bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biomarkers in pulmonary hypertension
Authors: Warwick G. , Thomas P. S. , Yates D. H. 
Published: July 2008

There have been significant recent advances in the understanding of the pathophysiology of pulmonary hypertension, and a growing number of therapeutic agents have become available to the treating physician. Traditional methods of diagnosing and monitoring this condition have comprised echocardiography and right heart catheterisation, in addition to functional measures, such as estimation of functional class and the 6-min walk test. An increasing number of biomarkers have been described that are elevated in pulmonary hypertension and which may assist the clinician in diagnosis and in the assessment of disease severity and response to treatment.The present article details the more important biomarkers, their potential applications and the evidence supporting their use.
The plant Apolipoprotein D ortholog protects Arabidopsis against oxidative stress
Authors: Charron Jean-Benoit F , Ouellet Francois , Houde Mario , Sarhan Fathey 
Published: July 2008

Abstract

Background
Lipocalins are a large and diverse family of small, mostly extracellular proteins implicated in many important functions. This family has been studied in bacteria, invertebrate and vertebrate animals but little is known about these proteins in plants. We recently reported the identification and molecular characterization of the first true lipocalins from plants, including the Apolipoprotein D ortholog AtTIL identified in the plant model Arabidopsis thaliana. This study aimed to determine its physiological role in planta.

Results
Our results demonstrate that the AtTIL lipocalin is involved in modulating tolerance to oxidative stress. AtTIL knock-out plants are very sensitive to sudden drops in temperature and paraquat treatment, and dark-grown plants die shortly after transfer to light. These plants accumulate a high level of hydrogen peroxide and other ROS, which causes an oxidative stress that is associated with a reduction in hypocotyl growth and sensitivity to light. Complementation of the knock-out plants with the AtTIL cDNA restores the normal phenotype. On the other hand, overexpression enhances tolerance to stress caused by freezing, paraquat and light. Moreover, this overexpression delays flowering and maintains leaf greenness. Microarray analyses identified several differentially-regulated genes encoding components of oxidative stress and energy balance.

Conclusion
This study provides the first functional evidence that a plant lipocalin is involved in modulating tolerance to oxidative stress. These findings are in agreement with recently published data showing that overexpression of ApoD enhances tolerance to oxidative stress and increases life span in mice and Drosophila. Together, the three papers strongly support a similar function of lipocalins in these evolutionary-distant species.
Study Protocol – Metabolic syndrome, vitamin D and bone status in South Asian women living in Auckland, New Zealand: A randomised, placebo-controlled, double-blind vitamin D intervention
Authors: von Hurst Pamela R , Stonehouse Welma , Matthys Christophe , Conlon Cathryn , Kruger Marlena C , Coad Jane 
Published: July 2008

AbstractBackgroundThe identification of the vitamin D receptor in the endocrine pancreas suggests a role for vitamin D in insulin secretion. There is also some limited evidence that vitamin D influences insulin resistance, and thus the early stages of the development of type 2 diabetes.MethodsEighty-four women of South Asian origin, living in Auckland, New Zealand, were randomised to receive either a supplement (4000IU 25(OH)D3per day) or a placebo for 6 months. At baseline, all participants were vitamin D deficient (serum 25(OH)D3<50 nmol/L), insulin resistant (HOMA-IR > 1.93) and/or hyperinsulinaemic, hyperglycemic or had clinical signs of dislipidaemia. Changes in HOMA-IR, lipids, parathyroid hormone, calcium and bone markers were monitored at 3 months and 6 months.DiscussionThis randomised, controlled trial will be the first to investigate the effect of vitamin D supplementation on insulin resistance in non-diabetic subjects. It will subsequently contribute to the growing body of evidence about the role of vitamin D in metabolic syndrome.Registered clinical.Trial registrationRegistered clinical trial – Registration No. ACTRN12607000642482
Weight loss and brown adipose tissue reduction in rat model of sleep apnea
Authors: Martinez Denis , Vasconcellos Luiz FT , de Oliveira Patricia G , Konrad Signorá P 
Published: July 2008

Abstract

Background -
Obesity is related to obstructive sleep apnea-hypopnea syndrome (OSAHS), but its roles in OSAHS as cause or consequence are not fully clarified. Isocapnic intermittent hypoxia (IIH) is a model of OSAHS. We verified the effect of IIH on body weight and brown adipose tissue (BAT) of Wistar rats.

Methods
Nine-month-old male breeders Wistar rats of two groups were studied: 8 rats submitted to IIH and 5 control rats submitted to sham IIH. The rats were weighed at the baseline and at the end of three weeks, after being placed in the IIH apparatus seven days per week, eight hours a day, in the lights on period, simulating an apnea index of 30/hour. After experimental period, the animals were weighed and measured as well as the BAT, abdominal, perirenal, and epididymal fat, the heart, and the gastrocnemius muscle.

Results
Body weight of the hypoxia group decreased 17 ± 7 grams, significantly different from the variation observed in the control group (p = 0,001). The BAT was 15% lighter in the hypoxia group and reached marginally the alpha error probability (p = 0.054).

Conclusion
Our preliminary results justify a larger study for a longer time in order to confirm the effect of isocapnic intermittent hypoxia on body weight and BAT.
Cutaneous Nociception Evoked by 15-delta PGJ2 via Activation of Ion Channel TRPA1
Authors: Cruz-Orengo Lillian , Dhaka Ajay , Heuermann Robert J , Young Timothy J , Montana Michael C , Cavanaugh Eric J , Kim Donghee , Story Gina M 
Published: July 2008

Background: A number of prostaglandins (PGs) sensitize dorsal root ganglion (DRG) neurons and contribute to inflammatory hyperalgesia by signaling through specific G protein-coupled receptors (GPCRs). One mechanism whereby PGs sensitize these neurons is through modulation of “thermoTRPs,” a subset of ion channels activated by temperature belonging to the Transient Receptor Potential ion channel superfamily. Acrid, electrophilic chemicals including cinnamaldehyde (CA) and allyl isothiocyanate (AITC), derivatives of cinnamon and mustard oil respectively, activate thermoTRP member TRPA1 via direct modification of channel cysteine residues. Results: Our search for endogenous chemical activators utilizing a bioactive lipid library screen identified a cyclopentane PGD2 metabolite, 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), as a TRPA1 agonist. Similar to CA and AITC, this electrophilic molecule is known to modify cysteines of cellular target proteins. Electophysiological recordings verified that 15d-PGJ2 specifically activates TRPA1 and not TRPV1 or TRPM8 (thermoTRPs also enriched in DRG). Accordingly, we identified a population of mouse DRG neurons responsive to 15d-PGJ2 and AITC that is absent in cultures derived from TRPA1 knockout mice. The irritant molecules that activate TRPA1 evoke nociceptive responses. However, 15d-PGJ2 has not been correlated with painful sensations; rather, it is considered to mediate anti-inflammatory processes via binding to the nuclear peroxisome proliferator-activated receptor gamma (PPARγ). Our in vivo studies revealed that 15d-PGJ2 induced acute nociceptive responses when administered cutaneously. Moreover, mice deficient in the TRPA1 channel failed to exhibit such behaviors. Conclusion: In conclusion, we show that 15d-PGJ2 induces acute nociception when administered cutaneously and does so via a TRPA1-specific mechanism.
Predicting suicide attempts in young adults with histories of childhood abuse
Authors: Brezo Jelena , Paris Joel , Vitaro Frank , Hébert Martine , Tremblay Richard E. , Turecki Gustavo 
Published: July 2008

BackgroundAlthough childhood abuse is an important correlate of suicidality, not all individuals who were abused as children attempt suicide.AimsTo identify correlates and moderators of suicide attempts in adults reporting childhood physical abuse, contact sexual abuse, or both.MethodA French-Canadian, school-based cohort (n=1684) was prospectively followed.ResultsThe identity of the abuser moderated the relationship of abuse frequency and suicide attempts, with individuals abused by their immediate family being at highest risk. Although paternal education exhibited negative associations (OR=0.71, 95% CI 0.58–0.88), several externalising phenotypes had positive associations with suicide attempts: disruptive disorders (OR=3.10, 95% CI 1.05–9.15), conduct problems (OR=1.09, 95% CI 1.01–1.19) and childhood aggression (OR=1.41, 95% CI 1.08–1.83).ConclusionsCharacteristics of the abuser and abusive acts may be important additional indicators of risk for suicide attempts. Future research needs to employ developmental approaches to examine the extent and mechanisms by which childhood abuse contributes to the shared variance of suicidality, maladaptive traits and psychopathology.
Abnormal anterior cingulum integrity in bipolar disorder determined through diffusion tensor imaging
Authors: Wang Fei , Jackowski Marcel , Kalmar Jessica H. , Chepenik Lara G. , Tie Karen , Qiu Maolin , Gong Gaolang , Pittman Brian P. , Jones Monique M. , Shah Maulik P. , Spencer Linda , Papademetris Xenophon , Constable R. Todd , Blumberg Hilary P. 
Published: July 2008

BackgroundConvergent evidence implicates white matter abnormalities in bipolar disorder. The cingulum is an important candidate structure for study in bipolar disorder as it provides substantial white matter connections within the corticolimbic neural system that subserves emotional regulation involved in the disorder.AimsTo test the hypothesis that bipolar disorder is associated with abnormal white matter integrity in the cingulum.MethodFractional anisotropy in the anterior and posterior cingulum was compared between 42 participants with bipolar disorder and 42 healthy participants using diffusion tensor imaging.ResultsFractional anisotropy was significantly decreased in the anterior cingulum in the bipolar disorder group compared with the healthy group (P=0.003); however, fractional anisotropy in the posterior cingulum did not differ significantly between groups.ConclusionsOur findings demonstrate abnormalities in the structural integrity of the anterior cingulum in bipolar disorder. They extend evidence that supports involvement of the neural system comprising the anterior cingulate cortex and its corticolimbic gray matter connection sites in bipolar disorder to implicate abnormalities in the white matter connections within the system provided by the cingulum.
Lithium and eGFR: A new routinely available tool for the prevention of chronic kidney disease
Authors: Morriss Richard , Benjamin Benson 
Published: July 2008

SummaryThe National Strategic Framework for Renal Services introduced the routine reporting of estimated glomerular filtration rates (eGFR) on serum urea and electrolyte tests. Estimated glomerular filtration rates might reduce renal failure induced by lithium and cardiovascular mortality but there are many false positives. We propose how eGFR might be used in lithium monitoring.
Differences in psychological effects in hospital doctors with and without post-traumatic stress disorder
Authors: Einav Sharon , Shalev Arieh Y. , Ofek Hadas , Freedman Sara , Matot Idit , Weiniger Carolyn F. 
Published: July 2008

SummaryPost-traumatic stress disorder (PTSD) can reduce performance. The association between PTSD and other psychopathologies among hospital doctors was examined using self-report questionnaires during a wave of suicide bombing in Jerusalem. Thirty-three doctors with PTSD symptoms and 155 without were compared on coping, burnout and acceptance of treatment. Doctors with PTSD symptoms demonstrated significantly more anxiety, depression, negative coping strategies and burnout. Hospital doctors who develop PTSD symptoms suffer greater burnout and manifest negative coping strategies but are reluctant to receive treatment.
Providing a liaison psychiatry service in the absence of a consultant liaison psychiatrist
Authors: Flahavan Claire , Flahavan Claire 
Published: July 2008

Aims and MethodLiaison psychiatry services in Ireland are currently unequally distributed. In the absence of a specialist liaison psychiatry team, general adult psychiatrists may provide a consultation service to their local hospital. Demographic and clinical characteristics pertaining to all psychiatric consultations at the Louth County Hospital were collected over 12 months to examine one such local service and to highlight the challenges of this mode of service delivery.ResultsA total of 232 consults were audited. the most frequent reasons for referral were assessment following deliberate self-harm (38%), affective symptoms (28%) and alcohol or substance misuse (25%). This differs from documented referral patterns to specialist liaison teams. Referring physicians had a low diagnostic ‘hit-rate’ with respect to affective disorders. Difficulties in service provision included poor communication by referring teams and time constraints due to other sectoral commitments.Clinical ImplicationsRefinements to service delivery may be beneficial in managing the workload more effectively. Priority should be placed on fostering communication with non-psychiatric colleagues.
Nurse-led liaison psychiatry service for older adults: service evaluation
Authors: Anderson Daniel , Cattell Howard , Bentley Elaine 
Published: July 2008

Aims and MethodTo comprehensively describe a nurse-led consultation liaison service for older adults by retrospectively reviewing all referrals received in 2006 and comparing them against other services and benchmark reports.ResultsOf the 298 individuals referred to psychiatric services from other hospital wards, 120 were aged 85–94 years old (40%), 193 were male (65%) and 152 were referred from geriatrics (51%). A majority of 204 have not had previous contact with psychiatric services (69%). the most common diagnosis was dementia (33%, n=88), with 27% individuals (n=65) being referred onwards to secondary care.Clinical ImplicationsThis nurse-led service, using a novel approach of a support worker providing further community support, functions well compared with traditional consultation models. It helps identify many individuals with dementia and engages them into community psychiatric services.
Quality of Life in Patients With Metastatic Renal Cell Carcinoma Treated With Sunitinib or Interferon Alfa: Results From a Phase III Randomized Trial
Authors: Cella David , Li Jim Z. , Cappelleri Joseph C. , Bushmakin Andrew , Charbonneau Claudie , Kim Sindy T. , Chen Isan , Motzer Robert J. 
Published: July 2008

PurposeIn an international, randomized phase III trial, sunitinib demonstrated statistically significant efficacy over interferon alfa (IFN-α) as first-line therapy in patients with metastatic renal cell carcinoma (mRCC) (progression-free survival time, 11 v 5 months, respectively; P < .001; objective response rate, 31% v 6%, respectively; P < .001). We report health-related quality-of-life (QOL) results from this trial.Patients and MethodsSeven hundred fifty mRCC patients were randomly assigned to sunitinib (6-week cycles: 50 mg orally once daily for 4 weeks, followed by 2 weeks off) or IFN-α (9 million units subcutaneous injections, three times weekly). QOL measures included the Functional Assessment of Cancer Therapy–General (FACT-G), the FACT-Kidney Symptom Index–15 item (FKSI-15), and the EuroQoL-5D's utility score (EQ-5D Index) and its visual analog scale (EQ-VAS). The primary QOL end point was the FKSI Disease-Related Symptoms (FKSI-DRS) subscale. Higher scores indicated better outcomes (better QOL or fewer symptoms). Data were analyzed for the intent-to-treat population using mixed-effects models, supplemented with pattern-mixture models.ResultsPatients receiving sunitinib reported higher FKSI-15 and FKSI-DRS scores at each cycle than those receiving IFN-α, with a significant difference in the overall least squares means (3.27 and 1.98, respectively; P < .0001). Similarly, differences in least squares means for FACT-G (and all subscales), EQ-5D Index, and EQ-VAS were all significantly favorable for sunitinib (P < .01). Per pre-established thresholds, between-treatment differences in the mean scores were clinically meaningful after cycle 4 for FKSI-DRS and at all assessments for FKSI-15, FACT-G, and the FACT-G functional well-being subscale.ConclusionSunitinib provides superior QOL compared with IFN-α in mRCC patients.
Phase II Stopping Rules That Employ Response Rates and Early Progression
Authors: Goffin John R. , Tu Dongsheng 
Published: July 2008

Purpose Phase II oncology trials traditionally have used response rate (RR) as the primary end point, but newer targeted agents require the consideration of alternative end points. High rates of early progressive disease (EPD) suggest inadequate drug activity and may be useful in the early stopping of trials. This study used a simulation to define a set of rules to assess a combined end point of RR and EPD. Methods The simulation assumed a two-stage trial with a specified α error and power. It randomly generated the true response rate, r, of the agent under study and its true rate of early progressive disease, epd, for each run of the simulation. Two pairs of parameters were specified: (rnul, epdnul) and (ralt, epdalt). A drug was considered uninteresting for further development if r was less than or equal to rnul and epd was greater than or equal to epdnul (ie, the null hypothesis) and interesting for further development if r was greater than or equal to ralt or epd was less than or equal to epdalt (ie, the alternate hypotheses). Thresholds for the required number of patients with responses, nr and EPD, np, were generated for each set of parameters. Results Thresholds for nr and np that satisfied the specified error rates were generated. There was at least an 89% likelihood that a study would be stopped at the first stage of accrual if r and epd were uninteresting. Conclusion The simulation was able to establish stopping rules by combining the RR and the EPD that achieved the desired error rates. High rates of early stopping suggest that this design could shorten phase II trials of inactive agents.
Survival End Point Reporting in Randomized Cancer Clinical Trials: A Review of Major Journals
Authors: Mathoulin-Pelissier Simone , Gourgou-Bourgade Sophie , Bonnetain Franck , Kramar Andrew 
Published: July 2008

Purpose Several publications showed that the standards for reporting randomized clinical trials (RCTs) might not be entirely suitable. Our aim was to evaluate the reporting of survival end points in cancer RCTs. Methods A search in MEDLINE databases identified 274 cancer RCTs published in 2004 in four general medical journals and four clinical oncology journals. Eligible articles were those that reported primary analyses of RCT with survival end points. Methodologists reviewed and scored the articles according to seven key points: prevalence of complete definition of survival end points (time of origin, survival events, censoring events) and relevant information about their analyses (estimation or effect size, precision, number of events, patients at risk). Concordance of key points was evaluated from a random subsample. Results After screening, 125 articles were selected; 104 trials were phase III (83%) and 98 publications (78%) were obtained from oncology journals. Among these RCTs, a total of 267 survival end points were recorded, and overall survival (OS) was the most frequent outcome (118 terms, 44%). Survival terms were totally defined for 113 end points (42%) in 65 articles (52%). Accurate information about analysis was retrieved for 73 end points (27%) in 40 articles (32%). The less well-defined information was the number of patients at risk (55%). The reliability was good (κ = 0.72). Finally, according to the key points, optimal reporting was found in 33 end points (12%) or 10 publications. Conclusion A majority of articles failed to provide a complete reporting of survival end points, thus adding another source of uncontrolled variability.
Clinical Importance of Estrogen Receptor-β Evaluation in Breast Cancer Patients Treated With Adjuvant Tamoxifen Therapy
Authors: Honma Naoko , Horii Rie , Iwase Takuji , Saji Shigehira , Younes Mamoun , Takubo Kaiyo , Matsuura Masaaki , Ito Yoshinori , Akiyama Futoshi , Sakamoto Goi 
Published: July 2008

Purpose The clinicopathologic importance of a second estrogen receptor (ER), ER-β, in breast cancers has been intensely studied; however, there is still no real consensus regarding the clinical utility of an ER-β assay, probably because of the lack of standardized methodology, the presence of several ER-β isotypes (ER-β1-5, and so on), and, more importantly, the lack of convincing data on whether the ER-β status provides clinically useful information over what is already provided by the traditional ER-α/progesterone receptor (PR) assay. A large and systematic study is needed to address these important issues. Patients and Methods Archival materials of 442 invasive breast cancers from women treated with adjuvant tamoxifen monotherapy and with a long follow-up period (median, 11.1 years) were subjected to immunohistochemical study using three commercially available anti–ER-β antibodies that detect ER-β1-3 (ER-βN), ER-β1, and ER-βcx (ER-β2). Results Positive staining for ER-βN or ER-β1 was associated with significantly better survival. By contrast, ER-βcx status did not influence survival. In multivariate analysis, ER-β1 status emerged as an independent predictor of recurrence and mortality. ER-β1 status was significantly associated with survival in postmenopausal, but not premenopausal, women. Importantly, ER-β1 positivity was associated with significantly better survival in patients with ER-α–negative/PR-negative or ER-α–negative/PR–negative/human epidermal growth factor receptor 2–negative (triple-negative) tumors, which are widely believed to be hormone unresponsive, have poor prognosis, and require chemotherapy. Conclusion Immunohistochemical examination of ER-β1 in addition to ER-α and PR is clinically important in patients with breast cancer treated with tamoxifen monotherapy. Further studies are needed to confirm our findings.