bluuebunny/crossref_metadata_2025 huggingface dataset:
Predicting early mortality in acute exacerbation of chronic obstructive pulmonary disease using the CURB65 score
Authors: CHANG Catherina L. , SULLIVAN Glenda D. , KARALUS Noel C. , MILLS Graham D. , MCLACHLAN John D. , HANCOX Robert J.
Published: September 2010

Background and Objective:  Hospitalization for exacerbation of COPD is associated with a high risk of mortality. A risk‐prediction model using information easily obtained on admission could help to identify high‐risk individuals. The CURB65 score was developed to predict mortality risk in community acquired pneumonia. A retrospective study found that this score was also associated with mortality in COPD exacerbations. We conducted a prospective study to assess the utility of the CURB65 score in acute COPD exacerbations.

Methods:  Consecutive patients with physician diagnosed COPD exacerbations admitted to a public hospital during a 1‐year period were studied prospectively. The CURB65 scores were calculated from information obtained at initial hospital presentation. CURB65 = one point each for Confusion, Urea > 7 mmol/L, Respiratory rate ≥ 30/min, low Blood pressure, age ≥ 65 years.

Results:  30‐day mortality data were available for 249 of 252 patients. CURB65 scores on admission significantly predicted risk of death during the hospital admission and at 30 days. The 30‐day mortality by score groups were: low risk (scores 0–1) 2.0% (2/98), moderate risk (score 2) 6.7% (6/90) and high risk (scores 3–5) 21.3% (13/61). CURB65 scores were not predictive of 1‐year mortality.

Conclusions:  A simple 6‐point score based on confusion, blood urea, respiratory rate, blood pressure and age can be used to stratify patients with COPD exacerbation into different management groups. The CURB65 score was as effective in predicting early mortality in our cohort of acute COPD exacerbations as it was in previous cohorts with community acquired pneumonia. Our findings suggest that CURB65 scores can help clinicians to assess patients with exacerbation of COPD.
Effects of adding salmeterol/fluticasone propionate to tiotropium on airway dimensions in patients with chronic obstructive pulmonary disease
Authors: HOSHINO Makoto , OHTAWA Junichi
Published: September 2010

Background and objective:  Although salmeterol/fluticasone propionate combination (SFC) therapy has been widely used for the treatment of COPD, the relationship between airway dimensions and improvement in pulmonary function remains unknown. The aim of this study was to compare the effects of SFC in combination with tiotropium (Tio) and Tio alone, on airway dimensions and pulmonary function in COPD patients.

Methods:  Thirty COPD patients were randomized to receive inhaled Tio (18 µg once daily) or inhaled SFC (50/250 µg twice daily) plus Tio for 12 weeks. Spirometry and CT were performed, and the St. George's Respiratory Questionnaire (SGRQ) was completed, before and after the trial. Airway dimensions were assessed by a validated CT technique, and airway wall area (WA) corrected for body surface area (BSA), percentage wall area (WA%), absolute wall thickness (T)/√BSA, and luminal area (Ai)/BSA at the right apical segmental bronchus, were measured.

Results:  Treatment with SFC plus Tio significantly decreased WA/BSA (P < 0.05), WA% (P < 0.01) and T/√BSA (P < 0.01), and increased Ai/BSA (P < 0.01), whereas treatment with Tio alone had no effect. The changes in WA/BSA and Ai/BSA were significantly correlated with increases in FEV1 (r = 0.48, P < 0.05, and r = 0.36, P < 0.05, respectively). There were significant improvements in SGRQ scores after treatment with SFC plus Tio.

Conclusions:  Airway wall thickening and airway narrowing decreased after treatment with SFC plus Tio, and the changes in airway dimensions were proportional to the improvements in FEV1. These results suggest that SFC plus Tio is more effective than Tio alone in the management of COPD patients.
Comparison of 21‐gauge and 22‐gauge aspiration needle during endobronchial ultrasound‐guided transbronchial needle aspiration
Authors: NAKAJIMA Takahiro , YASUFUKU Kazuhiro , TAKAHASHI Ryo , SHINGYOJI Masato , HIRATA Tetsushi , ITAMI Makiko , MATSUI Yukiko , ITAKURA Meiji , IIZASA Toshihiko , KIMURA Hideki
Published: September 2010

Background and objective:  Endobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA) has typically been performed using the 22gauge (G) dedicated TBNA needle. Recently a new 21G TBNA needle has been introduced. The efficacy of using a larger gauge biopsy needle during EBUS‐TBNA has not been reported. The purpose of this study was to compare the diagnostic yield and utility of 21G and 22G needles during EBUS‐TBNA.

Methods:  EBUS‐TBNA was performed using both 21G and 22G needles. Cytological and histological findings were recorded for each samples obtained by an independent cytologist and pathologist. The cellularity and blood contamination were evaluated in the cytological samples. The quality of the histological core was evaluated by the amount of blood clots versus the actual tissue. Each factor was compared within two slides from the two different size needles. The diagnostic yield and the differences of the cytology and histology were analysed.

Results:  The evaluation of 45 lesions by EBUS‐TBNA revealed that tumour cells were equally detected by both 21G and 22G needles. Two patients of adenocarcinoma were histologically diagnosed only by the 21G needle. Although histological structure was better preserved in five lesions collected by the 21G needle, there was more blood contamination with the 21G needle (P < 0.0001).

Conclusions:  There were no differences in the diagnostic yield between the 21G and 22G needles during EBUS‐TBNA. The preserved histological structure of the samples obtained by the 21G needle may be useful for the diagnosis of mediastinal and hilar adenopathy of unknown aetiology which may be a challenge with the 22G needle.
Effect of HIV‐1 infection and increasing immunosuppression on menstrual function
Authors: Ezechi Oliver C. , Jogo Andrea , Gab‐Okafor Chidinma , Onwujekwe Dan I. , Ezeobi Paschal M. , Gbajabiamila Titi , Adu Rosemary A. , Audu Rosemary A. , Musa Adesola Z. , Salu Olumuyiwa B. , Meschack Emily , Herbertson Ebiere , Odunukwe Nkiru , Idigbe Oni E.
Published: September 2010

Aim:  The aim of this study was to determine the prevalence, pattern and determinants of menstrual abnormalities in HIV‐positive Nigerian women.

Methods:  A cross‐sectional study was carried out involving 3473 (2549 HIV‐seropositive and 924 seronegative) consecutive and consenting women seen at the HIV treatment centers at the Nigerian Institute of Medical Research, Lagos and the Federal Medical Centre, Markurdi.

Results:  The sociodemographic characteristics of the two groups were comparable, except for body mass index (BMI): the HIV‐negative women (28.1 ± 8.1) had statistically significantly (P < 0.005) higher BMI compared to the HIV‐positive women (21.9 ± 7.5).

Menstrual abnormalities were significantly more common in women living with HIV/AIDS (29.1%) compared to the HIV‐negative (18.9%) women (P < 0.001). The proportions of women in the two groups with intermenstrual bleeding, menorrhagia, hypermenorrhea, and postcoital bleeding were similar (P > 0.005), however amenorrhea, oligomenorrhea, irregular periods and secondary dysmenorrhea were more common in the HIV‐positive women (P < 0.02). Primary dysmenorrhea was less common in HIV‐positive women (P < 0.03). Among the HIV‐positive women, menstrual dysfunction was more common in women living with HIV/AIDS with opportunistic infections, CD4 count < 200, not undertaking therapy, symptomatic disease and BMI < 20. However, after controlling for cofounders, only CD4 < 200 (odds ratio [OR], 3.65; 95% confidence interval [CI], 1.2–9.7), BMI < 20 (OR, 2.4; 95%CI, 1.3–3.5) and not taking antiretroviral drugs (OR, 2.05; CI, 1.7–6.5) were associated with amenorrhea, oligomenorrhea, irregular periods and secondary dysmenorrhea.

Conclusion:  HIV‐positive women in this study experienced more menstrual abnormalities of amenorrhea, oligomenorrhea, and irregular periods compared to the HIV‐negative controls. HIV‐positive women with CD4 count < 200, BMI < 20 and who do not take antiretroviral drugs are at the greatest risk.
Ruptured ovarian endodermal sinus tumor diagnosed during pregnancy: Case report and review of the literature
Authors: Benjapibal Mongkol , Chaopotong Pattama , Leelaphatanadit Chairatana , Jaishuen Atthapon
Published: September 2010

Pregnancy complicated by endodermal sinus tumor of the ovary is a very rare event. We present a case report of a pregnant woman with a ruptured primary endodermal sinus tumor of the ovary that was diagnosed at 13 weeks of gestation. After right salpingo‐oophorectomy had been performed the patient received four cycles of combination chemotherapy (bleomycin, etoposide, and cisplatin) starting at the 15th week of pregnancy. The patient did not have any evidence of tumor recurrence for 23 months. Her baby did not have any evidence of malformations and showed normal growth and development at 21 months of follow up.
Preoperative transvaginal ultrasound guided needle biopsy for primary squamous cell carcinoma of the endometrium
Authors: Kashima Katsunori , Iwasaki Chikako , Yahata Tetsuro , Tanaka Kenichi
Published: September 2010

Primary squamous cell carcinoma of the endometrium (PSCCE) is an extremely rare tumor and little information is available about its treatment and prognosis. We report a case of PSCCE diagnosed with preoperative transvaginal ultrasound guided needle biopsy. A 73‐year‐old woman presented with prolonged abdominal pain. Her endometrium was found to be slightly thickened, and endometrial biopsy showed no carcinoma tissues. Magnetic resonance imaging (MRI) demonstrated a uterine tumor and transvaginal ultrasound guided needle biopsy specimens of the tumor showed squamous cell carcinoma. The patient underwent laparotomy and was given a diagnosis of PSCCE in International Federation of Gynecology and Obstetrics (FIGO) stage IIIa. After the operation, the patient was treated with concurrent chemoradiation therapy (CCRT) using cisplatin. She remains free of disease at 6 months after CCRT. Preoperative needle biopsy may be helpful to make a diagnosis of PSCCE.
Recurrent cervical cancer presented with lymphangitic carcinomatosis
Authors: Baiocchi Glauco , Neto Renato Cagnacci , Fukazawa Elza Mieko , Faloppa Carlos Chaves , Avertano‐Rocha Antonio Bomfim , Begnami Maria Dirlei
Published: September 2010

Lymphangitic carcinomatosis of the lungs secondary to cervical cancer is a rare condition. It still has an unknown pathophysiology and is related to high mortality rates. Diagnosis is often delayed due to the common symptoms of nonproductive cough and dyspnea. There are only 10 cases described in the literature. Most of the reported cases received only supportive care due to low performance status. Only three reported patients received palliative chemotherapy. We describe a case that has successfully received platinum‐based chemotherapy.
Alterations of CXCR4 function in μ‐opioid receptor‐deficient glia
Authors: Burbassi Silvia , Sengupta Rajarshi , Meucci Olimpia
Published: September 2010

The chemokine receptor CXCR4 and the μ‐opioid receptor (MOR) are G‐protein‐coupled receptors that are essential for normal function of the nervous and immune systems. Several studies have suggested that MOR is a key regulator of CXCR4 in the brain; however, the molecular basis of the opioid–chemokine interaction is not fully understood, and it may involve different mechanisms in neuronal and glial cells. Our previous studies demonstrated that MOR stimulation specifically upregulates the protein ferritin heavy chain – an inhibitor of CXCR4 – in neurons, and suggested that additional mechanisms could be operative in glia. In this study, we investigated CXCR4 function in brains and astroglial cultures deprived of MOR. Reduced coupling of CXCR4 to G‐proteins was found in brain slices and tissue homogenates of MOR−/− mice as compared with wild‐type controls. CXCR4‐induced signaling was also reduced in glial cultures from MOR−/− mice, as shown by analysis of CXCR4 downstream targets (Akt and ERK1/2). Pharmacological studies with δ‐opioid receptor (DOR)‐specific ligands suggested that DOR–CXCR4 interactions are implicated in the inhibition of CXCR4 in MOR‐deficient cells both in vitro and in vivo. Moreover, increased CXCR4/DOR co‐immunoprecipitation was found in brain tissue and cultured glia from MOR−/− mice. Importantly, CXCR4 function was restored by pretreatment with a DOR antagonist. Overall, these findings indicate that DOR plays a crucial role in the regulation of CXCR4 in glia, probably via silent receptor heterodimers. The data also suggest that the opiate system interferes with normal CXCR4 function in different ways, depending on receptor subtypes.
Amygdala, deep cerebellar nuclei and red nucleus contribute to delay eyeblink conditioning in C57BL /6 mice
Authors: Sakamoto Toshiro , Endo Shogo
Published: September 2010

That the cerebellum plays an essential role in delay eyeblink conditioning is well established in the rabbit, but not in the mouse. To elucidate the critical brain structures involved in delay eyeblink conditioning in mice, we examined the roles of the deep cerebellar nuclei (DCN), the amygdala and the red nucleus (RN) through the use of electrolytic lesions and reversible inactivation. All mice received eyeblink training of 50 trials during a daily session in the higher‐intensity conditioned stimulus (CS) condition (10 kHz, 70 dB). DCN lesions caused severe ataxia; nonetheless, the mice acquired conditioned responses (CRs). Reversible inactivation of DCN, by muscimol (MSC) injection, led to a severe CR impairment in the early sessions of conditioning; however, in later sessions, the mice acquired CRs. Amygdala lesions impaired the acquisition of CRs, which did not reach the level of sham‐operated mice, even after prolonged training sessions. MSC injections into the lateral amygdala severely impaired CRs, which began to recover after the removal of MSC. RN inactivation with MSC completely abolished CRs, and removal of MSC immediately restored CRs to the level of control mice. The results indicate that: (i) the DCN are important, but not essential, at least for the late acquisition in mouse eyeblink conditioning; (ii) the amygdala plays an important role in the acquisition and expression of CRs; and (iii) the RN is essential for the expression of CRs. Our findings reveal the various brain areas critically involved in mouse eyeblink conditioning, which include the cerebellum, amygdala and RN.
A mutation in dnaK causes stabilization of the heat shock sigma factor σ32, accumulation of heat shock proteins and increase in toluene‐resistance in Pseudomonas putida
Authors: Kobayashi Yuka , Ohtsu Iwao , Fujimura Makoto , Fukumori Fumiyasu
Published: September 2010

Heat shock gene expression is regulated by the cellular level and activity of the stress sigma factor σ32 in Gram‐negative bacteria. A toluene‐resistant, temperature‐sensitive derivative strain of Pseudomonas putida KT2442, designated KT2442‐R2 (R2), accumulated several heat shock proteins (HSPs) under non‐stress conditions. Genome sequencing of strain R2 revealed that its genome contains a number of point mutations, including a CGT to CCT change in dnaK resulting in an Arg445 to Pro substitution in DnaK. DNA microarray and real‐time reverse transcription polymerase chain reaction analyses revealed that the mRNA levels of representative hsp genes (e.g. dnaK, htpG and groEL) were upregulated in R2 cells in the stationary phase. Wild‐type and R2 cells showed similar heat shock responses at hsp mRNA and HSP levels; however, the σ32 level in the mutant was not downregulated in the shut‐off stage. Strain R2 harbouring plasmid‐borne dnaK grew at 37°C, did not accumulate HSPs, and was more sensitive to toluene than strain R2. It is worth to note that that revertant of R2 able to grow at 37°C were isolated and exhibited a replacement of Pro445 by Ser or Leu in DnaK. Thus, the mutation in dnaK causes the temperature‐sensitive phenotype, improper stabilization of σ32 leading to HSP accumulation and increased toluene resistance in strain R2.
DddQ, a novel, cupin‐containing, dimethylsulfoniopropionate lyase in marine roseobacters and in uncultured marine bacteria
Authors: Todd Jonathan D. , Curson Andrew R. J. , Kirkwood Mark , Sullivan Matthew J. , Green Robert T. , Johnston Andrew W. B.
Published: September 2010

Ruegeria (previously Silicibacter) pomeroyi DSS‐3, a marine roseobacter, can catabolize dimethylsulfoniopropionate (DMSP), a compatible solute that is made in large amounts by marine plankton and algae. This strain was known to demethylate DMSP via a demethylase, encoded by the dmdA gene, and it can also cleave DMSP, releasing the environmentally important volatile dimethyl sulfide (DMS) in the process. We found that this strain has two different genes, dddP and dddQ, which encode enzymes that cleave DMSP, generating DMS plus acrylate. DddP had earlier been found in other roseobacters and is a member of the M24 family of peptidases. The newly discovered DddQ polypeptide contains a predicted cupin metal‐binding pocket, but has no other similarity to any other polypeptide with known function. DddP‐ and DddQ‐ mutants each produced DMS at significantly reduced levels compared with wild‐type R. pomeroyi DSS‐3, and transcription of the corresponding ddd genes was enhanced when cells were pre‐grown with DMSP. Ruegeria pomeroyi DSS‐3 also has a gene product that is homologous to DddD, a previously identified enzyme that cleaves DMSP, but which forms DMS plus 3‐OH‐propionate as the initial catabolites. However, mutations in this dddD‐like gene did not affect DMS production, and it was not transcribed under our conditions. Another roseobacter strain, Roseovarius nubinhibens ISM, also contains dddP and has two functional copies of dddQ, encoded by adjacent genes. Judged by their frequencies in the Global Ocean Sampling metagenomic databases, DddP and DddQ are relatively abundant among marine bacteria compared with the previously identified DddL and DddD enzymes.
Evolutionary analysis and distribution of type III effector genes in pathogenic Escherichia coli from human, animal and food sources
Authors: Creuzburg Kristina , Middendorf Barbara , Mellmann Alexander , Martaler Tatjana , Holz Christina , Fruth Angelika , Karch Helge , Schmidt Herbert
Published: September 2010

Molecular analysis of Shiga toxin‐producing Escherichia coli (STEC) from different sources is considered as a major approach to assess their risk potential. However, only limited data are available about the correlation of evolutionary relationship, the presence of major virulence factor genes and the putative risk of an STEC strain for human infection. In this study, we analysed the evolutionary relationship of 136 pathogenic E. coli strains from human, animal and food sources by multi‐locus sequence typing (MLST) and molecular subtyping of their Shiga toxin (stx) and intimin (eae) genes. Moreover, the distribution of three type III effector genes, encoded within the locus of enterocyte effacement (LEE), and 16 effector genes, which are encoded outside the LEE, was analysed. One hundred and five strains from different sources harboured 5–15 of the analysed non‐LEE‐encoded effector genes. In 101 of these strains, the LEE genes eae, map, espF and espG were present simultaneously. Thirty‐one isolates deriving mainly from food and patients suffering from haemolytic uraemic syndrome (HUS) were eae‐negative and did not carry any of the analysed effector genes. By combination of MLST and virulence gene data, we defined five genetic clusters. Within these clusters a clear‐cut affiliation of particular sequence types and the occurrence of certain effector genes was observed. However, in contrast to other studies, a significant correlation between the amount and type of effector genes and the risk to cause HUS could not be demonstrated.
Radical nephrectomy with vena caval thrombectomy: a contemporary experience
Authors: Kaag Matthew G. , Toyen Christien , Russo Paul , Cronin Angel , Thompson R. Houston , Schiff Jeffrey , Bernstein Melanie , Bains Manjit
Published: September 2010

Study Type – Therapy (case series)  Level of Evidence 4

What’s known on the subject? and What does the study add?

Renal tumours with caval thrombus are relatively rare. Surgical management is the standard of care for lesions of this nature. Small series have been published by other groups, but our understanding of the optimal management continues to evolve.

We present the Memorial Sloan‐Kettering Cancer Center series, with a discussion of techniques and complications. Of interest, we include several patients with high‐level caval thrombi which were managed without bypass, supporting previous publications by the group from University of Miami.

OBJECTIVE

To report on the contemporary Memorial Sloan‐Kettering Cancer Center experience with radical nephrectomy and vena caval thrombectomy.

PATIENTS AND METHODS

Patients who underwent radical nephrectomy and vena caval thrombectomy without the use of bypass techniques were retrospectively identified.

Data were collected on intraoperative and pathological findings as well as postoperative complications and oncological outcomes.

RESULTS

In all, 78 patients underwent radical nephrectomy with off‐bypass resection of vena caval thrombus between 1989 and 2009.

The median (interquartile range, IQR) operation duration was 293 (226–370) min, and median (IQR) blood loss was 1300 (750–2500) mL. In all, 10 patients (13%) were confirmed to have intra‐ or supra‐hepatic tumour thrombus (level 3/4), eight of whom required supra‐hepatic control of the inferior vena cava (IVC).

Major (grade 3–5) postoperative complications occurred in 14 (18%), with five postoperative deaths. Disease recurred in 27/62 patients who were considered completely resected at surgery and had adequate follow‐up.

The overall 5‐year survival (95% confidence interval) probability was 48% (35–60%).

CONCLUSIONS

Radical nephrectomy with vena caval thrombectomy is associated with acceptable postoperative morbidity and mortality, and long‐term survival is possible in some patients.

Many level 3/4 thrombi could be safely approached without the use of bypass techniques.
Phosphodiesterase 5 inhibitors for lower urinary tract symptoms secondary to benign prostatic hyperplasia: a systematic review
Authors: Laydner Humberto K. , Oliveira Paulo , Oliveira Carlos Roberto A. , Makarawo Tafadzwa P. , Andrade Weslley S. , Tannus Matheus , Araújo José Luciano R.
Published: September 2010

Study Type – Therapy (systematic review) Level of Evidence 1a

What’s known on the subject? and What does the study add?

Phosphodiesterase 5 inhibitors improve lower urinary tract symptoms (LUTS), however the maximum urinary flow rate is not significantly affected. Also, the underlying mechanism of action of these drugs on LUTS is not well understood.

This systematic review confirms the findings of the individual studies included; however the high heterogeneity between them precluded meta‐analysis and further recommendations.

OBJECTIVE

• To review the evidence in support of the effectiveness of phosphodiesterase 5 inhibitors in lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH).

METHODS

• Relevant studies were identified by performing a literature search using MEDLINE® and The Cochrane Library®. The criteria used during the search included randomized, placebo‐controlled trials of treatment for LUTS secondary to BPH using the International Prostate Symptom Score as an outcome measure.

RESULTS

• Four trials that included a total of 1928 patients met the inclusion criteria. All four studies showed a statistically significant difference in the International Prostate Symptom Score, quality of life and erectile function in favour of phosphodiesterase 5 inhibitors.

• No study showed a statistically significant improvement of the maximum urinary flow.

• Meta‐analysis of the results was not possible because of heterogeneity across the studies.

CONCLUSIONS

• Phosphodiesterase 5 inhibitors used in the clinical setting can significantly improve LUTS secondary to BPH, erectile function and quality of life. Maximum urinary flow improvement is not statistically significant.

• Future research should focus on pathophysiological principles and cost analysis.
Mid‐term results for the retroluminar transobturator sling suspension for stress urinary incontinence after prostatectomy
Authors: Bauer Ricarda M. , Soljanik Irina , Füllhase Claudius , Karl Alexander , Becker Armin , Stief Christian G. , Gozzi Christian
Published: September 2010

Study Type – Therapy (case series)  Level of Evidence 4

What’s known on the subject? and What does the study add?

Several studies showed encouraging early results of the AdVance® sling.

However, mid‐term and long‐term results are missing. We were able to show that the AdVance® sling is also, in a longer follow up (median follow‐up of 27 months), an effective, safe and attractive treatment option with stable results for male SUI after radical prostatectomy.

OBJECTIVE

• To evaluate prospectively the efficacy of the retroluminar transobturator male sling (AdVance® sling) for the functional treatment of stress urinary incontinence (SUI) after prostatectomy.

PATIENTS AND METHODS

• A total of 137 patients with grade II–IV SUI, resulting from radical prostatectomy, were treated with the AdVance® sling in a prospective clinical study. In all, 11 patients were lost to follow‐up. A total of 17 patients (13.5%) had additional adjuvant radiotherapy before sling implantation.

• Before and after sling implantation, a standardized 1‐h pad test was performed and post‐void residual urine, uroflowmetry, quality‐of‐life scores and the International Index of Erectile Function (IIEF‐5) were assessed.

• When calculating the cure and improvement rates, ‘cure’ was defined as no pad use or one dry prophylactic pad; and ‘improved’ was defined as 1–2 pads or reduction of pads ≥50%.

RESULTS

• After a median (range) follow‐up of 27 (20–37) months, and a mean follow‐up of 27.2 months, the success rate was 75.4% with 51.6%‘cured’ and 23.8%‘improved’.

• Overall daily pad use, urine loss in the 1‐h pad test and quality‐of‐life scores improved significantly after sling implantation.

• Compared with 1‐year follow‐up data, no worsening over time was noticed and no additional complications were seen.

CONCLUSION

• With a mid‐term follow‐up, the retroluminar transobturator male sling is an effective, safe and attractive treatment option for SUI after radical prostatectomy. Results are stable over time.
Series Estimation in Partially Linear In‐Slide Regression Models
Authors: YOU JINHONG , ZHOU XIAN , ZHOU YONG
Published: September 2010

Abstract.  The partially linear in‐slide model (PLIM) is a useful tool to make econometric analyses and to normalize microarray data. In this article, by using series approximations and a least squares procedure, we propose a semiparametric least squares estimator (SLSE) for the parametric component and a series estimator for the non‐parametric component. Under weaker conditions than those imposed in the literature, we show that the SLSE is asymptotically normal and that the series estimator attains the optimal convergence rate of non‐parametric regression. We also investigate the estimating problem of the error variance. In addition, we propose a wild block bootstrap‐based test for the form of the non‐parametric component. Some simulation studies are conducted to illustrate the finite sample performance of the proposed procedure. An example of application on a set of economical data is also illustrated.
Efficient Covariance Estimation for Asynchronous Noisy High‐Frequency Data
Authors: BIBINGER MARKUS
Published: September 2010

Abstract.  We focus on estimating the integrated covariance of log‐price processes in the presence of market microstructure noise. We construct a consistent asymptotically unbiased estimator for the quadratic covariation of two Itô processes in the case where high‐frequency asynchronous discrete returns under market microstructure noise are observed. This estimator is based on synchronization and multi‐scale methods and attains the optimal rate of convergence. A lower bound for the rate of convergence is derived from the local asymptotic normality property of the simpler parametric model with equidistant and synchronous observations. A Monte Carlo study analyses the finite sample size characteristics of our estimator.
Closing the gap in academic readiness and achievement: the role of early childcare
Authors: Geoffroy Marie‐Claude , Côté Sylvana. M. , Giguère Charles‐Édouard , Dionne Ginette , Zelazo Philip David , Tremblay Richard E. , Boivin Michel , Séguin Jean. R.
Published: September 2010

Background:  Socially disadvantaged children with academic difficulties at school entry are at increased risk for poor health and psychosocial outcomes. Our objective is to test the possibility that participation in childcare – at the population level – could attenuate the gap in academic readiness and achievement between children with and without a social disadvantage (indexed by low levels of maternal education).

Methods:  A cohort of infants born in the Canadian province of Quebec in 1997/1998 was selected through birth registries and followed annually until 7 years of age (n = 1,863). Children receiving formal childcare (i.e., center‐based or non‐relative out‐of‐home) were distinguished from those receiving informal childcare (i.e., relative or nanny). Measures from 4 standardized tests that assessed cognitive school readiness (Lollipop Test for School Readiness), receptive vocabulary (Peabody Picture Vocabulary Test Revised), mathematics (Number Knowledge Test), and reading performance (Kaufman Assessment Battery for children) were administered at 6 and 7 years.

Results:  Children of mothers with low levels of education showed a consistent pattern of lower scores on academic readiness and achievement tests at 6 and 7 years than those of highly educated mothers, unless they received formal childcare. Specifically, among children of mothers with low levels of education, those who received formal childcare obtained higher school readiness (d = 0.87), receptive vocabulary (d = 0.36), reading(d = 0.48) and math achievement scores (d = 0.38; although not significant at 5%) in comparison with those who were cared for by their parents. Childcare participation was not associated with cognitive outcomes among children of mothers with higher levels of education.

Conclusions:  Public investments in early childcare are increasing in many countries with the intention of reducing cognitive inequalities between disadvantaged and advantaged children. Our findings provide further evidence suggesting that formal childcare could represent a preventative means of attenuating effects of disadvantage on children’s early academic trajectory.
Temporal attention shortens perceptual latency: A temporal prior entry effect
Authors: Seibold Verena C. , Fiedler Anja , Rolke Bettina
Published: September 2010

The prior entry hypothesis of attention holds that attended stimuli are perceived earlier than unattended stimuli. Whereas this speeding of perceptual processing has been repeatedly demonstrated for spatial attention, it has not been reported within the temporal domain. To fill this gap, we tested whether temporal attention accelerates auditory perceptual processing by employing event‐related potentials as on‐line indicators of perceptual processing. In a modified oddball paradigm, we presented a single tone in each trial, either a frequent standard tone or an infrequent deviant or target tone. Temporal attention to tones was manipulated via constant foreperiods. We observed that the latency of the N2, an event‐related potential reflecting perceptual processing, is shortened by temporal attention. This result provides first evidence for the idea that temporal attention accelerates perceptual processing as suggested by the prior entry hypothesis.
Divergent engagements: roles and strategies of Taiwanese and mainland Chinese returnee entrepreneurs in the IT industry
Authors: ZHOU YU , HSU JINN‐YUH
Published: September 2010

Professionals and entrepreneurs returning to developing countries from developed countries play key roles in the technological ‘catch‐up’ of their home countries, but they are rarely well‐conceptualized by the theories of globalization. This is especially the case in Asia. The American‐trained Chinese engineers who returned to Taiwan were instrumental in creating Taiwan's excellent semiconductor industry during the 1980s and 1990s. In a similar vein, since the late 1990s, Chinese professionals returning to the mainland have also emerged as the most innovative industrial and capital agents in the technological industry. In this article we compare the roles and business strategies of transnational entrepreneurs on the two sides of Taiwan Strait in the information communication industry (ICT). While these Chinese returnees share striking similarities in their educational and personal trajectories, we identify major structural differences underlying their particular resources and commercial strategies. These empirical findings move beyond the assumptions of common behaviour by overseas Chinese, for they highlight the different political economic dynamics between mainland China, Taiwan and the United States in shaping the divergent engagements of these entrepreneurs in the emerging global technology industry.
Peroxynitrite decomposition catalyst prevents matrix metalloproteinase activation and neurovascular injury after prolonged cerebral ischemia in rats
Authors: Suofu Yalikun , Clark Joseph , Broderick Joseph , Wagner Kenneth R. , Tomsick Thomas , Sa Yalian , Lu Aigang
Published: September 2010

J. Neurochem.(2010)115, 1266–1276.

Matrix metalloproteinases (MMPs) play an important role in reperfusion‐induced brain injury following ischemia. To define the effects of peroxynitrite decomposition catalyst on MMP activation and neurovascular reperfusion injury, 5,10,15,20‐tetrakis (2,4,6‐trimethyl‐3,5‐disulfonatophenyl)‐porphyrin iron (III) (FeTMPyP) was administered intravenously 30 min prior to reperfusion following a middle cerebral artery occlusion. Activation of MMP was assessed byin situand gel zymography. Neurovascular injury was assessed using endothelial barrier antigen, collagen IV immunohistochemistry and Cresyl violet staining. Results were compared with sham and ischemia alone groups. We found that administration of FeTMPyP just before reperfusion after ischemia inhibited MMP‐9 activation and total MMP‐2 increases in the cortex and decreased active MMP‐9 along with the total amounts of active MMP‐9 and active MMP‐2 in the striatum. Reperfusion‐induced injury to the basal lamina of collagen IV‐immunopositive microvasculature and neural cells in cortex and striatum was ameliorated by FeTMPyP. Losses of blood vessel endothelium produced by ischemia or reperfusion were also decreased in the cortex. These results suggest that administration of FeTMPy prior to reperfusion decreases MMP activation and neurovascular injury after prolonged cerebral ischemia. This strategy may be useful for future therapies targeted at preventing breakdown of the blood–brain barrier and hemorrhagic transformation.
The effects of caffeic acid phenethyl ester and melatonin on age‐related vascular remodeling and cardiac damage
Authors: Eşrefoğlu Mukaddes , Gül Mehmet , Ateş Burhan , Erdoğan Ali
Published: September 2010

Oxidative stress has been implicated with cardiovascular aging. Most antioxidant intervention studies have involved long‐term treatments as a potential means to eliminate age‐related oxidative damage in many systems. In the present study, not only light and electron microscopic pictures of the heart and thoracic aorta of young and aged and, caffeic acid phenethyl ester (CAPE) and melatonin and administered aged Sprague Dawley rats, but also antioxidant system status was evaluated. Significantly elevated levels of malondialdehyde (MDA) were observed in the heart and thoracic aorta of aged rats (P < 0.05 and P < 0.001, respectively). Chronic melatonin and CAPE administration significantly reduced the levels of MDA in the heart (P = 0.005 and P = 0.05, respectively) and thoracic aorta (P < 0.001 and P < 0.05, respectively) of aged animals. Additionally, melatonin and CAPE were efficient in stimulating the activities and increasing the levels of the antioxidant enzymes in the heart and aorta. Prominent electron microscopic alterations in cardiac myocytes such as nuclear irregularity, mitochondrial degeneration, myofilament disorganization and disruption, and lipofuscin accumulation were observed in aged rats. The main age‐related histologic modifications observed in aorta were irregularity in endothelial cells and their nuclei, divergence of endothelial cells from basement membrane and neighboring cells, and elastic fibril fragmentation and reduction. Melatonin and CAPE obviously reduced these alterations in both heart and aorta of aged rats. Taking the results together, we suggest that supplemental administration of CAPE and melatonin is beneficial in delaying age‐related cellular damage in cardiovascular system.
Identification of evolutionarily conserved genetic regulators of cellular aging
Authors: Laschober Gerhard T. , Ruli Doris , Hofer Edith , Muck Christoph , Carmona‐Gutierrez Didac , Ring Julia , Hutter Eveline , Ruckenstuhl Christoph , Micutkova Lucia , Brunauer Regina , Jamnig Angelika , Trimmel Daniela , Herndler‐Brandstetter Dietmar , Brunner Stefan , Zenzmaier Christoph , Sampson Natalie , Breitenbach Michael , Fröhlich Kai‐Uwe , Grubeck‐Loebenstein Beatrix , Berger Peter , Wieser Matthias , Grillari‐Voglauer Regina , Thallinger Gerhard G. , Grillari Johannes , Trajanoski Zlatko , Madeo Frank , Lepperdinger Günter , Jansen‐Dürr Pidder
Published: September 2010

To identify new genetic regulators of cellular aging and senescence, we performed genome‐wide comparative RNA profiling with selected human cellular model systems, reflecting replicative senescence, stress‐induced premature senescence, and distinct other forms of cellular aging. Gene expression profiles were measured, analyzed, and entered into a newly generated database referred to as the GiSAO database. Bioinformatic analysis revealed a set of new candidate genes, conserved across the majority of the cellular aging models, which were so far not associated with cellular aging, and highlighted several new pathways that potentially play a role in cellular aging. Several candidate genes obtained through this analysis have been confirmed by functional experiments, thereby validating the experimental approach. The effect of genetic deletion on chronological lifespan in yeast was assessed for 93 genes where (i) functional homologues were found in the yeast genome and (ii) the deletion strain was viable. We identified several genes whose deletion led to significant changes of chronological lifespan in yeast, featuring both lifespan shortening and lifespan extension. In conclusion, an unbiased screen across species uncovered several so far unrecognized molecular pathways for cellular aging that are conserved in evolution.
Double‐transfected MDCK cells expressing human OCT1/MATE1 or OCT2/MATE1: determinants of uptake and transcellular translocation of organic cations
Authors: König J , Zolk O , Singer K , Hoffmann C , Fromm MF
Published: September 2010

BACKGROUND AND PURPOSE The organic cation transporters 1 (OCT1) and 2 (OCT2) mediate drug uptake into hepatocytes and renal proximal tubular cells, respectively. Multidrug and toxin extrusion protein 1 (MATE1) is a major component of subsequent export into bile and urine. However, the functional interaction of OCTs and MATE1 for uptake and transcellular transport of the oral antidiabetic drug metformin or of the cation 1‐methyl‐4‐phenylpyridinium (MPP+) has not fully been characterized.

EXPERIMENTAL APPROACH Single‐transfected Madin‐Darby canine kidney (MDCK) cells as well as double‐transfected MDCK‐OCT1‐MATE1 and ‐OCT2‐MATE1 cells were used to study metformin and MPP+ uptake into and transcellular transport across cell monolayers, along with their concentration and pH dependence.

KEY RESULTS Cellular accumulation of MPP+ and metformin was significantly reduced by 31% and 46% in MDCK‐MATE1 single‐transfected cells compared with MDCK control cells (10 µM; P < 0.01). Over a wide concentration range (10–2500 µM) metformin transcellular transport from the basal into the apical compartment was significantly higher in the double‐transfected cells compared with the MDCK control and MDCK‐MATE1 monolayers. This process was not saturated up to metformin concentrations of 2500 µM. In MDCK‐OCT2‐MATE1 cells basal to apical MPP+ and metformin transcellular translocation decreased with increasing pH from 6.0 to 7.5.

CONCLUSIONS AND IMPLICATIONS Our data demonstrate functional interplay between OCT1/OCT2‐mediated uptake and efflux by MATE1. Moreover, MATE1 function in human kidney might be modified by changes in luminal pH values.
Teneurin C‐terminal associated peptide‐1 blocks the effects of corticotropin‐releasing factor on reinstatement of cocaine seeking and on cocaine‐induced behavioural sensitization
Authors: Kupferschmidt David A. , Lovejoy David A. , Rotzinger Susan , Erb Suzanne
Published: September 2010

BACKGROUND AND PURPOSE

The stress‐related neuropeptide, corticotropin‐releasing factor (CRF), has become an important focus of studies of cocaine addiction, and in particular, the effects of stress on cocaine‐related behaviours. A recently discovered peptide system, the teneurin C‐terminal associated peptides (TCAP), has been implicated in the regulation of the stress response, via a CRF‐related mechanism. Here we have determined whether treatment with TCAP‐1, a synthetic analogue of TCAP, modulated two cocaine‐related behaviours induced by CRF: reinstatement of cocaine seeking, and expression of cocaine‐induced behavioural sensitization.

EXPERIMENTAL APPROACH

In Experiment 1, rats trained to self‐administer cocaine were given acute or repeated (once daily for 5 days) i.c.v. injections of TCAP‐1 before tests for reinstatement in response to CRF (105 pmol, i.c.v.), intermittent footshock stress (0.9 mA), or cocaine (15 mg·kg−1, i.p.). In Experiment 2, rats pre‐exposed to cocaine (15–30 mg·kg−1, i.p.) or saline for 7 days were treated with TCAP‐1 (once daily for 5 days; i.c.v.) and subsequently tested for locomotor responses to CRF (105 pmol, i.c.v.) or cocaine (15 mg·kg−1, i.p.).

KEY RESULTS

Five day pre‐exposure with TCAP‐1 blocked CRF‐, but not footshock‐ or cocaine‐induced reinstatement of cocaine seeking; acute pretreatment with TCAP‐1 was without effect in all test conditions. Similarly, repeated TCAP‐1 pre‐exposure blocked the cocaine‐sensitized locomotor response to CRF, but not to cocaine.

CONCLUSIONS AND IMPLICATIONS

Repeated TCAP‐1 exposure induced robust and selective inhibition of cocaine‐related behavioural responses to CRF, suggesting that TCAP‐1 may normalize signalling within CRF systems dysregulated by cocaine exposure.
Thyroid hormone potentiates insulin  signaling and attenuates hyperglycemia and insulin resistance in a mouse model of type 2 diabetes
Authors: Lin Yi , Sun Zhongjie
Published: September 2010

BACKGROUND AND PURPOSE

The thyroid hormone, triiodothyronine (T3) has many metabolic functions. Unexpectedly, exogenous T3 lowered blood glucose in db/db mice, a model of type 2 diabetes. Here, we have explored this finding and its possible mechanisms further.

EXPERIMENTAL APPROACH

db/db and lean mice were treated with T3, the phosphoinositide 3‐ kinase (PI3‐kinase) inhibitor, LY294002, plus T3, or vehicles. Blood glucose, insulin sensitivity, levels and synthesis were measured. Effects of T3 on intracellular insulin signaling were analyzed in 3T3‐L1 pre‐adipocytes with Western blotting. Knock‐down of the thyroid hormone receptor α1 (TRα1) in 3T3‐L1 cells was achieved with an appropriate silencing RNA (siRNA).

KEY RESULTS

Single injections of T3 (7 ng·g−1 i.p.) rapidly and markedly attenuated hyperglycemia. Treatment with T3 (14 ng·g−1·day−1, 18 days) dose‐dependently attenuated blood glucose and increased insulin sensitivity in db/db mice. Higher doses of T3 (28 ng·g−1·day−1) reversed insulin resistance in db/db mice. T3 also increased insulin levels in plasma and the neurogenic differentiation factor (an insulin synthesis transcription factor) and insulin storage in pancreatic islets in db/db mice. These anti‐diabetic effects of T3 were abolished by the PI3‐kinase inhibitor (LY294002). In 3T3‐L1 preadipocytes, T3 enhanced insulin‐induced tyrosine phosphorylation of insulin receptor substrate (IRS)‐1 and activation of PI3‐kinase, effects blocked by siRNA for TRα1.

CONCLUSIONS AND IMPLICATIONS

T3 potentiated insulin signaling, improved insulin sensitivity, and increased insulin synthesis, which may contribute to its anti‐diabetic effects. These findings may provide new approaches to the treatment of type 2 diabetes.
Lubiprostone targets prostanoid EP4 receptors in ovine airways
Authors: Cuthbert AW
Published: September 2010

BACKGROUND AND PURPOSE Lubiprostone, a prostaglandin E1 derivative, is reported to activate ClC‐2 chloride channels located in the apical membranes of a number of transporting epithelia. Lack of functioning CFTR chloride channels in epithelia is responsible for the genetic disease cystic fibrosis, therefore, surrogate channels that can operate independently of CFTR are of interest. This study explores the target receptor(s) for lubiprostone in airway epithelium.

EXPERIMENTAL APPROACH All experiments were performed on the ventral tracheal epithelium of sheep. Epithelia were used to measure anion secretion from the apical surface as short circuit current or as fluid secretion from individual airway submucosal glands, using an optical method.

KEY RESULTS The EP4 antagonists L‐161982 and GW627368 inhibited short circuit current responses to lubiprostone, while EP1,2&3 receptor antagonists were without effect. Similarly, lubiprostone induced secretion in airway submucosal glands was inhibited by L‐161982. L‐161982 effectively competed with lubiprostone with a Kd value of 0.058 µM, close to its value for binding to human EP4 receptors (0.024 µM). The selective EP4 agonist L‐902688 and lubiprostone behaved similarly with respect to EP4 receptor antagonists. Results of experiments with H89, a protein kinase A inhibitor, were consistent with lubiprostone acting through a Gs‐protein coupled EP4 receptor/cAMP cascade.

CONCLUSIONS AND IMPLICATIONS Lubiprostone‐induced short‐circuit currents and submucosal gland secretions were inhibited by selective EP4 receptor antagonists. The results suggest EP4 receptor activation by lubiprostone triggers cAMP production necessary for CFTR activation and the secretory responses, a possibility precluded in CF tissues.