bluuebunny/crossref_metadata_2025 huggingface dataset:
A BAC-based physical map of Brachypodium distachyon and its comparative analysis with rice and wheat
Authors: Gu Yong Q , Ma Yaqin , Huo Naxin , Vogel John P , You Frank M , Lazo Gerard R , Nelson William M , Soderlund Carol , Dvorak Jan , Anderson Olin D , Luo Ming-Cheng
Published: October 2009

Background

Brachypodium distachyon(Brachypodium) has been recognized as a new model species for comparative and functional genomics of cereal and bioenergy crops because it possesses many biological attributes desirable in a model, such as a small genome size, short stature, self-pollinating habit, and short generation cycle. To maximize the utility ofBrachypodium as a model for basic and applied research it is necessary to develop genomic resources for it. A BAC-based physical map is one of them. A physical map will facilitate analysis of genome structure, comparative genomics, and assembly of the entire genome sequence.

Results

A total of 67,151BrachypodiumBAC clones were fingerprinted with the SNaPshot HICF fingerprinting method and a genome-wide physical map of theBrachypodiumgenome was constructed. The map consisted of 671 contigs and 2,161 clones remained as singletons. The contigs and singletons spanned 414 Mb. A total of 13,970 gene-related sequences were detected in the BAC end sequences (BES). These gene tags aligned 345 contigs with 336 Mb of rice genome sequence, showing thatBrachypodiumand rice genomes are generally highly colinear. Divergent regions were mainly in the rice centromeric regions. A dot-plot ofBrachypodiumcontigs against the rice genome sequences revealed remnants of the whole-genome duplication caused by paleotetraploidy, which were previously found in rice and sorghum.Brachypodiumcontigs were anchored to the wheat deletion bin maps with the BES gene-tags, opening the door toBrachypodium-Triticeae comparative genomics.

Conclusion

The construction of theBrachypodiumphysical map, and its comparison with the rice genome sequence demonstrated the utility of the SNaPshot-HICF method in the construction of BAC-based physical maps. The map represents an important genomic resource for the completion ofBrachypodiumgenome sequence and grass comparative genomics. A draft of the physical map and its comparisons with rice and wheat are available athttp://phymap.ucdavis.edu/brachypodium/.
The inhibitory receptor LILRB4 (ILT3) modulates antigen presenting cell phenotype and, along with LILRB2 (ILT4), is upregulated in response to Salmonella infection
Authors: Brown Damien P , Jones Des C , Anderson Katie J , Lapaque Nicolas , Buerki Robin A , Trowsdale John , Allen Rachel L
Published: October 2009

Background

Leukocyte Ig-like receptors (LILR) are a family of innate immune receptors with immunomodulatory functions. High-level expression of the receptors LILRB2 (ILT4) and LILRB4 (ILT3) is a feature of tolerogenic antigen presenting cells and has been observed in cancer and transplant situations. There are relatively few studies regarding these receptors in the context of infection and it is not yet clear how LILRB4 exerts its inhibitory effects.

Results

We studied the effects of LILRB4 ligation on antigen presenting cell phenotype, and the expression of LILRB2 and LILRB4 on Salmonella- infected antigen presenting cells. Ligation of LILRB4 throughout in vitro culture of dendritic cells led to an upregulation of the co-stimulatory protein CD86. Alterations in the production of IL-8 and IL-10 by LILRB4-ligated macrophages were also observed. Infection with Salmonella typhimurium or TLR stimulation with Salmonella components led to an upregulation of LILRB2 and LILRB4.

Conclusion

Our results indicate that the inhibitory effects of LILRB4 do not result from a failure to upregulate co-stimulatory proteins. In addition to the high level expression that can render antigen presenting cells tolerogenic, there may be a role for lower level expression and activity of LILRB2 and LILRB4 in response to TLR signalling during an immune response to bacterial infection.
Evaluation of the bacterial diversity among and within individual venous leg ulcers using bacterial tag-encoded FLX and Titanium amplicon pyrosequencing and metagenomic approaches
Authors: Wolcott Randall D , Gontcharova Viktoria , Sun Yan , Dowd Scot E
Published: October 2009

Background

Approximately 1 out of every 100 individuals has some form of venous insufficiency, which can lead to chronic venous disease and Venous Leg Ulcer (VLU). There are known underlying pathologies which contribute to the chronic nature of VLU including biofilm phenotype infections.

Results

Using pyrosequencing based approaches we evaluated VLU to characterize their microbial ecology. Results show that VLU infections are polymicrobial with no single bacterium colonizing the wounds. The most ubiquitous and predominant organisms include a previously uncharacterized bacteroidales, various anaerobes, Staphylococcus, Corynebacterium, and Serratia. Topological analysis of VLU show some notable differences in bacterial populations across the surface of the wounds highlighting the importance of sampling techniques during diagnostics. Metagenomics provide a preliminary indication that there may be protozoa, fungi and possibly an undescribed virus associated with these wounds.

Conclusion

The polymicrobial nature of VLU and previous research on diabetic foot ulcers and surgical site infections suggest that the future of therapy for such wounds lies in the core of the logical and proven multiple concurrent strategy approach, which has been termed "biofilm-based wound care" and the use of individualized therapeutics rather than in a single treatment modality.
Downregulation of MIP-1α/CCL3 with praziquantel treatment in Schistosoma haematobiumand HIV-1 co-infected individuals in a rural community in Zimbabwe
Authors: Zinyama-Gutsire RBL , Gomo E , Kallestrup P , Erikstrup C , Ullum H , Butterworth AE , Munyati S , Mduluza T
Published: October 2009

Background

Chemokines have been reported to play an important role in granulomatous inflammation duringSchistosoma mansoniinfection. However there is less information on their role inSchistosoma haematobiuminfection, or on the effect of concurrent HIV-1 infection, as a potential modifying influence.

Methods

To determine levels of MIP-1α/CCL3 chemokine in plasma ofS. haematobiumand HIV-1 co-infected and uninfected individuals in a rural black Zimbabwean community.

A cohort was established of HIV-1 and schistosomiasis infection and co-infection comprising 379 participants. Outcome measures consisted of HIV-1 and schistosomiasis status and levels of MIP-1α/CCL3 in plasma at baseline and three months post treatment. An association was established between MIP-1α/CCL3 plasma levels with HIV-1 andS. haematobiuminfections.

Results

A total of 379 adults formed the established cohort comprising 76 (20%) men and 303 (80%) women. Mean age was 33.25, range 17 - 62 years. The median MIP-1α/CCL3 plasma concentration was significantly higher inS. haematobiuminfected compared with uninfected individuals (p = 0.029). In contrast, there was no difference in the median MIP-1α/CCL3 levels between HIV-1 positive and negative individuals (p = 0.631). MIP-1α/CCL3 concentration in plasma was significantly reduced at three months after treatment with praziquantel (p = 000).

Conclusion

The results of our study show that the MIP-1α/CCL3 levels were positively associated withS. haematobiumegg counts at baseline but not with HIV-1 infection status. MIP-1α/CCL3 levels were significantly reduced at three months post treatment with praziquantel. We therefore conclude that MIP-1α/CCL3 is produced during infection withS haematobium.S. haematobiuminfection is associated with increased MIP-1α/CCL3 levels in an egg intensity-dependent manner and treatment ofS. haematobiumis associated with a reduction in MIP-1α/CCL3.
Suggestive linkage detected for blood pressure related traits on 2q and 22q in the population on the Samoan islands
Authors: Åberg Karolina , Dai Feng , Viali Satupaitea , Tuitele John , Sun Guangyun , Indugula Subba R , Deka Ranjan , Weeks Daniel E , McGarvey Stephen T
Published: October 2009

Background

High blood pressure or hypertension is a major risk factor involved in the development of cardiovascular diseases. We conducted genome-wide variance component linkage analyses to search for loci influencing five blood pressure related traits including the quantitative traits systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse pressure (PP), the dichotomous trait hypertension (HT) and the bivariate quantitative trait SBP-DBP in families residing in American Samoa and Samoa, as well as in the combined sample from the two polities. We adjusted the traits for a number of environmental covariates such as smoking, alcohol consumption, physical activity and material life style.

Results

We found suggestive univariate linkage for SBP on chromosome 2q35-q37 (LOD 2.4) and for PP on chromosome 22q13 (LOD 2.2), two chromosomal regions that recently have been associated with SBP and PP, respectively.

Conclusion

We have detected additional evidence for a recently reported locus associated with SBP on chromosome 2q and a susceptibility locus for PP on chromosome 22q. However, differences observed between the results from our three partly overlapping genetically homogenous study samples from the Samoan islands suggest that additional studies should be performed in order to verify these results.
Risk factors for chronic kidney disease in Japan: a community-based study
Authors: Takamatsu Norimichi , Abe Hideharu , Tominaga Tatsuya , Nakahara Kunihiko , Ito Yumi , Okumoto Yoko , Kim Jiyoong , Kitakaze Masafumi , Doi Toshio
Published: October 2009

Background

Chronic kidney disease (CKD) is increasingly being recognized as a predictor for both end-stage renal disease and cardiovascular disease. The present study, conducted on individuals from a community in Arita, Japan, was designed to evaluate biomarkers that can be used to determine the associated factors for CKD.

Methods

This study involved 1554 individuals. Kidney function was evaluated in terms of the creatinine-based estimated glomerular filtration rate (eGFR), which was determined using the Modification of Diet in Renal Disease equation. Low eGFR was defined as eGFR < 60 mL/min per 1.73 m2. The concentration of both urinary albumin and urinary type IV collagen were measured.

Results

In the younger participants (age, <65 years), the odds ratio (95% confidence interval [CI]) of low eGFR was 1.17 (1.02 to 1.34) for each 1 year older age, 6.28 (1.41 to 28.03) for urinary albumin creatinine ratio (ACR) over 17.9 mg/g and 9.43 (2.55 to 34.91) for hyperlipidemia. On the other hand, among the elderly participants (age, ≥ 65 years), the odds ratio (95% CI) of low eGFR was 2.97 (1.33 to 6.62) for gender, 1.62 (1.06 to 2.50) for hypertension and 1.97 (1.19 to 3.28) for hyperlipidemia. Urinary type IV collagen creatinine ratio was not identified as an associated factor for low eGFR.

Conclusion

In this present cross-sectional community-based study, ACR is associated with CKD, which was defined as an eGFR of less than 60 mL/min per 1.73 m2, in the younger participants but not in the older participants.
Tissue-specific cytokine release from human extra-placental membranes stimulated by lipopolysaccharide in a two-compartment tissue culture system
Authors: Thiex Natalie W , Chames Mark C , Loch-Caruso Rita K
Published: October 2009

Background

The extra-placental gestational membranes secrete cytokines in response to bacteria and other infectious agents, with potentially adverse consequences for pregnancy. The present study used lipopolysaccharide (LPS) as a prototype endotoxin to investigate the pattern of stimulated cytokine release from the amniotic and choriodecidual sides of full-thickness human gestational membranes in a two-compartment tissue culture system.

Methods

Gestational membranes were collected from healthy non-laboring caesarean deliveries at term. Full-thickness membranes from each placenta were cut into pieces, mounted on Transwell frames, and placed in culture wells to create a two-compartment culture with the gestational membranes serving as the barrier between compartments. The LPS (100 ng/ml) was added to the amniotic, choriodecidual or both chambers of the culture, and cytokines were assayed in the medium of the amniotic and choriodecidual chambers after 8 h of LPS exposure. Cytokine concentrations were analyzed by two-way analysis of variance for effects of treatment and side specificity of cytokine release from the membranes.

Results

LPS exposure on the choriodecidual side of the membranes significantly increased TNF-alpha, IL-6, IL-10 and IL-8 in the choriodecidual compartment, whereas TNF-alpha was the only cytokine observed to increase in the amniotic compartment. When LPS treatment was to the amniotic side of the membranes, there were significant increases in TNF-alpha and IL-6 in the amniotic compartment as well as increased concentrations of TNF-alpha, IL-6 and IL-8 in the choriodecidual compartment; however, there were no statistically significant differences for IL-10 in either compartment. No statistically significant differences were observed for IL-1beta, TGF-beta or IL-4 concentrations in response to LPS, regardless of the exposure modality.

Conclusion

The amnion and choriodecidua exhibited distinct patterns of response to LPS with evidence of inflammatory signaling across the layers of the gestational membranes. These results suggest a complicated network of signaling within the gestational membranes, in which cytokine- and tissue-specific responses to inflammatory stimulation may have important implications for maintaining pregnancy in the challenge of microbial invasion of the uterine compartment.
Assessing the intake of obesity-related foods and beverages in young children: comparison of a simple population survey with 24 hr-recall
Authors: Bennett Cheryl-Ann , de Silva-Sanigorski Andrea M , Nichols Melanie , Bell Andrew C , Swinburn Boyd A
Published: October 2009

Background

With an increasing focus on obesity prevention there is a need for simple, valid tools to assess dietary indicators that may be the targets of intervention programs. The objective of this study was to determine the relative validity of previous day dietary intake using a newly developed parent-proxy questionnaire (EPAQ) for two to five year old children.

Methods

A convenience sample of participants (n = 90) recruited through preschools and the community in Geelong, Australia provided dietary data for their child via EPAQ and interviewer-administered 24-hour dietary recall (24 hr-recall). Comparison of mean food and beverage group servings between the EPAQ and 24 hr-recall was conducted and Spearman rank correlations were computed to examine the association between the two methods.

Results

Mean servings of food/beverage groups were comparable between methods for all groups except water, and significant correlations were found between the servings of food and beverages using the EPAQ and 24-hr recall methods (ranging from 0.57 to 0.88).

Conclusion

The EPAQ is a simple and useful population-level tool for estimating the intake of obesity-related foods and beverages in children aged two to five years. When compared with 24-hour recall data, the EPAQ produced an acceptable level of relative validity and this short survey has application for population monitoring and the evaluation of population-based obesity prevention interventions for young children.
Oscillating magnetic field disrupts magnetic orientation in Zebra finches, Taeniopygia guttata
Authors: Keary Nina , Ruploh Tim , Voss Joe , Thalau Peter , Wiltschko Roswitha , Wiltschko Wolfgang , Bischof Hans-Joachim
Published: October 2009

Background

Zebra finches can be trained to use the geomagnetic field as a directional cue for short distance orientation. The physical mechanisms underlying the primary processes of magnetoreception are, however, largely unknown. Two hypotheses of how birds perceive magnetic information are mainly discussed, one dealing with modulation of radical pair processes in retinal structures, the other assuming that iron deposits in the upper beak of the birds are involved. Oscillating magnetic fields in the MHz range disturb radical pair mechanisms but do not affect magnetic particles. Thus, application of such oscillating fields in behavioral experiments can be used as a diagnostic tool to decide between the two alternatives.

Methods

In a setup that eliminates all directional cues except the geomagnetic field zebra finches were trained to search for food in the magnetic north/south axis. The birds were then tested for orientation performance in two magnetic conditions. In condition 1 the horizontal component of the geomagnetic field was shifted by 90 degrees using a helmholtz coil. In condition 2 a high frequently oscillating field (1.156 MHz) was applied in addition to the shifted field. Another group of birds was trained to solve the orientation task, but with visual landmarks as directional cue. The birds were then tested for their orientation performance in the same magnetic conditions as applied for the first experiment.

Results

The zebra finches could be trained successfully to orient in the geomagnetic field for food search in the north/south axis. They were also well oriented in test condition 1, with the magnetic field shifted horizontally by 90 degrees. In contrast, when the oscillating field was added, the directional choices during food search were randomly distributed. Birds that were trained to visually guided orientation showed no difference of orientation performance in the two magnetic conditions.

Conclusion

The results indicate that zebra finches use a receptor that bases on radical pair processes for sensing the direction of the earth magnetic field in this short distance orientation behavior.
Role of L2 cysteines in papillomavirus infection and neutralization
Authors: Gambhira Ratish , Jagu Subhashini , Karanam Balasubramanyam , Day Patricia M , Roden Richard
Published: October 2009

Vaccination of mice with minor capsid protein L2 or passive transfer with the L2-specific neutralizing monoclonal antibody RG-1 protects against human papillomavirus type 16 (HPV16) challenge. Here we explored the nature of the RG-1 epitope and its contribution to viral infectivity. RG-1 bound equivalently HPV16 L2 residues 17-36 with or without an intact C22-C28 disulphide bridge. HPV16 L2 mutations K20A, C22A, C22S, C28A, C28S, or P29A prevented RG-1 binding, whereas Y19A, K23A or Q24A had no impact. Mutation of either C22 or C28 to alanine or serine compromises HPV16 pseudoviral infectivity both in vitro and in the murine vaginal tract, but does not impact pseudovirion assembly. Despite their lack of infectivity, HPV16 pseudovirions containing C22S or C28S mutant L2 bind to cell surfaces, are taken up, and expose the 17-36 region on the virion surface as for wild type HPV16 pseudovirions suggesting normal furin cleavage of L2. Mutation of the second cysteine residue in Bovine papillomavirus type 1 (BPV1) L2 to serine (C25S) dramatically reduced the infectivity of BPV1 pseudovirions. Surprisingly, in contrast to the double mutation in HPV16 L2, the BPV1 L2 C19S, C25S double mutation reduced BPV1 pseudovirion infectivity of 293TT cells by only half.
Age-dependent resistance to Porcine reproductive and respiratory syndrome virus replication in swine
Authors: Klinge Kelly L , Vaughn Eric M , Roof Michael B , Bautista Elida M , Murtaugh Michael P
Published: October 2009

Background

Porcine reproductive and respiratory syndrome virus (PRRSV) causes a prolonged, economically devastating infection in pigs, and immune resistance to infection appears variable. Since the porcine adaptive immune system is not fully competent at birth, we hypothesized that age influences the dynamics of PRRSV infection. Thus, young piglets, growing 16-20-week-old finisher pigs, and mature third parity sows were infected with virulent or attenuated PRRSV, and the dynamics of viral infection, disease, and immune response were monitored over time.

Results

Virulent PRRSV infection and disease were markedly more severe and prolonged in young piglets than in finishers or sows. Attenuated PRRSV in piglets also produced a prolonged viremia that was delayed and reduced in magnitude, and in finishers and sows, about half the animals showed no viremia. Despite marked differences in infection, antibody responses were observed in all animals irrespective of age, with older pigs tending to seroconvert sooner and achieve higher antibody levels than 3-week-old animals. Interferon γ (IFN γ) secreting peripheral blood mononuclear cells were more abundant in sows but not specifically increased by PRRSV infection in any age group, and interleukin-10 (IL-10) levels in blood were not correlated with PRRSV infection status.

Conclusion

These findings show that animal age, perhaps due to increased innate immune resistance, strongly influences the outcome of acute PRRSV infection, whereas an antibody response is triggered at a low threshold of infection that is independent of age. Prolonged infection was not due to IL-10-mediated immunosuppression, and PRRSV did not elicit a specific IFN γ response, especially in non-adult animals. Equivalent antibody responses were elicited in response to virulent and attenuated viruses, indicating that the antigenic mass necessary for an immune response is produced at a low level of infection, and is not predicted by viremic status. Thus, viral replication was occurring in lung or lymphoid tissues even though viremia was not always observed.
Mid-term results and factors affecting outcome of a metal-backed unicompartmental knee design: a case series
Authors: Seyler Thorsten M , Mont Michael A , Lai Lawrence P , Xie Jipan , Marker David R , Zywiel Michael G , Bonutti Peter M
Published: October 2009

Background

Controversies exist regarding the indications for unicompartmental knee arthroplasty. The objective of this study is to report the mid-term results and examine predictors of failure in a metal-backed unicompartmental knee arthroplasty design.

Methods

At a mean follow-up of 60 months, 80 medial unicompartmental knee arthroplasties (68 patients) were evaluated. Implant survivorship was analyzed using Kaplan-Meier method. The Knee Society objective and functional scores and radiographic characteristics were compared before surgery and at final follow-up. A Cox proportional hazard model was used to examine the association of patient's age, gender, obesity (body mass index > 30 kg/m2), diagnosis, Knee Society scores and patella arthrosis with failure.

Results

There were 9 failures during the follow up. The mean Knee Society objective and functional scores were respectively 49 and 48 points preoperatively and 95 and 92 points postoperatively. The survival rate was 92% at 5 years and 84% at 10 years. The mean age was younger in the failure group than the non-failure group (p < 0.01). However, none of the factors assessed was independently associated with failure based on the results from the Cox proportional hazard model.

Conclusion

Gender, pre-operative diagnosis, preoperative objective and functional scores and patellar osteophytes were not independent predictors of failure of unicompartmental knee implants, although high body mass index trended toward significance. The findings suggest that the standard criteria for UKA may be expanded without compromising the outcomes, although caution may be warranted in patients with very high body mass index pending additional data to confirm our results.

Level of Evidence: IV
Bcl-2 expression is altered with ovarian tumor progression: an immunohistochemical evaluation
Authors: Anderson Nicole S , Turner Leslie , Livingston Sandra , Chen Ren , Nicosia Santo V , Kruk Patricia A
Published: October 2009

Background

Ovarian cancer is the most lethal gynecologic malignancy. The ovarian tumor microenvironment is comprised of tumor cells, surrounding stroma, and circulating lymphocytes, an important component of the immune response, in tumors. Previous reports have shown that the anti-apoptotic protein Bcl-2 is overexpressed in many solid neoplasms, including ovarian cancers, and contributes to neoplastic transformation and drug-resistant disease, resulting in poor clinical outcome. Likewise, studies indicate improved clinical outcome with increased presence of lymphocytes. Therefore, we sought to examine Bcl-2 expression in normal, benign, and cancerous ovarian tissues to determine the potential relationship between epithelial and stromal Bcl-2 expression in conjunction with the presence of lymphocytes for epithelial ovarian tumor progression.

Methods

Ovarian tissue sections were classified as normal (n = 2), benign (n = 17) or cancerous (n = 28) and immunohistochemically stained for Bcl-2. Bcl-2 expression was assessed according to cellular localization, extent, and intensity of staining. The number of lymphocyte nests as well as the number of lymphocytes within these nests was counted.

Results

While Bcl-2 staining remained cytoplasmic, both percent and intensity of epithelial and stromal Bcl-2 staining decreased with tumor progression. Further, the number of lymphocyte nests dramatically increased with tumor progression.

Conclusion

The data suggest alterations in Bcl-2 expression and lymphocyte infiltration correlate with epithelial ovarian cancer progression. Consequently, Bcl-2 expression and lymphocyte status may be important for prognostic outcome or useful targets for therapeutic intervention.
Five‐year follow up of genotypic resistance patterns in HIV‐1 subtype C infected patients in Botswana after failure of thymidine analogue‐based regimens
Authors: Doualla‐Bell Florence , Gaolathe Tendani , Avalos Ava , Cloutier Suzanne , Ndwapi Ndwapi , Holcroft Christina , Moffat Howard , Dickinson Diana , Essex Max , Wainberg Mark A , Mine Madisa
Published: October 2009

Objective

Our objective was to establish genotypic resistance profiles among the 4% of Batswana patients who experienced virologic failure while being followed within Botswana's National Antiretroviral Treatment Program between 2002 and 2007.

Methods

At the beginning of the national program in 2002, almost all patients received stavudine (d4T), together with didanosine (ddI), as part of their first nucleoside reverse transcriptase inhibitor (NRTI)‐based regimen (Group 1). In contrast, the standard of care for all patients subsequently enrolled (2002‐2007) included zidovudine/lamivudine (ZDV/3TC) (Group 2). Genotypes were analyzed in 26 patients from Group 1 and 37 patients from Group 2. Associations between mutations were determined using Pearson's correlation coefficient and Jaccard's coefficient of similarity.

Results

Seventy‐eight percent of genotyped patients possessed mutations associated with protease inhibitor (PI) resistance while 87% and 90%, respectively, exhibited mutations associated with NRTIs and non‐nucleoside reverse transcriptase inhibitors (NNRTIs). The most frequent PI mutations involving resistance to NFV were L90M (25.2%) and D30N (16.2%), but mutations at positions K45Q and D30N were often observed in tandem (P = 60.5, J = 50; p = 0.002; Group 2) alongside Q61E in 42.8% of patients who received ZDV/3TC. Both major patterns of thymidine analogue mutations, TAM 1 (48%) and TAM 2 (59%), were represented in patients from Group 1 and 2, although M184V was higher among individuals who had initially received ddI (61% versus 40.5%). In contrast, L74V was more frequent among individuals from Group 2 (16.2% versus 7.7%). Differences in regard to NNRTI mutations were also observed between Group 1 and Group 2 patients.

Conclusion

Despite a low rate of therapeutic failure (4%) among these patients, those who failed possessed high numbers of resistance mutations as well as novel resistance mutations and/or polymorphisms at sites within reverse transcriptase and protease.
Health-Related Quality of Life in Long-Term Survivors of Testicular Cancer
Authors: Rossen Philip Blach , Pedersen Anette Fischer , Zachariae Robert , von der Maase Hans
Published: October 2009

Purpose

A growing number of patients with testicular cancer (TC) become long-term survivors. As a consequence, quality-of-life (QOL) issues become increasingly important. The objective of this study was to investigate QOL among Danish TC survivors.

Methods

A long-term follow-up assessment of all patients with TC treated at Aarhus University Hospital in Denmark between 1990 and 2000 was conducted. A total of 401 survivors (response rate, 66%) completed questionnaires concerning QOL (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30), depression (Beck Depression Inventory-II), fatigue (Multidimensional Fatigue Inventory-20), and health-related issues such as neurotoxic symptoms and Raynaud-like phenomena. On the basis of their treatment, participants were categorized as having received surveillance, radiotherapy, or chemotherapy.

Results

QOL among patients with TC was equal to that of men from the general population. Although patients who received chemotherapy reported higher levels of peripheral sensory neuropathy, ototoxicity, and Raynaud-like phenomena, treatment strategies were generally unrelated to QOL and depressive symptoms.

Conclusion

Overall, the patients in this study reported high levels of QOL. The results suggest that patients treated for TC should be informed about the anticipated good post-therapeutic QOL and the low risk of psychosocial and physical long-term effects.
Association of Molecular Markers With Toxicity Outcomes in a Randomized Trial of Chemotherapy for Advanced Colorectal Cancer: The FOCUS Trial
Authors: Braun Michael S. , Richman Susan D. , Thompson Lindsay , Daly Catherine L. , Meade Angela M. , Adlard Julian W. , Allan James M. , Parmar Mahesh K.B. , Quirke Philip , Seymour Matthew T.
Published: October 2009

Purpose

Predicting efficacy and toxicity could potentially allow individualization of cancer therapy. We investigated putative pharmacogenetic markers of chemotherapy toxicity in a large randomized trial.

Patients, Materials, and Methods

Patients were randomly assigned to different sequences of chemotherapy for advanced colorectal cancer. First-line therapy was fluorouracil (FU), irinotecan/FU (IrFU) or oxaliplatin/FU (OxFU). Patients allocated first-line FU had planned second-line irinotecan alone, IrFU, or OxFU. The primary toxicity outcome measure was toxicity-induced delay or dose reduction; the secondary outcome was Common Terminology Criteria of Adverse Events grade ≥ 3 toxicity. DNA was analyzed in 1,188 patients; 1,036 were assessable for the primary outcome, including 688 treated with FU, 270 with IrFU (first or second line), 280 with OxFU (first or second line), 184 with irinotecan alone, and 454 with any irinotecan-containing regimen. Ten polymorphisms were assessed: thymidylate synthase–enhancer region (TYMS-ER), thymidylate synthase 1494 (TYMS-1494), dihydropyrimidine dehydrogenase (DPYD), methylenetetrahydrofolate reductase (MTHFR), mutL homolog 1 (MLH1), UDP glucuronyltransferase (UGT1A1), ATP-binding cassette group B gene 1 (ABCB1), x-ray cross-complementing group 1 (XRCC1), glutathione-S-transferase P1 (GSTP1), and excision repair cross-complementing gene 2 (ERCC2).

Results

Using the primary outcome measure, no polymorphism was significantly associated (P < .01) with the toxicity of any regimen or with the difference in toxicity of IrFU or OxFU versus FU alone. Trends (of doubtful significance) were seen for associations of XRCC1, ERCC2, and GSTP1 with toxicity during irinotecan regimens: XRCC1, primary end point, any irinotecan-containing regimen (P = .045); ERCC2, secondary end point, irinotecan alone (P = .003); GSTP1, secondary end point; IrFU (P = .039); and irinotecan alone (P = .05). There was no evidence of association of UGT1A1*28 with irinotecan toxicity.

Conclusion

These results do not support the routine clinical use of the evaluated polymorphisms, including UGT1A1*28. Further investigation of XRCC1, ERCC2, and GSTP1 as potential predictors of irinotecan toxicity is warranted.
Personalized Cancer Therapy With Selective Kinase Inhibitors: An Emerging Paradigm in Medical Oncology
Authors: McDermott Ultan , Settleman Jeff
Published: October 2009

Selective kinase inhibitors have emerged as an important class of anticancer agents, with demonstrated clinical efficacy and generally favorable toxicity profiles in several common disease settings where conventional treatments have previously provided only modest benefit. Consequently, a substantial effort is now underway to identify additional therapeutically relevant kinase targets and to develop and test inhibitors of those proteins in a variety of human malignancies. However, it has also become clear that the clinical benefit associated with these agents is typically limited to a subset of treated patients, who in many cases are defined by a specific genomic lesion within their tumor cells—frequently, an activating mutation within the gene encoding the target kinase. This discovery has prompted efforts to stratify patients before treatment with kinase inhibitors based on specific genomic biomarkers, with the goal of optimizing clinical outcomes through the effective personalization of treatment (ie, matching the right patients with the right therapies). With recent advances in our understanding of the relationship between tumor genotypes and cancer cell sensitivity to kinase inhibition, together with improved technologies for rapidly genotyping tumor biopsies for relevant lesions, the implementation of personalized cancer care with this exciting new class of inhibitors is now becoming a reality. In this review, we summarize recent developments in this area, and we highlight some of the logistical challenges posed by this emerging paradigm in medical oncology.
Phase III Randomized Comparison of Gemcitabine Versus Gemcitabine Plus Capecitabine in Patients With Advanced Pancreatic Cancer
Authors: Cunningham David , Chau Ian , Stocken Deborah D. , Valle Juan W. , Smith David , Steward William , Harper Peter G. , Dunn Janet , Tudur-Smith Catrin , West Julia , Falk Stephen , Crellin Adrian , Adab Fawzi , Thompson Joyce , Leonard Pauline , Ostrowski Joe , Eatock Martin , Scheithauer Werner , Herrmann Richard , Neoptolemos John P.
Published: October 2009

Purpose

Both gemcitabine (GEM) and fluoropyrimidines are valuable treatment for advanced pancreatic cancer. This open-label study was designed to compare the overall survival (OS) of patients randomly assigned to GEM alone or GEM plus capecitabine (GEM-CAP).

Patients and Methods

Patients with previously untreated histologically or cytologically proven locally advanced or metastatic carcinoma of the pancreas with a performance status ≤ 2 were recruited. Patients were randomly assigned to GEM or GEM-CAP. The primary outcome measure was survival. Meta-analysis of published studies was also conducted.

Results

Between May 2002 and January 2005, 533 patients were randomly assigned to GEM (n = 266) and GEM-CAP (n = 267) arms. GEM-CAP significantly improved objective response rate (19.1% v 12.4%; P = .034) and progression-free survival (hazard ratio [HR], 0.78; 95% CI, 0.66 to 0.93; P = .004) and was associated with a trend toward improved OS (HR, 0.86; 95% CI, 0.72 to 1.02; P = .08) compared with GEM alone. This trend for OS benefit for GEM-CAP was consistent across different prognostic subgroups according to baseline stratification factors (stage and performance status) and remained after adjusting for these stratification factors (P = .077). Moreover, the meta-analysis of two additional studies involving 935 patients showed a significant survival benefit in favor of GEM-CAP (HR, 0.86; 95% CI, 0.75 to 0.98; P = .02) with no intertrial heterogeneity.

Conclusion

On the basis of our trial and the meta-analysis, GEM-CAP should be considered as one of the standard first-line options in locally advanced and metastatic pancreatic cancer.
Serum Markers of Bone Turnover Are Increased at Six and 18 Months after Roux-En-Y Bariatric Surgery: Correlation with the Reduction in Leptin
Authors: Bruno Carolina , Fulford Angie D. , Potts Jenna R. , McClintock Ronald , Jones RoseMarie , Cacucci Brenda M. , Gupta Christine E. , Peacock Munro , Considine Robert V.
Published: October 2009

Objective: The aim of the study was to examine serum markers of bone turnover at 6 and 18 months after Roux-en-Y gastric bypass surgery.

Participants: Ten women and 10 men [body mass index (BMI), 50.2 ± 8.4 kg/m2] were studied at 6 months; 10 women and nine men (BMI, 47.2 ± 6.6 kg/m2) were studied at 18 months after surgery.

Main Outcome Measures: Serum osteocalcin, bone specific alkaline phosphatase (BAP), N-telopeptide of type 1 collagen (NTX), PTH, 25-hydroxy vitamin D, and leptin were measured.

Results: BMI was reduced 32.7 ± 6.2% at 6 months after surgery. Serum osteocalcin (6.9 ± 2.4 to 10.9 ± 2.6 ng/ml; P < 0.0001), BAP (14.2 ± 3.7 to 16.4 ± 4.5 ng/ml; P = 0.04), and NTX (10.9 ± 1.7 to 19.6 ± 5.3 nm bone collagen equivalents; P < 0.0001) were increased. Calcium, phosphate, and PTH were unchanged, but 25-hydroxy vitamin D increased (16.0 ± 8.9 vs. 26.9 ± 10.6 ng/ml; P <0.0001). The increase in NTX correlated with reduction in serum leptin (r = 0.58; P = 0.007). BMI was reduced 40.9 ± 7.5% at 18 months after surgery. Serum BAP (17.6 ± 5.3 to 22.2 ± 7.8 ng/ml; P = 0.0017) and NTX (10.8 ± 2.7 to 16.9 ± 5.5 nm bone collagen equivalents; P < 0.0001) were increased. Calcium, phosphate, and PTH were unchanged, but 25-hydroxy vitamin D increased (17.7 ± 7.6 to 25.6 ± 6.8 ng/ml; P < 0.0001). The increase in NTX correlated with reduction in BMI (r = 0.58; P = 0.009) and leptin (r = 0.45; P = 0.04) and the increase in serum 25-hydroxy vitamin D (r = 0.43; P = 0.05). In multiple regression (adjusted model R2 0.263; P = 0.013), reduction in leptin was a significant predictor of increase in NTX (P = 0.016), but changes in BMI and 25-hydroxy vitamin D were not.

Conclusions: Weight loss after bariatric surgery is associated with long-term increase in serum markers of bone turnover. The increase in NTX is related to the decrease in leptin, which may signal caloric restriction to the skeleton.
Design of a vibration-isolated cushion to reduce the noise and vibration of a hydraulic breaker
Authors: Kim B-S , Kim M-G , Lee S-H , Lee M G
Published: October 2009

The objective of this research is to develop a low-noise and low-vibration hydraulic breaker that is able to meet the proposed strict noise certification and environmental regulations on construction equipment. Noise and vibration characteristics of a conventional hydraulic breaker are examined using a noise test and acoustic analysis. A dynamic absorption mechanism is applied to the current upper cushion to lower the noise energy and vibration force transmitted by the operating mechanism. The high effectiveness of the developed hydraulic breaker system on the noise and vibration problem is verified using a noise test and acoustic analysis.
Photocatalytic Aerobic Epoxidation of Alkenes under Visible Light Irradiation by an Iron(III) Porphyrin with Mg–Al Hydrotalcite Anionic Clay
Authors: Teramura Kentaro , Ogura Kentaro , Sugimoto Takashi , Tsuneoka Hideo , Shishido Tetsuya , Tanaka Tsunehiro
Published: October 2009

In photocatalytic aerobic oxidation of cyclohexene catalyzed by 5,10,15,20-tetrakis(pentafluorophenyl)porphyriniron(III) chloride [Fe(TPFPP)Cl] under visible light irradiation, the coexistence of solid bases was found to enhance the selectivity to cyclohexene oxide drastically. In the absence of solid bases, however, only the allylic oxidation of cyclohexene was catalyzed by the porphyrin complex acting as a sensitizer. Among the various metal oxides investigated, hydrotalcite exhibited the highest conversion of cyclohexene and selectivity to cyclohexene oxide.
Accidental induced seizures in three cynomologus macaques following administration of ceftriaxone dissolved in 1% lidocaine diluent
Authors: Dror Moti
Published: October 2009

Following initial signs of dural infection, or as prophylactic postoperative therapy, three cynomologus macaques were given an intramuscular or a subcutaneous injection of ceftriaxone dissolved in a 1% lidocaine diluent (CL). Two to 15 min later, all three monkeys experienced a long-lasting generalized apnoeic clonic convulsive seizure. The injected doses of lidocaine (0.7-2 mg/kg) were as low as 7-20-fold less than the experimental intravenous dosage (14.2 ± 3.2 mg/kg) previously reported to induce seizure in healthy rhesus monkeys. Under different clinical conditions, the same three animals were either once (1 animal) or repeatedly given CL without any resultant neurological alterations. The monkeys had a cranial device implanted and two of them were craniotomized. This first report of accidental lidocaine-induced seizure in laboratory non-human primates following CL injection strongly suggests increased susceptibility when lidocaine administration is associated with central nervous system alteration. A novel hypothesis, the possible role of cytokine in lowering the lidocaine seizure threshold, is suggested.
Crossing Boundaries, Claiming a Homeland: The Mexican Chinese Transpacific Journey to Becoming Mexican, 1930s–1960s
Authors: Camacho Julia María Schiavone
Published: October 2009

This article follows Mexican Chinese families from Mexico, across the Mexican-U.S. border, to China, and back to Mexico. Settling in northern Mexico in the nineteenth century, Chinese formed multiple ties with Mexicans. An anti-Chinese movement emerged during the Mexican Revolution and peaked during the Great Depression. The Mexican government deported several thousand Chinese men and their Mexican-origin families from Sonora and neighboring Sinaloa, some directly to China and others to the United States, whose immigration agents also deported the families to China. They arrived in Guangdong (Canton) Province but eventually congregated in Macau where they forged a coherent Mexican Chinese enclave. Developing a strategic Mexican nationalism, they appealed for repatriation. The Mexican Chinese "became Mexican" only after authorities compelled them to struggle for years from abroad for the inclusion of their mixed-race families in the nation. They became diasporic citizens and fashioned hybrid identities to survive in Mexico and China.
Estimating Breeding Values With Molecular Relatedness and Reconstructed Pedigrees in Natural Mating Populations of Common Sole, Solea Solea
Authors: Blonk Robbert J W , Komen Hans , Kamstra Andries , van Arendonk Johan A M
Published: October 2009

Captive populations where natural mating in groups is used to obtain offspring typically yield unbalanced population structures with highly skewed parental contributions and unknown pedigrees. Consequently, for genetic parameter estimation, relationships need to be reconstructed or estimated using DNA marker data. With missing parents and natural mating groups, commonly used pedigree reconstruction methods are not accurate and lead to loss of data. Relatedness estimators, however, infer relationships between all animals sampled. In this study, we compared a pedigree relatedness method and a relatedness estimator (“molecular relatedness”) method using accuracy of estimated breeding values. A commercial data set of common sole, Solea solea, with 51 parents and 1953 offspring (“full data set”) was used. Due to missing parents, for 1338 offspring, a pedigree could be reconstructed with 10 microsatellite markers (“reduced data set”). Cross-validation of both methods using the reduced data set showed an accuracy of estimated breeding values of 0.54 with pedigree reconstruction and 0.55 with molecular relatedness. Accuracy of estimated breeding values increased to 0.60 when applying molecular relatedness to the full data set. Our results indicate that pedigree reconstruction and molecular relatedness predict breeding values equally well in a population with skewed contributions to families. This is probably due to the presence of few large full-sib families. However, unlike methods with pedigree reconstruction, molecular relatedness methods ensure availability of all genotyped selection candidates, which results in higher accuracy of breeding value estimation.
Social Inequality and Racial Discrimination: Risk Factors for Health Disparities in Children of Color
Authors: Sanders-Phillips Kathy , Settles-Reaves Beverlyn , Walker Doren , Brownlow Janeese
Published: October 2009

A child's sense of control over life and health outcomes as well as perceptions of the world as fair, equal, and just are significantly influenced by his or her social experiences and environment. Unfortunately, the social environment for many children of color includes personal and family experiences of racial discrimination that foster perceptions of powerlessness, inequality, and injustice. In turn, these perceptions may influence child health outcomes and disparities by affecting biological functioning (eg, cardiovascular and immune function) and the quality of the parent-child relationship and promoting psychological distress (eg, self-efficacy, depression, anger) that can be associated with risk-taking and unhealthy behaviors. In this article we review existing theoretical models and empirical studies of the impact of racial discrimination on the health and development of children of color in the United States. On the basis of this literature, a conceptual model of exposure to racial discrimination as a chronic stressor and a risk factor for poor health outcomes and child health disparities is presented.
Leaching of borate waste cement matrices: pore solution and solid phase characterization
Authors: Hernández S. , Guerrero A. , Gonñi S.
Published: October 2009

The chemical composition of the pore solution expressed from matrices of simulated borate liquid waste (containing H3BO3, Na2SO4, Na2HPO4 and Ca3(PO4)2) and pozzolanic cement (Spanish type IV-35) and the changes caused by leaching over 180 days in deionized water at temperatures of 20 and 40°C were studied. The leaching was carried out according to the ANSI/ANS-16.1-1986 test. In addition, the change of the solid phase was characterized by X-ray diffraction, infrared spectroscopy and scanning electron microscopy.
Calculations of Portland cement clinkering reactions
Authors: Barry T. I. , Glasser F. P.
Published: October 2009

Calculations have been undertaken of both equilibrium and non-equilibrium chemistry of relevant parts of the CaO—Fe2O3—Al2O3—SiO2 system and related reactions in the gas phase. The examples provide new insights into topics of current concern in the manufacture of Portland cement, including the early stages of melting, the undesirable retention of lime, the ferrous iron content and the phases formed during non-equilibrium cooling, their proportions and composition. The proportion of the C3S (alite) phase depends exclusively on the early stages of cooling, when neither ferrite nor C3A is present. This and the fact that the phases do not have fixed compositions illuminate the limitations of the Bogue calculation for estimation of C3S. Calculations involving the gas and liquid salts are used to investigate reactions of sodium and its build-up in the hot zone of the kiln. The scope and limitations of the database and methods for calculations on these processes are discussed.