bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of selective cyclooxygenase‐2 inhibitor‐induced small bowel injury: Randomized cross‐over study compared with loxoprofen in healthy subjects
Authors: Mizukami Kazuhiro , Murakami Kazunari , Yamauchi Mika , Matsunari Osamu , Ogawa Ryo , Nakagawa Yoshifumi , Okimoto Tadayoshi , Kodama Masaaki , Fujioka Toshio 
Published: September 2012

AimNon‐steroidal anti‐inflammatory drugs have the potential to injure the mucosa of the upper digestive tract and small bowel, whereas celecoxib (a selective cyclooxygenase‐2 inhibitor) has less influence on the entire digestive tract mucosa. The present study was conducted to compare the extents of small bowel mucosal injury induced by celecoxib and loxoprofen (the most frequently used non‐steroidal anti‐inflammatory drugs in Japan).MethodsTen healthy adult males were given celecoxib (200 mg/day, Group C) and loxoprofen (180 mg/day, Group L) in a cross‐over design for 14 days, and the influence of each drug on small bowel mucosa was evaluated by comparing pre‐ and post‐treatment capsule endoscopy findings. We measured the percentage of patients with small bowel mucosal injury following administration of these drugs as primary endpoint. Additionally, mean number of small bowel mucosal injuries per subject was analyzed as secondary endpoint.ResultsThe percentage of subjects experiencing small bowel mucosal injury as primary endpoint was 10% in Group C and 70% in Group L after treatment. This magnitude of the difference of between Group C and Group L was statistically significant (P = 0.031). The number of small bowel mucosal injuries as secondary endpoint differed significantly between the two groups, and the influence of celecoxib on small bowel injury was less than that of loxoprofen.ConclusionThese results indicate that celecoxib has less influence on small bowel mucosa than loxoprofen and can be used safely.
Statin use and the risk of biochemical recurrence of prostate cancer after definitive local therapy: a meta‐analysis of eight cohort studies
Authors: Scosyrev Emil , Tobis Scott , Donsky Heather , Wu Guan , Joseph Jean , Rashid Hani , Messing Edward 
Published: September 2012

What's known on the subject? and What does the study add?Over the last few years, several observational studies examined the association of statin use with the risk of biochemical recurrence of prostate cancer after definitive local therapy. The objective of our present study was to summarise available evidence on this subject using the method of meta‐analysis.Combined evidence from eight cohort studies did not definitively support the hypothesis that statins influence the risk of biochemical recurrence. However, there was considerable disagreement between individual studies in reported findings and conclusions.OBJECTIVE
To perform a systematic review and meta‐analysis of clinical studies with statin use as the exposure variable and biochemical recurrence after definitive local therapy for prostate cancer as the outcome.
METHODS
Relevant publications were identified through PubMed/Medline/Embase databases.
Pooled estimates of the hazard ratios (HRs) were computed using the inverse‐variance weighting approach.
Heterogeneity was assessed using the Cochran's Q test.
RESULTS
We identified a total of eight eligible studies, all based on the retrospective cohort design. Five of these were based on radical prostatectomy (RP) series and three on radiotherapy (RT) series.
There was evidence of heterogeneity in the entire set of eight studies (P= 0.002) as well as in the RP series (P= 0.05) and in the RT series (P= 0.01), when these were considered separately.
Based on the random effects inverse‐variance weighting approach, pooled estimates of the HRs for the risk of biochemical recurrence in statin users v non‐users were 0.91 (95% confidence interval [CI] 0.72–1.13) for the entire set of eight studies, 1.02 (95% CI 0.80–1.29) for the RP series and 0.71 (95% CI 0.44–1.16) for the RT series.
CONCLUSION
The pooled estimates of the HRs were not significantly different from the null value in this meta‐analysis; however, evidence of heterogeneity between the studies was present.
Phase I study of concurrent weekly docetaxel, high‐dose intensity‐modulated radiation therapy (IMRT) and androgen‐deprivation therapy (ADT) for high‐risk prostate cancer
Authors: Chen Ronald C. , Rosenman Julian G. , Hoffman Leroy G. , Chiu Wing‐Keung , Wang Andrew Z. , Pruthi Raj S. , Wallen Eric M. , Crane Jeffrey M. , Kim William Y. , Rathmell W. Kimryn , Godley Paul A. , Whang Young E. 
Published: September 2012

Study Type – Therapy (phase 1)Level of Evidence 2aWhat's known on the subject? and What does the study add?High‐risk and locally advanced prostate cancers are difficult to cure with the standard regimen of radiation therapy (RT) with concurrent androgen‐deprivation therapy (ADT). Multiple studies have explored the addition of docetaxel chemotherapy in attempt to improve patient outcomes. Prior Phase I studies have shown that docetaxel 20 mg/m2 is a safe dose, when given concurrently with 70 Gy of radiation. But current standard RT for prostate cancer uses higher doses, and it is unclear if concurrent chemotherapy is safe with modern RT.This is a Phase I study that explored the addition of concurrent docetaxel chemotherapy to modern RT (intensity‐modulated RT to 78 Gy) plus ADT. The study showed that weekly docetaxel at 20 mg/m2 is safe with modern RT. At a median follow‐up of 2.2 years, biochemical progression‐free survival was 94%. This triple‐therapy regimen is safe and promising for further evaluation in prospective trials.OBJECTIVE
To evaluate in a phase I trial, the feasibility of adding concurrent weekly docetaxel chemotherapy to high‐dose intensity modulated radiation therapy (IMRT) and androgen‐deprivation therapy (ADT) for treatment of high‐risk prostate cancer.
PATIENTS AND METHODS
Patients with high‐risk prostate cancer were treated with a luteinising hormone‐releasing hormone agonist (starting 2–3 months before IMRT and lasting 2 years), IMRT of 78 Gy to the prostate and seminal vesicles, and weekly docetaxel during RT.
All patients had computed tomography and bone scans to exclude metastatic disease.
A standard 3 + 3 design was used for docetaxel dose escalation. Successive patients were treated on dose levels of 10, 15, and 20 mg/m2 of weekly docetaxel.
RESULTS
In all, 18 patients participated in the study: 15 (83%) had Gleason 8–10 disease; the other three had either clinical T3 disease and/or a prostate‐specific antigen (PSA) level of >20 ng/mL.
Grade 3 diarrhoea (a defined dose‐limiting toxicity, DLT) occurred in one patient in each of the first two dose levels. However, when the cohorts were expanded, no further DLT was seen.
Weekly docetaxel at 20 mg/m2 (dose level 3) was successfully given without DLT.
No patient had grade 4 or 5 toxicity.
At a median follow‐up of 2.2 years, all patients achieved a PSA nadir of <1 ng/mL, including 13 patients who had an undetectable PSA level. The 2‐year biochemical progression‐free survival was 94%.
CONCLUSION
A dose of 20 mg/m2 of weekly docetaxel given concurrently with high‐dose IMRT and ADT appears safe for further study in patients with high‐risk prostate cancer.
Pathological findings after primary chemotherapy in patients undergoing simultaneous orchidectomy and retroperitoneal lymph node dissection for advanced germ cell tumours
Authors: Miller Rowan E. , Dudderidge Tim , Huddart Robert , Seckl Michael J. , Rustin Gordon J.S. , Christmas Timothy J. 
Published: September 2012

What's known on the subject? and What does the study add?Testicular cancer is a chemosensitive disease. Treatment with primary chemotherapy leads to eradication of metastatic disease and high cure rates. Completion orchidectomy is usually performed after primary chemotherapy with viable tumour and teratoma often identified in the orchidectomy specimen. The need for completion orchidectomy in patients with a complete response to systemic chemotherapy is uncertain.The present study confirms the discordance in pathology in patients undergoing simultaneous orchidectomy and retroperitoneal lymph node dissection (RPLND) after chemotherapy for metastatic disease. Viable tumour is frequently present in the testis despite tumour‐free RPLNs. These findings support the need for completion orchidectomy as part of the management for advanced testicular germ cell cancer.OBJECTIVE
To determine the differential response to systemic chemotherapy in patients undergoing simultaneous orchidectomy and retroperitoneal lymph node dissection (RPLND) after chemotherapy for metastatic testicular cancer.
PATIENTS AND METHODS
Patients who underwent simultaneous RPLND and orchidectomy after chemotherapy were identified from our clinical databases.
Postoperative pathological findings and patient characteristics were reviewed.
RESULTS
In all, 42 patients were identified.
After chemotherapy, necrosis, teratoma and cancer were identified in 25 (59.5%), 14 (33.3%) and three (7.1%) RPLN specimens and 15 (35.7%), 15 (35.7%) and 12 (28.6%) orchidectomy specimens respectively.
Of the 25 patients with necrotic RPLN specimens 12 (48.0%) had active disease within the orchidectomy specimen (eight invasive cancer and four mature teratoma).
The overall histological discordance rate was 38.1%. Findings in the orchidectomy specimens were more aggressive than those in the RPLN specimens (i.e. cancer worse than teratoma, which is worse than necrosis) in 33.3%.
CONCLUSIONS
There is significant disparity between orchidectomy and RPLND findings with viable tumour appearing frequently in the testis despite tumour‐free RPLNs.
These findings support completion orchidectomy as part of advanced testicular germ cell treatment.
Speculating on Slums: Infrastructural Fixes in Informal Housing in the Global South
Authors: Desai Vandana , Loftus Alex 
Published: September 2012

AbstractIn this paper, we seek to revisit earlier work on the theory of rent, situating it in the current period of economic crisis and in relation to informal housing in the global South. More than ever, land is treated as a pure financial asset. Finance capital now exerts a profound influence over the production of space and exposes the built environment to the kinds of speculative binges that we have witnessed over the last decade. This is now as much a feature of living conditions in the poorest settlements of the global South as it is in the financial heartlands of the global North. We question key assumptions behind development interventions by arguing that infrastructural upgrading may decrease the security of tenure of residents of informal housing and call for a more nuanced approach that recognises the (post)colonial histories of urbanisation structuring access to land and housing.
Identification of Effective Strategies to Promote Language in Deaf Children With Cochlear Implants
Authors: Cruz Ivette , Quittner Alexandra L. , Marker Craig , DesJardin Jean L. ,   CDaCI Investigative Team
Published: September 2012

Parental involvement and communication are essential for language development in young children. However, hearing parents of deaf children face challenges in providing language input to their children. This study utilized the largest national sample of deaf children receiving cochlear implants, with the aim of identifying effective facilitative language techniques. Ninety‐three deaf children (≤ 2 years) were assessed at 6 implant centers prior to and for 3 years following implantation. All parent–child interactions were videotaped, transcribed, and coded at each assessment. Analyses using bivariate latent difference score modeling indicated that higher versus lower level strategies predicted growth in expressive language and word types predicted growth in receptive language over time. These effective, higher level strategies could be used in early intervention programs.
Stigma, Ex-convicts and Labour Markets
Authors: Dominguez Alvarez Rocio , Loureiro Maria L. 
Published: September 2012

Abstract
Rasmusen (1996) has shown that inmates not only suffer public penalties but also economic and social stigma. In this article, we analyse the economic consequences of imprisonment which can be identified as lower wages and difficulty in re-entering the labour market. Analysing data from a German survey, we find that having been in prison reduces the probability of finding a job and that the total time sentenced to imprisonment reduces both labour market opportunities and earnings. The penalty is worst for those who have committed murder.
RNA interference‐mediated phosphodiesterase 4D splice variants knock‐down in the prefrontal cortex produces antidepressant‐like and cognition‐enhancing effects
Authors: Wang Zhen‐Zhen , Zhang Yi , Liu Yan‐Qin , Zhao Nan , Zhang You‐Zhi , Yuan Li , An Lei , Li Jing , Wang Xiao‐Yun , Qin Juan‐Juan , Wilson Steven P , O'Donnell James M , Zhang Han‐Ting , Li Yun‐Feng 
Published: September 2012

Background and PurposePhosphodiesterase 4 (PDE4) inhibitors produce potent antidepressant‐like and cognition‐enhancing effects. However, their clinical utility is limited by the major side effect of emesis, which appears to be PDE4 isoform‐specific. Although PDE4D subtype plays the pivotal role in these therapeutic profiles, it is also the primary subtype responsible for emesis. Therefore, the aim of present research was to investigate whether long‐form PDE4D variants mediate antidepressant‐like and cognition‐enhancing effects, but are irrespective with emesis.Experimental ApproachIn mice microinfused with lentiviral vectors that contained shRNA‐mir hairpin structure targeting long‐form PDE4Ds into bilateral prefrontal cortices, the tail‐suspension and forced‐swim tests were used to measure antidepressant‐like effects; novel object recognition and Morris water‐maze tasks were used to determine cognition‐enhancing effects. The emetic potential was assessed by alpha2 adrenergic receptor‐mediated anaesthesia, a surrogate measure of emesis. Intracellular cAMP signalling was analysed by time‐resolved FRET immunoassay and Western‐blot. Dendritic complexity was assessed by Golgi staining.Key ResultsMicroinfusions of lentiviral PDE4D‐shRNA down‐regulated PDE4D4 and PDE4D5, and imitated the antidepressant‐like and cognition‐enhancing effects of the prototypical PDE4 inhibitor rolipram. The behavioural effects were related to dendritic complexity and mediated by the increased cAMP signalling. In addition, these effects were not enhanced in the presence of rolipram. Finally, while rolipram shortened the duration of combined anaesthesia, RNA interference‐mediated PDE4D knock‐down in the prefrontal cortex did not.Conclusion and ImplicationsThese data suggest that long‐form PDE4Ds, at least PDE4D4 and PDE4D5, may be the promising targets for the development of PDE4 variant‐selective inhibitors as the new pharmacotherapies for depressive disorders and neurodegenerative diseases involving memory deficits.
Effects of ρ‐Da1a a peptidic α1A‐adrenoceptor antagonist in human isolated prostatic adenoma and anaesthetized rats
Authors: Palea S , Maiga A , Guilloteau V , Rekik M , Guérard M , Rouget C , Rischmann P , Botto H , Camparo P , Lluel P , Gilles N 
Published: September 2012

Background and Purposeρ‐Da1a, a 65 amino‐acid peptide, has subnanomolar affinity and high selectivity for the human α1A‐adrenoceptor subtype. The purpose of this study was to characterize the pharmacological effects of ρ‐Da1a on prostatic function, both in vivo and in vitro.Experimental Approachρ‐Da1a was tested as an antagonist of adrenaline‐induced effects on COS cells transfected with the human α1A‐adrenoceptor as well as on human isolated prostatic adenoma obtained from patients suffering from benign prostatic hyperplasia. Moreover, we compared the effects of ρ‐Da1a and tamsulosin on phenylephrine (PHE)‐induced increases in intra‐urethral (IUP) and arterial pressures (AP) in anaesthetized rats, following i.v. or p.o. administration.Key ResultsOn COS cells expressing human α1A‐adrenoceptors and on human prostatic strips, ρ‐Da1a inhibited adrenaline‐ and noradrenaline‐induced effects. In anaesthetized rats, ρ‐Da1a and tamsulosin administered i.v. 30 min before PHE significantly antagonized the effects of PHE on IUP. The pKB values for tamsulosin and ρ‐Da1a for this effect were similar. With regards to AP, ρ‐Da1a only reduced the effect of PHE on AP at the lowest dose tested (10 μg·kg−1), whereas tamsulosin significantly reduced PHE effects at doses between 10 and 150 μg·kg−1.Conclusions and Implicationsρ‐Da1a exhibited a relevant effect on IUP and a small effect on AP. In contrast, tamsulosin antagonized the effects of PHE on both IUP and AP. We conclude that ρ‐Da1a is more uroselective than tamsulosin. ρ‐Da1a is the most selective peptidic antagonist for α1A‐adenoceptors identified to date and could be a new treatment for various urological diseases.
Modulation of Kv7 potassium channels by a novel opener pyrazolo[1,5‐a]pyrimidin‐7(4H)‐one compound QO‐58
Authors: Zhang F , Mi Y , Qi JL , Li JW , Si M , Guan BC , Du XN , An HL , Zhang HL 
Published: September 2012

Background and PurposeModulation of Kv7/M channel function represents a relatively new strategy to treat neuronal excitability disorders such as epilepsy and neuropathic pain. We designed and synthesized a novel series of pyrazolo[1,5‐a] pyrimidin‐7(4H)‐one compounds, which activate Kv7 channels. Here, we characterized the effects of the lead compound, QO‐58, on Kv7 channels and investigated its mechanism of action.Experimental ApproachA perforated whole‐cell patch technique was used to record Kv7 currents expressed in mammalian cell lines and M‐type currents from rat dorsal root ganglion neurons. The effects of QO‐58 in a rat model of neuropathic pain, chronic constriction injury (CCI) of the sciatic nerve, were also examined.Key ResultsQO‐58 increased the current amplitudes, shifted the voltage‐dependent activation curve in a more negative direction and slowed the deactivation of Kv7.2/Kv7.3 currents. QO‐58 activated Kv7.1, Kv7.2, Kv7.4 and Kv7.3/Kv7.5 channels with a more selective effect on Kv7.2 and Kv7.4, but little effect on Kv7.3. The mechanism of QO‐58's activation of Kv7 channels was clearly distinct from that used by retigabine. A chain of amino acids, Val224Val225Tyr226, in Kv7.2 was important for QO‐58 activation of this channel. QO‐58 enhanced native neuronal M currents, resulting in depression of evoked action potentials. QO‐58 also elevated the pain threshold of neuropathic pain in the sciatic nerve CCI model.Conclusions and ImplicationsThe results indicate that QO‐58 is a potent modulator of Kv7 channels with a mechanism of action different from those of known Kv7 openers. Hence, QO‐58 shows potential as a treatment for diseases associated with neuronal hyperexcitability.
Association between Adverse Life Events and Addictive Behaviors among Male and Female Adolescents
Authors: Lee Grace P , Storr Carla L , Ialongo Nicholas S , Martins Silvia S 
Published: September 2012

Background: Adverse life events have been associated with gambling and substance use as they can serve as forms of escapism. Involvement in gambling and substance use can also place individuals in adversely stressful situations.Objectives: To explore potential male–female differences in the association between addictive behavior and adverse life events among an urban cohort of adolescents.Method: The study sample comprised of 515 adolescent participants in a randomized prevention trial. With self‐reported data, four addictive behavior groups were created: nonsubstance users and nongamblers, substance users only, gamblers only, and substance users and gamblers. Multinomial logistic regression analyses with interaction terms of sex and adverse life events were conducted.Results: Adverse life events and engaging in at least one addictive behavior were common for both sexes. Substance users and gamblers had more than twice the likelihood of nonsubstance users and nongamblers to experience any event as well as events of various domains (ie, relationship, violence, and instability). Neither relationship nor instability events’ associations with the co‐occurrence of substance use and gambling significantly differed between sexes. Conversely, females exposed to violence events were significantly more likely than similarly exposed males to report the co‐occurrence of substance use and gambling.Conclusion: Findings from the current study prompt future studies to devote more attention to the development of effective programs that teach adaptive coping strategies to adolescents, particularly to females upon exposure to violence. (Am J Addict 2012;21:516–523)
Effect of Specialty and Recent Experience on Perioperative Decision‐Making for Abdominal Aortic Aneurysm Repair
Authors: Dale William , Hemmerich Joshua , Moliski Elizabeth , Schwarze Margaret L. , Tung Avery 
Published: September 2012

ObjectivesTo determine whether recent experience and specialty choice would affect physician adherence to evidence‐based guidelines.DesignIn a series of computer‐simulated encounters, participants weighed the risk of spontaneous abdominal aortic aneurysm (AAA) rupture against the risk of perioperative death to determine timing for elective repair. Guideline recommendations and statistical information on the risks of rupture and surgical death were provided.SettingAnnual meetings of the American Geriatrics Society, American College of Surgeons, and American Society of Anesthesiologists.ParticipantsPhysicians.InterventionBefore the simulation, each participant was randomly exposed to one of three simulated outcomes: death during watchful waiting (WWD), perioperative death (PD), or successful outcome (SO).MeasurementsAdherence to recommended guidelines for AAA treatment.ResultsAgainst guideline recommendations, 67% of geriatricians, 74% of anesthesiologists, and 77% of surgeons chose surgery when the rupture risk was lower than the risk of perioperative death (P < .05). Surgeons exposed to the WWD experience chose surgery significantly earlier than if they were exposed to a PD or SO experience (P < .001). Anesthesiologist choices did not differ with recent experience.ConclusionGeriatrician decisions more closely followed guideline recommendations for AAA management than those of two other specialties typically involved in AAA care. A prior WWD affected surgeons most, geriatricians next, and anesthesiologists least. Geriatricians referring patients for AAA surgery should be aware of specialty‐specific differences in perioperative decision behavior.