bluuebunny/crossref_metadata_2025 huggingface dataset:
Aggressive Angiomyxoma Admixed With Endometriosis
Authors: Coyne John D.
Published: August 2011

Aggressive angiomyxoma and endometriosis are two apparently unrelated lesions which commonly arise within the pelvis. However, whilst their simultaneous occurrence in this site may be fortuitous, a shared pathogenesis cannot be entirely excluded.
Perceived Causal Relations
Authors: Frewen Paul A. , Allen Samantha L. , Lanius Ruth A. , Neufeld Richard W. J.
Published: August 2011

Researchers have argued that the investigation of causal interrelationships between symptoms may help explain the high comorbidity rate between certain psychiatric disorders. Clients’ own attributions concerning the causal interrelationships linking the co-occurrence of their symptoms represent data that may inform their clinical case conceptualization, treatment, and psychological theory regarding the etiology of comorbid disorders. The present study developed and evaluated a novel psychological assessment methodology for measuring Perceived Causal Relations (PCR) and examined its psychometric properties as applied to the question of whether posttraumatic stress and anxiety symptoms represent causal risk factors for depressive symptoms in 225 undergraduates. Participants attributed their symptoms of anxiety and posttraumatic reexperiencing as significant causes of their depressive symptoms. Exploratory analyses identified a listing of symptoms reliably attributed as significant causes of other symptoms and functional impairment, as well as a listing of symptoms reliably attributed as significant effects (outcomes) of other symptoms and functional impairment. The PCR method has promise as an idiographic approach to assessing the causes and consequences of comorbid psychiatric symptoms and associated functional impairment. Research is required to assess the relevance and replicate these findings in distinct psychiatric groups experiencing various symptomatic presentations. Future research may also examine PCR ratings associating other individual differences, for example, between measures of history (e.g., life events), life choices, and personality.
Alteration of Hypothalamic–Pituitary–Thyroid Axis Function in Non-Small-Cell Lung Cancer Patients
Authors: Mazzoccoli Gianluigi , Pazienza Valerio , Piepoli Ada , Muscarella Lucia Anna , Giuliani Francesco , Sothern Robert B.
Published: August 2011

The aim of this study was to evaluate the hypothalamic–pituitary–thyroid (HPT) axis function in patients suffering from lung cancer. Thyrotropin-releasing hormone (TRH), thyroid-stimulating hormone (TSH), free thyroxine (FT4), interleukin (IL)-2, and melatonin serum levels were measured in blood samples collected every 4 hours for 24 hours from 11 healthy participants (H; ages 35-53 years) and 9 patients suffering from non-small-cell lung cancer (C; ages 43-63 years). Relationships between hormone levels overall and over time of day were evaluated within and among groups. A prominent circadian rhythm with peaks near midnight was present for TSH and melatonin serum levels in both H and C, indicating similar synchronization of the main body clock to the 24-hour environmental light–dark cycle. As regards 24-hour means in H and C, TSH was lower in C, whereas TRH, FT4, and IL-2 were higher in C, with no difference in melatonin levels. Simple linear regression, FT4 versus TRH, showed a positive correlation in H and a negative correlation in C, whereas FT4 versus TSH showed a negative correlation in both groups. For FT4 versus IL-2, a negative correlation was found in C but not for H, whereas TSH versus TRH showed no correlation for either group. Both groups were found to be similarly synchronized to the 24-hour sleep–wake schedule, but HPT axis function was altered in patients suffering from lung cancer. When compared with healthy controls, cancer patients showed modifications of hormone serum levels overall and a negative correlation between individual TRH and FT4 levels.
Doing, Redoing, and Undoing Gender
Authors: Morash Merry , Haarr Robin N.
Published: August 2011

For a study of police women’s identities, qualitative data were generated from in-depth interviews with 21 women working in two metropolitan police departments and varying in race, ethnicity, rank, and tenure. Most women identified female-male differences but noted exceptions. Many felt characteristics concentrated among women enhanced job performance, and men’s characteristics damaged performance. Several insisted that sex-category differences in key attributes accounting for good police work were nonexistent or minimal. Women do not simply reproduce old female-male stereotypes and the hierarchies that devalue female-associated traits. They fashion complex, positive occupational identities that are not necessarily tied to their sex category.
Diagnosis and Treatment of Pediatric Feeding and Swallowing Disorders
Authors: Cerezo Carolina S. , Lobato Debra J. , Pinkos Beth , LeLeiko Neal S.
Published: August 2011

Pediatric feeding and swallowing disorders are common. Given the multiple and overlapping factors playing major roles in the development of normal feeding and swallowing, a multidisciplinary team approach is recommended to provide a comprehensive assessment and directed therapy. Patient care is provided in a coordinated and collaborative fashion, thus providing the most efficient and easiest access to care. In this regard, the quality of care for children with feeding and swallowing problems is improved.
Intracellular trafficking as a determinant of AS-DACA cytotoxicity in rhabdomyosarcoma cells
Authors: Wolf Steven J , Huynh Tony , Bryce Nicole S , Hambley Trevor W , Wakelin Laurence PG , Stewart Bernard W , Catchpoole Daniel R
Published: August 2011

Background

Rhabdomyosarcoma (RMS) is a malignant soft tissue sarcoma derived from skeletal muscle precursor cells, which accounts for 5-8% of all childhood malignancies. Disseminated RMS represents a major clinical obstacle, and the need for better treatment strategies for the clinically aggressive alveolar RMS subtype is particularly apparent. Previously, we have shown that the acridine-4-carboxamide derivative AS-DACA, a known topoisomerase II poison, is potently cytotoxic in the alveolar RMS cell line RH30, but is 190-fold less active in the embryonal RMS cell line RD. Here, we investigate the basis for this selectivity, and demonstrate in these RMS lines, and in an AS-DACA- resistant subclone of RH30, that AS-DACA-induced cytotoxicity correlates with the induction of DNA double strand breaks.

Results

We show that inhibition of the multidrug-resistance associated protein (MRP1) has no effect on AS-DACA sensitivity. By exploiting the pH-dependent fluorescence properties of AS-DACA, we have characterized its intracellular distribution, and show that it concentrates in the cell nucleus, as well as in acidic vesicles of the membrane trafficking system. We show that fluorescence microscopy can be used to determine the localization of AS-DACA to the nuclear and cytoplasmic compartments of RMS cells grown as spheroids, penetrance being much greater in RH30 than RD spheroids, and that the vesicular signal leads the way into the spheroid mass. EEA1 and Rab5 proteins, molecular markers expressed on early-endosomal vesicles, are reduced by > 50% in the sensitive cell lines.

Conclusion

Taking the evidence as a whole, suggests that endosomal vesicle trafficking influences the toxicity of AS-DACA in RMS cells.
Electron transport in acetate-grown Methanosarcina acetivorans
Authors: Wang Mingyu , Tomb Jean-Francois , Ferry James G
Published: August 2011

Background

Acetate is the major source of methane in nature. The majority of investigations have focused on acetotrophic methanogens for which energy-conserving electron transport is dependent on the production and consumption of H2 as an intermediate, although the great majority of acetotrophs are unable to metabolize H2. The presence of cytochrome c and a complex (Ma-Rnf) homologous to the Rnf (

R

hodobacter

n

itrogen

f

ixation) complexes distributed in the domain Bacteria distinguishes non-H2-utilizing Methanosarcina acetivorans from H2-utilizing species suggesting fundamentally different electron transport pathways. Thus, the membrane-bound electron transport chain of acetate-grown M. acetivorans was investigated to advance a more complete understanding of acetotrophic methanogens.

Results

A component of the CO dehydrogenase/acetyl-CoA synthase (CdhAE) was partially purified and shown to reduce a ferredoxin purified using an assay coupling reduction of the ferredoxin to oxidation of CdhAE. Mass spectrometry analysis of the ferredoxin identified the encoding gene among annotations for nine ferredoxins encoded in the genome. Reduction of purified membranes from acetate-grown cells with ferredoxin lead to reduction of membrane-associated multi-heme cytochrome c that was re-oxidized by the addition of either the heterodisulfide of coenzyme M and coenzyme B (CoM-S-S-CoB) or 2-hydoxyphenazine, the soluble analog of methanophenazine (MP). Reduced 2-hydoxyphenazine was re-oxidized by membranes that was dependent on addition of CoM-S-S-CoB. A genomic analysis of Methanosarcina thermophila, a non-H2-utilizing acetotrophic methanogen, identified genes homologous to cytochrome c and the Ma-Rnf complex of M. acetivorans.

Conclusions

The results support roles for ferredoxin, cytochrome c and MP in the energy-conserving electron transport pathway of non-H2-utilizing acetotrophic methanogens. This is the first report of involvement of a cytochrome c in acetotrophic methanogenesis. The results suggest that diverse acetotrophic Methanosarcina species have evolved diverse membrane-bound electron transport pathways leading from ferredoxin and culminating with MP donating electrons to the heterodisulfide reductase (HdrDE) for reduction of CoM-S-S-CoB.
Does the principle of minimum work apply at the carotid bifurcation: a retrospective cohort study
Authors: Beare Richard J , Das Gita , Ren Mandy , Chong Winston , Sinnott Matthew D , Hilton James E , Srikanth Velandai , Phan Thanh G
Published: August 2011

Background

There is recent interest in the role of carotid bifurcation anatomy, geometry and hemodynamic factors in the pathogenesis of carotid artery atherosclerosis. Certain anatomical and geometric configurations at the carotid bifurcation have been linked to disturbed flow. It has been proposed that vascular dimensions are selected to minimize energy required to maintain blood flow, and that this occurs when an exponent of 3 relates the radii of parent and daughter arteries. We evaluate whether the dimensions of bifurcation of the extracranial carotid artery follow this principle of minimum work.

Methods

This study involved subjects who had computed tomographic angiography (CTA) at our institution between 2006 and 2007. Radii of the common, internal and external carotid arteries were determined. The exponent was determined for individual bifurcations using numerical methods and for the sample using nonlinear regression.

Results

Mean age for 45 participants was 56.9 ± 16.5 years with 26 males. Prevalence of vascular risk factors was: hypertension-48%, smoking-23%, diabetes-16.7%, hyperlipidemia-51%, ischemic heart disease-18.7%.

The value of the exponent ranged from 1.3 to 1.6, depending on estimation methodology.

Conclusions

The principle of minimum work (defined by an exponent of 3) may not apply at the carotid bifurcation. Additional factors may play a role in the relationship between the radii of the parent and daughter vessels.
Lack of association between gene polymorphisms of Angiotensin converting enzyme, Nod-like receptor 1, Toll-like receptor 4, FAS/FASL and the presence of Helicobacter pylori-induced premalignant gastric lesions and gastric cancer in Caucasians
Authors: Kupcinskas Juozas , Wex Thomas , Bornschein Jan , Selgrad Michael , Leja Marcis , Juozaityte Elona , Kiudelis Gediminas , Jonaitis Laimas , Malfertheiner Peter
Published: August 2011

Background

Several polymorphisms of genes involved in the immunological recognition of Helicobacter pylori and regulating apoptosis and proliferation have been linked to gastric carcinogenesis, however reported data are partially conflicting. The aim of our study was to evaluate potential associations between the presence of gastric cancer (GC) and high risk atrophic gastritis (HRAG) and polymorphisms of genes encoding Angiotensin converting enzyme (ACE), Nod-like receptor 1 (NOD1), Toll-like receptor 4 (TLR4) and FAS/FASL.

Methods

Gene polymorphisms were analyzed in 574 subjects (GC: n = 114; HRAG: n = 222, controls: n = 238) of Caucasian origin. ACE I/D (rs4646994), NOD1 796G>A (rs5743336), TLR4 3725G>C (rs11536889), FAS 1377G>A (rs2234767), FAS 670A>G (rs1800682) and FASL 844T>C (rs763110) were genotyped by different PCR approaches and restriction fragment length polymorphism analysis.

Results

Frequencies of genotypes in our study are similar to the data reported on subjects of Caucasian ethnicity. There was a tendency for NOD1 796G/G genotype to be associated with increased risk of HRAG (62.4% vs. 54.5% in controls, p = 0.082). FAS 670G/G genotype was more frequent in HRAG when compared to controls, 23.9% and 17.2% respectively, however it failed to reach significance level (p = 0.077). We did not find any significant associations for all polymorphisms in relation to GC or HRAG. NOD1 796G>A and TLR4 3725G>C gene polymorphisms were also not associated with Helicobacter pylori infection.

Conclusions

ACE, NOD1, TRL4 and FAS/FASL gene polymorphisms are not linked with gastric carcinogenesis in Caucasians, and therefore they should not be considered as potential biomarkers for identifying individuals with higher risk for GC.
Effects of shared medical appointments on quality of life and cost-effectiveness for patients with a chronic neuromuscular disease. Study protocol of a randomized controlled trial
Authors: Seesing Femke M , Drost Gea , van der Wilt Gert-Jan , van Engelen Baziel GM
Published: August 2011

Background

Shared medical appointments are a series of one-to-one doctor-patient contacts, in presence of a group of 6-10 fellow patients. This group visits substitute the annual control visits of patients with the neurologist. The same items attended to in a one-to- one appointment are addressed. The possible advantages of a shared medical appointment could be an added value to the present management of neuromuscular patients. The currently problem-focused one-to-one out-patient visits often leave little time for the patient's psychosocial needs, patient education, and patient empowerment.

Methods/design

A randomized, prospective controlled study (RCT) with a follow up of 6 months will be conducted to evaluate the clinical and cost-effectiveness of shared medical appointments compared to usual care for 300 neuromuscular patients and their partners at the Radboud University Nijmegen Medical Center. Every included patient will be randomly allocated to one of the two study arms. This study has been reviewed and approved by the medical ethics committee of the region Arnhem-Nijmegen, the Netherlands. The primary outcome measure is quality of life as measured by the EQ-5D, SF-36 and the Individualized neuromuscular Quality of Life Questionnaire. The primary analysis will be an intention-to-treat analysis on the area under the curve of the quality of life scores. A linear mixed model will be used with random factor group and fixed factors treatment, baseline score and type of neuromuscular disease. For the economic evaluation an incremental cost-effectiveness analysis will be conducted from a societal perspective, relating differences in costs to difference in health outcome. Results are expected in 2012.

Discussion

This study will be the first randomized controlled trial which evaluates the effect of shared medical appointments versus usual care for neuromuscular patients. This will enable to determine if there is additional value of shared medical appointments to the current therapeutical spectrum. When this study shows that group visits produce the alleged benefits, this may help to increase the acceptance of this innovative and creative way of using one of the most precious resources in health care more efficiently: time.

Trial registration

DutchTrial Register http://www.trialregister.nl
NTR1412
Betulinic acid inhibits colon cancer cell and tumor growth and induces proteasome-dependent and -independent downregulation of specificity proteins (Sp) transcription factors
Authors: Chintharlapalli Sudhakar , Papineni Sabitha , Lei Ping , Pathi Satya , Safe Stephen
Published: August 2011

Background

Betulinic acid (BA) inhibits growth of several cancer cell lines and tumors and the effects of BA have been attributed to its mitochondriotoxicity and inhibition of multiple pro-oncogenic factors. Previous studies show that BA induces proteasome-dependent degradation of specificity protein (Sp) transcription factors Sp1, Sp3 and Sp4 in prostate cancer cells and this study focused on the mechanism of action of BA in colon cancer cells.

Methods

The effects of BA on colon cancer cell proliferation and apoptosis and tumor growth in vivo were determined using standardized assays. The effects of BA on Sp proteins and Sp-regulated gene products were analyzed by western blots, and real time PCR was used to determine microRNA-27a (miR-27a) and ZBTB10 mRNA expression.

Results

BA inhibited growth and induced apoptosis in RKO and SW480 colon cancer cells and inhibited tumor growth in athymic nude mice bearing RKO cells as xenograft. BA also decreased expression of Sp1, Sp3 and Sp4 transcription factors which are overexpressed in colon cancer cells and decreased levels of several Sp-regulated genes including survivin, vascular endothelial growth factor, p65 sub-unit of NFκB, epidermal growth factor receptor, cyclin D1, and pituitary tumor transforming gene-1. The mechanism of action of BA was dependent on cell context, since BA induced proteasome-dependent and proteasome-independent downregulation of Sp1, Sp3 and Sp4 in SW480 and RKO cells, respectively. In RKO cells, the mechanism of BA-induced repression of Sp1, Sp3 and Sp4 was due to induction of reactive oxygen species (ROS), ROS-mediated repression of microRNA-27a, and induction of the Sp repressor gene ZBTB10.

Conclusions

These results suggest that the anticancer activity of BA in colon cancer cells is due, in part, to downregulation of Sp1, Sp3 and Sp4 transcription factors; however, the mechanism of this response is cell context-dependent.
Preliminary study of the antioxidant properties of flowers and roots of Pyrostegia venusta (Ker Gawl) Miers
Authors: Roy Purabi , Amdekar Sarika , Kumar Avnish , Singh Vinod
Published: August 2011

Background

Free radical stress leads to tissue injury and can eventually to arthritis, atherosclerosis, diabetes mellitus, neurodegenerative diseases and carcinogenesis. Several studies are ongoing worldwide to find natural antioxidants of plant origin. We assessed the in-vitro antioxidant activities and screened the phytochemical constituents of methanolic extracts of Pyrostegia venusta (Ker Gawl) Miers.

Methods

We evaluated the antioxidant potential and phytochemical constituents of P. venusta using 1,1-Diphenyl-2-picrylhydrazyl (DPPH), 2, 2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and ferric reducing antioxidant power (FRAP) assays. Gas chromatography-mass spectroscopy (GC-MS) studies were also undertaken to assess the phytochemical composition of the flower extracts.

Results

Phytochemical analyses revealed the presence of terpenoids, alkaloids, tannins, steroids, and saponins. The reducing ability of both extracts was in the range (in μm Fe(II)/g) of 112.49-3046.98 compared with butylated hydroxytoluene (BHT; 63.56 ± 2.62), catechin (972.02 ± 0.72 μm) and quercetin 3208.27 ± 31.29. A significant inhibitory effect of extracts of flowers (IC50 = 0.018 ± 0.69 mg/ml) and roots (IC50 = 0.026 ± 0.94 mg/ml) on ABTS free radicals was detected. The antioxidant activity of the extracts of flowers (95%) and roots (94%) on DPPH radicals was comparable with that of ascorbic acid (98.9%) and BHT (97.6%). GC-MS study revealed the presence of myoinositol, hexadecanoic acid, linoleic acid, palmitic acid and oleic acid in the flower extracts.

Conclusion

These data suggest that P. venusta is a natural source of antioxidants. The extracts of flowers and roots of P. venusta contain significant amounts of phytochemicals with antioxidative properties and could serve as inhibitors or scavengers of free radicals. P. venusta could be exploited as a potential source for plant-based pharmaceutical products. These results could form a sound basis for further investigation in the potential discovery of new natural bioactive compounds.
Air pollution & the brain: Subchronic diesel exhaust exposure causes neuroinflammation and elevates early markers of neurodegenerative disease
Authors: Levesque Shannon , Surace Michael J , McDonald Jacob , Block Michelle L
Published: August 2011

Background

Increasing evidence links diverse forms of air pollution to neuroinflammation and neuropathology in both human and animal models, but the effects of long-term exposures are poorly understood.

Objective

We explored the central nervous system consequences of subchronic exposure to diesel exhaust (DE) and addressed the minimum levels necessary to elicit neuroinflammation and markers of early neuropathology.

Methods

Male Fischer 344 rats were exposed to DE (992, 311, 100, 35 and 0 μg PM/m3) by inhalation over 6 months.

Results

DE exposure resulted in elevated levels of TNFα at high concentrations in all regions tested, with the exception of the cerebellum. The midbrain region was the most sensitive, where exposures as low as 100 μg PM/m3 significantly increased brain TNFα levels. However, this sensitivity to DE was not conferred to all markers of neuroinflammation, as the midbrain showed no increase in IL-6 expression at any concentration tested, an increase in IL-1β at only high concentrations, and a decrease in MIP-1α expression, supporting that compensatory mechanisms may occur with subchronic exposure. Aβ42 levels were the highest in the frontal lobe of mice exposed to 992 μg PM/m3 and tau [pS199] levels were elevated at the higher DE concentrations (992 and 311 μg PM/m3) in both the temporal lobe and frontal lobe, indicating that proteins linked to preclinical Alzheimer's disease were affected. α Synuclein levels were elevated in the midbrain in response to the 992 μg PM/m3 exposure, supporting that air pollution may be associated with early Parkinson's disease-like pathology.

Conclusions

Together, the data support that the midbrain may be more sensitive to the neuroinflammatory effects of subchronic air pollution exposure. However, the DE-induced elevation of proteins associated with neurodegenerative diseases was limited to only the higher exposures, suggesting that air pollution-induced neuroinflammation may precede preclinical markers of neurodegenerative disease in the midbrain.
Characterization of the HIV-1 RNA associated proteome identifies Matrin 3 as a nuclear cofactor of Rev function
Authors: Kula Anna , Guerra Jessica , Knezevich Anna , Kleva Danijela , Myers Michael P , Marcello Alessandro
Published: August 2011

Background

Central to the fully competent replication cycle of the human immunodeficiency virus type 1 (HIV-1) is the nuclear export of unspliced and partially spliced RNAs mediated by the Rev posttranscriptional activator and the Rev response element (RRE).

Results

Here, we introduce a novel method to explore the proteome associated with the nuclear HIV-1 RNAs. At the core of the method is the generation of cell lines harboring an integrated provirus carrying RNA binding sites for the MS2 bacteriophage protein. Flag-tagged MS2 is then used for affinity purification of the viral RNA. By this approach we found that the viral RNA is associated with the host nuclear matrix component MATR3 (Matrin 3) and that its modulation affected Rev activity. Knockdown of MATR3 suppressed Rev/RRE function in the export of unspliced HIV-1 RNAs. However, MATR3 was able to associate with Rev only through the presence of RRE-containing viral RNA.

Conclusions

In this work, we exploited a novel proteomic method to identify MATR3 as a cellular cofactor of Rev activity. MATR3 binds viral RNA and is required for the Rev/RRE mediated nuclear export of unspliced HIV-1 RNAs.
Hypothalamic inflammation is reversed by endurance training in anorectic-cachectic rats
Authors: Lira Fábio S , Yamashita Alex S , Rosa Jose C , Tavares Fábio L , Caperuto Erico , Carnevali Luiz C , Pimentel Gustavo D , Santos Ronaldo VT , Batista Miguel L , Laviano Alessandro , Rossi-Fanelli Filippo , Seelaender Marília
Published: August 2011

Aim

We tested the effects of a cancer cachexia-anorexia sydrome upon the balance of anti and pro-inflammatory cytokines in the hypothalamus of sedentary or trained tumour-bearing (Walker-256 carcinosarcoma) rats.

Methods

Animals were randomly assigned to a sedentary control (SC), sedentary tumour-bearing (ST), and sedentary pair-fed (SPF) groups or, exercised control (EC), exercised tumour-bearing (ET) and exercised pair-fed (EPF) groups. Trained rats ran on a treadmill (60%VO2max) for 60 min/d, 5 days/wk, for 8 wks. We evaluated food intake, leptin and cytokine (TNF-α, IL1β) levels in the hypothalamus.

Results

The cumulative food intake and serum leptin concentration were reduced in ST compared to SC. Leptin gene expression in the retroperitoneal adipose tissue (RPAT) was increased in SPF in comparison with SC and ST, and in the mesenteric adipose tissue (MEAT) the same parameter was decreased in ST in relation to SC. Leptin levels in RPAT and MEAT were decreased in ST, when compared with SC. Exercise training was also able to reduce tumour weight when compared to ST group. In the hypothalamus, IL-1β and IL-10 gene expression was higher in ST than in SC and SPF. Cytokine concentration in hypothalamus was higher in ST (TNF-α and IL-1β, p < 0.05), compared with SC and SPF. These pro-inflammatory cytokines concentrations were restored to control values (p < 0.05), when the animals were submitted to endurance training.

Conclusion

Cancer-induced anorexia leads towards a pro-inflammatory state in the hypothalamus, which is prevented by endurance training which induces an anti-inflammatory state, with concomitant decrease of tumour weight.
Upfront systemic chemotherapy and preoperative short-course radiotherapy with delayed surgery for locally advanced rectal cancer with distant metastases
Authors: Shin Sang Joon , Yoon Hong In , Kim Nam Kyu , Lee Kang Young , Min Byung Soh , Ahn Joong Bae , Keum Ki Chang , Koom Woong Sub
Published: August 2011

Background

Choosing the most effective approach for treating rectal cancer with mesorectal fascia (MRF) involvement or closeness and synchronous distant metastases is a current clinical challenge. The aim of this retrospective study was to determine if upfront systemic chemotherapy and short-course radiotherapy (RT) with delayed surgery enables R0 resection.

Methods

Between March 2009 and October 2009, six patients were selected for upfront chemotherapy and short-course RT (5 × 5 Gy) with delayed surgery. The patients had locally advanced primary tumors with MRF involvement or closeness, as well as synchronous and potentially resectable distant metastases. Chemotherapy was administered to five patients between the end of the RT and surgery. All patients underwent total mesorectal excision (TME).

Results

The median patient age was 54 years (range 39-63). All primary and metastatic lesions were resected simultaneously. The median duration between short-course RT and surgery was 13 weeks (range, 7-18). R0 resection of rectal lesions was achieved in 5 patients. One patient, who had a very low-lying tumor, had an R1 resection. The median follow-up duration for all patients was 16.7 months (range, 15.5-23.5). One patient developed liver metastasis at 15.7 months. There have been no local recurrences or deaths.

Conclusions

Upfront chemotherapy and short course RT with delayed surgery is a valuable alternative treatment approach for patients with MRF involvement or closeness of rectal cancer with distant metastases.
Application of DNA-based diagnostics in detection of schistosomal DNA in early infection and after drug treatment
Authors: Wang Cen , Chen Lin , Yin Xuren , Hua Wanquan , Hou Min , Ji Minjun , Yu Chuanxin , Wu Guanling
Published: August 2011

Background

Research is now focused on identification of sensitive and specific diagnostic tests for early identification of schistosomal infection and evaluation of chemotherapy in field situations in China.

Results

This study compared loop-mediated isothermal amplification (LAMP) with conventional PCR as DNA-based diagnostic techniques for the early detection of schistosomal DNA and the evaluation of chemotherapy. The results showed that both PCR and LAMP assays targeting a 301 base pair (bp) sequence of the highly repetitive retrotransposon, SjR2, amplified DNA from schistosomes but were unable to distinguish between schistosome species. LAMP and conventional PCR were shown to amplify the target sequence of the SjR2-pCR2.1 recombinant plasmid template with limits of detection of 10-4 ng and 10-2 ng, respectively, thus demonstrating the superior sensitivity of the LAMP method. Schistosoma japonicum DNA was detected in all serum samples obtained from the three experimental groups at 1 week post-infection by LAMP assay, while the rate of detection by conventional PCR ranged from 50% to 66%. The potential application of PCR and LAMP assays for the evaluation of artesunate and praziquantel chemotherapy was investigated. PCR was shown to be less sensitive for detection of schistosomal DNA in drug-treated rabbit sera than the LAMP method.

Conclusions

The data presented here indicate that LAMP is suitable for the detection of early infection in the groups primarily infected with Schistosoma japonicum, such as migrants, travellers, military personnel and the younger age groups. However, it is less suitable for evaluation of the efficacy of chemotherapy in the early stages because of its high sensitivity.
Subgroups of older adults with osteoarthritis based upon differing comorbid symptom presentations and potential underlying pain mechanisms
Authors: Murphy Susan L , Lyden Angela K , Phillips Kristine , Clauw Daniel J , Williams David A
Published: August 2011

Introduction

Although people with knee and hip osteoarthritis (OA) seek treatment because of pain, many of these individuals have commonly co-occurring symptoms (for example, fatigue, sleep problems, mood disorders). The purpose of this study was to characterize adults with OA by identifying subgroups with the above comorbid symptoms along with illness burden (a composite measure of somatic symptoms) to begin to examine whether subsets may have differing underlying pain mechanisms.

Methods

Community-living older adults with symptomatic knee and hip OA (n = 129) participated (68% with knee OA, 38% with hip OA). Hierarchical agglomerative cluster analysis was used. To determine the relative contribution of each variable in a cluster, multivariate analysis of variance was used.

Results

We found three clusters. Cluster 1 (n = 45) had high levels of pain, fatigue, sleep problems, and mood disturbances. Cluster 2 (n = 38) had intermediate degrees of depression and fatigue, but low pain and good sleep. Cluster 3 (n = 42) had the lowest levels of pain, fatigue, and depression, but worse sleep quality than Cluster 2.

Conclusions

In adults with symptomatic OA, three distinct subgroups were identified. Although replication is needed, many individuals with OA had symptoms other than joint pain and some (such as those in Cluster 1) may have relatively stronger central nervous system (CNS) contributions to their symptoms. For such individuals, therapies may need to include centrally-acting components in addition to traditional peripheral approaches.
Exceptional aerobic scope and cardiovascular performance of pink salmon (Oncorhynchus gorbuscha) may underlie resilience in a warming climate
Authors: Clark Timothy D. , Jeffries Kenneth M. , Hinch Scott G. , Farrell Anthony P.
Published: August 2011

Little is known of the physiological mechanisms underlying the effects of climate change on animals, yet it is clear that some species appear more resilient than others. As pink salmon (Oncorhynchus gorbuscha) in British Columbia, Canada, have flourished in the current era of climate warming in contrast to other Pacific salmonids in the same watershed, this study investigated whether the continuing success of pink salmon may be linked with exceptional cardiorespiratory adaptations and thermal tolerance of adult fish during their spawning migration. Sex-specific differences existed in minimum and maximum oxygen consumption rates ( and , respectively) across the temperature range of 8 to 28°C, reflected in a higher aerobic scope () for males. Nevertheless, the aerobic scope of both sexes was optimal at 21°C (Topt) and was elevated across the entire temperature range in comparison with other Pacific salmonids. As Topt for aerobic scope of this pink salmon population is higher than in other Pacific salmonids, and historic river temperature data reveal that this population rarely encounters temperatures exceeding Topt, these findings offer a physiological explanation for the continuing success of this species throughout the current climate-warming period. Despite this, declining cardiac output was evident above 17°C, and maximum attainable swimming speed was impaired above ∼23°C, suggesting negative implications under prolonged thermal exposure. While forecasted summer river temperatures over the next century are likely to negatively impact all Pacific salmonids, we suggest that the cardiorespiratory capacity of pink salmon may confer a selective advantage over other species.
Is breastfeeding safe with azathioprine?
Authors: Singh Mandeep , Qualie Jan , Currie Andrew , Howarth Edmund S , Khare Manjiri M
Published: August 2011

Background

Azathioprine is commonly used as an immunosuppressant during pregnancy in the management of various conditions such as connective tissue disorders, inflammatory bowel disease and pregnant women with organ transplant. Continuation of azathioprine through pregnancy and postpartum is vital for maternal reasons. However, there is limited evidence regarding safety of use of azathioprine with breastfeeding.

Methods and results

We report an observational case series of 10 mother–baby pairs managed at a tertiary teaching hospital. Mothers on azathioprine who were keen to breastfeed were counselled antenatally regarding limited short-term and long-term safety data for the babies. Mothers participating in this study completed a questionnaire at every visit. At follow-up visits, babies were examined by a neonatologist for clinical signs of infection and checked for adverse effects on haematological profile.

Conclusion

There was no clinically significant adverse effect on haematological profile or immunosuppression in these babies. Our case series supports safety of azathioprine in the short term. However, large numbers are needed to determine long-term safety of azathioprine and breastfeeding.
Factors influencing occurrence of postpartum haemorrhage in pregnant women with hepatitis E infection and deranged coagulation profile
Authors: Puri Manju , Patra Sharda , Singh Preeti , Malhotra Nidhi , Trivedi Shubha Sagar , Sharma Sunita , Kumar Ashish , Sarin Shiv Kumar
Published: August 2011

Coagulopathy is an important complication associated with hepatitis E virus (HEV) infection in pregnant women. Postpartum haemorrhage (PPH) remains a serious risk while managing the labour of these women. The aim of this paper is to study the factors influencing the occurrence of PPH in pregnant women with hepatitis E infection with coagulopathy. The labours of 38 pregnant women with hepatitis E and deranged coagulation profile were followed. Factors that may predict postpartum bleeding complications in women with HEV infection and deranged coagulation profile were statistically analysed. Of 38 pregnant women with acute viral hepatitis due to HEV, 13 (34%) suffered a PPH while 25 (66%) did not. On univariate analysis low alanine aminotransferase ( P = 0.016), high international normalized ratio ( P = 0.003), high levels of d-dimer ( P = 0.008), presence of hepatic encephalopathy ( P = 0.028), intrauterine fetal death ( P = 0.001) and gastrointestinal bleeding ( P = 0.004) were found to predict PPH. However, on multivariate analysis the only independent variable that predicted PPH was the presence gastrointestinal (GI) bleeding (odds ratio [OR] 11.363; 95% CI: 1.003, 125; P = 0.050). Women with GI bleeding have 11 times higher risk of PPH than those without a GI bleed; however, the confidence interval is very wide. Administration of fresh frozen plasma in the peripartum period reduces the risk of PPH. In conclusion, early recognition of factors which predict the risk of PPH and timely intervention with judicious use of blood and blood components in the peripartum period can improve the outcome of pregnant women with HEV infection with deranged coagulation.
Prevalence of vitamin D deficiency in a North London antenatal population
Authors: Parisaei M , Govind A , Clements J , Arora P , Lashkari H , Kapila P
Published: August 2011

Objective

We evaluated the prevalence of vitamin D deficiency in the antenatal patients attending North Middlesex University Hospital between March 2008 and March 2009.

Study design

A prospective study of maternal levels of vitamin D at booking.

Results

The prevalence of both deficient and insufficient levels of 25[OH]D was 87.6% across all included patients.

Conclusion

There is a high prevalence of asymptomatic vitamin D deficiency in the antenatal booking population.
Enhanced Measurement of Geosynthetic Interface Shear Strength Using a Modified Inclined Plane Device
Authors: Pitanga Heraldo Nunes , Gourc Jean-Pierre , Vilar Orencio Monje
Published: August 2011

Composite lining systems comprising different geosynthetics and soil are typical capping devices in modern landfills. Analyses of the behavior of capping devices have shown that they are very sensitive components thanks in part to the shear strength of geosynthetic interfaces, many of which were reported to have controlled slippage between capping lining components during landfill slope failures. There are some laboratory testing alternatives for measuring the shear strength of the interface between geosynthetics or between geosynthetics and soil. The inclined plane test is especially appropriate for shear strength tests under low normal pressure which is a specific condition of these geosynthetic systems on cap cover. However, the selected shear strengths, inferred from the laboratory experimentation, show considerable variability, which depends on the test procedure. This work proposes a new procedure and a new interpretation of the inclined plane test taking as an example the interface between geospacers and geomembranes often considered as a critical interface. The measurement of displacement acceleration during the test gives the possibility of more accurately defining the large sliding displacement shear strength, which may approach the true residual condition.
Evaluation of the Effects of Climatic Conditions on Modulus of Base Materials with Recycled Asphalt Pavement
Authors: Wen Haifang , Wu Mengqi , Uhlmeyer Jeff
Published: August 2011

The use of recycled materials for construction is beneficial to both the environment and the economy. Recycled asphalt pavement (RAP) is one of the most commonly used recycled materials. Different state departments of transportation allow the use of RAP in base materials at different percentages. Characterization of the resilient modulus of base materials with RAP is important for proper pavement design. In addition, the models used in the Mechanistic-Empirical Pavement Design Guide (MEPDG) for traditional materials need to be verified for base materials with RAP, due to the unique properties of asphalt in RAP. This study evaluated the effects of moisture and temperature on the resilient modulus of base materials with different percentages of RAP. The models for the effects of moisture content on the resilient modulus of unbound materials were evaluated using crushed aggregates with RAP. In addition, models were proposed to account for the effects of temperature on the resilient modulus of base materials with RAP. The effects of the percentage of RAP on frozen moduli were also investigated.
Bone Morphogenetic Protein Inhibition Promotes Neurological Recovery after Intraventricular Hemorrhage
Authors: Dummula Krishna , Vinukonda Govindaiah , Chu Philip , Xing Yiping , Hu Furong , Mailk Sabrina , Csiszar Anna , Chua Caroline , Mouton Peter , Kayton Robert J. , Brumberg Joshua C. , Bansal Rashmi , Ballabh Praveen
Published: August 2011

Intraventricular hemorrhage (IVH) results in neural cell death and white matter injury in premature infants. No therapeutic strategy is currently available against this disorder. Bone morphogenetic protein (BMP) signaling suppresses oligodendrocyte development through basic-helix-loop-helix (bHLH) transcription factors and promotes astrocytosis. Therefore, we hypothesized that IVH in premature newborns initiates degeneration and maturation arrest of oligodendrocyte lineage and that BMP inhibition alleviates hypomyelination, gliosis, and motor impairment in the survivors of IVH. To test the hypotheses, a rabbit model of IVH was used in which premature rabbit pups (E29) are treated with intraperitoneal glycerol at 2 h of age to induce IVH; and the pups with IVH exhibit hypomyelination and gliosis at 2 weeks of postnatal age. Maturation of oligodendrocyte lineage was evaluated by specific markers, and the expression of bHLH transcription factors was assessed. BMP levels were measured in both premature rabbit pups and autopsy materials from premature infants. Recombinant human noggin was used to suppress BMP action; and neurobehavioral performance, myelination and gliosis were assessed in noggin-treated pups compared with untreated controls. We found that IVH resulted in apoptosis and reduced proliferation of oligodendrocyte progenitors, as well as arrested maturation of preoligodendrocytes in rabbits. BMP4 levels were significantly elevated in both rabbit pups and human premature infants with IVH compared with controls. Importantly, BMP inhibition by recombinant human noggin restored the levels of phospho-Smad1/5/8, Olig2 transcription factor, oligodendrocyte maturation, myelination, astrocyte morphology, and motor function in premature pups with IVH. Hence, BMP inhibition might enhance neurological recovery in premature infants with IVH.
A Model of Intracellular Theta Phase Precession Dependent on Intrinsic Subthreshold Membrane Currents
Authors: Leung L. Stan
Published: August 2011

A hippocampal place cell fires at an increasingly earlier phase in relation to the extracellular theta rhythm as a rodent moves through the place field. The present report presents a compartment model of a CA1 pyramidal cell that explains the increase in amplitude and the phase precession of intracellular theta oscillations, with the assumption that the cell receives an asymmetric ramp depolarization (<10 mV) in the place field and rhythmic inhibitory and/or excitatory synaptic driving. Intracellular subthreshold membrane potential oscillations (MPOs) increase in amplitude and frequency, and show phase precession within the place field. Theta phase precession and MPO power and frequency increase in the place field are caused by a shift in excitatory–inhibitory response, intrinsic theta-frequency resonance, and intrinsic oscillations that depend on voltage-dependent persistent Na+and slowly inactivating K+currents, but not onIh. Phase precession is diminished when theta-frequency resonance is decreased. Simulated spikes fire near the peak of MPOs and precess similarly as the MPOs. The phase of the MPOs/spikes codes for distance in a one-dimensional place field, and phase precession is only weakly dependent on firing rate, running speed, or the duration needed to cross the place field. In addition, phase precession within the place field resumes quickly after disruption by maximal afferent pulse stimulation.
Endogenous Brain-Derived Neurotrophic Factor in the Nucleus Tractus Solitarius Tonically Regulates Synaptic and Autonomic Function
Authors: Clark Catharine G. , Hasser Eileen M. , Kunze Diana L. , Katz David M. , Kline David D.
Published: August 2011

Brain-derived neurotrophic factor (BDNF) and its receptor, TrkB, are highly expressed in the nucleus tractus solitarius (nTS), the principal target of cardiovascular primary afferent input to the brainstem. However, little is known about the role of BDNF signaling in nTS in cardiovascular homeostasis. We examined whether BDNF in nTS modulates cardiovascular functionin vivoand regulates synaptic and/or neuronal activity in isolated brainstem slices. Microinjection of BDNF into the rat medial nTS (mnTS), a region critical for baroreflex control of sympathetic outflow, produced dose-dependent increases in mean arterial pressure (MAP), heart rate (HR), and lumbar sympathetic nerve activity (LSNA) that were blocked by the tyrosine kinase inhibitor K252a. In contrast, immunoneutralization of endogenous BDNF (anti-BDNF), or microinjection of K252a alone, decreased MAP, HR, and LSNA. The effects of anti-BDNF were abolished by blockade of ionotropic glutamate receptors, indicating a role for glutamate signaling in the response to BDNF.In vitro, BDNF reduced the amplitude of miniature EPSCs as well as solitary tract (TS) evoked EPSC amplitude and action potential discharge (APD) in second-order nTS neurons. BDNF effects on EPSCs were independent of GABAergic signaling and abolished by AMPA receptor blockade. In contrast, K252a increased spontaneous EPSC frequency and TS evoked EPSC amplitude. BDNF also attenuated APD evoked by injection of depolarizing current into second-order neurons, indicating reduced intrinsic neuronal excitability. Our data demonstrate that BDNF signaling in mnTS plays a tonic role in regulating cardiovascular function, likely via modulation of primary afferent glutamatergic excitatory transmission and neural activity.
Hippocampal Telomerase Is Involved in the Modulation of Depressive Behaviors
Authors: Zhou Qi-Gang , Hu Yao , Wu Dan-Lian , Zhu Li-Juan , Chen Chen , Jin Xing , Luo Chun-Xia , Wu Hai-Yin , Zhang Jing , Zhu Dong-Ya
Published: August 2011

Telomere and telomerase alterations have been reported in mood disorders. However, the role of telomerase in depression remains unclear. Here we show that chronic mild stress (CMS) led to a significant decrease in telomerase reverse transcriptase (TERT) level and telomerase activity in the hippocampus. Treatment with antidepressant fluoxetine reversed the CMS-induced TERT and telomerase activity changes. Inhibiting telomerase by systemic administration (100 mg · kg−1· d−1, i.p., for 14 d), intrahippocampal microinjection (0.7 μmol, 2 μl), or infusion (using an osmotic minipump, 0.134 μg/μl, 0.25 μl/h) of 3′-azido-deoxythymidine (AZT) resulted in depression-like behaviors and impaired hippocampal neurogenesis in mice. In contrast, overexpressing telomerase by intrahippocampal infusion of recombinant adenovirus vector expressing mouse TERT (Ad-mTERT-GFP) led to neurogenesis upregulation, produced antidepressant-like behaviors, and prevented the CMS-induced behavioral modifications. Disrupting neurogenesis in the dentate gyrus by X-irradiation (15 Gy) of a restricted region of mouse brain containing the hippocampus abolished the antidepressant-like effect of Ad-mTERT-GFP. Additionally, AZT had no effect on DNA polymerase activity and did not cause cell damagein vitroandin vivo. Microinjection of AZT into the subventricular zone of lateral ventricle (0.7 μmol, 2 μl) inhibited local neurogenesis but had no behavioral effect. These results suggest that hippocampal telomerase is involved in the modulation of depression-related behaviors, possibly by regulating adult neurogenesis.