bluuebunny/crossref_metadata_2025 huggingface dataset:
Divergent adaptive and innate immunological responses are observed in humans following blunt trauma
Authors: Kasten Kevin R , Goetzman Holly S , Reid Maria R , Rasper Alison M , Adediran Samuel G , Robinson Chad T , Cave Cindy M , Solomkin Joseph S , Lentsch Alex B , Johannigman Jay A , Caldwell Charles C
Published: January 2010

Background

The immune response to trauma has traditionally been modeled to consist of the systemic inflammatory response syndrome (SIRS) followed by the compensatory anti-inflammatory response syndrome (CARS). We investigated these responses in a homogenous cohort of male, severe blunt trauma patients admitted to a University Hospital surgical intensive care unit (SICU). After obtaining consent, peripheral blood was drawn up to 96 hours following injury. The enumeration and functionality of both myeloid and lymphocyte cell populations were determined.

Results

Neutrophil numbers were observed to be elevated in trauma patients as compared to healthy controls. Further, neutrophils isolated from trauma patients had increased raft formation and phospho-Akt. Consistent with this, the neutrophils had increased oxidative burst compared to healthy controls. In direct contrast, blood from trauma patients contained decreased naïve T cell numbers. Upon activation with a T cell specific mitogen, trauma patient T cells produced less IFN-gamma as compared to those from healthy controls. Consistent with these results, upon activation, trauma patient T cells were observed to have decreased T cell receptor mediated signaling.

Conclusions

These results suggest that following trauma, there are concurrent and divergent immunological responses. These consist of a hyper-inflammatory response by the innate arm of the immune system concurrent with a hypo-inflammatory response by the adaptive arm.
Microbiological quality of drinking water from dispensers in Italy
Authors: Liguori Giorgio , Cavallotti Ivan , Arnese Antonio , Amiranda Ciro , Anastasi Daniela , Angelillo Italo F
Published: January 2010

Background

Water coolers are popular in office buildings and commercial stores and the quality of this source of drinking water has the potential to cause waterborne outbreaks, especially in sensitive and immunocompromised subjects. The aim of this study was to determine the quality of water plumbed in coolers from commercial stores in comparison with tap water in Italy.

Methods

For each sample, microbial parameters and chemical indicators of contamination were evaluated and information about the date of installation, time since last ordinary and extraordinary maintenance of water coolers was collected.

Results

In all samples the chemical parameters (nitrite, ammonium, free active chlorine residual) did not exceed the reference values of the drinking water regulation; the pH value in 86.8% samples of the carbonated waters was lower than the reference limit. The microbiological results indicated that the bacteria count at 22°C and 37°C was higher than the required values in 71% and 81% for the non-carbonated water and in 86% and 88% for the carbonated one, respectively. Enterococcus spp. and Escherichia coli were not detected in any of the water samples. Pseudomonas aeruginosa was found in only one sample of the tap water and in 28.9% and 23.7% of the non-carbonated and carbonated water samples, respectively. No statistically significant differences in bacterial counts at 22°C and 37°C have been found between the non-carbonated and carbonated water from the sampled coolers in relation with the time since the last filter was substituted. The bacteriological quality of tap water was superior to that of non-carbonated and carbonated water from coolers.

Conclusion

The results emphasize the importance of adopting appropriate routinely monitoring system in order to prevent or to diminish the chances of contamination of this water source.
Transcriptional regulatory network triggered by oxidative signals configures the early response mechanisms of japonica rice to chilling stress
Authors: Yun Kil-Young , Park Myoung Ryoul , Mohanty Bijayalaxmi , Herath Venura , Xu Fuyu , Mauleon Ramil , Wijaya Edward , Bajic Vladimir B , Bruskiewich Richard , de los Reyes Benildo G
Published: January 2010

Background

The transcriptional regulatory network involved in low temperature response leading to acclimation has been established inArabidopsis. In japonica rice, which can only withstand transient exposure to milder cold stress (10°C), an oxidative-mediated network has been proposed to play a key role in configuring early responses and short-term defenses. The components, hierarchical organization and physiological consequences of this network were further dissected by a systems-level approach.

Results

Regulatory clusters responding directly to oxidative signals were prominent during the initial 6 to 12 hours at 10°C. Early events mirrored a typical oxidative response based on striking similarities of the transcriptome to disease, elicitor and wounding induced processes. Targets of oxidative-mediated mechanisms are likely regulated by several classes of bZIP factors acting on as1/ocs/TGA-like element enriched clusters, ERF factors acting on GCC-box/JAre-like element enriched clusters and R2R3-MYB factors acting on MYB2-like element enriched clusters.

Temporal induction of several H2O2-induced bZIP, ERF and MYB genes coincided with the transient H2O2spikes within the initial 6 to 12 hours. Oxidative-independent responses involveDREB/CBF,RAP2andRAV1factors acting on DRE/CRT/rav1-like enriched clusters and bZIP factors acting on ABRE-like enriched clusters. Oxidative-mediated clusters were activated earlier than ABA-mediated clusters.

Conclusion

Genome-wide, physiological and whole-plant level analyses established a holistic view of chilling stress response mechanism of japonica rice. Early response regulatory network triggered by oxidative signals is critical for prolonged survival under sub-optimal temperature. Integration of stress and developmental responses leads to modulated growth and vigor maintenance contributing to a delay of plastic injuries.
Prostaglandin E2-induced colonic secretion in patients with and without colorectal neoplasia
Authors: Kaltoft Nicolai , Tilotta Maria C , Witte Anne-Barbara , Osbak Philip S , Poulsen Steen S , Bindslev Niels , Hansen Mark B
Published: January 2010

Background

The pathogenesis for colorectal cancer remains unresolved. A growing body of evidence suggests a direct correlation between cyclooxygenase enzyme expression, prostaglandin E2 metabolism and neoplastic development. Thus further understanding of the regulation of epithelial functions by prostaglandin E2 is needed. We hypothesized that patients with colonic neoplasia have altered colonic epithelial ion transport and express functionally different prostanoid receptor levels in this respect.

Methods

Patients referred for colonoscopy were included and grouped into patients with and without colorectal neoplasia. Patients without endoscopic findings of neoplasia served as controls. Biopsy specimens were obtained from normally appearing mucosa in the sigmoid part of colon. Biopsies were mounted in miniaturized modified Ussing air-suction chambers. Indomethacin (10 μM), various stimulators and inhibitors of prostanoid receptors and ion transport were subsequently added to the chamber solutions. Electrogenic ion transport parameters (short circuit current and slope conductance) were recorded. Tissue pathology and tissue damage before and after experiments was assessed by histology.

Results

Baseline short circuit current and slope conductance did not differ between the two groups. Patients with neoplasia were significantly more sensitive to indomethacin with a decrease in short circuit current of 15.1 ± 2.6 μA·cm-2 compared to controls, who showed a decrease of 10.5 ± 2.1 μA·cm-2 (p = 0.027). Stimulation or inhibition with theophylline, ouabain, bumetanide, forskolin or the EP receptor agonists prostaglandin E2, butaprost, sulprostone and prostaglandin E1 (OH) did not differ significantly between the two groups. Histology was with normal findings in both groups.

Conclusions

Epithelial electrogenic transport is more sensitive to indomethacin in normal colonic mucosa from patients with previous or present colorectal neoplasia compared to colonic mucosa from control patients. Stimulated epithelial electrogenic transport through individual prostanoid subtype receptors EP1, EP2, EP3, and EP4 is not significantly different between neoplasia diseased patients and controls. This indicates that increased indomethacin-sensitive mechanisms in colonic mucosa from neoplasia diseased patients are not related to differences in functional expression of EP receptor subtypes.
Diagnoses and visit length in complementary and mainstream medicine
Authors: Heiligers Phil JM , de Groot Judith , Koster Dick , van Dulmen Sandra
Published: January 2010

Background

The demand for complementary medicine (CM) is growing worldwide and so is the supply. So far, there is not much insight in the activities in Dutch CM practices nor in how these activities differ from mainstream general practice. Comparisons on diagnoses and visit length can offer an impression of how Dutch CM practices operate.

Methods

Three groups of regularly trained physicians specialized in CM participated in this study: 16 homeopathic physicians, 13 physician acupuncturists and 11 naturopathy physicians. Every CM physician was asked to include a maximum of 75 new patients within a period of six months. For each patient an inclusion registration form had to be completed and the activities during a maximum of five repeat visits were subsequently registered. Registrations included patient characteristics, diagnoses and visit length. These data could be compared with similar data from general practitioners (GPs) participating in the second Dutch national study in general practice (DNSGP-2). Differences between CM practices and between CM and mainstream GP data were tested using multilevel regression analysis.

Results

The CM physicians registered activities in a total of 5919 visits in 1839 patients. In all types of CM practices general problems (as coded in the ICPC) were diagnosed more often than in mainstream general practice, especially fatigue, allergic reactions and infections. Psychological problems and problems with the nervous system were also diagnosed more frequently. In addition, each type of CM physician encountered specific health problems: in acupuncture problems with the musculoskeletal system prevailed, in homeopathy skin problems and in naturopathy gastrointestinal problems. Comparisons in visit length revealed that CM physicians spent at least twice as much time with patients compared to mainstream GPs.

Conclusions

CM physicians differed from mainstream GPs in diagnoses, partly related to general and partly to specific diagnoses. Between CM practices differences were found on specific domains of complaints. Visit length was much longer in CM practices compared to mainstream GP visits, and such ample time may be one of the attractive features of CM for patients.
Developing counseling skills through pre-recorded videos and role play: a pre- and post-intervention study in a Pakistani medical school
Authors: Ahsen Noor F , Batul Syeda A , Ahmed Ahsen N , Imam Sardar Z , Iqbal Humaira , Shamshair Khayyam , Ali Hammad
Published: January 2010

Background

Interactive methods like role play, recorded video scenarios and objective structured clinical exam (OSCE) are being regularly used to teach and assess communication skills of medical students in the western world. In developing countries however, they are still in the preliminary phases of execution in most institutes. Our study was conducted in a naïve under resourced setup to assess the impact of such teaching methodologies on the counseling skills of medical students.

Methods

Fifty four 4th year MBBS students were identified to be evaluated for communication skills by trained facilitators in a pre-intervention OSCE. The same group of students was given a demonstration of ideal skill level by means of videos and role playing sessions in addition to real life interaction with patients during hospital and community rotations. A post-intervention evaluation was carried out six months later through OSCE and direct observation through structured checklist (DOS) in hospital and community settings. The combined and individual performance levels of these students were analyzed.

Results

There was a statistically significant difference in the communication skills of students when assessed in the post-intervention OSCE (p = 0.000). Individual post-intervention percentages of study participants displayed improvement as well (n = 45, p = 0.02). No difference was observed between the scores of male and female students when assessed for two specific competencies of antenatal care and breast feeding counseling (p = 0.11). The mean DOS (%) score of 12 randomly selected students was much lower as compared to the post-intervention (%) score but the difference between them was statistically non significant, a result that may have been affected by the small sample size as well as other factors that may come into play in real clinical settings and were not explored in this study (59.41 ± 7.8 against 82.43 ± 22.08, p = 0.88).

Conclusions

Videos and role play in combination with community and clinical exposure are effective modes of teaching counseling skills to medical students. They can be successfully utilized even in a limited resource setup, as demonstrated by our trial.
Malaria incidence and prevalence on Pemba Island before the onset of the successful control intervention on the Zanzibar Archipelago
Authors: Jaenisch Thomas , Sullivan David J , Dutta Arup , Deb Saikat , Ramsan Mahdi , Othman Mashavu K , Gaczkowski Roger , Tielsch James , Sazawal Sunil
Published: January 2010

Background

Malaria incidence has been reported to decrease substantially in parts of sub-Saharan Africa, including the Zanzibar Archipelago in East Africa. A cohort study with an intensive follow-up on Pemba Island just before the onset of the highly successful malaria control intervention was conducted. The reported estimates of parasite prevalence and incidence can serve as a robust baseline to evaluate the effect size of the successful interventions and the potential contribution of quality controls and other factors associated with research studies in the decreased estimate of transmission.

Methods

In a rural clinic, two successive cohorts of 537 children total aged 2-23 months were followed for six months each with an intensive visitation schedule of bi-weekly follow-up. Robust estimates of incidence and prevalence according to four different malaria definitions were obtained.

Results

Malaria incidence and prevalence placed Pemba Island in a hyperendemic rather than holoendemic setting for the years 2003-2005. Overall parasite prevalence was estimated to be 39% - with monthly estimates varying between 30% and 50%. Incidence of malaria varied between 2.3 and 3.8 malaria episodes per year based on a diagnosis of fever and various microscopy-based parasite thresholds and between 4.8 and 5.7 based on a diagnosis of fever and 100 parasites/microliter analogous to detection by rapid diagnostic tests. Both parasite densities and malaria incidence increased with age and rainy season. Malaria incidence also varied substantially between the individual villages within the study area.

Conclusions

Pemba Island was previously considered holo-endemic for Malaria. The data suggest that the transmission situation on Pemba Island was significantly lower in 2003-2005 suggesting a hyper-endemic or meso-endemic transmission environment. The figures were obtained just before the onset of the highly successful malaria control intervention by impregnated bed nets and IRS on the Zanzibar Archipelago and provide robust estimates of the malaria transmission situation prior to the control programme. Together with other published data, the results suggest that malaria transmission had started to decrease before the onset of the control programme. The local heterogeneity in malaria incidence highlights the importance of a micro-epidemiological approach in the context of malaria control and elimination.
Constitutively overexpressed 21 kDa protein in Hodgkin lymphoma and aggressive non-Hodgkin lymphomas identified as cytochrome B5b (CYB5B)
Authors: Murphy Derek , Parker Jeremy , Zhou Minglong , Fadlelmola Faisal M , Steidl Christian , Karsan Aly , Gascoyne Randy D , Chen Hong , Banerjee Diponkar
Published: January 2010

Background

We have previously reported a novel constitutively overexpressed 21 kDa protein in Hodgkin Lymphoma (HL) and aggressive Non-Hodgkin Lymphomas (NHL). The objective of the current study was to 1) identify this protein using two independent methods, 2) study the expression of the protein and its encoding mRNA in reactive lymph nodes, normal lymphocytes and CD34+ bone marrow precursor cells, 3) analyse patterns of expression of the protein in tissue microarrays assembled from a large number of diagnostic clinical biopsies from patients with HL, and 4) determine the copy number variation and mutation status of the encoding gene in HL cell lines.

Results

Peptide sequencing by LC-MS/MS and protein identification by protein array screening identified a single protein, CYB5B. No mutations were detected in theCYB5Bgene in HL cell lines. Quantitative PCR showedCYB5Bgene expression was increased in HL and NHL cell lines. Array CGH using a submegabase resolution tiling array revealed gains in theCYB5Blocus in HL cell lines KMH2 and L428. Membrane expression was seen in Reed-Sternberg cells in clinical biopsies from patients with HL but not in reactive lymph nodes. Bone marrow CD34+ precursor cells were CYB5B negative on the cell surface. RT-PCR assays of RNA extracted from T and B cell enriched fractions obtained from normal peripheral blood mononuclear cells, reactive lymph nodes, tonsils and normal bone marrow samples showed no evidence of increased mRNA levels ofCYB5Bin comparison to housekeeping geneGAPDH.

Conclusions

The 21 kDa protein overexpressed in HL and aggressive NHL is identical to CYB5B.CYB5Bgene expression is increased in a subset of HL and NHL cell lines tested. This is associated withCYB5Bgene amplification in HL cell lines KMH2 and L428. CYB5B may be a potential target for antibody-based therapy of HL and aggressive NHL as although cytoplasmic expression is present in reactive lymphocytes, it is not expressed on the cell surface of non-neoplastic lymphocytes or bone marrow precursor cells.
Cell-specific targeting of lentiviral vectors mediated by fusion proteins derived from Sindbis virus, vesicular stomatitis virus, or avian sarcoma/leukosis virus
Authors: Zhang Xian-Yang , Kutner Robert H , Bialkowska Agnieszka , Marino Michael P , Klimstra William B , Reiser Jakob
Published: January 2010

Background

The ability to efficiently and selectively target gene delivery vectors to specific cell types in vitro and in vivo remains one of the formidable challenges in gene therapy. We pursued two different strategies to target lentiviral vector delivery to specific cell types. In one of the strategies, vector particles bearing a membrane-bound stem cell factor sequence plus a separate fusion protein based either on Sindbis virus strain TR339 glycoproteins or the vesicular stomatitis virus G glycoprotein were used to selectively transduce cells expressing the corresponding stem cell factor receptor (c-kit). An alternative approach involved soluble avian sarcoma/leukosis virus receptors fused to cell-specific ligands including stem cell factor and erythropoietin for targeting lentiviral vectors pseudotyped with avian sarcoma/leukosis virus envelope proteins to cells that express the corresponding receptors.

Results

The titers of unconcentrated vector particles bearing Sindbis virus strain TR339 or vesicular stomatitis virus G fusion proteins plus stem cell factor in the context of c-kit expressing cells were up to 3.2 × 105 transducing units per ml while vector particles lacking the stem cell factor ligand displayed titers that were approximately 80 fold lower. On cells that lacked the c-kit receptor, the titers of stem cell factor-containing vectors were approximately 40 times lower compared to c-kit-expressing cells.

Lentiviral vectors pseudotyped with avian sarcoma/leukosis virus subgroup A or B envelope proteins and bearing bi-functional bridge proteins encoding erythropoietin or stem cell factor fused to the soluble extracellular domains of the avian sarcoma/leukosis virus subgroup A or B receptors resulted in efficient transduction of erythropoietin receptor or c-kit-expressing cells. Transduction of erythropoietin receptor-expressing cells mediated by bi-functional bridge proteins was found to be dependent on the dose, the correct subgroup-specific virus receptor and the correct envelope protein. Furthermore, transduction was completely abolished in the presence of anti-erythropoietin antibody.

Conclusions

Our results indicate that the avian sarcoma/leukosis virus bridge strategy provides a reliable approach for cell-specific lentiviral vector targeting. The background levels were lower compared to alternative strategies involving Sindbis virus strain TR339 or vesicular stomatitis virus fusion proteins.
KATP Channel Subunits in Rat Dorsal Root Ganglia: Alterations by Painful Axotomy
Authors: Zoga Vasiliki , Kawano Takashi , Liang Mei-Ying , Bienengraeber Martin , Weihrauch Dorothee , McCallum Bruce , Gemes Geza , Hogan Quinn , Sarantopoulos Constantine
Published: January 2010

Background:

ATP-sensitive potassium (KATP) channels in neurons mediate neuroprotection, they regulate membrane excitability, and they control neurotransmitter release. Because loss of DRG neuronal KATP currents is involved in the pathophysiology of pain after peripheral nerve injury, we characterized the distribution of the KATP channel subunits in rat DRG, and determined their alterations by painful axotomy using RT-PCR, immunohistochemistry and electron microscopy.

Results:

PCR demonstrated Kir6.1, Kir6.2, SUR1 and SUR2 transcripts in control DRG neurons. Protein expression for all but Kir6.1 was confirmed by Western blots and immunohistochemistry. Immunostaining of these subunits was identified by fluorescent and confocal microscopy in plasmalemmal and nuclear membranes, in the cytosol, along the peripheral fibers, and in satellite glial cells. Kir6.2 co-localized with SUR1 subunits. Kir6.2, SUR1, and SUR2 subunits were identified in neuronal subpopulations, categorized by positive or negative NF200 or CGRP staining. KATP current recorded in excised patches was blocked by glybenclamide, but preincubation with antibody against SUR1 abolished this blocking effect of glybenclamide, confirming that the antibody targets the SUR1 protein in the neuronal plasmalemmal membrane. In the myelinated nerve fibers we observed anti-SUR1 immunostaining in regularly spaced funneled-shaped structures. These structures were identified by electron microscopy as Schmidt-Lanterman incisures (SLI) formed by the Schwann cells. Immunostaining against SUR1 and Kir6.2 colocalized with anti-Caspr at paranodal sites. DRG excised from rats made hyperalgesic by spinal nerve ligation exhibited similar staining against Kir6.2, SUR1 or SUR2 as DRG from controls, but showed decreased prevalence of SUR1 immunofluorescent NF200 positive neurons. In DRG and dorsal roots proximal to axotomy SLI were smaller and showed decreased SUR1 immunofluorescence.

Conclusions:

We identified Kir6.2/SUR1 and Kir6.2/SUR2 KATP channels in rat DRG neuronal somata, peripheral nerve fibers, and glial satellite and Schwann cells, in both normal state and after painful nerve injury. This is the first report of KATP channels in paranodal sites adjacent to nodes of Ranvier and in the SLI of the Schwann cells. After painful axotomy KATP channels are downregulated in large, myelinated somata and also in SLI, which are also of smaller size compared to controls. Because KATP channels may have diverse functional roles in neurons and glia, further studies are needed to explore the potential of KATP channels as targets of therapies against neuropathic pain and neurodegeneration.
The B-VITAGE trial: A randomized trial of homocysteine lowering treatment of depression in later life
Authors: Ford Andrew H , Flicker Leon , McCaul Kieran , van Bockxmeer Frank , Hegarty Sarah , Hirani Varsha , Fenner Stephen , Almeida Osvaldo P
Published: January 2010

Background

Depression is a leading cause of disability worldwide and depressive symptoms are common in later life. Observational evidence suggests that depression is more prevalent among people with high plasma homocysteine (tHcy), but the results of randomized trials to date have been unable to show that lowering tHcy through the supplementation of vitamins B6, B12 and folate benefits depressive symptoms. We designed the B-VITAGE trial to determine whether adjunctive treatment with vitamins B6, B12 and folate increases the efficacy of standard antidepressant treatment.

Methods/Design

The B-VITAGE trial is a 12-month randomized, double-blind, placebo-controlled trial of daily citalopram (20 to 40 mg) plus B12(0.4 mg), B6 (25 mg) and folic acid (2 mg) or citalopram (20 to 40 mg) plus placebo for the treatment of depression in later life. The trial aims to recruit over 300 older adults with major depression (DSM-IV) and has been powered to detect the impact of an intervention associated with moderate effect size. Depressive symptoms will be rated with the Montgomery-Åsberg Depression Rating Scale (MADRS). The trial has two main outcomes of interest: a reduction of 50% or more in the MADRS total score between baseline and week 12 and the remission of the depressive episode at weeks 12, 26 and 52 according to DSM-IV criteria. We hypothesize that subjects randomly allocated to the vitamin arm of the study will be more likely to show a clinically significant improvement and achieve and maintain remission of symptoms at 12, 26 and 52 weeks. Secondary outcomes of interest include compliance with treatment, reduction in the severity of depressive symptoms, switching to different antidepressants, the use of non-pharmacological antidepressant treatments, response to treatment according to MTHFRC677T genotype, and changes in cognitive function over 52 weeks.

Conclusions

The results of this trial will clarify whether the systematic use of B-vitamins improves the response of older adults to standard antidepressant treatment. We anticipate that our findings will have implications for clinical practice and health policy development.

Trial Registration

The trial is registered with the Australian Clinical Trials Registry, trial number (())ACTRN12609000256279.
Blood flow controls coagulation onset via the positive feedback of factor VII activation by factor Xa
Authors: Shibeko Alexey M , Lobanova Ekaterina S , Panteleev Mikhail A , Ataullakhanov Fazoil I
Published: January 2010

Background

Blood coagulation is a complex network of biochemical reactions, which is peculiar in that it is time- and space-dependent, and has to function in the presence of rapid flow. Recent experimental reports suggest that flow plays a significant role in its regulation. The objective of this study was to use systems biology techniques to investigate this regulation and to identify mechanisms creating a flow-dependent switch in the coagulation onset.

Results

Using a detailed mechanism-driven model of tissue factor (TF)-initiated thrombus formation in a two-dimensional channel we demonstrate that blood flow can regulate clotting onset in the model in a threshold-like manner, in agreement with existing experimental evidence. Sensitivity analysis reveals that this is achieved due to a combination of the positive feedback of TF-bound factor VII activation by activated factor X (Xa) and effective removal of factor Xa by flow from the activating patch depriving the feedback of "ignition". The level of this trigger (i.e. coagulation sensitivity to flow) is controlled by the activity of tissue factor pathway inhibitor.

Conclusions

This mechanism explains the difference between red and white thrombi observed in vivo at different shear rates. It can be speculated that this is a special switch protecting vascular system from uncontrolled formation and spreading of active coagulation factors in vessels with rapidly flowing blood.
Chronic constipation due to presacral teratoma in a 36-year-old woman: a case report
Authors: Paramythiotis Daniel , Papavramidis Theodossis S , Michalopoulos Antonios , Papadopoulos Vassilios N , Apostolidis Stylianos , Televantou Despoina , Hytiroglou Prodromos
Published: January 2010

Introduction

Teratomas of the sacrococcygeal area are usually diagnosed in infancy and are rarely seen in adults.

Case presentation

We report the case of a 36-year-old Greek woman experiencing chronic constipation due to a benign presacral teratoma. Imaging examinations showed a pelvic mass without evidence of malignancy. An ovoid tumour with a maximum dimension of 6 cm was surgically removed. A histologic examination revealed a mature cystic teratoma. Two years after surgery, the patient is well, with no evidence of recurrence and no constipation.

Conclusion

Sacrococcygeal teratomas are rare in adults. A high index of suspicion is important in making an early diagnosis. Rectal examination and radiologic evaluation are also valuable.
Gene profiling of the erythro- and megakaryoblastic leukaemias induced by the Graffi murine retrovirus
Authors: Voisin Veronique , Legault Philippe , Ospina Diana Paulina Salazar , Ben-David Yaacov , Rassart Eric
Published: January 2010

Background

Acute erythro- and megakaryoblastic leukaemias are associated with very poor prognoses and the mechanism of blastic transformation is insufficiently elucidated. The murine Graffi leukaemia retrovirus induces erythro- and megakaryoblastic leukaemias when inoculated into NFS mice and represents a good model to study these leukaemias.

Methods

To expand our understanding of genes specific to these leukaemias, we compared gene expression profiles, measured by microarray and RT-PCR, of all leukaemia types induced by this virus.

Results

The transcriptome level changes, present between the different leukaemias, led to the identification of specific cancerous signatures. We reported numerous genes that may be potential oncogenes, may have a function related to erythropoiesis or megakaryopoiesis or have a poorly elucidated physiological role. The expression pattern of these genes has been further tested by RT-PCR in different samples, in a Friend erythroleukaemic model and in human leukaemic cell lines.

We also screened the megakaryoblastic leukaemias for viral integrations and identified genes targeted by these integrations and potentially implicated in the onset of the disease.

Conclusions

Taken as a whole, the data obtained from this global gene profiling experiment have provided a detailed characterization of Graffi virus induced erythro- and megakaryoblastic leukaemias with many genes reported specific to the transcriptome of these leukaemias for the first time.
RNAi-mediated CD40-CD154 interruption promotes tolerance in autoimmune arthritis
Authors: Zheng Xiufen , Suzuki Motohiko , Zhang Xusheng , Ichim Thomas E , Zhu Fei , Ling Hong , Shunnar Aminah , Wang Michael H , Garcia Bertha , Inman Robert D , Min Wei-Ping
Published: January 2010

Introduction

We have previously demonstrated that ex vivo inhibition of costimulatory molecules on antigen-pulsed dendritic cells (DCs) can be useful for induction of antigen-specific immune deviation and suppression of autoimmune arthritis in the collagen induced arthritis (CIA) model. The current study evaluated a practical method of immune modulation through temporary systemic inhibition of the costimulatory molecule CD40.

Methods

Mice with collagen II (CII)-induced arthritis (CIA) were administered siRNA targeting the CD40 molecule. Therapeutic effects were evaluated by clinical symptoms, histopathology, Ag-specific T cell and B cell immune responses.

Results

Systemic administration of CD40-targeting siRNA can inhibit antigen-specific T cell response to collagen II, as well as prevent pathogenesis of disease in both a pre- and post-immunization manner in the CIA model. Disease amelioration was associated with suppression of Th1 cytokines, attenuation of antibody production, and upregulation of T regulatory cells.

Conclusions

These studies support the feasibility of transient gene silencing at a systemic level as a mechanism of resetting autoreactive immunity.
Phase II Trial of a Trimodality Regimen for Stage III Non–Small-Cell Lung Cancer Using Chemotherapy As Induction Treatment With Concurrent Hyperfractionated Chemoradiation With Carboplatin and Paclitaxel Followed by Subsequent Resection: A Single-Center Study
Authors: Friedel Godehard , Budach Wilfried , Dippon Juergen , Spengler Werner , Eschmann Susanne Martina , Pfannenberg Christina , Al-Kamash Fawaz , Walles Thorsten , Aebert Hermann , Kyriss Thomas , Veit Stefanie , Kimmich Martin , Bamberg Michael , Kohlhaeufl Martin , Steger Volker , Hehr Thomas
Published: January 2010

Purpose

We started a phase II trial of induction chemotherapy and concurrent hyperfractionated chemoradiotherapy followed by either surgery or boost chemoradiotherapy in patients with advanced, stage III disease. The purpose is to achieve better survival in the surgery group with minimum morbidity and mortality.

Patients and Methods

Patients treated from 1998 to 2002 with neoadjuvant chemoradiotherapy and surgical resection for stage III NSCLC were analyzed. The treatment consisted of four cycles of induction chemotherapy with carboplatin/paclitaxel followed by chemoradiotherapy with a reduced dose of carboplatin/paclitaxel and accelerated hyperfractionated radiotherapy with 1.5 Gy twice daily up to 45 Gy. After restaging, operable patients underwent thoracotomy. Inoperable patients received chemoradiotherapy up to 63 Gy. Study end points included resectability, pathologic response, and survival.

Results

One hundred twenty patients were enrolled; 25% patients had stage IIIA, 73% had stage IIIB, and 2% stage IV. After treatment, 47.5% had downstaging, 29.2% had stable disease, and 23.3% had progressive disease. Thirty patients (25%) were not eligible for operation because of progressive disease, stable disease, and/or functional deterioration with one treatment-related death. The 30-day mortality was 5% in patients who underwent operation. The 5-year survival rate for 120 patients was 21.7%, and it was 43.1% in patients with complete resection. In postoperative patients with stage N0 disease, 5-year survival was 53.3%; if stage N2 or N3 disease was still present, 5-year survival was 33.3%.

Conclusion

Staging and treatment with chemoradiotherapy and complete resection performed in experienced centers achieve acceptable morbidity and mortality.
Molecular Mechanisms of Resistance to Cetuximab and Panitumumab in Colorectal Cancer
Authors: Bardelli Alberto , Siena Salvatore
Published: January 2010

Personalized cancer medicine based on the genetic milieu of individual colorectal tumors has long been postulated, but until recently this concept was not supported by clinical evidence. The advent of the epidermal growth factor receptor (EGFR) –targeted monoclonal antibodies cetuximab and panitumumab has paved the way to the individualized treatment of metastatic colorectal cancer (mCRC). Here we discuss the evidence that mCRCs respond differently to EGFR-targeted agents and that the tumor-specific response has a genetic basis. We outline how, from the initial observation that cetuximab or panitumumab as monotherapy is effective only in 10% to 20% of mCRCs, knowledge has being gained on the molecular mechanisms underlying primary resistance to these agents. The role of oncogenic activation of EGFR downstream effectors such as KRAS, BRAF, PIK3CA, and PTEN on response to therapy is discussed. We suggest that CRCs lacking oncogenic alterations in these four genes have the highest probability of response to anti-EGFR therapies and are defined as “quadruple negative.” The rapid and effective translation of these findings into predictive biomarkers to couple EGFR-targeted antibodies to the patients who benefit from them is presented as a paradigm of modern clinical oncology. Finally, unresolved questions such as understanding the molecular basis of response as well the mechanisms of secondary resistance are presented as the future fundamental goals in this research field.
Overall Survival Analysis of a Phase II Randomized Controlled Trial of a Poxviral-Based PSA-Targeted Immunotherapy in Metastatic Castration-Resistant Prostate Cancer
Authors: Kantoff Philip W. , Schuetz Thomas J. , Blumenstein Brent A. , Glode L. Michael , Bilhartz David L. , Wyand Michael , Manson Kelledy , Panicali Dennis L. , Laus Reiner , Schlom Jeffrey , Dahut William L. , Arlen Philip M. , Gulley James L. , Godfrey Wayne R.
Published: January 2010

Purpose

Therapeutic prostate-specific antigen (PSA) –targeted poxviral vaccines for prostate cancer have been well tolerated. PROSTVAC-VF treatment was evaluated for safety and for prolongation of progression-free survival (PFS) and overall survival (OS) in a randomized, controlled, and blinded phase II study.

Patients and Methods

In total, 125 patients were randomly assigned in a multicenter trial of vaccination series. Eligible patients had minimally symptomatic castration-resistant metastatic prostate cancer (mCRPC). PROSTVAC-VF comprises two recombinant viral vectors, each encoding transgenes for PSA, and three immune costimulatory molecules (B7.1, ICAM-1, and LFA-3). Vaccinia-based vector was used for priming followed by six planned fowlpox-based vector boosts. Patients were allocated (2:1) to PROSTVAC-VF plus granulocyte-macrophage colony-stimulating factor or to control empty vectors plus saline injections.

Results

Eighty-two patients received PROSTVAC-VF and 40 received control vectors. Patient characteristics were similar in both groups. The primary end point was PFS, which was similar in the two groups (P = .6). However, at 3 years post study, PROSTVAC-VF patients had a better OS with 25 (30%) of 82 alive versus 7 (17%) of 40 controls, longer median survival by 8.5 months (25.1 v 16.6 months for controls), an estimated hazard ratio of 0.56 (95% CI, 0.37 to 0.85), and stratified log-rank P = .0061.

Conclusion

PROSTVAC-VF immunotherapy was well tolerated and associated with a 44% reduction in the death rate and an 8.5-month improvement in median OS in men with mCRPC. These provocative data provide preliminary evidence of clinically meaningful benefit but need to be confirmed in a larger phase III study.
Predicting loop–helix tertiary structural contacts in RNA pseudoknots
Authors: Cao Song , Giedroc David P. , Chen Shi-Jie
Published: January 2010

Tertiary interactions between loops and helical stems play critical roles in the biological function of many RNA pseudoknots. However, quantitative predictions for RNA tertiary interactions remain elusive. Here we report a statistical mechanical model for the prediction of noncanonical loop–stem base-pairing interactions in RNA pseudoknots. Central to the model is the evaluation of the conformational entropy for the pseudoknotted folds with defined loop–stem tertiary structural contacts. We develop an RNA virtual bond-based conformational model (Vfold model), which permits a rigorous computation of the conformational entropy for a given fold that contains loop–stem tertiary contacts. With the entropy parameters predicted from the Vfold model and the energy parameters for the tertiary contacts as inserted parameters, we can then predict the RNA folding thermodynamics, from which we can extract the tertiary contact thermodynamic parameters from theory–experimental comparisons. These comparisons reveal a contact enthalpy (ΔH) of −14 kcal/mol and a contact entropy (ΔS) of −38 cal/mol/K for a protonated C+•(G–C) base triple at pH 7.0, and (ΔH = −7 kcal/mol, ΔS = −19 cal/mol/K) for an unprotonated base triple. Tests of the model for a series of pseudoknots show good theory–experiment agreement. Based on the extracted energy parameters for the tertiary structural contacts, the model enables predictions for the structure, stability, and folding pathways for RNA pseudoknots with known or postulated loop–stem tertiary contacts from the nucleotide sequence alone.
Understanding the role of coping in the development of depressive symptoms: Symptom specificity, gender differences, and cross‐cultural applicability
Authors: Auerbach Randy P. , Abela John R. Z. , Zhu Xiongzhao. , Yao Shuqiao.
Published: January 2010

Objectives. The primary aim examined whether coping deficits, a greater tendency to utilize maladaptive as opposed to adaptive coping strategies, was associated with increases in depressive symptoms following negative events. The secondary goals examined: the common vulnerability hypothesis, sex differences, and the cross‐cultural generalizability.

Design. Following the initial assessment, Canadian adolescents completed three follow‐up assessments every 6 weeks. The Chinese adolescents completed an initial assessment and six follow‐up assessments occurring monthly.

Methods. At Time 1, 150 Canadian and 397 Chinese adolescents completed self‐report measures assessing depressive symptoms, anxious symptoms, negative events, and coping. During each of the follow‐up assessments, participants completed self‐report measures assessing depressive symptoms, anxious symptoms, and negative events.

Results. In both samples, higher levels of coping deficits were associated with increases in depressive, but not anxious, symptoms following negative events. Gender differences did not emerge.

Conclusions. The present study provides a theoretically driven model to examine the impact of broad‐based coping on the development of depressive symptoms.
Selective exposure: The impact of collectivism and individualism
Authors: Kastenmüller Andreas. , Greitemeyer Tobias. , Jonas Eva. , Fischer Peter. , Frey Dieter.
Published: January 2010

Previous research has found that people prefer information that supports rather than conflicts with their decisions (selective exposure). In the present three studies, we investigated the impact of collectivism and individualism on this bias. First, based on previous findings showing that collectivists compared to individualists are inclined to seek the ‘middle way’ and tend towards self‐criticism, we predicted and found that the confirmation bias was more negative among collectivists compared to individualists. Second, we assumed that the difference between selected supporting versus conflicting information would move more in favour of conflicting information among both collectivists and individualists when the domain was important to them. As predicted (chronic and primed), collectivists and individualists, respectively, sought more conflicting (compared to supporting) information depending on whether collectivistic (e.g., the family) or individualistic (e.g., one's own uniqueness) attributes were important.
On the Complexity of n-Player Hackenbush
Authors: Cincotti Alessandro
Published: January 2010

Why are
A New Generalization of Fibonacci Sequence & Extended Binet's Formula
Authors: Edson Marcia , Yayenie Omer
Published: January 2010

Consider the Fibonacci sequence
Palindromes in Different Bases: A Conjecture of J. Ernest Wilkins
Authors: Goins Edray Herber
Published: January 2010

We show that there exist exactly 203 positive integers
Differences of Multiple Fibonacci Numbers
Authors: Alpert Hannah
Published: January 2010

We show that every integer can be written uniquely as a sum of Fibonacci numbers and their additive inverses, such that every two terms of the same sign differ in index by at least 4 and every two terms of different sign differ in index by at least 3. Furthermore, there is no way to use fewer terms to write a number as a sum of Fibonacci numbers and their additive inverses. This is an analogue of the Zeckendorf representation.
An Interspecific Plant Hybrid Shows Novel Changes in Parental Splice Forms of Genes for Splicing Factors
Authors: Scascitelli Moira , Cognet Marie , Adams Keith L
Published: January 2010

Interspecific hybridization plays an important role in plant adaptive evolution and speciation, and the process often results in phenotypic novelty. Hybrids can show changes in genome structure and gene expression compared with their parents including chromosomal rearrangments, changes in cytosine methylation, up- and downregulation of gene expression, and gene silencing. Alternative splicing (AS) is a fundamental aspect of the expression of many genes. However alternative splicing patterns have not been examined in multiple genes in an interspecific plant hybrid compared with its parents. Here we studied alternative splicing patterns in an interspecific Populus hybrid and its parents by assaying 40 genes using reverse transcription PCR. Most of the genes showed identical alternative splicing patterns between the parents and the hybrid. We found new alternative splicing variants present in the hybrid in two SR genes involved in the regulation of splicing and alternative splicing. The novel alternative splicing patterns included changes in donor and acceptor sites to create a new exon in one allele of PtRSZ22 in the hybrid and retention of an intron in both alleles of PtSR34a.1 in the hybrid, with effects on the function of the corresponding truncated proteins, if present. Our results suggest that novel alternative splicing patterns are present in a small percentage of genes in hybrids, but they could make a considerable impact on the expression of some genes. Changes in alternative splicing are likely to be an important component of the genetic changes that occur upon interspecific hybridization.
Cyclin Y Is a Novel Conserved Cyclin Essential for Development in Drosophila
Authors: Liu Dongmei , Finley Russell L
Published: January 2010

The Drosophila gene CG14939 encodes a member of a highly conserved family of cyclins, the Y-type cyclins, which have not been functionally characterized in any organism. Here we report the generation and phenotypic characterization of a null mutant of CG14939, which we rename Cyclin  Y (CycY). We show that the null mutant, CycYE8, is homozygous lethal with most mutant animals arresting during pupal development. The mutant exhibits delayed larval growth and major developmental defects during metamorphosis, including impaired gas bubble translocation, head eversion, leg elongation, and adult tissue growth. Heat-shock-induced expression of CycY at different times during development resulted in variable levels of rescue, the timing of which suggests a key function for zygotic CycY during the transition from third instar larvae to prepupae. CycY also plays an essential role during embryogenesis since zygotic null embryos from null mothers fail to hatch into first instar larvae. We provide evidence that the CycY protein (CycY) interacts with Eip63E, a cyclin-dependent kinase (Cdk) for which no cyclin partner had previously been identified. Like CycY, the Eip63E gene has essential functions during embryogenesis, larval development, and metamorphosis. Our data suggest that CycY/Eip63E form a cyclin/Cdk complex that is essential for several developmental processes.