bluuebunny/crossref_metadata_2025 huggingface dataset:
Factor VIII inhibitors in hemophilia A: rationale and latest evidence
Authors: Witmer Char , Young Guy
Published: October 2012

Factor VIII (FVIII) replacement therapy is the foundation of treatment in hemophilia A and is effective unless a patient develops an alloantibody (inhibitor) against exogenous FVIII. Inhibitor development is currently the most significant treatment complication seen in patients with hemophilia and is associated with considerable morbidity and a decreased quality of life. The development of an inhibitor is the result of a complex interaction between a patient’s immune system and genetic and environmental risk factors. The mainstay of treatment is the eradication of the inhibitor through immune tolerance. This review summarizes the current evidence regarding inhibitor risk factors, eradication, and hemostatic bypassing agents.
Diabetes treatment in 2025: can scientific advances keep pace with prevalence?
Authors: Shomali Mansur
Published: October 2012

Despite the known benefits of a healthy lifestyle, many individuals find it hard to maintain such a lifestyle in our modern world, which facilitates sedentary behavior and overeating. As a consequence, the prevalence of type 2 diabetes mellitus is predicted to increase dramatically over the coming years. Will developments in treatments be able to counteract the resulting impact on morbidity and mortality? The various lines of research can be grouped into three main categories: technological, biological, and pharmacological. Technological solutions are focused on the delivery of insulin and glucagon via an artificial pancreas, and components of the system are already in use, suggesting this option may well be available within the next 10 years. Of the biological solutions, pancreas transplants seem unlikely to be used widely, and islet cell transplants have also been hampered by a lack of appropriate donor tissue and graft survival after transplant. However, significant progress has been made in these areas, and additional research suggests manipulating other cell types to replace beta cells may be a viable option in the longer term. The last category, pharmacological research, appears the most promising for significantly reducing the burden of type 2 diabetes mellitus. In recent years, research has concentrated on reducing blood glucose, and the increasing pace of research has been reflected in a growing number of antidiabetic agents. In the past few years, studies of the complementary approach of protecting cells from the damaging effects of high blood glucose have also been reported, as has research into the control of energy intake and energy expenditure. Evidence from studies of dietary restriction and bariatric surgery suggests it may be possible to reset metabolism to effectively cure diabetes, and research into pharmacological agents that could selectively restore energy balance is currently the most exciting prospect for future treatments for people with type 2 diabetes mellitus.
Effect of minor Sr on precipitates in AZ31 magnesium alloys
Authors: Cheng R J , Pan F S , Jiang S , Jiang X Q , Li C
Published: October 2012

Minor Sr can effectively improve the mechanical properties such as yield strength, ultimate tensile strength and elongation of AZ31 magnesium alloys. In the present work the authors try to explain the mechanisms from the effect of minor Sr on the precipitates in AZ31 magnesium alloys. The research results indicate that 0·25Sr addition has obvious influence on the precipitates both in the as cast and as extruded AZ31 alloys, resulting in the improvement of the mechanical properties. For the as cast AZ31 magnesium alloys, after Sr addition the precipitates were refined and Al4Sr phase formed, while for the as extruded AZ31 magnesium alloys the Sr addition was found to refine both the micrometre sized and nanometre sized precipitates, and also helping their solution during hot extruding.
Multi-scale RNA comparison based on RNA triple vector curve representation
Authors: Li Ying , Duan Ming , Liang Yanchun
Published: October 2012

Background

In recent years, the important functional roles of RNAs in biological processes have been repeatedly demonstrated. Computing the similarity between two RNAs contributes to better understanding the functional relationship between them. But due to the long-range correlations of RNA, many efficient methods of detecting protein similarity do not work well. In order to comprehensively understand the RNA’s function, the better similarity measure among RNAs should be designed to consider their structure features (base pairs). Current methods for RNA comparison could be generally classified into alignment-based and alignment-free.

Results

In this paper, we propose a novel wavelet-based method based on RNA triple vector curve representation, named multi-scale RNA comparison. Firstly, we designed a novel numerical representation of RNA secondary structure termed as RNA triple vectors curve (TV-Curve). Secondly, we constructed a new similarity metric based on the wavelet decomposition of the TV-Curve of RNA. Finally we also applied our algorithm to the classification of non-coding RNA and RNA mutation analysis. Furthermore, we compared the results to the two well-known RNA comparison tools: RNAdistance and RNApdist. The results in this paper show the potentials of our method in RNA classification and RNA mutation analysis.

Conclusion

We provide a better visualization and analysis tool named TV-Curve of RNA, especially for long RNA, which can characterize both sequence and structure features. Additionally, based on TV-Curve representation of RNAs, a multi-scale similarity measure for RNA comparison is proposed, which can capture the local and global difference between the information of sequence and structure of RNAs. Compared with the well-known RNA comparison approaches, the proposed method is validated to be outstanding and effective in terms of non-coding RNA classification and RNA mutation analysis. From the numerical experiments, our proposed method can capture more efficient and subtle relationship of RNAs.
Myotubularin family phosphatase ceMTM3 is required for muscle maintenance by preventing excessive autophagy in Caenorhabditis elegans
Authors: Yu Xiaokun , Ma Junfeng , Lin Feng , Zhao Wanke , Fu Xueqi , Zhao Zhizhuang Joe
Published: October 2012

Background

Autophagy is a ubiquitous cellular process responsible for the bulk degradation of cytoplasmic components through the autophagosomal-lysosomal pathway. In skeletal muscle, autophagy has been regarded as a key regulator for muscle mass maintenance, and its imbalance leads to sarcopenia. However, the underlying mechanism is poorly understood.

Results

In this study, we demonstrate that ceMTM3, a FYVE-domain containing myotubalarin family phosphatase, is required for the maintenance of muscle fibers by preventing excessive autophagy in Caenorhabditis elegans. Knockdown of ceMTM3 by using feeding-based RNA interference caused loss of muscle fibers accompanied by shortening of muscle cell and body size in aged C. elegans worms. This was preceded by the occurrence of excessive autophagy in the muscle and other tissues, which subsequently resulted in increased lysosomal activity and necrotic cell death. However, knockdown of ceMTM3 did not aggravate the abnormalities of muscle wasting in autophagy-deficient atg-18 mutant worms.

Conclusions

Our data suggest an important role of ceMTM3 in regulating autophagy and maintaining muscle fibers. This study may have clinical implications for prevention and treatment of sarcopenia.
Identification of essential genes of the periodontal pathogen Porphyromonas gingivalis
Authors: Klein Brian A , Tenorio Elizabeth L , Lazinski David W , Camilli Andrew , Duncan Margaret J , Hu Linden T
Published: October 2012

Background

Porphyromonas gingivalisis a Gram-negative anaerobic bacterium associated with periodontal disease onset and progression. Genetic tools for the manipulation of bacterial genomes allow for in-depth mechanistic studies of metabolism, physiology, interspecies and host-pathogen interactions. Analysis of the essential genes, protein-coding sequences necessary for survival ofP. gingivalisby transposon mutagenesis has not previously been attempted due to the limitations of available transposon systems for the organism. We adapted a Mariner transposon system for mutagenesis ofP. gingivalisand created an insertion mutant library. By analyzing the location of insertions using massively-parallel sequencing technology we used this mutant library to define genes essential forP. gingivalissurvival underin vitroconditions.

Results

In mutagenesis experiments we identified 463 genes inP. gingivalisstrain ATCC 33277 that are putatively essential for viabilityin vitro. Comparing the 463P. gingivalisessential genes with previous essential gene studies, 364 of the 463 are homologues to essential genes in other species; 339 are shared with more than one other species. Twenty-five genes are known to be essential inP. gingivalisandB. thetaiotaomicrononly. Significant enrichment of essential genes within Cluster of Orthologous Groups ‘D’ (cell division), ‘I’ (lipid transport and metabolism) and ‘J’ (translation/ribosome) were identified. Previously, theP. gingivaliscore genome was shown to encode 1,476 proteins out of a possible 1,909; 434 of 463 essential genes are contained within the core genome. Thus, for the speciesP. gingivalistwenty-two, seventy-seven and twenty-three percent of the genome respectively are devoted to essential, core and accessory functions.

Conclusions

A Mariner transposon system can be adapted to create mutant libraries inP. gingivalisamenable to analysis by next-generation sequencing technologies.In silicoanalysis of genes essential forin vitrogrowth demonstrates that although the majority are homologous across bacterial species as a whole, species and strain-specific subsets are apparent. Understanding the putative essential genes ofP. gingivaliswill provide insights into metabolic pathways and niche adaptations as well as clinical therapeutic strategies.
The endocrine stress response is linked to one specific locus on chromosome 3 in a mouse model based on extremes in trait anxiety
Authors: Gonik Mariya , Frank Elisabeth , Keßler Melanie S , Czamara Darina , Bunck Mirjam , Yen Yi-Chun , Pütz Benno , Holsboer Florian , Bettecken Thomas , Landgraf Rainer , Müller-Myhsok Bertram , Touma Chadi , Czibere Ludwig
Published: October 2012

Background

The hypothalamic-pituitary-adrenal (HPA) axis is essential to control physiological stress responses in mammals. Its dysfunction is related to several mental disorders, including anxiety and depression. The aim of this study was to identify genetic loci underlying the endocrine regulation of the HPA axis.

Method

High (HAB) and low (LAB) anxiety-related behaviour mice were established by selective inbreeding of outbred CD-1 mice to model extremes in trait anxiety. Additionally, HAB vs. LAB mice exhibit comorbid characteristics including a differential corticosterone response upon stress exposure. We crossbred HAB and LAB lines to create F1 and F2 offspring. To identify the contribution of the endocrine phenotypes to the total phenotypic variance, we examined multiple behavioural paradigms together with corticosterone secretion-based phenotypes in F2 mice by principal component analysis. Further, to pinpoint the genomic loci of the quantitative trait of the HPA axis stress response, we conducted genome-wide multipoint oligogenic linkage analyses based on Bayesian Markov chain Monte Carlo approach as well as parametric linkage in three-generation pedigrees, followed by a two-dimensional scan for epistasis and association analysis in freely segregating F2 mice using 267 single-nucleotide polymorphisms (SNPs), which were identified to consistently differ between HAB and LAB mice as genetic markers.

Results

HPA axis reactivity measurements and behavioural phenotypes were represented by independent principal components and demonstrated no correlation. Based on this finding, we identified one single quantitative trait locus (QTL) on chromosome 3 showing a very strong evidence for linkage (2ln (L-score) > 10, LOD > 23) and significant association (lowest Bonferroni adjusted p < 10-28) to the neuroendocrine stress response. The location of the linkage peak was estimated at 42.3 cM (95% confidence interval: 41.3 - 43.3 cM) and was shown to be in epistasis (p-adjusted < 0.004) with the locus at 35.3 cM on the same chromosome. The QTL harbours genes involved in steroid synthesis and cardiovascular effects.

Conclusion

The very prominent effect on stress-induced corticosterone secretion of the genomic locus on chromosome 3 and its involvement in epistasis highlights the critical role of this specific locus in the regulation of the HPA axis.
Macropinocytosis is responsible for the uptake of pathogenic and non-pathogenic mycobacteria by B lymphocytes (Raji cells)
Authors: García-Pérez Blanca Estela , De la Cruz-López Juan José , Castañeda-Sánchez Jorge Ismael , Muñóz-Duarte Ana Rosa , Hernández-Pérez Alma Delia , Villegas-Castrejón Hilda , García-Latorre Ethel , Caamal-Ley Angel , Luna-Herrera Julieta
Published: October 2012

Background

The classical roles of B cells include the production of antibodies and cytokines and the generation of immunological memory, these being key factors in the adaptive immune response. However, their role in innate immunity is currently being recognised. Traditionally, B cells have been considered non-phagocytic cells; therefore, the uptake of bacteria by B cells is not extensively documented. In this study, we analysed some of the features of non-specific bacterial uptake by B lymphocytes from the Raji cell line. In our model, B cells were infected withMycobacterium tuberculosis(MTB),Mycobacterium smegmatis(MSM), andSalmonella typhimurium(ST).

Results

Our observations revealed that the Raji B cells were readily infected by the three bacteria that were studied. All of the infections induced changes in the cellular membrane during bacterial internalisation.M. smegmatisandS. typhimuriumwere able to induce important membrane changes that were characterised by abundant filopodia and lamellipodia formation. These membrane changes were driven by actin cytoskeletal rearrangements. The intracellular growth of these bacteria was also controlled by B cells.M. tuberculosisinfection also induced actin rearrangement-driven membrane changes; however, the B cells were not able to control this infection. The phorbol 12-myristate 13-acetate (PMA) treatment of B cells induced filopodia and lamellipodia formation, the production of spacious vacuoles (macropinosomes), and the fluid-phase uptake that is characteristic of macropinocytosis.S. typhimuriuminfection induced the highest fluid-phase uptake, although both mycobacteria also induced fluid uptake. A macropinocytosis inhibitor such as amiloride was used and abolished the bacterial uptake and the fluid-phase uptake that is triggered during the bacterial infection.

Conclusions

Raji B cells can internaliseS. typhimuriumand mycobacteria through an active process, such as macropinocytosis, although the resolution of the infection depends on factors that are inherent in the virulence of each pathogen.
Biogenic amine production by the wine Lactobacillus brevis IOEB 9809 in systems that partially mimic the gastrointestinal tract stress
Authors: Russo Pasquale , Fernández de Palencia Pilar , Romano Andrea , Fernández María , Lucas Patrick , Spano Giuseppe , López Paloma
Published: October 2012

Background

Ingestion of fermented foods containing high levels of biogenic amines (BA) can be deleterious to human health. Less obvious is the threat posed by BA producing organisms contained within the food which, in principle, could form BA after ingestion even if the food product itself does not initially contain high BA levels. In this work we have investigated the production of tyramine and putrescine by Lactobacillus brevis IOEB 9809, of wine origin, under simulated gastrointestinal tract (GIT) conditions.

Results

An in vitro model that simulates the normal physiological conditions in the human digestive tract, as well as Caco-2 epithelial human cell lines, was used to challenge L. brevis IOEB 9809, which produced both tyramine and putrescine under all conditions tested. In the presence of BA precursors and under mild gastric stress, a correlation between enhancement of bacterial survival and a synchronous transcriptional activation of the tyramine and putrescine biosynthetic pathways was detected. High levels of both BA were observed after exposure of the bacterium to Caco-2 cells.

Conclusions

L. brevis IOEB 9809 can produce tyramine and putrescine under simulated human digestive tract conditions. The results indicate that BA production may be a mechanism that increases bacterial survival under gastric stress.
Morphological and behavioural changes occur following the X-ray irradiation of the adult mouse olfactory neuroepithelium
Authors: Cunha Carla , Hort Yvonne , Shine John , Doyle Kharen L
Published: October 2012

Background

The olfactory neuroepithelium lines the upper nasal cavity and is in direct contact with the external environment and the olfactory bulbs. The ability to self-renew throughout life and the reproducible recovery after injury, make it a model tissue to study mechanisms underlying neurogenesis. In this study, X-rays were used to disrupt proliferating olfactory stem cell populations and to assess their role in the cellular and morphological changes involved in olfactory neurogenic processes.

Results

We have analysed the histological and functional effects of a sub-lethal dose of X-rays on the adult mouse olfactory neuroepithelium at 2 hours, 24 hours, 1 week, 2 weeks and 5 weeks. We have shown an immediate cessation of proliferating olfactory stem cells as shown by BrdU, Ki67 and pH3 expression. At 24 hours there was an increase in the neural transcription factors Mash1 and Pax6 expression, and a disruption of the basal lamina and increase in glandular cell marker expression at 1 week post-irradiation. Coincident with these changes was an impairment of the olfactory function in vivo.

Conclusions

We have shown significant changes in basal cell proliferation as well as morphological changes in the olfactory neuroepithelium following X-ray irradiation. There is involvement of the basal lamina as well as a clear role for glandular and sustentacular cells.
The REFER (REFer for EchocaRdiogram) protocol: a prospective validation of a clinical decision rule, NT-proBNP, or their combination, in the diagnosis of heart failure in primary care. Rationale and design
Authors: Tait Lynda , Roalfe Andrea K , Mant Jonathan , Cowie Martin R , Deeks Jonathan J , Iles Rachel , Barton Pelham M , Taylor Clare J , Derit Marites , Hobbs FD Richard
Published: October 2012

Background

Heart failure is a major cause of mortality and morbidity. As mortality rates are high, it is important that patients seen by general practitioners with symptoms suggestive of heart failure are identified quickly and treated appropriately. Identifying patients with heart failure or deciding which patients need further tests is a challenge. All patients with suspected heart failure should be diagnosed using objective tests such as echocardiography, but it is expensive, often delayed, and limited by the significant skill shortage of trained echocardiographers. Alternative approaches for diagnosing heart failure are currently limited. Clinical decision tools that combine clinical signs, symptoms or patient characteristics are designed to be used to support clinical decision-making and validated according to strict methodological procedures. The REFER Study aims to determine the accuracy and cost-effectiveness of our previously derived novel, simple clinical decision rule, a natriuretic peptide assay, or their combination, in the triage for referral for echocardiography of symptomatic adult patients who present in general practice with symptoms suggestive of heart failure.

Methods/design

This is a prospective, Phase II observational, diagnostic validation study of a clinical decision rule, natriuretic peptides or their combination, for diagnosing heart failure in primary care. Consecutive adult primary care patients 55 years of age or over presenting to their general practitioner with a chief complaint of recent new onset shortness of breath, lethargy or peripheral ankle oedema of over 48 hours duration, with no obvious recurrent, acute or self-limiting cause will be enrolled. Our reference standard is based upon a three step expert specialist consensus using echocardiography and clinical variables and tests.

Discussion

Our clinical decision rule offers a potential solution to the diagnostic challenge of providing a timely and accurate diagnosis of heart failure in primary care. Study results will provide an evidence-base from which to develop heart failure care pathway recommendations and may be useful in standardising care. If demonstrated to be effective, the clinical decision rule will be of interest to researchers, policy makers and general practitioners worldwide.

Trial registration

ISRCTN17635379
Using a generalized additive model with autoregressive terms to study the effects of daily temperature on mortality
Authors: Yang Lei , Qin Guoyou , Zhao Naiqing , Wang Chunfang , Song Guixiang
Published: October 2012

Background

Generalized Additive Model (GAM) provides a flexible and effective technique for modelling nonlinear time-series in studies of the health effects of environmental factors. However, GAM assumes that errors are mutually independent, while time series can be correlated in adjacent time points. Here, a GAM with Autoregressive terms (GAMAR) is introduced to fill this gap.

Methods

Parameters in GAMAR are estimated by maximum partial likelihood using modified Newton’s method, and the difference between GAM and GAMAR is demonstrated using two simulation studies and a real data example. GAMM is also compared to GAMAR in simulation study 1.

Results

In the simulation studies, the bias of the mean estimates from GAM and GAMAR are similar but GAMAR has better coverage and smaller relative error. While the results from GAMM are similar to GAMAR, the estimation procedure of GAMM is much slower than GAMAR. In the case study, the Pearson residuals from the GAM are correlated, while those from GAMAR are quite close to white noise. In addition, the estimates of the temperature effects are different between GAM and GAMAR.

Conclusions

GAMAR incorporates both explanatory variables and AR terms so it can quantify the nonlinear impact of environmental factors on health outcome as well as the serial correlation between the observations. It can be a useful tool in environmental epidemiological studies.
Linkage disequilibrium analysis reveals an albuminuria risk haplotype containing three missense mutations in the cubilin gene with striking differences among European and African ancestry populations
Authors: Tzur Shay , Wasser Walter G , Rosset Saharon , Skorecki Karl
Published: October 2012

Background

A recent meta-analysis described a variant (p.Ile2984Val) in the cubilin gene (CUBN) that is associated with levels of albuminuria in the general population and in diabetics.

Methods

We implemented a Linkage Disequilibrium (LD) search with data from the 1000 Genomes Project, on African and European population genomic sequences.

Results

We found that the p.Ile2984Val variation is part of a larger haplotype in European populations and it is almost absent in west Africans. This haplotype contains 19 single nucleotide polymorphisms (SNPs) in very high LD, three of which are missense mutations (p.Leu2153Phe, p.Ile2984Val, p.Glu3002Gly), and two have not been previously reported. Notably, this European haplotype is absent in west African populations, and the frequency of each individual polymorphism differs significantly in Africans.

Conclusions

Genotyping of these variants in existing African origin sample sets coupled to measurements of urine albumin excretion levels should reveal which is the most likely functional candidate for albuminuria risk. The unique haplotypic structure of CUBN in different populations may leverage the effort to identify the functional variant and to shed light on evolution of the CUBN gene locus.
Hydroxyethyl starch 130/0.4 and sodium chloride injection as adjunctive therapy in patients with cerebral hypoperfusion
Authors: Han Junliang , Yang Fang , Jiang Wenrui , Zhang Guangyun , Liu Zhirong , Liu Xuedong , Xia Feng , Bai Ya , He Junhong , Chao Manxiang , Zhao Gang
Published: October 2012

Background

Both severe stenosis and completed occlusion in internal carotid artery or its distal branches have been considered the main reasons of cerebral hypoperfusion, which contributes to the washout disturbances of embolism in low perfusion territories distal to stenosis. An aggravated hypoperfusion state in certain brain region may induce ischemic stroke and further cognitive decline. However, the effective medication for cerebral hypoperfusion is largely unsettled.

Methods/design

By using computed tomography perfusion (CTP) imaging, the trial will evaluate the effectiveness, safety and tolerability of hydroxyethyl starch (HES) 130/0.4 for patients with extra-/intra-cranial artery stenosis and cerebral hypoperfusion. From 5 neurological inpatient wards, 300 patients will be randomly recruited for administered routine medications plus intravascular volume therapies using the equal volume of HES 130/0.4 or 0.9% sodium chloride solution. Cerebral hypoperfusion state after 7-day intervention is the primary outcome measure. The secondary outcome measures includes, impaired renal function, abnormal heart function, hematological changes, neurological dysfunctions and cerebrovascular events in peri-intervention period and/or 3-month follow-up. The sample size will allow the detection of a two-sided 5% significance level between groups in the endpoint with a power of 80%.

Discussion

The trial would provide important efficacy and safety data on the intravascular administration of HES 130/0.4 in patients with unilateral cerebral hypoperfusion. The effects on kidney function, heart function, coagulation, neurological function and cerebralvascular events will be assessed.

Trial registration

ClinicalTrials.gov (Identifier: NCT01192581)
Identification of PADI2 as a potential breast cancer biomarker and therapeutic target
Authors: McElwee John L , Mohanan Sunish , Griffith Obi L , Breuer Heike C , Anguish Lynne J , Cherrington Brian D , Palmer Ashley M , Howe Louise R , Subramanian Venkataraman , Causey Corey P , Thompson Paul R , Gray Joe W , Coonrod Scott A
Published: October 2012

Background

We have recently reported that the expression of peptidylarginine deiminase 2 (PADI2) is regulated by EGF in mammary cancer cells and appears to play a role in the proliferation of normal mammary epithelium; however, the role of PADI2 in the pathogenesis of human breast cancer has yet to be investigated. Thus, the goals of this study were to examine whether PADI2 plays a role in mammary tumor progression, and whether the inhibition of PADI activity has anti-tumor effects.

Methods

RNA-seq data from a collection of 57 breast cancer cell lines was queried for PADI2 levels, and correlations with known subtype and HER2/ERBB2 status were evaluated. To examine PADI2 expression levels during breast cancer progression, the cell lines from the MCF10AT model were used. The efficacy of the PADI inhibitor, Cl-amidine, was tested in vitro using MCF10DCIS cells grown in 2D-monolayers and 3D-spheroids, and in vivo using MCF10DCIS tumor xenografts. Treated MCF10DCIS cells were examined by flow-cytometry to determine the extent of apoptosis and by RT2 Profiler PCR Cell Cycle Array to detect alterations in cell cycle associated genes.

Results

We show by RNA-seq that PADI2 mRNA expression is highly correlated with HER2/ERBB2 (p = 2.2 × 106) in luminal breast cancer cell lines. Using the MCF10AT model of breast cancer progression, we then demonstrate that PADI2 expression increases during the transition of normal mammary epithelium to fully malignant breast carcinomas, with a strong peak of PADI2 expression and activity being observed in the MCF10DCIS cell line, which models human comedo-DCIS lesions. Next, we show that a PADI inhibitor, Cl-amidine, strongly suppresses the growth of MCF10DCIS monolayers and tumor spheroids in culture. We then carried out preclinical studies in nude (nu/nu) mice and found that Cl-amidine also suppressed the growth of xenografted MCF10DCIS tumors by more than 3-fold. Lastly, we performed cell cycle array analysis of Cl-amidine treated and control MCF10DCIS cells, and found that the PADI inhibitor strongly affects the expression of several cell cycle genes implicated in tumor progression, including p21, GADD45α, and Ki67.

Conclusion

Together, these results suggest that PADI2 may function as an important new biomarker for HER2/ERBB2+ tumors and that Cl-amidine represents a new candidate for breast cancer therapy.
Herpes zoster is associated with an increased risk of subsequent lymphoid malignancies - A nationwide population-based matched-control study in Taiwan
Authors: Liu Yi-Chang , Yang Yi-Hsin , Hsiao Hui-Hua , Yang Wen-Chi , Liu Ta-Chih , Chang Chao-Sung , Yang Ming-Yu , Lin Pai-Mei , Hsu Jui-Feng , Chang Pi-Yu , Lin Sheng-Fung
Published: October 2012

Background

Infectious agents have been shown to contribute to the development of lymphoid malignancies. The different distribution of lymphoid malignancies in Asian and Western populations suggests possibly different etiologies in Asian populations. Herpes zoster infection, commonly seen in immunocompromised persons, has been reported to be associated with lymphoid malignancies in retrospective case–control studies from Western populations, but the results are controversial and large-scale prospective studies from Asian populations are lacking.

Methods

A nationwide population-based matched-controlled prospective study on Taiwanese patients was performed using the National Health Insurance Research Database from 1996 to 2007. Herpes zoster and malignancies were defined by compatible ICD-9-CM (International Classification of Disease, 9th Revision, Clinical Modification) codes. Patients who had been diagnosed with any malignancies before herpes zoster, with known viral infections including human immunodeficiency virus, and duration from herpes zoster to diagnosis of malignancies less than 6 months were excluded.

Results

Of 42,498 patients with herpes zoster prior to the diagnosis of any malignancies, the cumulative incidence for lymphoid malignancies was 0.11% (n = 48), compared with 0.06% (n = 106) in 169,983 age- and gender-matched controls (univariate hazard ratio (HR): 1.82, 95%CI: 1.29-2.55). The most common lymphoid malignancy was non-Hodgkin’s lymphoma (60.4%, n = 29), followed by multiple myeloma (27.1%, n = 13). Risk for developing lymphoid malignancies is significantly higher in herpes zoster patients (log rank P = 0.005). After adjusting for presence of any comorbidities in Charlson comorbidity index, time-dependent covariate for herpes group, and income category using Cox proportional hazard regressions, herpes zoster patients had an increased risk of developing lymphoid malignancies (adjusted HR: 1.68, 95%CI: 1.35-2.42, P = 0.0026), but did not have an increased risk of developing non-lymphoid malignancies (adjusted HR: 1.00, 95%CI: 0.91-1.05, P = 0.872).

Conclusion

Preceding herpes zoster infection is an independent risk marker for subsequent lymphoid malignancies in Taiwanese subjects. Further studies are warranted for pathogenesis exploration and preventive strategies in Asian populations.
Efficacy of an adjunctive brief psychodynamic psychotherapy to usual inpatient treatment of depression: rationale and design of a randomized controlled trial
Authors: Ambresin Gilles , Despland Jean-Nicolas , Preisig Martin , de Roten Yves
Published: October 2012

Background

A few recent studies have found indications of the effectiveness of inpatient psychotherapy for depression, usually of an extended duration. However, there is a lack of controlled studies in this area and to date no study of adequate quality on brief psychodynamic psychotherapy for depression during short inpatient stay exists. The present article describes the protocol of a study that will examine the relative efficacy, the cost-effectiveness and the cost-utility of adding an Inpatient Brief Psychodynamic Psychotherapy to pharmacotherapy and treatment-as-usual for inpatients with unipolar depression.

Methods/Design

The study is a one-month randomized controlled trial with a two parallel group design and a 12-month naturalistic follow-up. A sample of 130 consecutive adult inpatients with unipolar depression and Montgomery-Asberg Depression Rating Scale score over 18 will be recruited. The study is carried out in the university hospital section for mood disorders in Lausanne, Switzerland. Patients are assessed upon admission, and at 1-, 3- and 12- month follow-ups. Inpatient therapy is a manualized brief intervention, combining the virtues of inpatient setting and of time-limited dynamic therapies (focal orientation, fixed duration, resource-oriented interventions). Treatment-as-usual represents the best level of practice for a minimal treatment condition usually proposed to inpatients. Final analyses will follow an intention–to-treat strategy. Depressive symptomatology is the primary outcome and secondary outcome includes measures of psychiatric symptomatology, psychosocial role functioning, and psychodynamic-emotional functioning. The mediating role of the therapeutic alliance is also examined. Allocation to treatment groups uses a stratified block randomization method with permuted block. To guarantee allocation concealment, randomization is done by an independent researcher.

Discussion

Despite the large number of studies on treatment of depression, there is a clear lack of controlled research in inpatient psychotherapy during the acute phase of a major depressive episode. Research on brief therapy is important to take into account current short lengths of stay in psychiatry. The current study has the potential to scientifically inform appropriate inpatient treatment. This study is the first to address the issue of the economic evaluation of inpatient psychotherapy.

Trial registration

Australian New Zealand Clinical Trial Registry (ACTRN12612000909820)
Clinical utility of the Snaith-Hamilton-Pleasure scale in the Chinese settings
Authors: Liu Wen-hua , Wang Ling-zhi , Zhu Yu-hua , Li Min-hui , Chan Raymond CK
Published: October 2012

Background

The Snaith-Hamilton-Pleasure-Scale (SHAPS) is a self-reported scale evaluating anhedonia for neuropsychiatric disorders. It has demonstrated with impressive psychometric properties and advantages in its applicability over other similar instruments. However, very few studies have been conducted to examine the clinical utility of the SHAPS in the context of Chinese settings. The current study aimed to examine the clinical utility of the translated version of the SHAPS in the Chinese clinical settings.

Methods

A Chinese version of SHAPS was administered to 336 college students to examine the internal consistency and test-retest reliability at a 4-week interval. Moreover, the translated SHAPS was also administered to 141 patients with major depression, 72 patients with schizophrenia, and 72 healthy controls to examine its clinical discrimination.

Results

The internal consistency of the SHAPS for the non-clinical sample and test-retest reliability at a 4- week interval were 0.85 and 0.64, respectively. Moreover, the SHAPS also showed an excellent internal consistency (alpha was 0.93) and a one-factor solution with the first factor accounted for 51.53% of the variance in the clinical psychiatric samples. ANOVA of the SHAPS total score indicated that the patients with depression scored significantly more anhedonia than the patients with schizophrenia and healthy controls (p<0.001), and the patients with schizophrenia scored significantly more anhedonia than the healthy controls (P<0.02).

Conclusions

These findings suggest that the Chinese version of the SHAPS is a useful and promising instrument in assessing anhedonia for clinical patients and non-clinical individuals in the Chinese settings.
Diabetes MILES – The Netherlands: rationale, design and sample characteristics of a national survey examining the psychosocial aspects of living with diabetes in Dutch adults
Authors: Nefs Giesje , Bot Mariska , Browne Jessica L , Speight Jane , Pouwer François
Published: October 2012

Background

As the number of people with diabetes is increasing rapidly worldwide, a more thorough understanding of the psychosocial aspects of living with this condition has become an important health care priority. While our knowledge has grown substantially over the past two decades with respect to the physical, emotional and social difficulties that people with diabetes may encounter, many important issues remain to be elucidated. Under the umbrella of the Diabetes MILES (Management and Impact for Long-term Empowerment and Success) Study International Collaborative, Diabetes MILES – The Netherlands aims to examine how Dutch adults with diabetes manage their condition and how it affects their lives. Topics of special interest in Diabetes MILES - The Netherlands include subtypes of depression, Type D personality, mindfulness, sleep and sexual functioning.

Methods/design

Diabetes MILES – The Netherlands was designed as a national online observational study among adults with diabetes. In addition to a main set of self-report measures, the survey consisted of five complementary modules to which participants were allocated randomly. From September to October 2011, a total of 3,960 individuals with diabetes (40% type 1, 53% type 2) completed the battery of questionnaires covering a broad range of topics, including general health, self-management, emotional well-being and contact with health care providers. People with self-reported type 1 diabetes (specifically those on insulin pump therapy) were over-represented, as were those using insulin among respondents with self-reported type 2 diabetes. People from ethnic minorities were under-represented. The sex distribution was fairly equal in the total sample, participants spanned a broad age range (19–90 years), and diabetes duration ranged from recent diagnosis to living with the condition for over fifty years.

Discussion

The Diabetes MILES Study enables detailed investigation of the psychosocial aspects of living with diabetes and an opportunity to put these findings in an international context. With several papers planned resulting from a pooled Australian-Dutch dataset and data collections planned in other countries, the Diabetes MILES Study International Collaborative will contribute substantially to identifying potentially unmet needs of those living with diabetes and to inform clinical research and care across the globe.
Characteristics of myogenic response and ankle torque recovery after lengthening contraction-induced rat gastrocnemius injury
Authors: Song Hongsun , Ochi Eisuke , Lee Kihyuk , Hiranuma Kenji , Nakazato Koichi
Published: October 2012

Background

Although muscle dysfunction caused by unfamiliar lengthening contraction is one of most important issues in sports medicine, there is little known about the molecular events on regeneration process. The purpose of this study was to investigate the temporal and spatial expression patterns of myogenin, myoD, pax7, and myostatin after acute lengthening contraction (LC)-induced injury in the rat hindlimb.

Methods

We employed our originally developed device with LC in rat gastrocnemius muscle (n = 24). Male Wistar rats were anesthetized with isoflurane (aspiration rate, 450 ml/min, concentration, 2.0%). The triceps surae muscle of the right hindlimb was then electrically stimulated with forced isokinetic dorsi-flexion (180°/sec and from 0 to 45°). Tissue contents of myoD, myogenin, pax7, myostatin were measured by western blotting and localizations of myoD and pax7 was measured by immunohistochemistry. After measuring isometric tetanic torque, a single bout of LC was performedin vivo.

Results

The torque was significantly decreased on days 2 and 5 as compared to the pre-treatment value, and recovered by day 7. The content of myoD and pax7 showed significant increases on day 2. Myogenin showed an increase from day 2 to 5. Myostatin on days 5 and 7 were significantly increased. Immunohistochemical analysis showed that myoD-positive/pax7-positive cells increased on day 2, suggesting that activated satellite cells play a role in the destruction and the early recovery phases.

Conclusion

We, thus, conclude that myogenic events associate with torque recovery after LC-induced injury.
Evaluation of radial distribution of cartilage degeneration and necessity of pre-contrast measurements using radial dGEMRIC in adults with acetabular dysplasia
Authors: Xu Li , Su Yongbin , Kienle Karl-Philipp , Hayashi Daichi , Guermazi Ali , Zhang Jing , Dai Yongming , Cheng Xiaoguang
Published: October 2012

Background

The purpose of the present study was to investigate the radial distribution patterns of cartilage degeneration in dysplastic hips at different stages of secondary osteoarthritis (OA) by using radial delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC), and to assess whether pre-contrast measurements are necessary.

Methods

Thirty-five hips in 21 subjects (mean age ± SD, 27.6 ± 10.8 years) with acetabular dysplasia (lateral CE angle < 25°) were studied. Severity of OA was assessed on radiographs using Tönnis grading. Pre- (T1pre) and post-contrast T1 (T1Gd) values were measured at 7 sub-regions on radial reformatted slices acquired from a 3-dimensional (3D) T1 mapping sequence using a 1.5 T MR scanner. Values of radial T1pre, T1Gd and ΔR1 (1/T1Gd - 1/T1pre) of subgroups with different severity of OA were compared to those of the subgroup without OA using nonparametric tests, and bivariate linear Pearson correlations between radial T1Gd and ΔR1 were analyzed for each subgroup.

Results

Compared to the subgroup without OA, the subgroup with mild OA was observed with a significant decrease in T1Gd in the anterosuperior to superior sub-regions (mean, 476 ~ 507 ms, p = 0.026 ~ 0.042) and a significant increase in ΔR1 in the anterosuperior to superoposterior and posterior sub-regions (mean, 0.93 ~ 1.37 s-1, p = 0.012 ~ 0.042). The subgroup with moderate to severe OA was observed with a significant overall decrease in T1Gd (mean, 404 ~ 452 ms, p = 0.001 ~ 0.020) and an increase in ΔR1 (mean, 1.17 ~1.69 s-1, p = 0.001 ~ 0.020). High correlations were observed between radial T1Gd and ΔR1 for all subgroups (r = −0.869 ~ −0.944, p < 0.001).

Conclusions

Radial dGEMRIC without pre-contrast measurements is useful for evaluating different patterns of cartilage degeneration in the entire hip joint of patients with hip dysplasia, particularly for those in early stages of secondary OA.
Quality of life after pertrochanteric femoral fractures treated with a gamma nail: a single center study of 62 patients
Authors: Giessauf Christian , Glehr Mathias , Bernhardt Gerwin A , Seibert Franz J , Gruber Karl , Sadoghi Patrick , Leithner Andreas , Gruber Gerald
Published: October 2012

Background

Intramedullary nailing of pertrochanteric femoral fractures has grown in popularity over the past 2 decades likely because this procedure is associated with a low risk for postoperative morbidity and a fast recovery of function. The evaluation of outcomes associated with pertrochanteric nailing has mainly been based on objective measures. The purpose of the present study is to correlate patients’ health-related quality of life results after intramedullary nailing of pertrochanteric fractures with objective outcome measures.

Methods

We conducted a single-center study including 62 patients (mean age 80 ± 10 years) with pertrochanteric fractures treated with a Gamma 3 Nail. Health related quality of life was measured using the Short Form-36. These results were compared to both US and Austrian age and sex-adjusted population norms. The objective outcome measures studied at one year postoperatively included Harris Hip Score, range of motion, leg length, body mass index, neck-shaft angle and grade of osteoarthritis.

Results

According to the Harris Hip Score 43 patients (67%) had excellent or good results. There was no significant difference in the average neck-shaft angle comparing affected hip to non-affected hip at 12 months postoperatively. The average osteoarthritis score, for both the injured and uninjured hip, did not differ significantly. We found significant differences between the bodily pain, social functioning and mental health subscales and two summary scores of the Short-Form 36 in comparison to Austrian population norms. Complication rate was 8%.

Conclusions

The results of this study confirm that intramedullary nailing with the use of a Gamma Nail is a safe treatment option for stable and unstable pertrochanteric fractures. Despite good functional and radiographic results we noticed a substantial fall off in patients’ quality of life up to 12 months after operation.
Reliability and group differences in quantitative cervicothoracic measures among individuals with and without chronic neck pain
Authors: Shahidi Bahar , Johnson Cynthia L , Curran-Everett Douglas , Maluf Katrina S
Published: October 2012

Background

Clinicians frequently rely on subjective categorization of impairments in mobility, strength, and endurance for clinical decision-making; however, these assessments are often unreliable and lack sensitivity to change. The objective of this study was to determine the inter-rater reliability, minimum detectable change (MDC), and group differences in quantitative cervicothoracic measures for individuals with and without chronic neck pain (NP).

Methods

Nineteen individuals with NP and 20 healthy controls participated in this case control study. Two physical therapists performed a 30-minute examination on separate days. A handheld dynamometer, gravity inclinometer, ruler, and stopwatch were used to quantify cervical range of motion (ROM), cervical muscle strength and endurance, and scapulothoracic muscle length and strength, respectively.

Results

Intraclass correlation coefficients for inter-rater reliability were significantly greater than zero for most impairment measures, with point estimates ranging from 0.45 to 0.93. The NP group exhibited reduced cervical ROM (P ≤ 0.012) and muscle strength (P ≤ 0.038) in most movement directions, reduced cervical extensor endurance (P = 0.029), and reduced rhomboid and middle trapezius muscle strength (P ≤ 0.049).

Conclusions

Results demonstrate the feasibility of obtaining objective cervicothoracic impairment measures with acceptable inter-rater agreement across time. The clinical utility of these measures is supported by evidence of impaired mobility, strength, and endurance among patients with NP, with corresponding MDC values that can help establish benchmarks for clinically significant change.