bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of TNF-α genetic variants and CCR5Δ32 on the vulnerability to HIV-1 infection and disease progression in Caucasian Spaniards
Authors: Veloso Sergi , Olona Montserrat , García Felipe , Domingo Pere , Alonso-Villaverde Carlos , Broch Montserrat , Peraire Joaquim , Viladés Consuelo , Plana Montserrat , Pedrol Enric , López-Dupla Miguel , Aguilar Carmen , Gutiérrez Mar , Leon Agathe , Tasias Mariona , Ma Gatell Josep , Richart Cristóbal , Vidal Francesc
Published: April 2010

Background

Tumor necrosis factor alpha (TNF-α) is thought to be involved in the various immunogenetic events that influence HIV-1 infection.

Methods

We aimed to determine whether carriage of theTNF-α-238G>A, -308G>Aand-863 C>Agene promoter single nucleotide polymorphisms (SNP) and theCCR5Δ32variant allele influence the risk of HIV-1 infection and disease progression in Caucasian Spaniards. The study group consisted of 423 individuals. Of these, 239 were uninfected (36 heavily exposed but uninfected [EU] and 203 healthy controls [HC]) and 184 were HIV-1-infected (109 typical progressors [TP] and 75 long-term nonprogressors [LTNP] of over 16 years' duration).TNF-αSNP and theCCR5Δ32allele were assessed using PCR-RFLP and automatic sequencing analysis methods on white blood cell DNA. Genotype and allele frequencies were compared using the χ 2 test and the Fisher exact test. Haplotypes were compared by logistic regression analysis.

Results

The distribution ofTNF-α-238G>A, -308G>Aand-863 C>Agenetic variants was non-significantly different in HIV-1-infected patients compared with uninfected individuals:-238G>A, p = 0.7 and p = 0.3;-308G>A, p = 0.05 and p = 0.07;-863 C>A, p = 0.7 and p = 0.4, for genotype and allele comparisons, respectively. Haplotype analyses, however, indicated that carriers of the haplotype H3 were significantly more common among uninfected subjects (p = 0.04). Among the infected patients, the distribution of the threeTNF-αgenetic variants assessed was non-significantly different between TP and LTNP:-238G>A, p = 0.35 and p = 0.7;-308G>A, p = 0.7 and p = 0.6:-863 C>A, p = 0.2 and p = 0.2, for genotype and allele comparisons, respectively. Haplotype analyses also indicated non-significant associations. Subanalyses in the LTNP subset indicated that theTNF-α-238Avariant allele was significantly overrepresented in patients who spontaneously controlled plasma viremia compared with those who had a detectable plasma viral load (genotype comparisons, p = 0.02; allele comparisons, p = 0.03). TheCCR5Δ32distribution was non-significantly different in HIV-1-infected patients with respect to the uninfected population (p = 0.15 and p = 0.2 for genotype and allele comparisons, respectively) and in LTNP vs TP (p = 0.4 and p = 0.5 for genotype and allele comparisons, respectively).

Conclusions

In our cohort of Caucasian Spaniards,TNF-αgenetic variants could be involved in the vulnerability to HIV-1 infection.TNF-αgenetic variants were unrelated to disease progression in infected subjects. The-238G>ASNP may modulate the control of viremia in LTNP. Carriage of theCCR5Δ32variant allele had no effect on the risk of infection and disease progression.
Understanding young adult physical activity, alcohol and tobacco use in community colleges and 4-year post-secondary institutions: A cross-sectional analysis of epidemiological surveillance data
Authors: VanKim Nicole A , Laska Melissa Nelson , Ehlinger Edward , Lust Katherine , Story Mary
Published: April 2010

Background

Young adults experience many adverse health behavior changes as they transition from adolescence into adulthood. A better understanding of the relationships between health promoting and risky health behaviors may aid in the development of health promotion interventions for various types of young adult post-secondary students. Therefore, the purpose of this study was to examine associations between alcohol and tobacco use and physical activity among 2-year and 4-year college students.

Methods

Cross-sectional analyses were conducted using 2007 survey data, collected as part of an on-going post-secondary health surveillance system in Minnesota. Students were randomly selected to participant from 14 Minnesota colleges and universities (six 2-year community and/or technical colleges, eight 4-year post-secondary institutions). The 2007 surveillance data included 9,931 respondents.

Results

The prevalence of demographic characteristics and health behaviors (e.g., physical activity, tobacco use) differed between young adults attending 2-year and 4-year post-secondary institutions; in general, those attending 2-year institutions are representative of more at-risk populations. Overall, higher levels of moderate, vigorous and strengthening physical activity were associated with higher levels of alcohol consumption and lower levels of smoking. In general, despite the disparities in the prevalence of these risk behaviors, the associations between the behaviors did not differ substantially between 2-year and 4-year post-secondary populations.

Conclusions

These findings illustrate links between leading risk behaviors. Interventions targeting multiple risk behaviors among young adults may warrant further consideration. Overall, future research is needed to support and inform young adult health promotion efforts that may be implemented in a wide array of post-secondary institutions.
A patient survey of the impact of fibromyalgia and the journey to diagnosis
Authors: Choy Ernest , Perrot Serge , Leon Teresa , Kaplan Joan , Petersel Danielle , Ginovker Anna , Kramer Erich
Published: April 2010

Background

Fibromyalgia is a painful, debilitating illness with a prevalence of 0.5-5.0% that affects women more than men. It has been shown that the diagnosis of fibromyalgia is associated with improved patient satisfaction and reduced healthcare utilization. This survey examined the patient journey to having their condition diagnosed and studied the impact of the condition on their life.

Methods

A questionnaire survey of 800 patients with fibromyalgia and 1622 physicians in 6 European countries, Mexico and South Korea. Patients were recruited via their physician.

Results

Over half the patients (61%) were aged 36-59 years, 84% were women, and the mean time since experiencing fibromyalgia symptoms was 6.5 years. Patients had experienced multiple fibromyalgia symptoms (mean of 7.3 out of 14), with pain, fatigue, sleeping problems and concentration difficulties being the most commonly reported. Most patients rated their chronic widespread pain as moderate or severe and fibromyalgia symptoms were on average "fairly" to "very" disruptive, and had a "moderate" to "strong" impact on patients' lives. 22% were unable to work and 25% were not able to work all the time because of their fibromyalgia. Patients waited on average almost a year after experiencing symptoms before presenting to a physician, and it took an average of 2.3 years and presenting to 3.7 different physicians before receiving a diagnosis of fibromyalgia. Patients rated receiving a diagnosis as somewhat difficult on average and had difficulties communicating their symptoms to the physician. Over one third (35%) felt their chronic widespread pain was not well managed by their current treatment.

Conclusions

This survey provides further evidence that fibromyalgia is characterized by multiple symptoms and has a notable impact on quality of life and function. The diagnosis of fibromyalgia is delayed. Patients wait a significant period of time before presenting to a physician, adding to the prolonged time to diagnosis. Patients typically present with a multitude of symptoms, all resulting in a delay in diagnosis and eventual management. Helping clinicians to diagnose and manage patients with fibromyalgia should benefit both patients and funders of healthcare.
Stepwise engineering of a Pichia pastoris D-amino acid oxidase whole cell catalyst
Authors: Abad Sandra , Nahalka Jozef , Bergler Gabriele , Arnold S Alison , Speight Robert , Fotheringham Ian , Nidetzky Bernd , Glieder Anton
Published: April 2010

Background

Trigonopsis variabilisD-amino acid oxidase (TvDAO) is a well characterized enzyme used for cephalosporin C conversion on industrial scale. However, the demands on the enzyme with respect to activity, operational stability and costs also vary with the field of application. Processes that use the soluble enzyme suffer from fast inactivation ofTvDAO while immobilized oxidase preparations raise issues related to expensive carriers and catalyst efficiency. Therefore, oxidase preparations that are more robust and active than those currently available would enable a much broader range of economically viable applications of this enzyme in fine chemical syntheses. A multi-step engineering approach was chosen here to develop a robust and highly activePichia pastoris TvDAO whole-cell biocatalyst.

Results

As compared to the nativeT. variabilishost, a more than seven-fold enhancement of the intracellular level of oxidase activity was achieved inP. pastoristhrough expression optimization by codon redesign as well as efficient subcellular targeting of the enzyme to peroxisomes. Multi copy integration further doubled expression and the specific activity of the whole cell catalyst. From a multicopy production strain, about 1.3 × 103U/g wet cell weight (wcw) were derived by standard induction conditions feeding pure methanol. A fed-batch cultivation protocol using a mixture of methanol and glycerol in the induction phase attenuated the apparent toxicity of the recombinant oxidase to yield final biomass concentrations in the bioreactor of ≥ 200 g/L compared to only 117 g/L using the standard methanol feed. Permeabilization ofP. pastorisusing 10% isopropanol yielded a whole-cell enzyme preparation that showed 49% of the total available intracellular oxidase activity and was notably stabilized (by three times compared to a widely usedTvDAO expressingEscherichia colistrain) under conditions ofD-methionine conversion using vigorous aeration.

Conclusions

Stepwise optimization using a multi-level engineering approach has delivered a newP. pastoriswhole cellTvDAO biocatalyst showing substantially enhanced specific activity and stability under operational conditions as compared to previously reported preparations of the enzyme. The production of the oxidase through fed-batch bioreactor culture and subsequent cell permeabilization is high-yielding and efficient. Therefore thisP. pastoriscatalyst has been evaluated for industrial purposes.
Gene expression profiles help identify the Tissue of Origin for metastatic brain cancers
Authors: Wu Alan HB , Drees Julia C , Wang Hangpin , VandenBerg Scott R , Lal Anita , Henner William D , Pillai Raji
Published: April 2010

Background

Metastatic brain cancers are the most common intracranial tumor and occur in about 15% of all cancer patients. In up to 10% of these patients, the primary tumor tissue remains unknown, even after a time consuming and costly workup. The Pathwork® Tissue of Origin Test (Pathwork Diagnostics, Redwood City, CA, USA) is a gene expression test to aid in the diagnosis of metastatic, poorly differentiated and undifferentiated tumors. It measures the expression pattern of 1,550 genes in these tumors and compares it to the expression pattern of a panel of 15 known tumor types. The purpose of this study was to evaluate the performance of the Tissue of Origin Test in the diagnosis of primary sites for metastatic brain cancer patients.

Methods

Fifteen fresh-frozen metastatic brain tumor specimens of known origins met specimen requirements. These specimens were entered into the study and processed using the Tissue of Origin Test. Results were compared to the known primary site and the agreement between the two results was assessed.

Results

Fourteen of the fifteen specimens produced microarray data files that passed all quality metrics. One originated from a tissue type that was off-panel. Among the remaining 13 cases, the Tissue of Origin Test accurately predicted the available diagnosis in 12/13 (92.3%) cases.

Discussion

This study demonstrates the accuracy of the Tissue of Origin Test when applied to predict the tissue of origin of metastatic brain tumors. This test could be a very useful tool for pathologists as they classify metastatic brain cancers.
Interventions aimed at improving the nursing work environment: a systematic review
Authors: Schalk Donna MJ , Bijl Marloes LP , Halfens Ruud JG , Hollands Louk , Cummings Greta G
Published: April 2010

Background

Nursing work environments (NWEs) in Canada and other Western countries have increasingly received attention following years of restructuring and reported high workloads, high absenteeism, and shortages of nursing staff. Despite numerous efforts to improve NWEs, little is known about the effectiveness of interventions to improve NWEs. The aim of this study was to review systematically the scientific literature on implemented interventions aimed at improving the NWE and their effectiveness.

Methods

An online search of the databases CINAHL, Medline, Scopus, ABI, Academic Search Complete, HEALTHstar, ERIC, Psychinfo, and Embase, and a manual search of Emerald and Longwoods was conducted. (Quasi-) experimental studies with pre/post measures of interventions aimed at improving the NWE, study populations of nurses, and quantitative outcome measures of the nursing work environment were required for inclusion. Each study was assessed for methodological strength using a quality assessment and validity tool for intervention studies. A taxonomy of NWE characteristics was developed that would allow us to identify on which part of the NWE an intervention targeted for improvement, after which the effects of the interventions were examined.

Results

Over 9,000 titles and abstracts were screened. Eleven controlled intervention studies met the inclusion criteria, of which eight used a quasi-experimental design and three an experimental design. In total, nine different interventions were reported in the included studies. The most effective interventions at improving the NWE were: primary nursing (two studies), the educational toolbox (one study), the individualized care and clinical supervision (one study), and the violence prevention intervention (one study).

Conclusions

Little is known about the effectiveness of interventions aimed at improving the NWE, and published studies on this topic show weaknesses in their design. To advance the field, we recommend that investigators use controlled studies with pre/post measures to evaluate interventions that are aimed at improving the NWE. Thereby, more evidence-based knowledge about the implementation of interventions will become available for healthcare leaders to use in rebuilding nursing work environments.
Decrease in the expression of the type 1 PTH/PTHrP receptor (PTH1R) on chondrocytes in animals with osteoarthritis
Authors: Becher Christoph , Szuwart Thomas , Ronstedt Philipp , Ostermeier Sven , Skwara Adrian , Fuchs-Winkelmann Susanne , Tibesku Carsten O
Published: April 2010

Background

To evaluate the expression of the type 1 PTH/PTHrP receptor (PTH1R) on chondrocytes from hyaline cartilage over the course of osteoarthritis (OA).

Methods

In 12 NZW rabbits, the anterior cruciate ligament (ACL) was resected to create anterior instability of the knee. In 12 control rabbits, only a sham operation, without resection of the ACL, was performed. Four animals from each group were killed at 3, 6, and 12 weeks. After opening the knee joint, OA was macroscopically graded and hyaline cartilage of the load-bearing area was evaluated histologically according to the Mankin scale and by immunostaining for PTH1R.

Results

There was a positive linear correlation between the time after surgery and the macroscopic and histologic OA scores. The scores in the control group were constant over the time course. Immunostaining showed significantly less expression of PTH1R in the experimental compared to the control group after 6 (P < 0.05) and 12 weeks (P < 0.01). In the experimental group, a negative linear correlation between PTH1R expression and macroscopic and histologic grades was found.

Conclusions

The results show an in vivo decrease in the expression of PTH1R on chondrocytes over the time course of OA. Further studies are needed to evaluate whether new treatment approaches could evolve from this knowledge.
Determinants of psychological morbidity in survivors of the earthquake and tsunami in Aceh and Nias
Authors: Irmansyah I , Dharmono Suryo , Maramis Albert , Minas Harry
Published: April 2010

Background

The goal of this study was to collect information to inform the design of a mental health response following the massive December 2004 earthquake and tsunami in Aceh and North Sumatra, Indonesia. As well as exploring the effect on mental health of direct exposure to the tsunami the study was designed to examine the effect on mental health of immediate post-disaster changes in life circumstances (impact).

Methods

Information was collected from a sample of 783 people aged 15 years and over in earthquake and tsunami-affected areas of Aceh and Nias, 616 Internally Displaced Persons (IDPs) and 167 non-IDPs. The structured questionnaire that was designed for data collection consisted of demographic information, measures of disaster exposure and of changes in life circumstances (impact), the extended version of the Self-Reporting Questionnaire (SRQ), and a brief measure of resilience. Group comparisons, contrasting responses of IDPs and non-IDPs, were by chi-square for frequency data and t-tests for ordinal or continuous data. Hierarchical multiple linear regression analyses were performed to examine the relative contributions to psychopathology of demographic variables and measures of exposure, impact and resilience.

Results

High rates of psychopathology, including symptoms of anxiety and affective disorders and post-traumatic stress syndrome, were recorded in the overall sample, particularly in Internally Displaced Persons (IDPs) who experienced more substantial post-disaster changes in life circumstances (impact). The IDP group experienced significantly more SRQ symptoms than did the non-IDP group. Demographic factors alone accounted for less two percent of variance in SRQ-scores. Higher SRQ-20 scores were observed among women, those with lower education, those with diminished resilience beliefs, those experiencing high scores on disaster impact, those experiencing direct exposures to the disaster, and due to (unmeasured) conditions related to being an IDP. The greatest effect among these was due to disaster impacts. The pattern was similar when considering post-traumatic stress symptoms separately.

Conclusions

Negative changes in a person's life circumstances following a disaster appear to have as important an effect on psychopathology as the direct experience of the disaster. Ameliorating the extent and duration of post-disaster negative changes in life circumstances may play an important role in prevention of post-disaster psychological morbidity.
Validation of "Signs of Inflammation in Children that Kill" (SICK) score for immediate non-invasive assessment of severity of illness
Authors: Gupta Manoj A , Chakrabarty Anjan , Halstead Ruth , Sahni Mohit , Rangasami Jayanti , Puliyel Ashish , Sreenivas Vishnubhatla , Green David A , Puliyel Jacob M
Published: April 2010

Objective

To validate the SICK scoring system's ability to differentiate between individuals with higher and lower probabilities of death

Method

We performed a one year two-centre prospective evaluation of all children aged between one month and 12 years referred to the Paediatric team at St Stephens Hospital in Delhi and admitted to the Paediatric Department at West Middlesex University Hospital in London. We calculated SICK scores at presentation and correlated them with subsequent in-hospital mortality. We used discrimination by areas under receiver operating characteristic (ROC) curves to measure performance.

Results

We prospectively evaluated 3895 children in Delhi and 1473 children in London. The areas under the ROC curves were 84.8% in Delhi, 81.0% in London and 84.1% (95% CI 77.4 - 90.8%) for combined data. Hosmer-Lemeshow goodness of fit for the combined data was good (Hosmer-Lemeshow Chi-square = 2.13 (p = 0.345).

Conclusions

We propose the SICK score as a useful triage tool at initial presentation and highlight its particular suitability for resource poor settings.
Lack of replication of genetic predictors for the rheumatoid arthritis response to anti-TNF treatments: a prospective case-only study
Authors: Suarez-Gestal Marian , Perez-Pampin Eva , Calaza Manuel , Gomez-Reino Juan J , Gonzalez Antonio
Published: April 2010

Introduction

We aimed to replicate the strong associations that a recent genome wide association study (GWAS) has found between 16 single nucleotide polymorphisms (SNPs) and response to anti-tumour necrosis factor (TNF) treatment in 89 patients with rheumatoid arthritis (RA). This study is very important because, according to published simulations, associations as strong as the reported ones will mean that these SNPs could be used as predictors of response at the individual level.

Methods

Disease activity score (DAS28) was evaluated in 151 anti-TNF treated patients with RA of Spanish ancestry at baseline and every 3 months thereafter. Genotypes of the 16 putative predictor SNPs were obtained by single-base extension. Association between the relative change in DAS28 and SNP genotypes was tested by linear regression. In addition, logistic regression was applied to compare genotypes in non-responders (n = 34) versus good-responders (n = 61) following the EULAR response criteria.

Results

None of the analyses showed any significant association between the 16 SNPs and response to anti-TNF treatments at 3 or 6 months. Results were also negative when only patients treated with infliximab (66.9% of the total) were separately analyzed. These negative results were obtained in spite of a very good statistical power to replicate the reported strong associations.

Conclusions

We still do not have any sound evidence of genetic variants associated with RA response to anti-TNF treatments. In addition, the possibility we had envisaged of using the results of a recent GWAS for prediction in individual patients should be dismissed.
Expression Signature of E2F1 and Its Associated Genes Predict Superficial to Invasive Progression of Bladder Tumors
Authors: Lee Ju-Seog , Leem Sun-Hee , Lee Sang-Yeop , Kim Sang-Cheol , Park Eun-Sung , Kim Sang-Bae , Kim Seon-Kyu , Kim Yong-June , Kim Wun-Jae , Chu In-Sun
Published: April 2010

Purpose

In approximately 20% of patients with superficial bladder tumors, the tumors progress to invasive tumors after treatment. Current methods of predicting the clinical behavior of these tumors prospectively are unreliable. We aim to identify a molecular signature that can reliably identify patients with high-risk superficial tumors that are likely to progress to invasive tumors.

Patients and Methods

Gene expression data were collected from tumor specimens from 165 patients with bladder cancer. Various statistical methods, including leave-one-out cross-validation methods, were applied to identify a gene expression signature that could predict the likelihood of progression to invasive tumors and to test the robustness of the expression signature in an independent cohort. The robustness of the gene expression signature was validated in an independent (n = 353) cohort.

Results

Supervised analysis of gene expression data revealed a gene expression signature that is strongly associated with invasive bladder tumors. A molecular classifier based on this gene expression signature correctly predicted the likelihood of progression of superficial tumor to invasive tumor.

Conclusion

We present a molecular signature that can predict, at diagnosis, the likelihood of bladder cancer progression and, possibly, lead to improvements in patient therapy.
Oral Clofarabine in the Treatment of Patients With Higher-Risk Myelodysplastic Syndrome
Authors: Faderl Stefan , Garcia-Manero Guillermo , Estrov Zeev , Ravandi Farhad , Borthakur Gautam , Cortes Jorge E. , O'Brien Susan , Gandhi Varsha , Plunkett William , Byrd Anna , Kwari Monica , Kantarjian Hagop M.
Published: April 2010

Purpose

Efficacy and toxicity profile of orally administered clofarabine were evaluated in patients with higher-risk myelodysplastic syndrome (MDS).

Patients and Methods

Thirty-two patients were treated, of whom 22 had intermediate-2 or high-risk disease (International Prognostic Scoring System). Median age was 70 years (range, 53 to 86), nine patients had secondary MDS, and 20 patients experienced prior therapy failure with hypomethylating agents. Three doses of clofarabine were evaluated: 40 mg/m2, 30 mg/m2, and 20 mg/m2 daily for 5 days. Courses were repeated every 4 to 8 weeks.

Results

Eight patients (25%) achieved complete remission (CR), three had (9%) hematologic improvement (HI), and three had (9%) clinical benefit (CB; overall response rate, 43%). Responses in patients who experience treatment failure with hypomethylating agents included CR in two (10%), HI in two (10%), and CB in two patients (10%). No patients died within 6 weeks of induction. Renal failure occurred in four patients in the context of myelosuppresssion-associated infectious complications. Common adverse events were gastrointestinal and hepatic. Myelosuppression was common, but prolonged myelosuppression (> 42 days) was rare. The toxicity profile was better with lower doses of clofarabine, whereas response rates did not differ significantly.

Conclusion

Oral clofarabine has achieved a response rate of 43% in patients with higher-risk MDS. The optimal dose and schedule and the appropriate patient population for such therapy remain to be further defined.
Phase II Parallel Group Study Showing Comparable Efficacy Between Premenopausal Metastatic Breast Cancer Patients Treated With Letrozole Plus Goserelin and Postmenopausal Patients Treated With Letrozole Alone As First-Line Hormone Therapy
Authors: Park In Hae , Ro Jungsil , Lee Keun Seok , Kim Eun-A , Kwon Youngmee , Nam Byoung-Ho , Jung So-Youn , Lee Seeyoun , Kim Seok Won , Kang Han Sung
Published: April 2010

Purpose

Goserelin and letrozole in premenopausal patients can result in clinical outcomes comparable to those obtained by letrozole alone in postmenopausal patients with metastatic breast cancer (MBC).

Patients and Methods

A total of 73 patients with hormone-responsive MBC were included. Of those, 35 premenopausal patients received goserelin (3.6 mg subcutaneously every 28 days) plus letrozole (2.5 mg orally daily), and 38 postmenopausal patients received letrozole alone as their first-line endocrine therapy in a metastatic setting.

Results

Baseline characteristics were similar in the two groups, except for a younger age (median, 41 v 53.5 years; P < .001) and a shorter disease-free interval (median, 1.8 v 3.3 years; P = .03) in the premenopausal group. Clinical benefit rates were comparable between the two groups (77% v 74%; P = .77). With the median follow-up of 27.4 months, there was no statistical difference in the median time to progression between the two groups (9.5 months [95% CI, 6.4 to 12.1 months] v 8.9 months [95% CI, 6.4 to 13.3 months]). In patients who did not receive bisphosphonate, letrozole ± goserelin caused a greater loss of bone mineral density at 6 months compared with that of patients receiving bisphosphonate treatment (premenopausal group, −16.7% v 53.9%; P = .002 and postmenopausal group, −13.3% v 17.4%; P = .04 at the lumbar spine).

Conclusion

Clinical efficacies in premenopausal MBC patients with combined letrozole and goserelin therapy were comparable to those in postmenopausal patients treated with letrozole alone. Although letrozole ± goserelin resulted in a modest increase in bone resorption, concurrent treatment with bisphosphonate could prevent bone loss at 6 months.
Statin Use and Risk of Prostate Cancer Recurrence in Men Treated With Radiation Therapy
Authors: Gutt Ruchika , Tonlaar Nathan , Kunnavakkam Rangesh , Karrison Theodore , Weichselbaum Ralph R. , Liauw Stanley L.
Published: April 2010

Purpose

There has been growing interest in the potential anticancer activity of statins based on preclinical evidence of their antiproliferative, proapoptotic, and radiosensitizing properties. The primary objective of this study was to determine whether statin use is associated with improved clinical outcomes in patients treated with radiotherapy (RT) for prostate cancer.

Patients and Methods

In total, 691 men with prostate adenocarcinoma treated with curative-intent RT between 1988 and 2006 were retrospectively analyzed. Of those, 189 patients (27%) were using statins, either during initial consultation or during follow-up. Lipid panels were collected (n = 298) a median of 5 months before RT start. Median follow-up was 50 months after RT.

Results

Statin use was associated with improved freedom from biochemical failure (FFBF; P < .001), freedom from salvage androgen deprivation therapy (FFADT; P = .0011), and relapse-free survival (RFS; P < .001). Improved FFBF for statin users was seen in low-, intermediate-, and high-risk groups (P = .0401, P = .0331, and P = .0034, respectively). The improvement in FFBF with statin use was independent of ADT use or radiation dose. On multivariable analysis, statin use was associated with improved FFBF (P < .001) along with pretreatment prostate-specific antigen ≤ 8.4 (P < .001), stage less than T2b (P = .0111), and Gleason score < 7 (P = .0098). On univariate analysis, pretreatment total cholesterol < 187 (89% v 80%; P = .0494) and low-density lipoprotein (LDL) < 110 (96% v 85%; P = .0462) were associated with improved 4-year FFBF.

Conclusion

Statin use was associated with a significant improvement in FFBF, FFADT, and RFS in this cohort of men treated with RT for prostate cancer. The favorable effect of statins may be mediated by direct effect or via the LDL-lowering effect of these medications.
Anatomical Grading of Supratentorial Arteriovenous Malformations for Determining Operability
Authors: Luessenhop Alfred J. , Gennarelli Thomas A.
Published: April 2010

After the study of over 300 angiograms of supratentorial cerebral arteriovenous malformations (AVM's), the authors have formulated an anatomical grading scheme of I to IV to correspond to the degrees of surgical difficulty for total obliteration. The grading is based upon the number of directly participating arteries for which there is a standardized nomenclature. Occasionally, allowance for clinical grading, in addition to this anatomical grading, must be made. Also, for the anticipation of morbidity, but not mortality, the location of the lesion is important. The authors present the postoperative results in a series of 49 patients to demonstrate the clinical usefulness of the grading scheme.
Recirculatory Spinal Subarachnoid Perfusions in Dogs
Authors: Sklar Frederick H. , Long Donlin M.
Published: April 2010

Open-ended ventriculocisternal perfusion techniques for determining cerebrospinal fluid production and absorption rates are severely restricted by the absolute requirement that steady state conditions be present. A new closed recirculatory spinal perfusion technique is described. Because steady state equilibrium is not necessary, numerous determinations at multiple intracranial pressures or under varied experimental conditions are possible within relatively brief perfusion periods. Cerebrospinal fluid (CSF) and nondiffusible albumin tracer are rapidly recirculated through the spinal subarachnoid space in a cephalad direction. The concentration of fluorescein-tagged albumin is continuously monitored as the CSF is circulated through a fluorometric flow cell. Measured continuously, intracranial pressure (ICP) is regulated by changing the volume of the external perfusion circuit with a syringe pump connected in series to the recirculatory spinal perfusion. CSF formation and absorption rates are calculated from measurements of albumin concentration, concentration changes with time, ICP, syringe pump infusion rate, and the external perfusion circuit volume. In dogs, data can be collected after only 45 minutes for mixing; perfusions at four or five intracranial pressures in addition to normal resting pressure can be completed within 2 to 3 hours. The data from 15 perfusions in 14 dogs are presented. The method provides normal resting pressure values of CSF production and absorption consistent with those values in the literature determined by traditional ventriculocisternal perfusion techniques. Determinations at multiple intracranial pressures suggest a proportional relationship between absorption and ICP. No consistent acute change in CSF formation with pressures to 50 mm Hg can be inferred from these data.
Cortical domain correction repositions the polarity boundary to match the cytokinesis furrow in C. elegans embryos
Authors: Schenk Christian , Bringmann Henrik , Hyman Anthony A. , Cowan Carrie R.
Published: April 2010

In asymmetrically dividing cells, a failure to coordinate cell polarity with the site of cell division can lead to cell fate transformations and tumorigenesis. Cell polarity in C. elegans embryos is defined by PAR proteins, which occupy reciprocal halves of the cell cortex. During asymmetric division, the boundary between the anterior and posterior PAR domains precisely matches the site of cell division, ensuring exclusive segregation of cell fate. The PAR domains determine the site of cell division by positioning the mitotic spindle, suggesting one means by which cell polarity and cell division might be coordinated. Here, we report that cell polarity and cell division are coordinated through an additional mechanism: the site of cell division repositions the PAR-2 boundary. Gα-mediated microtubule-cortex interactions appear to direct cortical flows of PAR-2 and myosin toward the site of cell division, which acts as a PAR-2 and myosin sink. Embryos with defects in PAR-2 boundary correction undergo mis-segregation of cortical polarity and cytoplasmic determinants, suggesting that PAR domain correction might help prevent cell fate transformation.
Mutation of Eif4g3, encoding a eukaryotic translation initiation factor, causes male infertility and meiotic arrest of mouse spermatocytes
Authors: Sun Fengyun , Palmer Kristina , Handel Mary Ann
Published: April 2010

The ENU-induced repro8 mutation was identified in a screen to uncover genes that control mouse gametogenesis. repro8 causes male-limited infertility, with failure of spermatocytes to exit meiotic prophase via the G2/MI transition. The repro8 mutation is in the Eif4g3 gene, encoding eukaryotic translation initiation factor 4, gamma 3. Mutant germ cells appear to execute events of meiotic prophase normally, and many proteins characteristic of the prophase-to-metaphase transition are not obviously depleted. However, activity of CDC2A (CDK1) kinase is dramatically reduced in mutant spermatocytes. Strikingly, HSPA2, a chaperone protein for CDC2A kinase, is absent in mutant spermatocytes in spite of the presence of Hspa2 transcript, consistent with the observation that the repro8 phenotype is markedly similar to the phenotype of the Hspa2 knockout. Thus, EIF4G3 is required for HSPA2 translation in spermatocytes, a finding that provides the first genetic evidence for selective translational control of meiotic exit in mammalian spermatocytes.
Bazooka is required for polarisation of the Drosophila anterior-posterior axis
Authors: Doerflinger Hélène , Vogt Nina , Torres Isabel L. , Mirouse Vincent , Koch Iris , Nüsslein-Volhard Christiane , St Johnston Daniel
Published: April 2010

The Drosophila anterior-posterior (AP) axis is determined by the polarisation of the stage 9 oocyte and the subsequent localisation of bicoid and oskar mRNAs to opposite poles of the cell. Oocyte polarity has been proposed to depend on the same PAR proteins that generate AP polarity in C. elegans, with a complex of Bazooka (Baz; Par-3), Par-6 and aPKC marking the anterior and lateral cortex, and Par-1 defining the posterior. The function of the Baz complex in oocyte polarity has remained unclear, however, because although baz-null mutants block oocyte determination, egg chambers that escape this early arrest usually develop normal polarity at stage 9. Here, we characterise a baz allele that produces a penetrant polarity phenotype at stage 9 without affecting oocyte determination, demonstrating that Baz is essential for axis formation. The dynamics of Baz, Par-6 and Par-1 localisation in the oocyte indicate that the axis is not polarised by a cortical contraction as in C. elegans, and instead suggest that repolarisation of the oocyte is triggered by posterior inactivation of aPKC or activation of Par-1. This initial asymmetry is then reinforced by mutual inhibition between the anterior Baz complex and posterior Par-1 and Lgl. Finally, we show that mutation of the aPKC phosphorylation site in Par-1 results in the uniform cortical localisation of Par-1 and the loss of cortical microtubules. Since non-phosphorylatable Par-1 is epistatic to uninhibitable Baz, Par-1 seems to function downstream of the other PAR proteins to polarise the oocyte microtubule cytoskeleton.
Temperature Calibration Techniques for TMF Testing
Authors: Dudzinski David C. , Beres Wieslaw , Kersey Raymond K.
Published: April 2010

One of the methods to control the rapid temperature changes during a thermomechanical fatigue (TMF) test involves the use of an infrared pyrometer for temperature measurement. The infrared pyrometer relies on the emissivity of the test coupon. One way to determine this emissivity is to use a disappearing filament pyrometer. This paper presents two emissivity calibration techniques: Strain measurement and application of non-permanent thermocouples. Both techniques were applied for TMF testing, and the advantages and disadvantages of these techniques are described. The results show that the temperature indicated by these methods can significantly differ when compared to the actual temperature of the test specimen measured by thermocouples. However, these variances can be mitigated by calibration.
Cognitive effects of aromatase inhibitor therapy in peripubertal boys
Authors: Hero M , Maury S , Luotoniemi E , Service E , Dunkel L
Published: April 2010

Objective

Aromatase inhibitors, blockers of oestrogen biosynthesis, have emerged as a new potential treatment modality for boys with short stature. The cognitive effects of such therapy are unknown. In this study, we explored the effects of aromatase inhibition on cognitive performance in peripubertal boys.

Design

Prospective, double-blind, randomised, placebo-controlled clinical study.

Methods

Twenty-eight boys, aged 9.0–14.5 years, with idiopathic short stature were treated with the aromatase inhibitor letrozole (2.5 mg/day) or placebo, for 2 years. During the treatment, the progression of physical signs of puberty and the concentrations of sex hormones were followed up. A selection of cognitive tests, focusing on memory function, was administered to the participants at entry, at 12 months and at 24 months after the start of the treatment.

Results

Letrozole effectively inhibited the conversion of androgen to oestrogen, as indicated by high serum testosterone and low serum oestradiol concentrations in letrozole-treated boys who progressed into puberty. In both the groups, there was a gain in performance during the follow-up period in tests of verbal performance, in most of the tests of visuospatial performance and in some tests of verbal memory. No significant differences between the letrozole- and placebo-treated boys in development of cognitive performance were found in any of the tests during the follow-up period.

Conclusions

Our results suggest that blockade of oestrogen biosynthesis with an aromatase inhibitor does not influence cognitive performance in peripubertal males.
IscR Regulates RNase LS Activity by Repressing rnlA Transcription
Authors: Otsuka Yuichi , Miki Kumiko , Koga Mitsunori , Katayama Natsu , Morimoto Wakako , Takahashi Yasuhiro , Yonesaki Tetsuro
Published: April 2010

The Escherichia coli endoribonuclease LS was originally identified as a potential antagonist of bacteriophage T4. When the T4 dmd gene is defective, RNase LS cleaves T4 mRNAs and antagonizes T4 reproduction. This RNase also plays an important role in RNA metabolisms in E. coli. rnlA is an essential gene for RNase LS activity, but the transcriptional regulation of this gene remains to be elucidated. An Fe-S cluster protein, IscR, acts as a transcription factor and controls the expression of genes that are necessary for Fe-S cluster biogenesis. Here, we report that overexpression of IscR suppressed RNase LS activity, causing the loss of antagonist activity against phage T4. This suppressive effect did not require the ligation of Fe-S cluster into IscR. β-Galactosidase reporter assays showed that transcription from an rnlA promoter increased in iscR-deleted cells compared to wild-type cells, and gel-mobility shift assays revealed specific binding of IscR to the rnlA promoter region. RT–PCR analysis demonstrated that endogenous rnlA mRNA was reduced by overexpression of IscR and increased by deletion of iscR. From these results, we conclude that IscR negatively regulates transcription of rnlA and represses RNase LS activity.
Specific α- and β-Tubulin Isotypes Optimize the Functions of Sensory Cilia inCaenorhabditis elegans
Authors: Hurd Daryl D , Miller Renee M , Núñez Lizbeth , Portman Douglas S
Published: April 2010

Primary cilia have essential roles in transducing signals in eukaryotes. At their core is the ciliary axoneme, a microtubule-based structure that defines cilium morphology and provides a substrate for intraflagellar transport. However, the extent to which axonemal microtubules are specialized for sensory cilium function is unknown. In the nematode Caenorhabditis elegans, primary cilia are present at the dendritic ends of most sensory neurons, where they provide a specialized environment for the transduction of particular stimuli. Here, we find that three tubulin isotypes—the α-tubulins TBA-6 and TBA-9 and the β-tubulin TBB-4—are specifically expressed in overlapping sets of C. elegans sensory neurons and localize to the sensory cilia of these cells. Although cilia still form in mutants lacking tba-6, tba-9, and tbb-4, ciliary function is often compromised: these mutants exhibit a variety of sensory deficits as well as the mislocalization of signaling components. In at least one case, that of the CEM cephalic sensory neurons, cilium architecture is disrupted in mutants lacking specific ciliary tubulins. While there is likely to be some functional redundancy among C. elegans tubulin genes, our results indicate that specific tubulins optimize the functional properties of C. elegans sensory cilia.
Honoring Do-Not-Attempt-Resuscitation Requests in Schools
Authors:   Council on School Health and Committee on Bioethics
Published: April 2010

Increasingly, children and adolescents with complex chronic conditions are living in the community. Federal legislation and regulations facilitate their participation in school. Some of these children and adolescents and their families may wish to forego life-sustaining medical treatment, including cardiopulmonary resuscitation, because they would be ineffective or because the risks outweigh the benefits. Honoring these requests in the school environment is complex because of the limited availability of school nurses and the frequent lack of supporting state legislation and regulations. Understanding and collaboration on the part of all parties is essential. Pediatricians have an important role in helping school nurses incorporate a specific action plan into the student's individualized health care plan. The action plan should include both communication and comfort-care plans. Pediatricians who work directly with schools can also help implement policies, and professional organizations can advocate for regulations and legislation that enable students and their families to effectuate their preferences.
CS® körvarrógépek alkalmazása rectumanastomosisoknál – Multicentrikus prospektív klinikai vizsgálat
Authors: Kupcsulik Péter , Nagy Attila , Lázár György , Farkas József , Ottlakán Aurél , Martyin György , Oláh Tibor , Dinka Tibor , Oláh Attila , Jakab Ferenc
Published: April 2010

Absztrakt

Jóllehet a körvarrógépek használta világszerte elterjedt, különösen a rectumanastomosisok elkészítésére, a forgalomban lévő eszközök alkalmazhatóságáról kevés közlés lát napvilágot. 2008. május és 2009. március között 9 sebészeti osztályon összesen 136 betegen alkalmaztak CS® körvarrógépeket anastomosis készítésére a rectumon. A prospektív vizsgálat a rectum felső és középső harmadán készített varratokat elemezte, a vizsgálatba 5 olyan esetet is bevontak, ahol az anastomosis a rectum alsó harmadában készült. 115 adenocarcinoma, 16 egyéb malignus daganat, 5 benignus elváltozás miatt került sor infraperitonealis resectióra. 20 műtét laparoscoppal, 116 hagyományos módon történt. A 32 mm átmérőjű eszközt 50, a 28 mm-est 85, a 25 mm-est 1 esetben használták. Intraoperatív technikai hiba 4 esetben fordult elő, a kiegészítő beavatkozással az anastomosis korrigálható volt. Posztoperatív szövődmény ezekben az esetekben nem fordult elő. Késői varratelégtelenséget 5 esetben észleltek, ebből 3 spontán gyógyult, 2 esetben reoperációra került sor. A teljes beteganyagban 2 haláleset fordult elő, ez 1,4%-os mortalitásnak felel meg. A CS® körvarrógépek megfelelőnek bizonyultak infraperitonealis rectumanastomosis céljára.
A spontán mellkasfali sérvekről két operált eset kapcsán
Authors: Vincze Károly , Zádori Péter , Magyaródi Zsolt , Horváth Gyula
Published: April 2010

Absztrakt

A szerzők a világirodalmi ritkaságnak számító atraumaticus (spontán) mellkasfali tüdősérvet ismertetik. Két operált betegük kapcsán bemutatják a sérv kialakulását elősegítő körülményeket és a kórkép klinikai jellemzőit. Mindkét betegük spontán mellkasfali (intercostalis) sérvét chronicus obstructiv syndroma (COPD) okozta makacs köhögés váltotta ki. Az elvégzett multislice spirál CT (MSCT) vizsgálat, valamint a speciális szoftver segítségével készített másodlagos 3D „volume-rendering” (VRT) rekonstrukciós képek egyértelműen utaltak a ritka kórformára. Az MSCT-vizsgálatok a Kaposi Mór Oktató Kórházban készültek, Siemens Somatom Emotion 6 MSCT-berendezéssel. A pontos diagnózis birtokában végzett mellkasfali korrekciók tartós gyógyuláshoz vezettek. A szerzők röviden ismertetik a mellkasfali sérvekkel kapcsolatos hazai és fontosabb külföldi irodalmi vonatkozásokat. A kórkép rendkívüli ritkasága ellenére a kialakulásában szerepet játszó COPD elterjedtsége miatt érdemel figyelmet. A hasonló esetek diagnosztikájában nagy segítséget jelenthet a bemutatott korszerű képalkotó eljárás alkalmazása.
The amorphous to crystalline transition of ultrathin (Al,Mg)-oxide films grown by thermal oxidation of AlMg alloys: A high-resolution transmission electron microscopy investigation
Authors: Panda Emila , Jeurgens Lars P.H. , Richter Gunther , Mittemeijer Eric J.
Published: April 2010

The microstructural evolution of ultrathin (<3 nm) oxide films grown on bare Al-based AlMg alloy substrates, by thermal oxidation in the temperature range of 300 to 610 K and at partial oxygen pressures in the range 10−4–10−2 Pa, was investigated by high-resolution transmission electron microscopy. Angle-resolved x-ray photoelectron spectroscopy was applied to establish the chemical constitution of the analyzed oxide films (i.e., the overall Al/Mg cationic ratio, as well as the relative depth distributions of Al and Mg in the grown oxide films). The ˜0.8-nm-thick (Al,Mg)-oxide film grown at 300 K is fully amorphous. A gradual development of long-range order in the oxide film sets in for thickening (Al,Mg)-oxide films of relatively high Mg content at T ≥ 475 K. The amorphous-to-crystalline transition proceeds by a phase separation: still predominantly amorphous oxide regions exist next to crystallized oxide regions, which are constituted of an MgO-type of oxide phase with a face-centered-cubic oxygen sublattice and an average lattice parameter of 4.146 ± 0.1 Å.