bluuebunny/crossref_metadata_2025 huggingface dataset:
Circadian signatures in rat liver: from gene expression to pathways
Authors: Ovacik Meric A , Sukumaran Siddharth , Almon Richard R , DuBois Debra C , Jusko William J , Androulakis Ioannis P
Published: November 2010

Background

Circadian rhythms are 24 hour oscillations in many behavioural, physiological, cellular and molecular processes that are controlled by an endogenous clock which is entrained to environmental factors including light, food and stress. Transcriptional analyses of circadian patterns demonstrate that genes showing circadian rhythms are part of a wide variety of biological pathways.

Pathway activity method can identify the significant pattern of the gene expression levels within a pathway. In this method, the overall gene expression levels are translated to a reduced form, pathway activity levels, via singular value decomposition (SVD). A given pathway represented by pathway activity levels can then be as analyzed using the same approaches used for analyzing gene expression levels. We propose to use pathway activity method across time to identify underlying circadian pattern of pathways.

Results

We used synthetic data to demonstrate that pathway activity analysis can evaluate the underlying circadian pattern within a pathway even when circadian patterns cannot be captured by the individual gene expression levels. In addition, we illustrated that pathway activity formulation should be coupled with a significance analysis to distinguish biologically significant information from random deviations. Next, we performed pathway activity level analysis on a rich time series of transcriptional profiling in rat liver. The over-represented five specific patterns of pathway activity levels, which cannot be explained by random event, exhibited circadian rhythms. The identification of the circadian signatures at the pathway level identified 78 pathways related to energy metabolism, amino acid metabolism, lipid metabolism and DNA replication and protein synthesis, which are biologically relevant in rat liver. Further, we observed tight coordination between cholesterol biosynthesis and bile acid biosynthesis as well as between folate biosynthesis, one carbon pool by folate and purine-pyrimidine metabolism. These coupled pathways are parts of a sequential reaction series where the product of one pathway is the substrate of another pathway.

Conclusions

Rather than assessing the importance of a single gene beforehand and map these genes onto pathways, we instead examined the orchestrated change within a pathway. Pathway activity level analysis could reveal the underlying circadian dynamics in the microarray data with an unsupervised approach and biologically relevant results were obtained.
Structural modelling and comparative analysis of homologous, analogous and specific proteins from Trypanosoma cruzi versus Homo sapiens: putative drug targets for chagas' disease treatment
Authors: Capriles Priscila VSZ , Guimarães Ana CR , Otto Thomas D , Miranda Antonio B , Dardenne Laurent E , Degrave Wim M
Published: October 2010

Background

Trypanosoma cruzi is the etiological agent of Chagas' disease, an endemic infection that causes thousands of deaths every year in Latin America. Therapeutic options remain inefficient, demanding the search for new drugs and/or new molecular targets. Such efforts can focus on proteins that are specific to the parasite, but analogous enzymes and enzymes with a three-dimensional (3D) structure sufficiently different from the corresponding host proteins may represent equally interesting targets. In order to find these targets we used the workflows MHOLline and AnEnΠ obtaining 3D models from homologous, analogous and specific proteins of Trypanosoma cruzi versus Homo sapiens.

Results

We applied genome wide comparative modelling techniques to obtain 3D models for 3,286 predicted proteins of T. cruzi. In combination with comparative genome analysis to Homo sapiens, we were able to identify a subset of 397 enzyme sequences, of which 356 are homologous, 3 analogous and 38 specific to the parasite.

Conclusions

In this work, we present a set of 397 enzyme models of T. cruzi that can constitute potential structure-based drug targets to be investigated for the development of new strategies to fight Chagas' disease. The strategies presented here support the concept of structural analysis in conjunction with protein functional analysis as an interesting computational methodology to detect potential targets for structure-based rational drug design. For example, 2,4-dienoyl-CoA reductase (EC 1.3.1.34) and triacylglycerol lipase (EC 3.1.1.3), classified as analogous proteins in relation to H. sapiens enzymes, were identified as new potential molecular targets.
Transcriptome and proteome analysis of Pinctada margaritifera calcifying mantle and shell: focus on biomineralization
Authors: Joubert Caroline , Piquemal David , Marie Benjamin , Manchon Laurent , Pierrat Fabien , Zanella-Cléon Isabelle , Cochennec-Laureau Nathalie , Gueguen Yannick , Montagnani Caroline
Published: November 2010

Background

The shell of the pearl-producing bivalvePinctada margaritiferais composed of an organic cell-free matrix that plays a key role in the dynamic process of biologically-controlled biomineralization. In order to increase genomic resources and identify shell matrix proteins implicated in biomineralization inP. margaritifera, high-throughput Expressed Sequence Tag (EST) pyrosequencing was undertaken on the calcifying mantle, combined with a proteomic analysis of the shell.

Results

We report the functional analysis of 276 738 sequences, leading to the constitution of an unprecedented catalog of 82P. margaritiferabiomineralization-related mantle protein sequences. Components of the current "chitin-silk fibroin gel-acidic macromolecule" model of biomineralization processes were found, in particular a homolog of a biomineralization protein (Pif-177) recently discovered inP. fucata. Among these sequences, we could show the localization of two other biomineralization protein transcripts,pmarg-aspeinandpmarg-pearlin, in two distinct areas of the outer mantle epithelium, suggesting their implication in calcite and aragonite formation. Finally, by combining the EST approach with a proteomic mass spectrometry analysis of proteins isolated from theP. margaritiferashell organic matrix, we demonstrated the presence of 30 sequences containing almost all of the shell proteins that have been previously described from shell matrix protein analyses of thePinctadagenus. The integration of these two methods allowed the global composition of biomineralizing tissue and calcified structures to be examined in tandem for the first time.

Conclusions

This EST study made on the calcifying tissue ofP. margaritiferais the first description of pyrosequencing on a pearl-producing bivalve species. Our results provide direct evidence that our EST data set covers most of the diversity of the matrix protein ofP. margaritiferashell, but also that the mantle transcripts encode proteins present inP. margaritiferashell, hence demonstrating their implication in shell formation. Combining transcriptomic and proteomic approaches is therefore a powerful way to identify proteins involved in biomineralization. Data generated in this study supply the most comprehensive list of biomineralization-related sequences presently available among protostomian species, and represent a major breakthrough in the field of molluskan biomineralization.
Injuries to pedal cyclists on New Zealand roads, 1988-2007
Authors: Tin Tin Sandar , Woodward Alistair , Ameratunga Shanthi
Published: October 2010

Background

The risk of injury is one of the major barriers to engaging in cycling. We investigated exposure-based rates and profiles of traffic injuries sustained by pedal cyclists that resulted in death or hospital inpatient treatment in New Zealand, one of the most car dependent countries.

Methods

Pedal cyclist traffic injuries were identified from the Mortality Collection and the National Minimum Dataset. Total time spent cycling was used as the measure of exposure and computed from National Household Travel Surveys. Analyses were undertaken for the periods 1988-91, 1996-99 and 2003-07 in relation to other major road users and by age, gender and body region affected. A modified Barell matrix was used to characterise the profiles of pedal cyclist injuries by body region affected and nature of injury.

Results

Cyclists had the second highest rate of traffic injuries compared to other major road user categories and the rate increased from 1996-99 to 2003-07. During 2003-07, 31 injuries occurred per million hours spent cycling. Non-collision crashes (40%) and collisions with a car, pick-up truck or van (26%) accounted for two thirds of the cycling injuries. Children and adolescents aged under 15 years were at the highest risk, particularly of non-collision crashes. The rate of traumatic brain injuries fell from 1988-91 to 1996-99; however, injuries to other body parts increased steadily. Traumatic brain injuries were most common in collision cases whereas upper extremity fractures were most common in other crashes.

Conclusions

The burden of fatal and hospitalised injuries among pedal cyclists is considerable and has been increasing over the last decade. This underscores the development of road safety and injury prevention programmes for cyclists alongside the cycling promotion strategies.
Pattern of fractures across pediatric age groups: analysis of individual and lifestyle factors
Authors: Valerio Giuliana , Gallè Francesca , Mancusi Caterina , Di Onofrio Valeria , Colapietro Marianna , Guida Pasquale , Liguori Giorgio
Published: November 2010

Background

Knowledge of the epidemiology of children's fractures is essential to develop preventive strategies. The aim of this study was to analyze the individual/lifestyle determinants of fractures across pediatric age groups.

Methods

A cross-sectional study was performed in the first six months of 2008 through questionnaire on a sample of children from an outpatient clinic for pediatric fractures. Differences in gender, anatomic site, circumstances and location of fracture occurrence, behavioural lifestyle, and calcium intake were investigated among three different age classes (pre-school children, school children, and adolescents).

Results

The sample consisted of 382 subjects (2-14 years of age) sustaining a fracture after low or moderate trauma. Males were at a higher risk of fractures than females; greater than two-thirds of injuries occurred after low-energy trauma and the upper limb was more frequently involved. With increasing age, the male/female ratio and time spent in sports participation increased (p < 0.001), while calcium intake and time spent in sedentary behaviors decreased (p < 0.001 and < 0.003, respectively). Gender discordance existed in pre-school children with respect to the anatomic location, and in school children and adolescents with respect to the dynamics. In the adolescent group, males were more physically active and also more sedentary than females. Fractures most frequently occurred in homes (41.6%), followed by playgrounds and footpaths (26.2%), sports facilities (18.3%), and educational facilities (13.9%), with gender differences existing only in adolescence. Twenty-three percent of the subjects sustained one or more fractures in the past. The percentage of recurrent fractures increased with age (p = 0.001), with a similar trend in both genders.

Conclusions

Gender differences were shown in the prevalence of injuries, characteristics, and circumstances across ages. These differences may be explained by the related changes in behaviors, together with attending different places. Individual and lifestyle factors can in part explain the variability in the occurrence of fractures and can also address targeted preventive strategies.
Reproductive health care for asylum-seeking women - a challenge for health professionals
Authors: Kurth Elisabeth , Jaeger Fabienne N , Zemp Elisabeth , Tschudin Sibil , Bischoff Alexander
Published: November 2010

Background

Dealing with pregnancy, childbirth and the care of newborn babies is a challenge for female asylum seekers and their health care providers. The aim of our study was to identify reproductive health issues in a population of women seeking asylum in Switzerland, and to examine the care they received. The women were insured through a special Health Maintenance Organisation (HMO) and were attending the Women's Clinic of the University Hospital in Basel. We also investigated how the health professionals involved perceived the experience of providing health care for these patients.

Methods

A mixed methods approach combined the analysis of quantitative descriptive data and qualitative data obtained from semi-structured interviews with health care providers and from patients' files. We analysed the records of 80 asylum-seeking patients attending the Women's Clinic insured through an HMO. We conducted semi-structured interviews with 10 care providers from different professional groups. Quantitative data were analysed descriptively. Qualitative data analysis was guided by Grounded Theory.

Results

The principal health problems among the asylum seekers were a high rate of induced abortions (2.5 times higher than in the local population), due to inadequate contraception, and psychosocial stress due to the experience of forced migration and their current difficult life situation. The language barriers were identified as a major difficulty for health professionals in providing care. Health care providers also faced major emotional challenges when taking care of asylum seekers. Additional problems for physicians were that they were often required to act in an official capacity on behalf of the authorities in charge of the asylum process, and they also had to make decisions about controlling expenditure to fulfil the requirements of the HMO. They felt that these decisions sometimes conflicted with their duty towards the patient.

Conclusion

Health policies for asylum seekers need to be designed to assure access to adequate contraception, and to provide psychological care for this vulnerable group of patients. Care for asylum seekers may be emotionally very challenging for health professionals.
Eight week exposure to a high sugar high fat diet results in adiposity gain and alterations in metabolic biomarkers in baboons (Papio hamadryas sp.)
Authors: Higgins Paul B , Bastarrachea Raul A , Lopez-Alvarenga Juan Carlos , Garcia-Forey Maggie , Proffitt J Michael , Voruganti V Saroja , Tejero M Elizabeth , Mattern Vicki , Haack Karin , Shade Robert E , Cole Shelley A , Comuzzie Anthony G
Published: October 2010

Background

Baboons (Papio hamadryas Sp.) develop features of the cardiometabolic syndrome and represent a clinically-relevant animal model in which to study the aetiology of the disorder. To further evaluate the baboon as a model for the study of the cardiometabolic syndrome, we developed a high sugar high fat diet and hypothesized that it could be used to induce adiposity gain and affect associated circulating biomarkers.

Methods

We developed a diet enriched with monosaccharides and saturated fatty acids that was composed of solid and liquid energy sources. We provided a group of baboons (n = 9) ad libitum access to this diet for 8 weeks. Concurrently, a control group (n = 6) was maintained with ad libitum access to a low sugar low fat baseline diet and normal water for 8 weeks. Body composition was determined by dual-energy X-ray absorptiometry and circulating metabolic biomarkers were measured using standard methodology before and after the 8 week study period.

Results

Neither body composition nor circulating biomarkers changed in the control group. Following the 8 weeks, the intervention group had a significant increase in fat mass (1.71 ± 0.98 vs. 3.23 ± 1.70 kg, p = 0.004), triglyceride (55 ± 13 vs. 109 ± 67 mg/dL, p = 0.006,), and leptin (1.19 ± 1.40 vs. 3.29 ± 2.32 ng/mL, p = 0.001) and a decline in adiponectin concentrations (33530 ± 9744 vs. 23330 ± 7863 ng/mL, p = 0.002). Percentage haemoglobin A1C (4.0 ± 0.3 vs. 6.0 ± 1.4, p = 0.002) also increased in the intervention group.

Conclusions

Our findings indicate that when exposed to a high sugar high fat diet, young adult male baboons develop increased body fat and triglyceride concentrations, altered adipokine concentrations, and evidence of altered glucose metabolism. Our findings are in keeping with observations in humans and further demonstrate the potential utility of this highly clinically-relevant animal model for studying diet-induced metabolic dysregulation.
Changing trends in blood transfusion in children and neonates admitted in Kilifi District Hospital, Kenya
Authors: Pedro Rosalon , Akech Samuel , Maitland Kathryn
Published: October 2010

Background

Severe anaemia is a common cause for hospitalization in children in sub-Saharan Africa. Malaria plays an important aetiological role, resulting in a substantial burden of paediatric transfusion in hospitals. A decline in malaria and paediatric admissions to the Kilifi District Hospital has been reported recently. This study aimed to investigate whether this trend affected clinical burden, clinical severity of anaemia and requirements for paediatric transfusion.

Methods

Eight-year retrospective review of paediatric admissions to Kilifi District Hospital, Kenya describing the frequency of moderate and severe anaemia, blood transfusion and case fatality over time. Definitions for severe anaemia were Hb <8 g/dl for newborns and <5 g/dl for other age groups and for moderate anaemia was Hb 8 to <11 g/dl for newborns and 5 to <9.3 g/dl for other age groups. Life threatening anaemia was defined as severe anaemia (Hb <5 g/dl) complicated by either deep breathing or prostration or profound anaemia (Hb <4 g/dl) alone.

Results

Of the 35,139 admissions 13,037 (37%) had moderate anaemia and 2,265 (6%) had severe anaemia; respiratory distress complicated 35% of cases with Hb <5 g/dl. Concurrent with the decline in malaria there was a marked decline in the prevalence of severe anaemia between 2002 (8%) and 2009 (< 4%) (chi2 for trend = 134, P < 0.0001). The number and proportion of admissions transfused also declined significantly over this time (chi2 for trend = 152, P < 0.0001). Of the 2,265 children with severe anaemia 191 (8%) died. Case fatality remained unchanged during this period (P < 0.26) and was largely explained by the unchanged proportion with life-threatening anaemia, present in 58-65% of cases throughout the study period.

Conclusion

The impact of reduced malaria transmission on child morbidity has positive public benefits on the demand and use of blood for paediatric transfusion. Despite an overall reduction in paediatric transfusion requirement, case fatality of severe anaemia remained unchanged over this decade. Further research is required to improve outcome from severe anaemia, particularly in the high-risk group with life threatening features.
Directly-observed therapy (DOT) for the radical 14-day primaquine treatment of Plasmodium vivax malaria on the Thai-Myanmar border
Authors: Takeuchi Rie , Lawpoolsri Saranath , Imwong Mallika , Kobayashi Jun , Kaewkungwal Jaranit , Pukrittayakamee Sasithon , Puangsa-art Supalap , Thanyavanich Nipon , Maneeboonyang Wanchai , Day Nicholas PJ , Singhasivanon Pratap
Published: November 2010

Background

Plasmodium vivax has a dormant hepatic stage, called the hypnozoite, which can cause relapse months after the initial attack. For 50 years, primaquine has been used as a hypnozoitocide to radically cure P. vivax infection, but major concerns remain regarding the side-effects of the drug and adherence to the 14-day regimen. This study examined the effectiveness of using the directly-observed therapy (DOT) method for the radical treatment of P. vivax malaria infection, to prevent reappearance of the parasite within the 90-day follow-up period. Other potential risk factors for the reappearance of P. vivax were also explored.

Methods

A randomized trial was conducted from May 2007 to January 2009 in a low malaria transmission area along the Thai-Myanmar border. Patients aged ≥ 3 years diagnosed with P. vivax by microscopy, were recruited. All patients were treated with the national standard regimen of chloroquine for three days followed by primaquine for 14 days. Patients were randomized to receive DOT or self-administered therapy (SAT). All patients were followed for three months to check for any reappearance of P. vivax.

Results

Of the 216 patients enrolled, 109 were randomized to DOT and 107 to SAT. All patients recovered without serious adverse effects. The vivax reappearance rate was significantly lower in the DOT group than the SAT group (3.4/10,000 person-days vs. 13.5/10,000 person-days, p = 0.021). Factors related to the reappearance of vivax malaria included inadequate total primaquine dosage received (< 2.75 mg/kg), duration of fever ≤ 2 days before initiation of treatment, parasite count on admission ≥ 10,000/µl, multiple P. vivax-genotype infection, and presence of P. falciparum infection during the follow-up period.

Conclusions

Adherence to the 14-day primaquine regimen is important for the radical cure of P. vivax malaria infection. Implementation of DOT reduces the reappearance rate of the parasite, and may subsequently decrease P. vivax transmission in the area.
ADP-ribose polymer - a novel and general biomarker of human cancers of head & neck, breast, and cervix
Authors: Lakadong Rennie O , Kataki Amal C , Sharan Rajeshwar N
Published: October 2010

Background

Poly-ADP-ribosylation, a reversible post-translational modification of primarily chromosomal proteins, is involved in various cellular and molecular processes including carcinogenesis. ADP-ribose polymer or poly-ADP-ribose adducts are enzymatically added onto or stripped off the target chromosomal proteins during this metabolic process. Due to this, the chromatin superstructure is reversibly altered, which significantly influences the pattern of gene expression. We hypothesize that a decrease in the concentration of total poly-ADP-ribose adducts of peripheral blood lymphocyte (PBL) proteins strongly correlates with the incidence of human cancer.

Results

Using a novel immunoprobe assay, we show a statistically significant (P ≤ 0.001) reduction (~ 42 to 49%) in the level of poly-ADP-ribose adducts of PBL proteins of patients with advanced cancers of head & neck (H & N) region (comprising fourteen distinct cancers at different sites), breast and cervix in comparison to healthy controls.

Conclusions

These findings imply potential utility of the poly-ADP-ribose adducts of PBL proteins as a novel and general biomarker of human cancers with potentials of significant clinical and epidemiological applications.
HE3286, an oral synthetic steroid, treats lung inflammation in mice without immune suppression
Authors: Conrad Douglas , Wang Angela , Pieters Raymond , Nicoletti Ferdinando , Mangano Katia , van Heeckeren Anna M , White Steven K , Frincke James M , Reading Christopher L , Stickney Dwight , Auci Dominick L
Published: October 2010

Background

17α-Ethynyl-5-androsten-3β, 7β, 17β-triol (HE3286) is a synthetic derivative of an endogenous steroid androstenetriol (β-AET), a metabolite of the abundant adrenal steroid deyhdroepiandrosterone (DHEA), with broad anti-inflammatory activities. We tested the ability of this novel synthetic steroid with improved pharmacological properties to limit non-productive lung inflammation in rodents and attempted to gauge its immunological impact.

Methods and Results

In mice, oral treatment with HE3286 (40 mg/kg) significantly (p< 0.05) decreased neutrophil counts and exudate volumes (~50%) in carrageenan-induced pleurisy, and myeloperoxidase in lipopolysaccharide-induced lung injury. HE3286 (40 mg/kg) was not found to be profoundly immune suppressive in any of the classical animal models of immune function, including those used to evaluate antigen specific immune responsesin vivo(ovalbumin immunization). When mice treated for two weeks with HE3286 were challenged withK. pneumoniae, nearly identical survival kinetics were observed in vehicle-treated, HE3286-treated and untreated groups.

Conclusions

HE3286 represents a novel, first-in-class anti-inflammatory agent that may translate certain benefits of β-AET observed in rodents into treatments for chronic inflammatory pulmonary disease.
Manufacture of IRDye800CW-coupled Fe3O4 nanoparticles and their applications in cell labeling and in vivo imaging
Authors: Hou Yong , Liu Yingxun , Chen Zhongping , Gu Ning , Wang Jinke
Published: October 2010

Background

In recent years, near-infrared fluorescence (NIRF)-labeled iron nanoparticles have been synthesized and applied in a number of applications, including the labeling of human cells for monitoring the engraftment process, imaging tumors, sensoring the in vivo molecular environment surrounding nanoparticles and tracing their in vivo biodistribution. These studies demonstrate that NIRF-labeled iron nanoparticles provide an efficient probe for cell labeling. Furthermore, the in vivo imaging studies show excellent performance of the NIR fluorophores. However, there is a limited selection of NIRF-labeled iron nanoparticles with an optimal wavelength for imaging around 800 nm, where tissue autofluorescence is minimal. Therefore, it is necessary to develop additional alternative NIRF-labeled iron nanoparticles for application in this area.

Results

This study manufactured 12-nm DMSA-coated Fe3O4 nanoparticles labeled with a near-infrared fluorophore, IRDye800CW (excitation/emission, 774/789 nm), to investigate their applicability in cell labeling and in vivo imaging. The mouse macrophage RAW264.7 was labeled with IRDye800CW-labeled Fe3O4 nanoparticles at concentrations of 20, 30, 40, 50, 60, 80 and 100 μg/ml for 24 h. The results revealed that the cells were efficiently labeled by the nanoparticles, without any significant effect on cell viability. The nanoparticles were injected into the mouse via the tail vein, at dosages of 2 or 5 mg/kg body weight, and the mouse was discontinuously imaged for 24 h. The results demonstrated that the nanoparticles gradually accumulated in liver and kidney regions following injection, reaching maximum concentrations at 6 h post-injection, following which they were gradually removed from these regions. After tracing the nanoparticles throughout the body it was revealed that they mainly distributed in three organs, the liver, spleen and kidney. Real-time live-body imaging effectively reported the dynamic process of the biodistribution and clearance of the nanoparticles in vivo.

Conclusion

IRDye800CW-labeled Fe3O4 nanoparticles provide an effective probe for cell-labeling and in vivo imaging.
Steroid hormones content and proteomic analysis of canine follicular fluid during the preovulatory period
Authors: Fahiminiya Somayyeh , Reynaud Karine , Labas Valérie , Batard Séverine , Chastant-Maillard Sylvie , Gérard Nadine
Published: November 2010

Background

Follicular fluid contains substances involved in follicle activity, cell differentiation and oocyte maturation. Studies of its components may contribute to better understanding of the mechanisms underlying follicular development and oocyte quality. The canine species is characterized by several ovarian activity features that are not extensively described such as preovulatory luteinization, oocyte ovulated at the GV stage (prophase 1) and poly-oocytic follicles. In this study, we examined the hypothesis that the preovulatory LH surge is associated with changes in steroid and protein content of canine follicular fluid prior to ovulation.

Methods

Follicular fluid samples were collected from canine ovaries during the preovulatory phase, before (pre-LH; n = 16 bitches) and after (post-LH; n = 16) the LH surge. Blood was simultaneously collected. Steroids were assayed by radioimmunoassay and proteomic analyses were carried out by 2D-PAGE and mass spectrometry.

Results

The concentrations of 17beta-estradiol and progesterone at the pre-LH stage were 737.2 +/- 43.5 ng/ml and 2630.1 +/- 287.2 ng/ml in follicular fluid vs. 53 +/- 4.1 pg/ml and 3.9 +/- 0.3 ng/ml in plasma, respectively. At that stage, significant positive correlations between follicular size and intra-follicular steroid concentrations were recorded. After the LH peak, the intrafollicular concentration of 17beta-estradiol decreased significantly (48.3 +/- 4.4 ng/ml; p < 0.001), whereas that of progesterone increased (11690.2 +/- 693.6 ng/ml; p < 0.001). Plasmatic concentration of 17beta-estradiol was not modified (49 +/- 9.6 pg/ml) after the LH peak, but that of progesterone significantly increased (9.8 +/- 0.63 ng/ml).

Proteomic analysis of canine follicular fluid identified 38 protein spots, corresponding to 21 proteins, some of which are known to play roles in the ovarian physiology. The comparison of 2D-PAGE patterns of follicular fluids from the pre- and post-LH stages demonstrated 3 differentially stained single spot or groups of spots. One of them was identified as complement factor B. A comparison of follicular fluid and plasma protein patterns demonstrated a group of 4 spots that were more concentrated in plasma than in follicular fluid, and a single spot specific to follicular fluid. These proteins were identified as gelsolin and clusterin, respectively.

Conclusion

Our results provide the first demonstration of size-related changes in the steroid concentrations in canine follicular fluid associated with the LH surge. 2D protein mapping allowed identification of several proteins that may play a role in follicle physiology and ovarian activity at the preovulatory stage. This may help in the future to explain and to better understand the species specificities that are described in dogs.
Modern concepts in facial nerve reconstruction
Authors: Volk Gerd F , Pantel Mira , Guntinas-Lichius Orlando
Published: November 2010

Background

Reconstructive surgery of the facial nerve is not daily routine for most head and neck surgeons. The published experience on strategies to ensure optimal functional results for the patients are based on small case series with a large variety of surgical techniques. On this background it is worthwhile to develop a standardized approach for diagnosis and treatment of patients asking for facial rehabilitation.

Conclusion

A standardized approach is feasible: Patients with chronic facial palsy first need an exact classification of the palsy's aetiology. A step-by-step clinical examination, if necessary MRI imaging and electromyographic examination allow a classification of the palsy's aetiology as well as the determination of the severity of the palsy and the functional deficits. Considering the patient's desire, age and life expectancy, an individual surgical concept is applicable using three main approaches: a) early extratemporal reconstruction, b) early reconstruction of proximal lesions if extratemporal reconstruction is not possible, c) late reconstruction or in cases of congenital palsy. Twelve to 24 months after the last step of surgical reconstruction a standardized evaluation of the therapeutic results is recommended to evaluate the necessity for adjuvant surgical procedures or other adjuvant procedures, e.g. botulinum toxin application. Up to now controlled trials on the value of physiotherapy and other adjuvant measures are missing to give recommendation for optimal application of adjuvant therapies.
Right ventricular exclusion for hepatocellular carcinoma metastatic to the heart
Authors: Liu Wan-Chi , Lui Kar-Wei , Ho Ming-Chi , Fan Shou-Zen , Chao Anne
Published: October 2010

We used for the first time a right ventricular exclusion procedure for the treatment of hepatocellular carcinoma metastatic to the right ventricle. Our case report shows that this surgical option can be effective as rescue therapy for right ventricular outflow tract obstruction secondary to myocardial metastasis in critically ill patients. Most notably, this technique can prevent inadvertent dislodgement of tumor cells.
Lack of interleukin-1 type 1 receptor enhances the accumulation of mutant huntingtin in the striatum and exacerbates the neurological phenotypes of Huntington's disease mice
Authors: Wang Chuan-En , Li Shihua , Li Xiao-Jiang
Published: November 2010

Huntington's disease results from expansion of a glutamine repeat (>36 glutamines) in the N-terminal region of huntingtin (htt) and is characterized by preferential neurodegeneration in the striatum of the brain. N171-82Q mice that express N-terminal 171 amino acids of htt with an 82-glutamine repeat show severe neurological phenotypes and die early, suggesting that N-terminal mutant htt is pathogenic. In addition, various cellular factors and genetic modifiers are found to modulate the cytotoxicity of mutant htt. Understanding the contribution of these factors to HD pathogenesis will help identify therapeutics for this disease. To investigate the role of interleukin type 1 (IL-1), a cytokine that has been implicated in various neurological diseases, in HD neurological symptoms, we crossed N171-82Q mice to type I IL-1 receptor (IL-1RI) knockout mice. Mice lacking IL-1RI and expressing N171-82Q show more severe neurological symptoms than N171-82Q or IL-1RI knockout mice, suggesting that lack of IL-1RI can promote the neuronal toxicity of mutant htt. Lack of IL-1RI also increases the accumulation of transgenic mutant htt in the striatum in N171-82Q mice. Since IL-1RI signaling mediates both toxic and protective effects on neurons, its basal function and protective effects may be important for preventing the neuropathology seen in HD.
Clinical guidelines for the recognition of melanoma of the foot and nail unit
Authors: Bristow Ivan R , de Berker David AR , Acland Katharine M , Turner Richard J , Bowling Jonathan
Published: November 2010

Malignant melanoma is a life threatening skin tumour which may arise on the foot. The prognosis for the condition is good when lesions are diagnosed and treated early. However, lesions arising on the soles and within the nail unit can be difficult to recognise leading to delays in diagnosis. These guidelines have been drafted to alert health care practitioners to the early signs of the disease so an early diagnosis can be sought.
Prognostic Significance of Nuclear Survivin Expression in Resected Adenoid Cystic Carcinoma of the Head and Neck
Authors: Ko Yoon Ho , Roh Sang-Young , Won Hye Sung , Jeon Eun Kyoung , Hong Sook Hee , Lee Myung Ah , Kang Jin Hyoung , Hong Young Seon , Kim Min Sik , Jung Chan-Kwon
Published: October 2010

Objectives

The expression of survivin, an inhibitor of apoptosis, in tumor cells is associated with poor clinical outcome for various cancers. We conducted this study to determine survivin expression in patients with adenoid cystic carcinoma (ACC) of the head and neck and to identify its clinical significance as a prognostic factor.

Materials and methods

We performed immunohistochemical staining for survivin, p53, bcl-2 protein, and Ki-67 in formalin fixed, paraffin-embedded blocks from 37 cases of head and neck ACC. We also reviewed the patients' clinical records to determine the association of staining with clinical course.

Results

Of the 37 cases of head and neck ACC, 31 (83.8%) were positive for cytoplasmic survivin expression, and 23 (62.2%) were positive for nuclear survivin expression. There was a significant association between nuclear survivin expression and bcl-2 (P = 0.031). A larger tumor was more commonly a survivin-positive tumor (cytoplasmic survivin, P = 0.043; nuclear survivin, P = 0.057). Median overall survival (OS) was significantly longer in patients not expressing nuclear survivin (P = 0.035). A multivariate analysis revealed that nuclear survivin expression significantly impacted OS (hazard ratio 8.567, P = 0.018) in addition to lymph node involvement (hazard ratio 7.704, P = 0.016).

Conclusions

The immunohistochemical expression of nuclear survivin has a prognostic impact in patients with head and neck ACC. These results suggest that nuclear survivin expression may be a useful biomarker for predicting prognosis in patients with head and neck ACC who were treated with surgical resection.
Conjugated Linoleic Acid: good or bad nutrient
Authors: Gonçalves Daniela C , Lira Fabio S , Carnevali Luiz C , Rosa Jose C , Pimentel Gustavo D , Seelaender Marília
Published: October 2010

Conjugated linoleic acid (CLA) is a class of 28 positional and geometric isomers of linoleic acid octadecadienoic.Currently, it has been described many benefits related to the supplementation of CLA in animals and humans, as in the treatment of cancer, oxidative stress, in atherosclerosis, in bone formation and composition in obesity, in diabetes and the immune system. However, our results show that, CLA appears to be not a good supplement in patients with cachexia.
Validity of the work productivity and activity impairment questionnaire - general health version in patients with rheumatoid arthritis
Authors: Zhang Wei , Bansback Nick , Boonen Annelies , Young Adam , Singh Amitabh , Anis Aslam H
Published: November 2010

Introduction

The Work Productivity and Activity Impairment (WPAI) questionnaire is a well validated instrument to measure impairments in work and activities. However, its validation among patients with rheumatoid arthritis (RA) has not been well established. The present study's purpose is to evaluate the construct validity of the WPAI-general health version among RA patients and its ability to differentiate between RA patients with varying health status.

Methods

Patients who were enrolled in the Early Rheumatoid Arthritis Network cohort and were employed at their most recent follow-up were recruited into this sub-study. A questionnaire battery incorporating the WPAI was administered along with a number of health outcomes including the Multidimensional Health Assessment Questionnaire, fatigue and patient assessment of disease activity. The construct validity of the WPAI was tested by the correlations between the WPAI and the health outcomes and other measures of productivity. Student's t tests were used to identify whether the WPAI outcomes differed between the two levels of heath status based on the median of health outcomes.

Results

A total of 150 patients completed the WPAI questionnaire. The average age was 52 years old and the disease duration was 37.5 months since the first rheumatology visit. Of the 137 patients who were working for pay, 26 reported missing work in the past week due to their health problem, accounting for 45.5% of their working time (absenteeism). While 123 patients were working, 24% of their work was impaired due to their health problem (presenteeism). In addition, 33% of the patients' regular daily activities (activity impairment) had been prevented due to their health problems. There were moderate correlations between the WPAI absenteeism and function, pain, fatigue, and disease severity (r = 0.34 to 0.39). The WPAI presenteeism and activity impairment were strongly correlated with the health outcomes (0.67 to 0.77). Patients with more severe disease status (for example, low/high functional disability by median) had significantly higher absenteeism (4%/15%), presenteeism (15%/39%), and activity impairment (19%/53%) than those with less severe disease status.

Conclusions

The WPAI is a valid questionnaire for assessing impairments in paid work and activities in RA patients and for measuring the relative differences between RA patients with different health status.
Increased HMGB1 expression and release by mononuclear cells following surgical/anesthesia trauma
Authors: Manganelli Valeria , Signore Michele , Pacini Ilaria , Misasi Roberta , Tellan Guglielmo , Garofalo Tina , Lococo Emanuela , Chirletti Piero , Sorice Maurizio , Delogu Giovanna
Published: November 2010

Introduction

High mobility group box 1 (HMGB1) is a key mediator of inflammation that is actively secreted by macrophages and/or passively released from damaged cells. The proinflammatory role of HMGB1 has been demonstrated in both animal models and humans, since the severity of inflammatory response is strictly related to serum HMGB1 levels in patients suffering from traumatic insult, including operative trauma. This study was undertaken to investigate HMGB1 production kinetics in patients undergoing major elective surgery and to address how circulating mononuclear cells are implicated in this setting. Moreover, we explored the possible relationship between HMGB1 and the proinflammatory cytokine interleukin-6 (IL-6).

Methods

Forty-seven subjects, American Society of Anesthesiologists physical status I and II, scheduled for major abdominal procedures, were enrolled. After intravenous medication with midazolam (0.025 mg/Kg), all patients received a standard general anesthesia protocol, by thiopentone sodium (5 mg/Kg) and fentanyl (1.4 μg/Kg), plus injected Vecuronium (0.08 mg/Kg). Venous peripheral blood was drawn from patients at three different times, t0: before surgery, t1: immediately after surgical procedure; t2: at 24 hours following intervention. Monocytes were purified by incubation with anti-CD14-coated microbeads, followed by sorting with a magnetic device. Cellular localization of HMGB1 was investigated by flow cytometry assay; HMGB1 release in the serum by Western blot. Serum samples were tested for IL-6 levels by ELISA. A one-way repeated-measures analysis ANOVA was performed to assess differences in HMGB1 concentration over time, in monocytes and serum.

Results

We show that: a) cellular expression of HMGB1 in monocytes at t1 was significantly higher as compared to t0; b) at t2, a significant increase of HMGB1 levels was found in the sera of patients. Such an increase was concomitant to a significant down-regulation of cellular HMGB1, suggesting that the release of HMGB1 might partially derive from mononuclear cells; c) treatment of monocytes with HMGB1 induced in vitro the release of IL-6; d) at t2, high amounts of circulating IL-6 were detected as compared to t0.

Conclusions

This study demonstrates for the first time that surgical/anesthesia trauma is able to induce an early intracellular upregulation of HMGB1 in monocytes of surgical patients, suggesting that HMGB1 derives, at least partially, from monocytes.
Impact of Introducing Stereotactic Lung Radiotherapy for Elderly Patients With Stage I Non–Small-Cell Lung Cancer: A Population-Based Time-Trend Analysis
Authors: Palma David , Visser Otto , Lagerwaard Frank J. , Belderbos Jose , Slotman Ben J. , Senan Suresh
Published: November 2010

Purpose

Stereotactic body radiotherapy (SBRT) for stage I non–small-cell lung cancer (NSCLC) is associated with high local control rates. The impact of introducing SBRT in patients 75 years of age or older was studied using a population-based cancer registry.

Methods

The Amsterdam Cancer Registry was assessed in three eras: 1999 to 2001 (period A, pre-SBRT); 2002 to 2004 (period B, some availability of SBRT), and 2005 to 2007 (period C, full access to SBRT). χ2, Kaplan-Meier, and Cox regression were used to compare treatment patterns and overall survival (OS) in three treatment groups: surgery, radiotherapy (RT), or neither.

Results

A total of 875 elderly patients were diagnosed with stage I NSCLC in the study period. Median follow-up was 54 months. Primary treatment was surgery in 299 patients (34%), RT in 299 patients (34%), and neither in 277 patients (32%). RT use increased between periods A and C (26% v 42%, P < .01), corresponding to a decrease in untreated patients. The percentage of RT patients undergoing SBRT in periods B and C was 23% and 55%, respectively. Median survival for all patients increased from 16 months in period A to 21 months in period C (log-rank P < .01; hazard ratio [HR] = 0.65; 95% CI, 0.54 to 0.80). The improvement in OS was confined to RT patients (HR = 0.70; 95% CI, 0.49 to 0.99), whereas no significant survival improvements were seen in the other groups.

Conclusion

SBRT introduction was associated with a 16% absolute increase in RT use, a decline in the proportion of untreated elderly patients, and an improvement in OS.
A nucleoporin, Nup60p, affects the nuclear and cytoplasmic localization of ASH1 mRNA in S. cerevisiae
Authors: Powrie Erin A. , Zenklusen Daniel , Singer Robert H.
Published: October 2010

The biogenesis of a localization-competent mRNP begins in the nucleus. It is thought that the coordinated action of nuclear and cytoplasmic components of the localization machinery is required for the efficient export and subsequent subcellular localization of these mRNAs in the cytoplasm. Using quantitative poly(A)+ and transcript-specific fluorescent in situ hybridization, we analyzed different nonessential nucleoporins and nuclear pore-associated proteins for their potential role in mRNA export and localization. We found that Nup60p, a nuclear pore protein located on the nucleoplasmic side of the nuclear pore complex, was required for the mRNA localization pathway. In a Δnup60 background, localized mRNAs were preferentially retained within the nucleus compared to nonlocalized transcripts. However, the export block was only partial and some transcripts could still reach the cytoplasm. Importantly, downstream processes were also affected. Localization of ASH1 and IST2 mRNAs to the bud was impaired in the Δnup60 background, suggesting that the assembly of a localization competent mRNP (“locasome”) was inhibited when NUP60 was deleted. These results demonstrate transcript specificity of a nuclear mRNA retention defect and identify a specific nucleoporin as a functional component of the localization pathway in budding yeast.
Paradoxes in Learning and the Marginal Value of Information
Authors: Frazier Peter I. , Powell Warren B.
Published: October 2010

We consider the Bayesian ranking and selection problem, in which one wishes to allocate an information collection budget as efficiently as possible to choose the best among several alternatives. In this problem, the marginal value of information is not concave, leading to algorithmic difficulties and apparent paradoxes. Among these paradoxes is that when there are many identical alternatives, it is often better to ignore some completely and focus on a smaller number than it is to spread the measurement budget equally across all the alternatives. We analyze the consequences of this nonconcavity in several classes of ranking and selection problems, showing that the value of information is “eventually concave,” i.e., concave when the number of measurements of each alternative is large enough. We also present a new fully sequential measurement strategy that addresses the challenge that nonconcavity it presents.
Integrating Dynamic Pricing and Replenishment Decisions Under Supply Capacity Uncertainty
Authors: Feng Qi
Published: October 2010

This paper examines an integrated decision-making process regarding pricing for uncertain demand and sourcing from uncertain supply, which are often studied separately in the literature. Our analysis of the integrated system suggests that the base stock list price policy fails to achieve optimality even under deterministic demand. Instead, the optimal policy is characterized by two critical values: a reorder point and a target safety stock. Under this policy, a positive order is issued if and only if the inventory level is below the reorder point. When this happens, the optimal order and price are coordinated to achieve a constant target safety stock, which aims at hedging the demand uncertainty. We further investigate the profit improvement obtained from deploying dynamic pricing, as opposed to static pricing. Our results indicate that either supply limit or supply uncertainty may induce a significant benefit from dynamic pricing, and the compound effect of supply limit and uncertainty can be much more pronounced than the individual effects. Whether or not the supply capacity is limited has a major implication on the value of dynamic pricing. Under unlimited supply, dynamic pricing is more valuable when procurement cost is high or when demand is more sensitive to price. With limited supply, however, the capacity restriction tends to be relaxed, reducing the value of dynamic pricing.