinal transcripts contributes to the observed retina defects.
Combined logical and data-driven models for linking signalling pathways to cellular response
Authors: Melas Ioannis N , Mitsos Alexander , Messinis Dimitris E , Weiss Thomas S , Alexopoulos Leonidas G
Published: July 2011

Background

Signalling pathways are the cornerstone on understanding cell function and predicting cell behavior. Recently, logical models of canonical pathways have been optimised with high-throughput phosphoproteomic data to construct cell-type specific pathways. However, less is known on how signalling pathways can be linked to a cellular response such as cell growth, death, cytokine secretion, or transcriptional activity.

Results

In this work, we measure the signalling activity (phosphorylation levels) and phenotypic behavior (cytokine secretion) of normal and cancer hepatocytes treated with a combination of cytokines and inhibitors. Using the two datasets, we construct "extended" pathways that integrate intracellular activity with cellular responses using a hybrid logical/data-driven computational approach. Boolean logic is used whenever a priori knowledge is accessible (i.e., construction of canonical pathways), whereas a data-driven approach is used for linking cellular behavior to signalling activity via non-canonical edges. The extended pathway is subsequently optimised to fit signalling and behavioural data using an Integer Linear Programming formulation. As a result, we are able to construct maps of primary and transformed hepatocytes downstream of 7 receptors that are capable of explaining the secretion of 22 cytokines.

Conclusions

We developed a method for constructing extended pathways that start at the receptor level and via a complex intracellular signalling pathway identify those mechanisms that drive cellular behaviour. Our results constitute a proof-of-principle for construction of "extended pathways" that are capable of linking pathway activity to diverse responses such as growth, death, differentiation, gene expression, or cytokine secretion.
Genome-wide analysis of the transcription factor binding preference of human bi-directional promoters and functional annotation of related gene pairs
Authors: Liu Bingchuan , Chen Jiajia , Shen Bairong
Published: July 2011

Background

Bi-directional gene pairs have received considerable attention for their prevalence in vertebrate genomes. However, their biological relevance and exact regulatory mechanism remain less understood. To study the inner properties of this gene organization and the difference between bi- and uni-directional genes, we conducted a genome-wide investigation in terms of their sequence composition, functional association and regulatory motif discovery.

Results

We identified 1210 bi-directional gene pairs based on the GRCh37 assembly data, accounting for 11.6% of all the human genes owning RNAs. CpG islands were detected in 98.42% of bi-directional promoters and 61.07% of unidirectional promoters. Functional enrichment analysis in GO and GeneGO both revealed that bi-directional genes tend to be associated with housekeeping functions in metabolism pathways and nuclear processes, and 46.84% of the pair members are involved in the same biological function. By fold-enrichment analysis, we characterized 73 and 43 putative transcription factor binding sites(TFBS) that preferentially occur in bi-directional promoters from TRANSFAC and JASPAR database respectively. By text mining, some of them were verified by individual experiments and several novel binding motifs were also identified.

Conclusions

Bi-directional promoters feature a significant enrichment of CpG-islands as well as a high GC content. We provided insight into the function constraints of bi-directional genes and found that paired genes are biased toward functional similarities. We hypothesized that the functional association underlies the co-expression of bi-directional genes. Furthermore, we proposed a set of putative regulatory motifs in the bi-directional promoters for further experimental studies to investigate transcriptional regulation of bi-directional genes.
MetaDBSite: a meta approach to improve protein DNA-binding sites prediction
Authors: Si Jingna , Zhang Zengming , Lin Biaoyang , Schroeder Michael , Huang Bingding
Published: July 2011

Background

Protein-DNA interactions play an important role in many fundamental biological activities such as DNA replication, transcription and repair. Identification of amino acid residues involved in DNA binding site is critical for understanding of the mechanism of gene regulations. In the last decade, there have been a number of computational approaches developed to predict protein-DNA binding sites based on protein sequence and/or structural information.

Results

In this article, we present metaDBSite, a meta web server to predict DNA-binding residues for DNA-binding proteins. MetaDBSite integrates the prediction results from six available online web servers: DISIS, DNABindR, BindN, BindN-rf, DP-Bind and DBS-PRED and it solely uses sequence information of proteins. A large dataset of DNA-binding proteins is constructed from the Protein Data Bank and it serves as a gold-standard benchmark to evaluate the metaDBSite approach and the other six predictors.

Conclusions

The comparison results show that metaDBSite outperforms single individual approach. We believe that metaDBSite will become a useful and integrative tool for protein DNA-binding residues prediction. The MetaDBSite web-server is freely available at http://projects.biotec.tu-dresden.de/metadbsite/ and http://sysbio.zju.edu.cn/metadbsite.
Atlantoaxial subluxation as an early manifestation in an adolescent with undifferentiated spondyloarthritis: a case report and review of the literature
Authors: Muscal Eyal , Satyan Krishna B , Jea Andrew
Published: July 2011

Introduction

Atlantoaxial instability has been described as a manifestation of ankylosing spondylitis (juvenile and adult onset), reactive arthritis, juvenile idiopathic arthritis, and rheumatoid arthritis; however, it has rarely been reported as an early manifestation of these disorders. We present this case report to increase awareness of the condition in the hope that earlier recognition of this disease may prevent further serious injury.

Case presentation

We report the case of a 17-year-old Hispanic adolescent woman who was initially diagnosed with undifferentiated spondyloarthritis due to peripheral arthritis, enthesitis, a positive human leukocyte antigen B27 result, and inflammatory spinal pain lasting two months. Our patient experienced persistent and worsening occipitocervical pain and signs of myelopathy three months after diagnosis; consequently, we found atlantoaxial instability along with cervical spine bone erosion and pannus formation. She was treated surgically with a C1-2 posterior instrumented fusion and at six weeks post-operatively was started on tumor necrosis factor α blockade. Her occipitocervical symptoms subsided following surgery and initiation of immunomodulation.

Conclusions

Our report serves to emphasize to pediatric and adult general practitioners, pediatricians, internists, family physicians, pediatric and adult rheumatologists and spine surgeons that atlantoaxial subluxation may be an early manifestation of spondyloarthritis, and that the condition is treatable by surgical intervention and immunomodulation.
Mycoplasma hominis brain abscess following uterus curettage: a case report
Authors: Al Masalma Mouhamad , Drancourt Michel , Dufour Henry , Raoult Didier , Fournier Pierre-Edouard
Published: July 2011

Introduction

Mycoplasma hominis is mostly known for causing urogenital infections. However, it has rarely been described as an agent of brain abscess.

Case presentation

We describe a case of M. hominis brain abscess in a 41-year-old Caucasian woman following uterus curettage. The diagnosis was obtained by 16S rDNA amplification, cloning and sequencing from the abscess pus, and confirmed by a specifically designed real-time polymerase chain reaction assay.

Conclusions

Findings from our patient's case suggest that M. hominis should be considered as a potential agent of brain abscess, especially following uterine manipulation.
Fulminant hemophagocytic lymphohistiocytosis induced by pandemic A (H1N1) influenza: a case report
Authors: Willekens Christophe , Cornelius Aurélie , Guerry Mary-Jane , Wacrenier Agnès , Fourrier François
Published: July 2011

Introduction

Hemophagocytic lymphohistiocytosis induced by viral diseases is a well recognized entity. Severe forms of H5N1 influenza are known to be associated with symptoms very similar to a reactive hemophagocytic syndrome. We report a case of fulminant lymphohistiocytosis associated with the pandemic A (H1N1) variant.

Case presentation

A 42-year-old Caucasian woman developed a syndrome of fatal hemophagocytic lymphohistiocytosis shortly after H1N1 influenza. Initial symptoms of the viral disease were unusual, with acute abdominal involvement. Our patient's course was complicated by diffuse skin rash and ileal ischemia. Our patient died of refractory shock and multi-organ failure. Skin, ileum and colon histology was consistent with an acute apoptosis combined with an increased cellular regeneration.

Conclusions

Influenza may be complicated by severe forms of hemophagocytic lymphohistiocytosis. To ensure early recognition and treatment, physicians should be aware of the possible induction of the syndrome by the novel H1N1 variant. The rapid occurrence of a multi-organ involvement with evocative biological features of macrophage activation should alert clinicians.
Surgical and anesthetic considerations of laryngeal saccular cyst: a case report
Authors: Aidonis Ioannis , Skalimis Anargyros , Kirodimos Efthimios
Published: July 2011

Introduction

Supraglottic laryngeal cysts are benign, uncommon lesions that have the potential to cause airway compromise.

Case Presentation

We present a case of a 46-year-old Caucasian woman who was scheduled for excision of a large neck growth (saccular cyst) and was managed successfully. There was thorough consideration regarding anesthetic and surgical management. Steps taken led to a successful excision with no recurrence during follow up.

Conclusion

This case was an opportunity to consider the challenges in the airway management associated with such cysts and provided reassurance that excision of these cysts is associated with a good post-operative outcome.
Acute heroin intoxication in a baby chronically exposed to cocaine and heroin: a case report
Authors: Joya Xavier , Fríguls Bibiana , Simó Marta , Civit Ester , de la Torre Rafael , Palomeque Antonio , Vall Oriol , Pichini Simona , Garcia-Algar Oscar
Published: July 2011

Introduction

Acute intoxication with drugs of abuse in children is often only the tip of the iceberg, actually hiding chronic exposure. Analysis using non-conventional matrices such as hair can provide long-term information about exposure to recreational drugs.

Case presentation

We report the case of a one-month-old Caucasian boy admitted to our pediatric emergency unit with respiratory distress and neurological abnormalities. A routine urine test was positive for opiates, suggesting an acute opiate ingestion. No other drugs of misuse, such as cocaine, cannabis, amphetamines or derivatives, were detected in the baby's urine. Subsequently, hair samples from the baby and the parents were collected to evaluate the possibility of chronic exposure to drug misuse by segmental analysis. Opiates and cocaine metabolites were detected in hair samples from the baby boy and his parents.

Conclusions

In light of these and previous results, we recommend hair analysis in babies and children from risky environments to detect exposure to heroin and other drug misuse, which could provide the basis for specific social and health interventions.
Improving the prevention, diagnosis and treatment of TB among people living with HIV: the role of operational research
Authors: Sculier Delphine , Getahun Haileyesus , Lienhardt Christian
Published: July 2011

Operational research is necessary to improve the access to and delivery of tuberculosis prevention, diagnosis and treatment interventions for people living with HIV. We conducted an extensive review of the literature and reports from recent expert consultations and research‐related meetings organized by the World Health Organization and the Stop TB Partnership to identify a TB/HIV operational research agenda. We present critical operational research questions in a series of key areas: optimizing TB prevention by enhancing the uptake of isoniazid preventive therapy and the implementation of infection control measures; assessing the effectiveness of existing diagnostic tools and scaling up new technologies; improving service delivery models; and reducing risk factors for mortality among TB patients living with HIV. We discuss the potential impact that addressing the operational research questions may have on improving programmes’ performance, assessing new strategies or interventions for TB control, or informing global or national policy formulation. Financial resources to implement these operational research questions should be mobilized from existing and new funding mechanisms. National TB and HIV/AIDS programmes should develop their operational research agendas based on these questions, and conduct the research that they consider crucial for improving TB and HIV control in their settings in collaboration with research stakeholders.
Case report: BRCA in the Ashkenazi population: are current testing guidelines too exclusive?
Authors: Saunders Katherine H , Nazareth Shivani , Pressman Peter I
Published: July 2011

The BRCA1/2 genes account for a significant portion of hereditary breast and ovarian cancers and they are especially prevalent in the Ashkenazi Jewish population. Women who have a mutation can prevent breast and ovarian cancer with surgical intervention. We describe an Ashkenazi Jewish patient who illustrates that current testing criteria are too restrictive, particularly for this population of patients. The patient's sister was diagnosed with breast cancer at age 33; however, she was not a mutation carrier. Based on practice guidelines, the patient was not recommended genetic testing. She subsequently underwent direct-to-consumer (DTC) testing and discovered that she was a mutation carrier. This case demonstrates the need for clinicians to be aware of the higher prevalence of BRCA mutations in the Ashkenazi population. It also exemplifies the need to involve medical professionals, including genetic counselors, in the dissemination of DNA test results.
A shortest-path graph kernel for estimating gene product semantic similarity
Authors: Alvarez Marco A , Qi Xiaojun , Yan Changhui
Published: July 2011

Background

Existing methods for calculating semantic similarity between gene products using the Gene Ontology (GO) often rely on external resources, which are not part of the ontology. Consequently, changes in these external resources like biased term distribution caused by shifting of hot research topics, will affect the calculation of semantic similarity. One way to avoid this problem is to use semantic methods that are "intrinsic" to the ontology, i.e. independent of external knowledge.

Results

We present a shortest-path graph kernel (spgk) method that relies exclusively on the GO and its structure. In spgk, a gene product is represented by an induced subgraph of the GO, which consists of all the GO terms annotating it. Then a shortest-path graph kernel is used to compute the similarity between two graphs. In a comprehensive evaluation using a benchmark dataset, spgk compares favorably with other methods that depend on external resources. Compared with simUI, a method that is also intrinsic to GO, spgk achieves slightly better results on the benchmark dataset. Statistical tests show that the improvement is significant when the resolution and EC similarity correlation coefficient are used to measure the performance, but is insignificant when the Pfam similarity correlation coefficient is used.

Conclusions

Spgk uses a graph kernel method in polynomial time to exploit the structure of the GO to calculate semantic similarity between gene products. It provides an alternative to both methods that use external resources and "intrinsic" methods with comparable performance.
Sex differences in the inflammatory response of primary astrocytes to lipopolysaccharide
Authors: Santos-Galindo María , Acaz-Fonseca Estefanía , Bellini María J , Garcia-Segura Luis M
Published: July 2011

Background

Numerous neurological and psychiatric disorders show sex differences in incidence, age of onset, symptomatology or outcome. Astrocytes, one of the glial cell types of the brain, show sex differences in number, differentiation and function. Since astrocytes are involved in the response of neural tissue to injury and inflammation, these cells may participate in the generation of sex differences in the response of the brain to pathological insults. To explore this hypothesis, we have examined whether male and female astrocytes show a different response to an inflammatory challenge and whether perinatal testosterone influences this response.

Methods

Cortical astrocyte cultures were prepared from postnatal day 1 (one day after birth) male or female CD1 mice pups. In addition, cortical astrocyte cultures were also prepared from female pups that were injected at birth with 100 μg of testosterone propionate or vehicle. Cultures were treated for 5 hours with medium containing lipopolysaccharide (LPS) or with control medium. The mRNA levels of IL6, interferon-inducible protein 10 (IP10), TNFα, IL1β, Toll-like receptor 4 (TLR4), steroidogenic acute regulatory protein and translocator protein were assessed by quantitative real-time polymerase chain reaction. Statistical significance was assessed by unpairedt-test or by one-way analysis of variance followed by the Tukeypost hoctest.

Results

The mRNA levels of IL6, TNFα and IL1β after LPS treatment were significantly higher in astrocytes derived from male or androgenized females compared to astrocytes derived from control or vehicle-injected females. In contrast, IP10 mRNA levels after LPS treatment were higher in astrocytes derived from control or vehicle-injected females than in those obtained from males or androgenized females. The different response of male and female astrocytes to LPS was due neither to differences in the basal expression of the inflammatory molecules nor to differences in the expression of the LPS receptor TLR4. In contrast, the different inflammatory response was associated with increased mRNA levels of translocator protein, a key steroidogenic regulator, in female astrocytes that were treated with LPS.

Conclusions

Male and female cortical astrocytes respond differentially to an inflammatory challenge and this may be predetermined by perinatal testosterone exposure.
Bicarbonate in diabetic ketoacidosis - a systematic review
Authors: Chua Horng Ruey , Schneider Antoine , Bellomo Rinaldo
Published: July 2011

Objective

This study was designed to examine the efficacy and risk of bicarbonate administration in the emergent treatment of severe acidemia in diabetic ketoacidosis (DKA).

Methods

PUBMED database was used to identify potentially relevant articles in the pediatric and adult DKA populations. DKA intervention studies on bicarbonate administration versus no bicarbonate in the emergent therapy, acid-base studies, studies on risk association with cerebral edema, and related case reports, were selected for review. Two reviewers independently conducted data extraction and assessed the citation relevance for inclusion.

Results

From 508 potentially relevant articles, 44 were included in the systematic review, including three adult randomized controlled trials (RCT) on bicarbonate administration versus no bicarbonate in DKA. We observed a marked heterogeneity in pH threshold, concentration, amount, and timing for bicarbonate administration in various studies. Two RCTs demonstrated transient improvement in metabolic acidosis with bicarbonate treatment within the initial 2 hours. There was no evidence of improved glycemic control or clinical efficacy. There was retrospective evidence of increased risk for cerebral edema and prolonged hospitalization in children who received bicarbonate, and weak evidence of transient paradoxical worsening of ketosis, and increased need for potassium supplementation. No studies involved patients with an initial pH < 6.85.

Conclusions

The evidence to date does not justify the administration of bicarbonate for the emergent treatment of DKA, especially in the pediatric population, in view of possible clinical harm and lack of sustained benefits.
Analogue-based approaches in anti-cancer compound modelling: the relevance of QSAR models
Authors: Bohari Mohammed Hussaini , Srivastava Hemant Kumar , Sastry Garikapati Narahari
Published: July 2011

Background

QSAR is among the most extensively used computational methodology for analogue-based design. The application of various descriptor classes like quantum chemical, molecular mechanics, conceptual density functional theory (DFT)- and docking-based descriptors for predicting anti-cancer activity is well known. Although in vitro assay for anti-cancer activity is available against many different cell lines, most of the computational studies are carried out targeting insufficient number of cell lines. Hence, statistically robust and extensive QSAR studies against 29 different cancer cell lines and its comparative account, has been carried out.

Results

The predictive models were built for 266 compounds with experimental data against 29 different cancer cell lines, employing independent and least number of descriptors. Robust statistical analysis shows a high correlation, cross-validation coefficient values, and provides a range of QSAR equations. Comparative performance of each class of descriptors was carried out and the effect of number of descriptors (1-10) on statistical parameters was tested. Charge-based descriptors were found in 20 out of 39 models (approx. 50%), valency-based descriptor in 14 (approx. 36%) and bond order-based descriptor in 11 (approx. 28%) in comparison to other descriptors. The use of conceptual DFT descriptors does not improve the statistical quality of the models in most cases.

Conclusion

Analysis is done with various models where the number of descriptors is increased from 1 to 10; it is interesting to note that in most cases 3 descriptor-based models are adequate. The study reveals that quantum chemical descriptors are the most important class of descriptors in modelling these series of compounds followed by electrostatic, constitutional, geometrical, topological and conceptual DFT descriptors. Cell lines in nasopharyngeal (2) cancer average R
2 = 0.90 followed by cell lines in melanoma cancer (4) with average R
2 = 0.81 gave the best statistical values.
Investigating a pathogenic role for TXNDC5 in rheumatoid arthritis
Authors: Chang Xiaotian , Zhao Yan , Yan Xinfeng , Pan Jihong , Fang Kehua , Wang Lin
Published: July 2011

Introduction

Expression of TXNDC5, which is induced by hypoxia, stimulates cell proliferation and angiogenesis. Our previous study detected increased TXNDC5 expression in the synovial tissues of rheumatoid arthritis (RA) patients using proteomic methods. The current study investigated a pathogenic role for TXNDC5 in RA.

Method

Expression of TXNDC5 in synovial membranes was quantitatively analyzed by immunohistochemistry, Western blotting and real-time polymerase chain reaction (PCR). Serum TXNDC5 levels and serum anti-TXNDC5 antibody levels were determined using sandwich enzyme-linked immunosorbent assay (ELISA). A total of 96 single nucleotide polymorphisms (SNPs) in or near the TXNDC5 gene were genotyped using custom-designed Illumina 96-SNP VeraCode microassay. Allele frequencies and genotype frequencies of SNPs were assessed using a case-control design in a cohort of 267 Chinese patients with RA, 51 patients with ankylosing spondylitis (AS) and 160 healthy controls. Additional genotyping of 951 patients with RA and 898 healthy controls was performed for four SNPs (rs2277105, rs369086, rs443861 and rs11962800) using the TaqMan method.

Results

Real-time PCR, Western blotting and immunohistochemistry detected significantly higher TXNDC5 expression in the synovial tissues of RA patients compared to samples from patients with osteoarthritis (OA) or AS. ELISA detected significantly higher levels of TXNDC5 in the blood of RA patients compared to OA, AS and systemic lupus erythematosus patients, and healthy controls. ELISA did not detect significantly different levels of anti-TXNDC5 antibody in the blood of RA, OA and AS patients and healthy controls. A total of 9 SNPs (rs9505298, rs41302895, rs1225936, rs1225938, rs372578, rs443861, rs408014, rs9392189 and rs2743992) showed significant association with RA, while 16 SNPs (rs1044104, rs1225937, rs1225938, rs372578, rs89715, rs378963, rs1225944, rs1225947, rs1238994, rs369086, rs408014, rs368074, rs1225954, rs1225955, rs13209404 and rs3812162) showed significant association with AS. Taqman SNP assay demonstrated that rs443861 has an association with RA, which correlates with the microassay results.

Conclusions

TXNDC5 is up-regulated in synovial tissues of RA patients. TXNDC5 has a genetic effect on the risk of RA and AS.
A randomized, double-blind study of AMG 108 (a fully human monoclonal antibody to IL-1R1) in patients with osteoarthritis of the knee
Authors: Cohen Stanley B , Proudman Susanna , Kivitz Alan J , Burch Francis X , Donohue John P , Burstein Deborah , Sun Yu-Nien , Banfield Christopher , Vincent Michael S , Ni Liyun , Zack Debra J
Published: July 2011

Introduction

AMG 108 is a fully human, immunoglobulin subclass G2 (IgG2) monoclonal antibody that binds the human interleukin-1 (IL-1) receptor type 1, inhibiting the activity of IL-1a and IL-1b. In preclinical studies, IL-1 inhibition was shown to be beneficial in models of osteoarthritis (OA). The purpose of this two-part study was to evaluate the safety and pharmacokinetics (PK; Part A) and clinical effect (Part B) of AMG 108 in a double-blind, placebo-controlled, multiple-dose study in patients with OA of the knee.

Methods

In Part A, patients received placebo or AMG 108 subcutaneously (SC; 75 mg or 300 mg) or intravenously (IV; 100 mg or 300 mg) once every 4 weeks for 12 weeks; in Part B, patients received placebo or 300 mg AMG 108 SC, once every 4 weeks for 12 weeks. The clinical effect of AMG 108 was measured in Part B by using the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index pain score.

Results

In Part A, 68 patients were randomized, and 64 received investigational product. In Part B, 160 patients were randomized, and 159 received investigational product. AMG 108 was well tolerated. Most adverse events (AEs), infectious AEs, serious AEs and infections, as well as withdrawals from the study due to AEs occurred at similar rates in both active and placebo groups. One death was reported in an 80-year-old patient (Part A, 300 mg IV AMG 108; due to complications of lobar pneumonia). AMG 108 serum concentration-time profiles exhibited nonlinear PK. The AMG 108 group in Part B had statistically insignificant but numerically greater improvement in pain compared with the placebo group, as shown by the WOMAC pain scores (median change, -63.0 versus -37.0, respectively).

Conclusions

The safety profile of AMG 108 SC and IV was comparable with placebo in patients with OA of the knee. Patients who received AMG 108 showed statistically insignificant but numerically greater improvements in pain; however, minimal, if any, clinical benefit was observed.

Trial Registration

This study is registered with ClinicalTrials.gov with the identifier NCT00110942.
Psychopathology of perpetrators of fabricated or induced illness
in children: case series
Authors: Bass Christopher , Jones David
Published: July 2011

Background

Munchausen's syndrome by proxy (recently renamed fabricated or induced
illness) is a rare form of child abuse, but relatively little is known
about the psychopathology of the perpetrators.

Aims

To examine the medical, psychiatric, social work and forensic records of
mothers referred for detailed psychiatric assessment from 1996 to
2009.

Method

Twenty-eight consecutive individuals with a putative diagnosis of
fabricated or induced illness were referred to the authors for detailed
psychiatric assessment and recommendations about management (25 from
family courts). We scrutinised all medical and psychiatric records and
interviewed them, as well as informants.

Results

In total, 16 (57%) had evidence of a current somatoform disorder, and
factitious disorders (either past or current) were identified in 18
(64%): 11 participants had both somatoform and factitious disorders. Nine
participants (32%) had non-epileptic attacks. We found evidence of
pathological lying (pseudologia fantastica) in 17 (61%) of the
participants; in some there were key links between early abusive
experiences, the development of pathological lying and the eventual
fabrication of illness in the child victim.

Conclusions

A chronic somatoform disorder or factitious disorder (or both) was
detected in almost two-thirds of the participants. Over half of the
mothers exhibited pathological lying, in some dating from adolescence,
and this often continued into adult life eventually involving the child
in a web of deceit and abuse. Psychiatrists whose work brings them into
contact with women with chronic somatoform or factitious disorders,
especially if there is evidence of lying from an early age, should always
be alert to the impact of these illnesses on any dependent children.
OPCRIT+: an electronic system for psychiatric diagnosis and data collection in clinical and research settings
Authors: Rucker James , Newman Stuart , Gray Joanna , Gunasinghe Cerisse , Broadbent Matthew , Brittain Philip , Baggaley Martin , Denis Mike , Turp John , Stewart Robert , Lovestone Simon , Schumann Gunter , Farmer Anne , McGuffin Peter
Published: July 2011

Background

The increasingly large sample size requirements of modern adult mental health research suggests the need for a data collection and diagnostic application that can be used across a broad range of clinical and research populations.

Aims

To develop a data collection and diagnostic application that can be used across a broad range of clinical and research settings.

Method

We expanded and redeveloped the OPCRIT system into a broadly applicable diagnostic and data-collection package and carried out an interrater reliability study of this new tool.

Results

OPCRIT+ performed well in an interrater reliability study with relatively inexperienced clinicians, giving a combined, weighted kappa of 0.70 for diagnostic reliability.

Conclusions

OPCRIT+ showed good overall interrater reliability scores for diagnoses. It is now incorporated in the electronic patient record of the Maudsley and associated hospitals. OPCRIT+ can be downloaded free of charge athttp://sgdp.iop.kcl.ac.uk/opcritplus.
Guidelines for screening and monitoring of cardiometabolic risk in schizophrenia: systematic evaluation
Authors: De Hert M. , Vancampfort D. , Correll C. U. , Mercken V. , Peuskens J. , Sweers K. , van Winkel R. , Mitchell A. J.
Published: July 2011

Background

Metabolic and cardiovascular health problems have become a major focus for clinical care and research in schizophrenia.

Aims

To evaluate the content and quality of screening guidelines for cardiovascular risk in schizophrenia.

Method

Systematic review and quality assessment of guidelines/recommendations for cardiovascular risk in people with schizophrenia published between 2000 and 2010, using the Appraisal of Guidelines for Research and Evaluation (AGREE).

Results

The AGREE domain scores varied between the 18 identified guidelines. Most guidelines scored best on the domains ‘scope and purpose’ and ‘clarity of presentation‘. The domain ‘rigour of development’ was problematic in most guidelines, and the domains ‘stakeholder involvement’ and ‘editorial independence’ scored the lowest. The following measurements were recommended (in order of frequency): fasting glucose, body mass index, fasting triglycerides, fasting cholesterol, waist, high-density lipoprotein/low-density lipoprotein, blood pressure and symptoms of diabetes. In terms of interventions, most guidelines recommended advice on physical activity, diet, psychoeducation of the patient, treatment of lipid abnormalities, treatment of diabetes, referral for advice and treatment, psychoeducation of the family and smoking cessation advice. Compared across all domains and content, four European guidelines could be recommended.

Conclusions

Four of the evaluated guidelines are of good quality and should guide clinicians' screening and monitoring practices. Future guideline development could be improved by increasing its rigour and assuring user and patient involvement.