bluuebunny/crossref_metadata_2025 huggingface dataset:
Neither retinal nor brain atrophy can be shown in patients with isolated unilateral optic neuritis at the time of presentation
Authors: Kallenbach Klaus , Sander Birgit , Tsakiri Anna , Wanscher Benedikte , Fuglø Dan , Larsen Michael , Larsson Henrik , Frederiksen Jette L
Published: September 2010

Background:Acute monosymptomatic optic neuritis (ON) may be the earliest manifestation of multiple sclerosis (MS). Atrophy has been shown to be a prominent feature of MS with great impact on disability.

Objectives:The objectives of this study were to evaluate retinal and brain atrophy and possible associations at the earliest possible stages of MS.

Methods:In a prospective observational cohort study we included 60 untreated patients with monosymptomatic ON and 19 healthy volunteers. Unaffected fellow eyes were examined with optical coherence tomography (OCT) and normalized brain volumes were calculated based on MRI. Additionally, visual evoked potentials (VEPs) were recorded.

Results:Neither OCT measurements nor brain volume measures revealed signs of localized or generalized atrophy in patients compared with healthy volunteers. Stratification of patients into high risk based on the presence of white matter lesions did not reveal differences. The association between OCT measures and brain volumes previously found could not be confirmed at the time of the first clinical event. VEP latency was significantly prolonged in patients with white matter lesions compared to those without lesions. A trend towards a relationship between VEP amplitude of fellow eyes and brain volumes was noted.

Conclusions:In this cohort we were not able to show atrophic features in the retina or the brain, and the association between structural measures of the retina and the brain as indicated in the later stages of MS could not be reproduced. These findings suggest that atrophy does require time to evolve and indicate the complexity of the relationship between local and general structural measures.
Acute severe memory impairment as a presenting symptom of multiple sclerosis: a clinical case study with 3D double inversion recovery MR imaging
Authors: Coebergh JAF , Roosendaal SD , Polman CH , Geurts JJ , van Woerkom TCAM
Published: September 2010

We present the case of a 21-year-old woman with acute memory impairment. It was initially not recognized as organic in nature. Repeated neuropsychological testing confirmed severely disturbed encoding and recall. Three-dimensional double inversion recovery (3D-DIR) MRI confirmed hippocampal and cortical lesions. Further clinical symptoms, visual evoked potential and MRI suggested a diagnosis of multiple sclerosis (MS). The amnestic syndrome has remained for 5 years. This case illustrates that MS can present with acute cortical symptoms which can be difficult to recognize. The hippocampus can be acutely affected and DIR MRI imaging can help to demonstrate cortical lesions that explain the clinical picture.
Being Prosthetic in the First World War and Weimar Germany
Authors: Neumann Boaz
Published: September 2010

In this article I discuss the prosthetic phenomenon during the First World War and Weimar Germany. As opposed to contemporary trends, with their inflationary use of the ‘prosthesis’, sometimes even hypothesizing ‘prostheticization’ as a paradigm, I seek to return the debate about the prosthesis to its historical concreteness. I describe the phenomenology of the prosthesis in three senses: first, in the statistical sense, in the form of a dramatic growth in the number of prostheses; second, in the visual sense, in the form of a dramatic growth in the visibility of the prosthesis. Basing myself on the Heideggerian perception of the ‘phenomenon’, I seek to reveal an additional, third, aspect of the phenomenology of the prosthesis. It is my contention, against the background of the major catastrophe of the First World War and the frequent crises that afflicted Weimar Germany, but also in the light of additional contexts — technological, economic, cultural — that the prosthesis was increasingly perceived as a phenomenon, i.e. as something which appeared in a wide range of ways — as prosthesis, as tool (hammer, writing instrument), as an organic limb (hand, leg), and even as a paradigm (man as ‘prosthetic God’, man as ‘Dasein’).
Microchimerism in the Mother(land): Blurring the Borders of Body and Nation
Authors: Martin Aryn
Published: September 2010

This article traces the ubiquitous geopolitical metaphors used by researchers in the field of pregnancy-related microchimerism. In this research domain, immunologists and medical geneticists locate ‘non-self’ cells in women by marking Y chromosomes in cells derived from their sons. In the course of this research trajectory, experiments have yielded a number of surprises, beginning with the very presence of these cells in women decades after pregnancy. This finding confounded the expectations predicted by classical immunology, which posits the destruction of such ‘foreign’ entities. Once they were known to be present, fetal cells were implicated in pathological and destructive activity. In a series of reorientations in which metaphor, theory and practice are entangled with matter, the characterization of these cells has shifted from invaders to insurgent foreigners to assimilated productive immigrants. The article reflects on this rich domain of material-semiotic practice to demonstrate that the case of fetomaternal cell trafficking contributes to a growing uneasiness with dominant ontologies of bodies as bounded, defended, pure collectives of homogeneous inhabitants.
Review article: Coagulation and fibrinolysis in diabetes
Authors: Alzahrani SH , Ajjan RA
Published: September 2010

Atherothrombotic complications are the main cause of mortality in subjects with diabetes. Premature atherosclerosis, increased platelet reactivity and activation of coagulation factors with associated hypofibrinolysis all contribute to increased cardiovascular risk in this population. Blood clot formation represents the last step in the atherothrombotic process, and the structure of the fibrin network has a role in determining predisposition to cardiovascular disease. In this review, we discuss alterations in coagulation factor plasma levels and/or activity in diabetes and clarify their role in predisposition to cardiovascular events. The effect of diabetes on fibrin network structure/fibrinolysis is reviewed and potential mechanisms that modify clot properties are discussed. Finally, modulation of clotting potential by the various therapeutic agents used in diabetes is examined. Understanding the mechanisms by which diabetes influences the coagulation pathway will help to develop more effective treatment strategies to reduce thrombotic events in subjects with this condition.
Assessing Children’s Home Language Environments Using Automatic Speech Recognition Technology
Authors: Greenwood Charles R. , Thiemann-Bourque Kathy , Walker Dale , Buzhardt Jay , Gilkerson Jill
Published: September 2010

The purpose of this research was to replicate and extend some of the findings of Hart and Risley using automatic speech processing instead of human transcription of language samples. The long-term goal of this work is to make the current approach to speech processing possible by researchers and clinicians working on a daily basis with families and young children. Twelve hour-long, digital audio recordings were obtained repeatedly in the homes of middle to upper SES families for a sample of typically developing infants and toddlers ( N = 30). These recordings were processed automatically using a measurement framework based on the work of Hart and Risley. Like Hart and Risley, the current findings indicated vast differences in individual children’s home language environments (i.e., adult word count), children’s vocalizations, and conversational turns. Automated processing compared favorably to the original Hart and Risley estimates that were based on transcription. Adding to Hart and Risley’s findings were new descriptions of patterns of daily talk and relationships to widely used outcome measures, among others. Implications for research and practice are discussed.
Return to Sports for Professional Baseball Players After Surgery of the Shoulder or Elbow
Authors: Cohen Steven B. , Sheridan Scott , Ciccotti Michael G.
Published: September 2010

Background:

The purpose of this study was to assess major and minor league baseball players’ return to professional baseball at a preinjury level or higher after surgery of the shoulder or elbow.

Hypothesis:

The majority of athletes will be able to return to their preinjury level after surgery.

Study Design:

Case series.

Methods:

Over a 4-season period, prospective injury and surgery records were reviewed for one professional baseball club. Forty-four players underwent 51 procedures (28 shoulder and 23 elbow) by multiple experienced surgeons; 7 players underwent more than 1 procedure.

Results:

Twenty-eight shoulder surgeries were performed on 27 players: 19 pitchers and 8 position players. The majority of the procedures were labral repairs (n = 21). Nine players returned to their preoperative level; 2 advanced to a higher level; 5 returned to a lower level; and 11 retired from professional baseball. Only 2 of the 12 players at the high professional level (Major League Baseball, triple-A, double-A) returned to the same level. Twenty-three elbow surgeries were performed on 21 players (20 pitchers). The majority of the procedures were ulnar collateral ligament reconstructions (n = 12). Seven players returned to their preoperative level; 4 advanced to a higher level; 4 returned to a lower level; and 6 retired from professional baseball. Of the 12 players at the high professional level, 3 returned to the same or higher level.

Conclusion:

Following surgery, 21 of 44 players (48%) returned to the same or higher level of professional baseball. For those players performing at a high professional level, 5 of 22 (23%) returned to the same or higher level. Return to the same or higher level was more likely with elbow surgery than with shoulder surgery.

Clinical Relevance:

Elite throwing athletes may not return to the same level at a high rate following shoulder or elbow surgery.
Gene therapy augments the efficacy of hematopoietic cell transplantation and fully corrects mucopolysaccharidosis type I phenotype in the mouse model
Authors: Visigalli Ilaria , Delai Stefania , Politi Letterio S. , Di Domenico Carmela , Cerri Federica , Mrak Emanuela , D'Isa Raffaele , Ungaro Daniela , Stok Merel , Sanvito Francesca , Mariani Elisabetta , Staszewsky Lidia , Godi Claudia , Russo Ilaria , Cecere Francesca , del Carro Ubaldo , Rubinacci Alessandro , Brambilla Riccardo , Quattrini Angelo , Di Natale Paola , Ponder Katherine , Naldini Luigi , Biffi Alessandra
Published: September 2010

Type I mucopolysaccharidosis (MPS I) is a lysosomal storage disorder caused by the deficiency of α-L-iduronidase, which results in glycosaminoglycan accumulation in tissues. Clinical manifestations include skeletal dysplasia, joint stiffness, visual and auditory defects, cardiac insufficiency, hepatosplenomegaly, and mental retardation (the last being present exclusively in the severe Hurler variant). The available treatments, enzyme-replacement therapy and hematopoietic stem cell (HSC) transplantation, can ameliorate most disease manifestations, but their outcome on skeletal and brain disease could be further improved. We demonstrate here that HSC gene therapy, based on lentiviral vectors, completely corrects disease manifestations in the mouse model. Of note, the therapeutic benefit provided by gene therapy on critical MPS I manifestations, such as neurologic and skeletal disease, greatly exceeds that exerted by HSC transplantation, the standard of care treatment for Hurler patients. Interestingly, therapeutic efficacy of HSC gene therapy is strictly dependent on the achievement of supranormal enzyme activity in the hematopoietic system of transplanted mice, which allows enzyme delivery to the brain and skeleton for disease correction. Overall, our data provide evidence of an efficacious treatment for MPS I Hurler patients, warranting future development toward clinical testing.
Treatment of tuberculosis: update 2010
Authors: Yew W.W. , Lange C. , Leung C.C.
Published: September 2010

Currently, the standard short-course chemotherapy for tuberculosis comprises a 6-month regimen, with a four-drug intensive phase and a two-drug continuation phase. Alternative chemotherapy using more costly and toxic drugs, often for prolonged durations generally >18 months, is required for multidrug-resistant and extensively drug-resistant tuberculosis. Directly observed treatment, as part of a holistic care programme, is a cost-effective strategy to ensure high treatment success and curtail development of drug resistance in tuberculosis. New antituberculosis drugs are urgently needed to improve the present standard short-course and alternative chemotherapies, by shortening administration durations and increasing cure rates, through the greater potency of these agents. At the same time, the role of adjunctive surgery for drug-resistant tuberculosis has to be better defined. Immunotherapy might improve treatment outcomes of both drug-susceptible and -resistant tuberculosis, and warrants further exploration.
Early treatment of obstructive apnoea and stroke outcome: a randomised controlled trial
Authors: Parra O. , Sánchez-Armengol Á. , Bonnin M. , Arboix A. , Campos-Rodríguez F. , Pérez-Ronchel J. , Durán-Cantolla J. , de la Torre G. , González Marcos J.R. , de la Peña M. , Carmen Jiménez M. , Masa F. , Casado I. , Luz Alonso M. , Macarrón J.L.
Published: September 2010

The aim of the present study was to assess the impact of nasal continuous positive airway pressure (nCPAP) in ischaemic stroke patients followed for 2 yrs.

Stroke patients with an apnoea–hypopnoea index ≥20 events·h−1were randomised to early nCPAP (n = 71; 3–6 days after stroke onset) or conventional treatment (n = 69). The Barthel Index, Canadian Scale, Rankin Scale and Short Form-36 were measured at baseline, and at 1, 3, 12 and 24 months.

The percentage of patients with neurological improvement 1 month after stroke was significantly higher in the nCPAP group (Rankin scale 90.9versus56.3% (p<0.01); Canadian scale 88.2versus72.7% (p<0.05)). The mean time until the appearance of cardiovascular events was longer in the nCPAP group (14.9versus7.9 months; p = 0.044), although cardiovascular event-free survival after 24 months was similar in both groups. The cardiovascular mortality rate was 0% in the nCPAP group and 4.3% in the control group (p = 0.161).

Early use of nCPAP seems to accelerate neurological recovery and to delay the appearance of cardiovascular events, although an improvement in patients’ survival or quality of life was not shown.
Increased upper airway cytokines and oxidative stress in severe obstructive sleep apnoea
Authors: Kimoff R.J. , Hamid Q. , Divangahi M. , Hussain S. , Bao W. , Naor N. , Payne R.J. , Ariyarajah A. , Mulrain K. , Petrof B.J.
Published: September 2010

Inflammation may contribute to upper airway pathophysiology in obstructive sleep apnoea (OSA). Our objective was to compare upper airway pro-inflammatory cytokine expression, oxidative stress and connective tissue deposition in severe (n = 25)versusmild (n = 17) OSA patients.

Upper airway surgical specimens were separated by predominance of either mucosal or muscle tissue. Expression levels of interleukin (IL)-1α, IL-6, interferon-γ, RANTES (regulated on activation, normal T-cell expressed and secreted), transforming growth factor (TGF)-β andl-selectin were measured by ribonuclease protection assay. Oxidative stress was assessedviaprotein carbonyl group detection by immunoblotting. Histochemistry was employed for immunolocalisation of selected cytokines and connective tissue morphometry.

In the severe OSA group, expression of IL-1α, IL-6 and TGF-β was significantly higher in mucosa-predominant tissues, whereas in muscle-predominant specimens, RANTES expression was greater in severe OSA. Increased protein carbonylation was observed in severe OSA within both mucosal and muscle compartments. Immunohistochemistry localised TGF-β to submucosal and perimuscular inflammatory cells, while IL-6 was primarily localised to myocytes. Consistent with the pro-fibrotic cytokine profile observed in mucosa-predominant tissue, morphometric analysis revealed greater submucosal and perimuscular connective tissue in severe OSA subjects.

There is increased pro-inflammatory and pro-fibrotic cytokine expression, oxidative stress, and connective tissue deposition in upper airway tissues from severeversusmild OSA patients.
Impact of aerobic exercise capacity and procedure-related factors in lung cancer surgery
Authors: Licker M. , Schnyder J-M. , Frey J-G. , Diaper J. , Cartier V. , Inan C. , Robert J. , Bridevaux P-O. , Tschopp J-M.
Published: September 2010

Over the past decades, major progress in patient selection, surgical techniques and anaesthetic management have largely contributed to improved outcome in lung cancer surgery. The purpose of this study was to identify predictors of post-operative cardiopulmonary morbidity in patients with a forced expiratory volume in 1 s <80% predicted, who underwent cardiopulmonary exercise testing (CPET).

In this observational study, 210 consecutive patients with lung cancer underwent CPET with completed data over a 9-yr period (2001–2009).

Cardiopulmonary complications occurred in 46 (22%) patients, including four (1.9%) deaths. On logistic regression analysis, peak oxygen uptake (peakV′O2) and anaesthesia duration were independent risk factors of both cardiovascular and pulmonary complications; age and the extent of lung resection were additional predictors of cardiovascular complications, whereas tidal volume during one-lung ventilation was a predictor of pulmonary complications. Compared with patients with peakV′O2>17 mL·kg−1·min−1, those with a peakV′O2<10 mL·kg−1·min−1had a four-fold higher incidence of cardiac and pulmonary morbidity.

Our data support the use of pre-operative CPET and the application of an intra-operative protective ventilation strategy. Further studies should evaluate whether pre-operative physical training can improve post-operative outcome.
Cystic fibrosis and survival to 40 years: a study of cystic fibrosis transmembrane conductance regulator function
Authors: Simmonds N.J. , D'Souza L. , Roughton M. , Alton E.W.F.W. , Davies J.C. , Hodson M.E.
Published: September 2010

Significant survival heterogeneity exists in cystic fibrosis. Our aim was to determine whether residual function of the cystic fibrosis transmembrane conductance regulator (CFTR) is present in long-term survivors with severe mutations.

Nasal potential difference (PD) and sweat chloride were measured in 34 long-term survivors (aged ≥40 yrs) and compared with young patients (18–23 yrs) with severe (n = 30) and mild (n = 31) lung disease.

Baseline PD was not significantly different across the three groups (long-term survivors, -42.8 (range -71.0– -20.5) mV; young/mild, -40.5 (-58.8– -19.5) mV; young/severe,-46.3 (-74.0– -20.0) mV). Response to amiloride (ΔAmil) was significantly different across the three groups (p = 0.01); long-term survivors had values (27.8 (range 8.5–46) mV) which were not different to either young group, but the young/severe group had significantly higher values (29.5 (11–47) mV) than those in the young/mild group (22.0 (7–39) mV; p<0.01). Baseline PD and ΔAmil were associated with forced expiratory volume in 1 s (FEV1) (co-efficient (95% CI) -0.13 (-0.23– -0.03); p = 0.009 and -0.12 (-0.20– -0.04); p = 0.003, respectively). Sweat chloride was lowest (p <0.05) in the young/severe group (93.5 (74–111) mmol·L−1versus98.8 (76.5–116.0) mmol·L−1; long-term survivors; and 99.5 (80.0–113.5) mmol·L−1; young/mild).

Δ Amil is associated with FEV1but our findings indicate that long-term survival cannot be explained by residual CFTR function when measurements are taken in later life.
Pseudomonas aeruginosaaccentuates epithelial-to-mesenchymal transition in the airway
Authors: Borthwick L.A. , Sunny S.S. , Oliphant V. , Perry J. , Brodlie M. , Johnson G.E. , Ward C. , Gould K. , Corris P.A. , De Soyza A. , Fisher A.J.
Published: September 2010

Epithelial-to-mesenchymal transition (EMT) has been implicated in the dysregulated epithelial wound repair that contributes to obliterative bronchiolitis (OB) after lung transplantation. Acquisition ofPseudomonas aeruginosain the transplanted airway has been shown to be a risk factor for the development of OB. We investigated the potential ofP. aeruginosato drive EMT in primary bronchial epithelial cells (PBECs) isolated from lung transplant recipients.

Changes in the expression of epithelial and mesenchymal markers was assessed in cells challenged with clinical isolates ofP. aeruginosaor co-cultured withP. aeruginosa-activated monocytic cells (THP-1) in the presence or absence of transforming growth factor (TGF)-β1.

P. aeruginosadid not drive or accentuate TGF-β1-driven EMT directly. Co-culturingP. aeruginosa-activated THP-1 cells with PBECs did not drive EMT. However, co-culturingP. aeruginosa-activated THP-1 cells with PBECs significantly accentuated TGF-β1-driven EMT.

P. aeruginosa,viathe activation of monocytic cells, can accentuate TGF-β1-driven EMT. Thesein vitroobservations may help explain thein vivoclinical observation of a link between acquisition ofP. aeruginosaand an increased risk of developing OB.
Determinants of prescription and choice of empirical therapy for hospital-acquired and ventilator-associated pneumonia
Authors: Rello J. , Ulldemolins M. , Lisboa T. , Koulenti D. , Mañez R. , Martin-Loeches I. , De Waele J.J. , Putensen C. , Guven M. , Deja M. , Diaz E.
Published: September 2010

The objectives of this study were to assess the determinants of empirical antibiotic choice, prescription patterns and outcomes in patients with hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP) in Europe.

We performed a prospective, observational cohort study in 27 intensive care units (ICUs) from nine European countries. 100 consecutive patients on mechanical ventilation for HAP, on mechanical ventilation >48 h or with VAP were enrolled per ICU.

Admission category, sickness severity andAcinetobacterspp. prevalence >10% in pneumonia episodes determined antibiotic empirical choice. Trauma patients were more often prescribed non-anti-Pseudomonascephalosporins (OR 2.68, 95% CI 1.50–4.78). Surgical patients received less aminoglycosides (OR 0.26, 95% CI 0.14–0.49). A significant correlation (p<0.01) was found between Simplified Acute Physiology Score II score and carbapenem prescription. BasalAcinetobacterspp. prevalence >10% dramatically increased the prescription of carbapenems (OR 3.5, 95% CI 2.0–6.1) and colistin (OR 115.7, 95% CI 6.9–1,930.9). Appropriate empirical antibiotics decreased ICU length of stay by 6 days (26.3±19.8 daysversus32.8±29.4 days; p = 0.04). The antibiotics that were prescribed most were carbapenems, piperacillin/tazobactam and quinolones. Median (interquartile range) duration of antibiotic therapy was 9 (6–12) days. Anti-methicillin-resistantStaphylococcus aureusagents were prescribed in 38.4% of VAP episodes.

Admission category, sickness severity and basalAcinetobacterprevalence >10% in pneumonia episodes were the major determinants of antibiotic choice at the bedside. Across Europe, carbapenems were the antibiotic most prescribed for HAP/VAP.
Augmentation of neovascularization in murine hindlimb ischemia by combined therapy with simvastatin and bone marrow-derived mesenchymal stem cells transplantation
Authors: Li Yong , Zhang Dingguo , Zhang Yuqing , He Guoping , Zhang Fumin
Published: September 2010

Objectives

We postulated that combining high-dose simvastatin with bone marrow derived-mesenchymal stem cells (MSCs) delivery may give better prognosis in a mouse hindlimb ischemia model.

Methods

Mouse hindlimb ischemia model was established by ligating the right femoral artery. Animals were grouped (n = 10) to receive local injection of saline without cells (control and simvastatin groups) or with 5 × 106 MSCs (MSCs group).Animals received either simvastatin (20 mg/kg/d, simvastatin and combination groups) or saline(control and MSCs group) gavages for continual 21 days. The blood flow was assessed by laser Doppler imaging at day 0,10 and 21 after surgery, respectively. Ischemic muscle was harvested for immunohistological assessments and for VEGF protein detection using western blot assay at 21 days post-surgery. In vitro, MSCs viability was measured by MTT and flow cytometry following culture in serum-free medium for 24 h with or without simvastatin. Release of VEGF by MSCs incubated with different doses of simvastatin was assayed using ELISA.

Results

Combined treatment with simvastatin and MSCs induced a significant improvement in blood reperfusion, a notable increase in capillary density, a highest level of VEGF protein and a significant decrease in muscle cell apoptosis compared with other groups. In vitro, simvastatin inhibited MSCs apoptosis and increased VEGF release by MSCs.

Conclusions

Combination therapy with high-dose simvastatin and bone marrow-derived MSCs would augment functional neovascularization in a mouse model of hindlimb ischemia.
Multivariate meta-analysis of proteomics data from human prostate and colon tumours
Authors: Rosenberg Lina Hultin , Franzén Bo , Auer Gert , Lehtiö Janne , Forshed Jenny
Published: September 2010

Background

There is a vast need to find clinically applicable protein biomarkers as support in cancer diagnosis and tumour classification. In proteomics research, a number of methods can be used to obtain systemic information on protein and pathway level on cells and tissues. One fundamental tool in analysing protein expression has been two-dimensional gel electrophoresis (2DE). Several cancer 2DE studies have reported partially redundant lists of differently expressed proteins. To be able to further extract valuable information from existing 2DE data, the power of a multivariate meta-analysis will be evaluated in this work.

Results

We here demonstrate a multivariate meta-analysis of 2DE proteomics data from human prostate and colon tumours. We developed a bioinformatic workflow for identifying common patterns over two tumour types. This included dealing with pre-processing of data and handling of missing values followed by the development of a multivariate Partial Least Squares (PLS) model for prediction and variable selection. The variable selection was based on the variables performance in the PLS model in combination with stability in the validation. The PLS model development and variable selection was rigorously evaluated using a double cross-validation scheme. The most stable variables from a bootstrap validation gave a mean prediction success of 93% when predicting left out test sets on models discriminating between normal and tumour tissue, common for the two tumour types. The analysis conducted in this study identified 14 proteins with a common trend between the tumour types prostate and colon, i.e. the same expression profile between normal and tumour samples.

Conclusions

The workflow for meta-analysis developed in this study enabled the finding of a common protein profile for two malign tumour types, which was not possible to identify when analysing the data sets separately.
The liposoluble proteome of Mycoplasma agalactiae: an insight into the minimal protein complement of a bacterial membrane
Authors: Cacciotto Carla , Addis Maria Filippa , Pagnozzi Daniela , Chessa Bernardo , Coradduzza Elisabetta , Carcangiu Laura , Uzzau Sergio , Alberti Alberto , Pittau Marco
Published: September 2010

Background

Mycoplasmas are the simplest bacteria capable of autonomous replication. Their evolution proceeded from gram-positive bacteria, with the loss of many biosynthetic pathways and of the cell wall. In this work, the liposoluble protein complement of Mycoplasma agalactiae, a minimal bacterial pathogen causing mastitis, polyarthritis, keratoconjunctivitis, and abortion in small ruminants, was subjected to systematic characterization in order to gain insights into its membrane proteome composition.

Results

The selective enrichment for M. agalactiae PG2T liposoluble proteins was accomplished by means of Triton X-114 fractionation. Liposoluble proteins were subjected to 2-D PAGE-MS, leading to the identification of 40 unique proteins and to the generation of a reference 2D map of the M. agalactiae liposoluble proteome. Liposoluble proteins from the type strain PG2 and two field isolates were then compared by means of 2D DIGE, revealing reproducible differences in protein expression among isolates. An in-depth analysis was then performed by GeLC-MS/MS in order to achieve a higher coverage of the liposoluble proteome. Using this approach, a total of 194 unique proteins were identified, corresponding to 26% of all M. agalactiae PG2T genes. A gene ontology analysis and classification for localization and function was also carried out on all protein identifications. Interestingly, the 11.5% of expressed membrane proteins derived from putative horizontal gene transfer events.

Conclusions

This study led to the in-depth systematic characterization of the M. agalactiae liposoluble protein component, providing useful insights into its membrane organization.
Incidence of genital warts among the Hong Kong general adult population
Authors: Lin Chunqing , Lau Joseph TF , Ho King-Man , Lau Man-Chun , Tsui Hi-Yi , Lo Kuen-Kong
Published: September 2010

Background

The objective of this study is to estimate the incidence of genital warts in Hong Kong and explore a way to establish a surveillance system for genital warts among the Hong Kong general population.

Methods

A total of 170 private doctors and all doctors working in the 5 local Social Hygiene Clinics (SHC) participated in this study. During the 14-day data collection period (January 5 through18, 2009), the participating doctors filled out a log-form on a daily basis to record the number of patients with genital warts. The total number of new cases of genital warts presented to private and public doctors in Hong Kong was projected using the stratification sampling method.

Results

A total of 721 (0.94%) adults presented with genital warts to the participating doctors during the two-week study period, amongst them 73 (10.1%) were new cases. The projected number of new cases of genital warts among Hong Kong adults was 442 (297 male and 144 female) during the study period. The incidence of genital warts in Hong Kong was estimated to be 203.7 per 100,000 person-years (respectively 292.2 and 124.9 per 100,000 person-years for males and females).

Conclusions

The incidence of genital warts is high among adults in Hong Kong. The study demonstrates the importance of collecting surveillance data from both private and public sectors.
Involvement of hyaluronidases in colorectal cancer
Authors: Bouga Helen , Tsouros Isidoros , Bounias Dimitrios , Kyriakopoulou Dora , Stavropoulos Michael S , Papageorgakopoulou Nikoletta , Theocharis Dimitrios A , Vynios Demitrios H
Published: September 2010

Background

Hyaluronidases belong to a class of enzymes that degrade, predominantly, hyaluronan. These enzymes are known to be involved in physiological and pathological processes, such as tumor growth, infiltration and angiogenesis, but their exact role in tumor promotion or suppression is not clear yet. Advanced colorectal cancer is associated with elevated amounts of hyaluronan of varying size. The aim of the present study was therefore to illuminate the importance of hyaluronidases in colon carcinoma progression.

Methods

The patients' samples (macroscopically normal and cancerous) were subjected to sequential extraction with PBS, 4 M GdnHCl and 4 M GdnHCl - 1% Triton X-100. The presence of the various hyaluronidases in the extracts was examined by zymography and western blotting. Their expression was also examined by RT-PCR.

Results

Among hyaluronidases examined, Hyal-1, -2, -3 and PH-20 were detected. Their activity was higher in cancerous samples. Hyal-1 and Hyal-2 were overexpressed in cancerous samples, especially in advanced stages of cancer. Both isoforms were mainly extracted with PBS. Hyal-3 was observed only in the third extract of advanced stages of cancer. PH-20 was abundant in all three extracts of all stages of cancer. The expression of only Hyal-1 and PH-20 was verified by RT-PCR.

Conclusion

A high association of hyaluronidases in colorectal cancer was observed. Each hyaluronidase presented different tissue distribution, which indicated the implication of certain isoforms in certain cancer stages. The results provided new evidence on the mechanisms involved in the progression of colorectal cancer.
Effectiveness of an intervention in groups of family caregivers of dependent patients for their application in primary health centers. Study protocol
Authors: Rodríguez-Sánchez Emiliano , Mora-Simón Sara , Porras-Santos Nieves , Patino-Alonso Maria C , Recio-Rodríguez José I , Becerro-Muñoz Concepción , Pérez-Arechaederra Diana , Gomez-Marcos Manuel A , Garcia-Ortiz Luis
Published: September 2010

Background

Although Primary Health Care (PHC) Teams are used to deal with prevention and treatment of sanitary problems in adults with chronic diseases, they usually have a lack of experience in development of psychotherapeutic interventions. However, these interventions are the ones that achieve better results to reduce symptomatology and improve emotional state of caregivers.

The study aims to evaluate the effectiveness of an intervention of psychotherapy in improving the mental health and Quality of life of caregivers. This intervention is based on theoretical approaches to care adjusted to cognitive theory, in order to be applied in primary health care centres.

Methods/Design

This is multicentre clinical trials study, randomized in two parallel groups, carry out in two PHC, Study population: 150 caregivers will be included by consecutive sampling and they will be randomized the half to experimental group and the other half to control group. They provide mostly all the assistance to care-dependent familiars receiving attention in PHC Centers.

Measurements: Each caregiver will be evaluated on a personal interview. The caregivers' assessment protocol: 1) Assessment of different socio-demographic related to care, and caregiver's personal situation. 2)Care-dependent individuals will also be assessed by Barthel Index and Pfeiffer Questionnaire (SPMSQ). 3)Change in caregivers will be the principal measure: family function (Family APGAR Questionnaire), burden short questionnaire (Short Zarit Burden Interview), quality of life (Ruiz & Baca: 1993 Questionnaire), the Duke-UNK Functional Social Support Questionnaire, the General Health Questionnaire-12, and changes in Dysfunctional Thoughts about caring. 4) Intervention implementation measures will also be assessed.

Intervention: A psychotherapeutic intervention will be 8 sessions of 90 minutes in groups. This intervention has been initially developed for family caregivers of patients with dementia.

Discussion

Psychotherapeutic interventions have been proved to obtain better results to reduce symptomatology and improve emotional state of caregivers. Moreover, this intervention has been proved to be effective in a different setting other than PHC, and was developed by professionals of Mental Health. If we found that this intervention is effective in PHC and with our professionals, it would be an important instrument to offer to caregivers of care-dependent patients.

Trial Registration

ClinicalTrials.gov Identifier NCT01177696
In vivo induction of phase II detoxifying enzymes, glutathione transferase and quinone reductase by citrus triterpenoids
Authors: Perez Jose L , Jayaprakasha Guddarangavvanahally K , Cadena Adriana , Martinez Elvia , Ahmad Hassan , Patil Bhimanagouda S
Published: September 2010

Background

Several cell culture and animal studies demonstrated that citrus bioactive compounds have protective effects against certain types of cancer. Among several classes of citrus bioactive compounds, limonoids were reported to prevent different types of cancer. Furthermore, the structures of citrus limonoids were reported to influence the activity of phase II detoxifying enzymes. The purpose of the study was to evaluate how variations in the structures of citrus limonoids (namely nomilin, deacetyl nomilin, and isoobacunoic acid) and a mixture of limonoids would influence phase II enzyme activity in excised tissues from a mouse model.

Methods

In the current study, defatted sour orange seed powder was extracted with ethyl acetate and subjected to silica gel chromatography. The HPLC, NMR and mass spectra were used to elucidate the purity and structure of compounds. Female A/J mice were treated with three limonoids and a mixture in order to evaluate their effect on phase II enzymes in four different tissues. Assays for glutathione S-transferase and NAD(P)H: quinone reductase (QR) were used to evaluate induction of phase II enzymatic activity.

Results

The highest induction of GST against 1-chloro-2,4-dinitrobenzene (CDNB) was observed in stomach (whole), 58% by nomilin, followed by 25% isoobacunoic acid and 19% deacetyl nomilin. Deacetyl nomilin in intestine (small) as well as liver significantly reduced GST activity against CDNB. Additionally isoobacunoic acid and the limonoid mixture in liver demonstrated a significant reduction of GST activity against CDNB. Nomilin significantly induced GST activity against 4-nitroquinoline 1-oxide (4NQO), intestine (280%) and stomach (75%) while deacetyl nomilin showed significant induction only in intestine (73%). Induction of GST activity was also observed in intestine (93%) and stomach (45%) treated with the limonoid mixture. Finally, a significant induction of NAD(P)H: quinone reductase (QR) activity was observed by the limonoid mixture in stomach (200%). In addition, the deacetyl nomilin treatment group displayed an increase in QR activity in liver (183%) and intestine (22%).

Conclusion

The results of the present study suggests that, dietary intake of citrus limonoids may provide a protective effect against the onset of various cancers by inducing the activity of certain phase II detoxifying enzymes in specific organs.
Cytotoxicity screening of Bangladeshi medicinal plant extracts on pancreatic cancer cells
Authors: George Sherine , Bhalerao Siddharth V , Lidstone Erich A , Ahmad Irfan S , Abbasi Atiya , Cunningham Brian T , Watkin Kenneth L
Published: September 2010

Background

There has been a long standing interest in the identification of medicinal plants and derived natural products for developing cancer therapeutics. Our study focuses upon pancreatic cancer, due to its high mortality rate, that is attributed in part to the lack of an effective chemotherapeutic agent. Previous reports on the use of medicinal plant extracts either alone or alongside conventional anticancer agents in the treatment of this cancer have shown promising results. This work aims to investigate the therapeutic properties of a library of medicinal plants from Bangladesh.

Methods

56 extracts of 44 unique medicinal plants were studied. The extracts were screened for cytotoxicity against the pancreatic adenocarcinoma cell line Panc-1, using a label-free biosensor assay. The top cytotoxic extracts identified in this screen were tested on two additional pancreatic cancer cell lines (Mia-Paca2 and Capan-1) and a fibroblast cell line (Hs68) using an MTT proliferation assay. Finally, one of the most promising extracts was studied using a caspase-3 colorimetric assay to identify induction of apoptosis.

Results

Crude extracts of Petunia punctata, Alternanthera sessilis, and Amoora chittagonga showed cytotoxicity to three cancer cell lines with IC50 values ranging between 20.3 - 31.4 μg/mL, 13.08 - 34.9 μg/mL, and 42.8 - 49.8 μg/mL, respectively. Furthermore, treatment of Panc-1 cells with Petunia punctata was shown to increase caspase-3 activity, indicating that the observed cytotoxicity was mediated via apoptosis. Only Amoora chittagonga showed low cytotoxicity to fibroblast cells with an IC50 value > 100 μg/mL.

Conclusion

Based upon the initial screening work reported here, further studies aimed at the identification of active components of these three extracts and the elucidation of their mechanisms as cancer therapeutics are warranted.
Study on association between genetic polymorphisms of haem oxygenase-1, tumour necrosis factor, cadmium exposure and malaria pathogenicity and severity
Authors: Kuesap Jiraporn , Hirayama Kenji , Kikuchi Mihoko , Ruangweerayut Ronnatrai , Na-Bangchang Kesara
Published: September 2010

Background

Malaria is the most important public health problems in tropical and sub-tropical countries. Haem oxygenase (HO) enzyme and the pro-inflammatory cytokine tumour necrosis factor (TNF) have been proposed as one of the factors that may play significant role in pathogenicity/severity of malaria infection. HO is the enzyme of the microsomal haem degradation pathway that yields biliverdin, carbon monoxide, and iron. In this study, the association between malaria disease pathogenicity/severity and (GT)nrepeat polymorphism in the promoter region of the inducible HO-1 including the effect of cadmium exposure (potent inducer of HO-1 transcription) as well as polymorphism of TNF were investigated.

Methods

Blood samples were collected from 329 cases non-severe malaria with acute uncomplicatedPlasmodium falciparummalaria (UM) and 80 cases withPlasmodium vivaxmalaria (VM), and 77 cases with severe or cerebral malaria (SM) for analysis of genetic polymorphisms of HO-1 and TNF and cadmium levels. These patients consisted of 123 (25.3%) Thai, 243 (50.0%) Burmese and 120 (24.7%) Karen who were present at Mae Sot General Hospital, Mae Sot, Tak Province, Thailand.

Results

The number of (GT)nrepeats of the HO-1 gene in all patients varied between 16 and 39 and categorized to short (S), medium (M) and long (L) GTnrepeats. The genotype of (GT)nrepeat of HO-1 was found to be significantly different among the three ethnic groups of patients. Significantly higher frequency of S/L genotype was found in Burmese compared with Thai patients, while significantly lower frequencies of S/S and M/L but higher frequency of M/M genotype was observed in Burmese compared with Karen patients. No significant association between HO-1 and TNF polymorphisms including the inducing effect of cadmium and malaria pathogenicity/severity was observed.

Conclusions

Difference in the expression of HO-1 genotype in different ethnic groups may contribute to different severity of malaria disease. With this limited sample size, the finding of the lack of association between malaria disease pathogenicity/severity genetic polymorphisms of HO-1 (GT)nrepeat as well as TNF observed in this study may not entirely exclude their possible link with malaria disease pathogenicity/severity. Further study in larger sample size is required.
The use of a commercial vegetable juice as a practical means to increase vegetable intake: a randomized controlled trial
Authors: Shenoy Sonia F , Kazaks Alexandra G , Holt Roberta R , Chen Hsin Ju , Winters Barbara L , Khoo Chor San , Poston Walker SC , Haddock C Keith , Reeves Rebecca S , Foreyt John P , Gershwin M Eric , Keen Carl L
Published: September 2010

Background

Recommendations for daily dietary vegetable intake were increased in the 2005 USDA Dietary Guidelines as consumption of a diet rich in vegetables has been associated with lower risk of certain chronic health disorders including cardiovascular disease. However, vegetable consumption in the United States has declined over the past decade; consequently, the gap between dietary recommendations and vegetable intake is widening. The primary aim of this study is to determine if drinking vegetable juice is a practical way to help meet daily dietary recommendations for vegetable intake consistent with the 2005 Dietary Guidelines and the Dietary Approaches to Stop Hypertension (DASH) diet. The secondary aim is to assess the effect of a vegetable juice on measures of cardiovascular health.

Methods

We conducted a 12-week, randomized, controlled, parallel-arm study consisting of 3 groups of free-living, healthy volunteers who participated in study visits at the Ragle Human Nutrition Research Center at the University of California, Davis. All subjects received education on the DASH diet and 0, 8 or 16 fluid ounces of vegetable juice daily. Assessments were completed of daily vegetable servings before and after incorporation of vegetable juice and cardiovascular health parameters including blood pressure.

Results

Without the juice, vegetable intake in all groups was lower than the 2005 Dietary Guidelines and DASH diet recommendations. The consumption of the vegetable juice helped participants reach recommended intake. In general, parameters associated with cardiovascular health did not change over time. However, in the vegetable juice intervention groups, subjects who were pre-hypertensive at the start of the study showed a significant decrease in blood pressure during the 12-week intervention period.

Conclusion

Including 1-2 cups of vegetable juice daily was an effective and acceptable way for healthy adults to close the dietary vegetable gap. Increase in daily vegetable intake was associated with a reduction in blood pressure in subjects who were pre-hypertensive at the start of the trial.

Trial Registration

Clinicaltrials.gov NCT01161706
Multiple functions of CXCL12 in a syngeneic model of breast cancer
Authors: Williams Sharon A , Harata-Lee Yuka , Comerford Iain , Anderson Robin L , Smyth Mark J , McColl Shaun R
Published: September 2010

Background

A growing body of work implicates chemokines, in particular CXCL12 and its receptors, in the progression and site-specific metastasis of various cancers, including breast cancer. Various agents have been used to block the CXCL12-CXCR4 interaction as a means of inhibiting cancer metastasis. However, as a potent chemotactic factor for leukocytes, CXCL12 also has the potential to enhance anti-cancer immunity. To further elucidate its role in breast cancer progression, CXCL12 and its antagonist CXCL12(P2G)were overexpressed in the syngeneic 4T1.2 mouse model of breast carcinoma.

Results

While expression of CXCL12(P2G)significantly inhibited metastasis, expression of wild-type CXCL12 potently inhibited both metastasis and primary tumor growth. The effects of wild-type CXCL12 were attributed to an immune response characterized by the induction of CD8+T cell activity, enhanced cell-mediated cytotoxicity, increased numbers of CD11c+cells in the tumor-draining lymph nodes and reduced accumulation of myeloid-derived suppressor cells in the spleen.

Conclusions

This study highlights the need to consider carefully therapeutic strategies that block CXCL12 signaling. Therapies that boost CXCL12 levels at the primary tumor site may prove more effective in the treatment of metastatic breast cancer.