bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of Cl− in the regulation of ion and liquid transport in the intact alveolus during β‐adrenergic stimulation
Authors: Alexandrou Dionysios , Walters Dafydd V. 
Published: August 2012

New findings
What is the central question of this study?The co‐ordinated regulation of ion transport across the pulmonary epithelium determines the volume of the thin liquid layer lining the normal lung. However, the integrated homeostasis of the liquid transport physiology of the intact alveolus remains elusive.
What is the main finding and its importance?Using a whole‐lung preparation, we explored the mechanism of the β‐agonist‐mediated upregulation of Na+ and alveolar liquid clearance, leading to resolution of pulmonary oedema. We demonstated the functional presence of secretory rather than absorptive Cl− channels, which implies that this upregulation is mediated via a direct effect on Na+ conductance and not through transepithelial Cl− absorption and an increased driving force for Na+.
The epithelium of the developing lung displays an evolving liquid transport phenotype, in which Cl− secretion during fetal life is rapidly switched to Na+ absorption perinatally. However, the mechanisms underlying the homeostasis of the thin layer of liquid lining the postnatal pulmonary epithelium remain elusive. In particular, it remains unclear whether the stimulated clearance of excess alveolar liquid is mediated via transepithelial Cl− transport. Our study is a pharmacological analysis with the aim of addressing this issue, which is of major physiological significance in cases of pulmonary oedema from any cause. We measured the rate of transepithelial liquid movement (Jv) with 125I‐albumin, in the in situ perfused adult rat lung. Transepithelial Cl− transport was studied with the use of the Cl− channel inhibitor NPPB in the resting state and during stimulation with the β2‐adrenergic agonist terbutaline. The study of Jv in these conditions revealed the following findings: (1) there is net absorption of excess of alveolar liquid in the resting, unstimulated state, which is predominantly amiloride sensitive; (2) inhibition of Cl− transport with NPPB in the resting state results in a 1.6‐fold increase in net absorption of alveolar liquid; and (3) the terbutaline‐stimulated net absorption of the excess liquid is enhanced by 2.8‐fold in the presence of NPPB. Our results are suggestive of the functional presence of secretory, but not absorptive, Cl− mechanisms and show that transepithelial Cl− transport is not part of the mechanism underlying lung liquid clearance in response to β‐adrenergic stimulation.
Is there a nitrergic modulation of the rat external anal sphincter?
Authors: Evers J. , Buffini M. , Craven S. , O’Connell P. R. , Jones J. F. X. 
Published: August 2012

New findings
What is the central question of this study?Nitric oxide is known to relax the internal anal sphincter, but its effect on the external anal sphincter is unknown. A topical NO donor (nitroglycerin) is used as an alternative to internal sphincterotomy in the treatment of chronic anal fissures. We investigated the potential effects of nitric oxide on the external anal sphincter and its motor nerve supply.
What is the main finding and its importance?This study is the first to investigate the effect of NO on the external anal sphincter and shows that its contraction is not modulated by NO, by pudendal nitrergic fibres or by NO diffusion from neighbouring nitrergic plexuses of the anal canal.
Nitric oxide is known to relax the internal anal sphincter, but its effect on the external anal sphincter (EAS) is unknown. The aim of this study was to investigate whether there is a nitrergic nerve plexus that modulates the EAS, similar to that found in oesophageal striated muscle. An in vitro ring preparation of rat anal canal was used to evaluate the effects of the nitric oxide synthase inhibitor Nω‐nitro‐l‐arginine (l‐NNA) and the NO donor sodium nitroprusside (SNP) on the EAS in conditions of neuromuscular blockade and the effect of SNP on nerve‐evoked contractions. Immunohistological experiments were conducted to determine whether the neuronal isoform of nitric oxide synthase (nNOS) is present in the EAS. During direct muscle stimulation neither l‐NNA (P= 0.32) nor SNP (P= 0.19) significantly changed the EF50, which is the frequency at which 50% of maximal contraction is reached, compared with a time‐dependent control. Nerve‐evoked contractions were also not altered by addition of SNP to the tissue bath. Immunohistohistological experiments clearly showed co‐localization of nNOS‐positive nerve fibres at motor endplates of the oesophagus but not in the EAS. The internal anal sphincter was richly innervated by nitrergic fibres, but these did not extend into the EAS. In conclusion, there are no nitrergic motor fibres innervating the EAS, neurotransmission at the motor endplates is not affected by NO, and NO does not affect muscle force directly in conditions of neuromuscular blockade. There is, therefore, no evidence that EAS contraction is directly modulated by NO or by pudendal nitrergic fibres or diffusion from neighbouring nitrergic plexuses of the anal canal.
Sweat loss during heat stress contributes to subsequent reductions in lower‐body negative pressure tolerance
Authors: Lucas Rebekah A. I. , Ganio Matthew S. , Pearson James , Crandall Craig G. 
Published: August 2012

New findings
What is the central question of this study?Heat stress compromises blood pressure control, reducing an individual's tolerance to a simulated hemorrhagic challenge. The contribution of sweating, and the resulting loss of total body water, during heat stress on heat‐induced reductions in haemorrhagic tolerance is unknown.
What is the main finding and its importance?Unreplaced sweat loss and the associated reduction in blood volume contribute to reductions in haemorrhagic tolerance in heat‐stressed individuals; however, this impairment is secondary to the negative impact of heat stress itself. These findings highlight the importance of adequate hydration in individuals who are exposed to heat stress and are at a higher risk for a haemorrhagic injury, such as soldiers, firefighters and construction workers.
The contribution of sweating to heat stress‐induced reductions in haemorrhagic tolerance is not known. This study tested the hypothesis that fluid loss due to sweating contributes to reductions in simulated haemorrhagic tolerance in conditions of heat stress. Eight subjects (35 ± 8 years old; 77 ± 5 kg) underwent a normothermic time control and two heat stress trials (randomized). The two heat stress trials were as follows: (i) with slow intravenous infusion of lactated Ringer solution sufficient to offset sweat loss (IV trial); or (ii) without intravenous infusion (dehydration; DEH trial). Haemorrhage was simulated via progressive lower‐body negative pressure (LBNP) to presyncope after core body (intestinal) temperature was raised by ∼1.5°C using a water‐perfused suit or a normothermic time control period. The LBNP tolerance was quantified via a cumulative stress index. Middle cerebral artery blood velocity (transcranial Doppler) and mean blood pressure (Finometer®) were measured continuously. Relative changes in plasma volume were calculated from haematocrit and haemoglobin. Increases in core body temperature and sweat loss (∼1.6% body mass deficit) were similar (P > 0.05) between heat stress trials. Slow intravenous infusion (1.2 ± 0.3 litres) prevented heat‐induced reductions in plasma volume (IV trial, −0.6 ± 6.1%; and DEH trial, −6.6 ± 5.1%; P= 0.01). Intravenous infusion improved LBNP tolerance (632 ± 64 mmHg min) by ∼20% when compared with the DEH trial (407 ± 117 mmHg min; P= 0.01), yet tolerance remained 44% lower in the IV trial relative to the time control normothermic trial (1138 ± 183 mmHg min; P < 0.01). These data indicate that although sweat‐induced dehydration impairs simulated haemorrhagic tolerance, this impairment is secondary to the negative impact of heat stress itself.
Relation of sleep quality and sleep duration to type 2 diabetes: a population-based cross-sectional survey
Authors: Lou Peian , Chen Peipei , Zhang Lei , Zhang Pan , Yu Jiaxi , Zhang Ning , Wu Hongmin , Zhao Jing 
Published: August 2012

ObjectivesTo investigate the association between self-reported sleep duration, sleep quality and the prevalence of diabetes in a contemporary sample of Chinese adults.DesignCross-sectional survey.SettingCommunity-based investigation in Xuzhou, China.Participants16 893 Chinese men and women aged 18–75 who fulfilled the inclusion and exclusion criteria were enrolled.Primary and secondary outcome measuresSelf-reported quality and duration of sleep were obtained by questionnaire, and type 2 diabetes was assessed by fasting blood glucose. Sleep quality was categorised as good, common or poor. Sleep duration was measured by average hours of sleep per night, with categories of ≤6 h, 6–8 h and ≥8 h. A logistic regression model was used to evaluate the association between sleep duration or sleep quality and diabetes.ResultsBoth poor quality of sleep and short sleep duration (≤6 h) were associated with increased prevalence of diabetes, with higher rates in relatively healthy Chinese people. Compared with the group with good quality of sleep and 6–8 h sleep duration, diabetes was the most prevalent in individuals with poor sleep quality and ≤6 h sleep duration (OR 1.41, 95% CI 1.07 to 1.85) and in those with poor sleep quality who slept ≥8 h (OR 1.39, 95% CI 0.85 to 2.26), even after adjustment for a large number of further possible factors.ConclusionsThe results suggest that sleep of poor quality and short duration is associated with diabetes.
Sanger sequencing in routine KRAS testing: a review of 1720 cases from a pathologist's perspective
Authors: Malapelle Umberto , Bellevicine Claudio , Salatiello Maria , de Luca Caterina , Rispo Elisabetta , Riccio Palmira , Sparano Lucianna , De Stefano Alfonso , Carlomagno Chiara , Maiello Francesco Maria , Vita Giulia , Nappi Oscar , Troncone Giancarlo 
Published: August 2012

BackgroundSanger sequencing (SS) of PCR products is still the most frequent method to test colorectal cancer for KRAS mutations in routine practice.MethodsAn audit of SS on 1720 routine cases was carried out, taking into account age, gender, specimen type (resection vs biopsies), tumour site (primary vs metastasis), tumour stage, neoplastic cells abundance (>30% vs <30%) and fixation type (buffered formalin vs simple formalin). In a subset of 50 wild-type (WT) patients correlations between SS findings and response rate (RR), progression-free survival (PFS) and overall survival (OS) were also evaluated.ResultsThe tests were informative in 1691 cases (98.3%). Mutations were detected in 671 cases (39.6%). No significant differences in mutation rates were observed with respect to age (p=0.2), gender (p=0.2), specimen type (p=0.3) and formalin fixation (p=0.08). Conversely, KRAS mutant rate was higher in metastatic tissue (50% vs 39%, p=0.02), in samples with over 30% of neoplastic cells (43.4% vs 26.6%, p=0.02) and in tumours tested in stage IV (p=0.05). The RR of SSKRASWT patients was 26% (one complete and 12 partial responses). The disease control rate (objective responses plus stable disease) was 56%. Median PFS was 4.4 months and median OS was 10.4 months.ConclusionsPathological criteria that make SS a more robust method for KRAS testing and treatment response prediction are neoplastic cell abundance, metastatic tissue sample and stage IV primary tumour.
The handling and sampling of radical prostatectomy specimens for reporting and research: the Oxford approach
Authors: Gill Pelvender Singh , Roberts Ian S D , Browning Lisa , Perera Ranmith , Warren Anne Y , Hamdy Freddie C , Verrill Clare 
Published: August 2012

This article reviews previously described methods of fresh tissue sampling from radical prostatectomy specimens for research and describes a method used in Oxford which is simple, logical and cost effective. The method utilises a systematic zonal approach to tissue procurement in order to meet the increasing requirement for research samples with detailed morphological information such as zone of origin, tumour stage and Gleason grade.The described method involves punch biopsy sampling from a 4mm thick transverse slice cut 8mm superior to the apex. 9 biopsies are taken from each specimen in the following zonal distribution: Mid anterior, right lateral, right peripheral zone lateral, right peripheral zone mid, left peripheral zone mid, left peripheral zone lateral, left lateral, left transition zone and right transition zone.The method was validated by successfully sampling tumour in 7 out of 8 cases (88%). In 6 of the positive cases, tumour was present in more than 1 punch biopsy. The mean time from receipt of the specimen to completion of the biopsy freezing was 23.5 minutes. Tumour stage, zone and Gleason grade were determined for all positive biopsies. All cases were reported to RCPath guidelines with no compromising of margins.A logical systematic method of fresh tissue sampling from radical prostatectomy specimens is presented, which balances the need for accurate routine histopathological reporting with the requirement for increasingly complex research samples to be taken with attention to morphological details such as zone and stage.
Selective measurement of anti-tTG antibodies in coeliac disease and IgA deficiency: an alternative pathway
Authors: Harrison Elizabeth , Li Ka-Kit , Petchey Michael , Nwokolo Chuka , Loft Duncan , Arasaradnam Ramesh P 
Published: August 2012

Abstract

Objective
To determine the ability of selective antibody testing to screen for coeliac disease in the presence of IgA deficiency and to define the sensitivity of a pathway using this method.

Method
All IgA and IgG anti-tTG tests performed at our centre between January 2008 and December 2009, using the Immunocap 250 analyser, were retrospectively reviewed. Positive results were correlated with histology. Results were used to validate our diagnostic pathway.

Results
12 289 consecutive serological tests were reviewed. IgA deficient patients gave either an ‘error’ reading or very low response on the Immunocap 250 analyser. Subsequent testing of this sub-group demonstrated raised IgG anti-tTG antibodies in those with histologically proven coeliac disease.

Conclusions
Using our antibody screening pathway, which involves the selective use of IgG anti-tTG, sensitivity increased from 87% to 92% in those with IgA deficiency. Adoption of this pathway for coeliac screening would negate the routine screening of immunoglobulin levels, with resultant cost saving.
The Fountain of Love Credit Union: A Vibrant Microfinance Institution in a Hostile Inter-Ethnic Society
Authors: Achwan Rochman 
Published: August 2012

The Fountain of Love Credit Union (FLCU) is a rare example of a vibrant microfinance institution in Indonesia. Located at the heart of a hostile inter-ethnic society in the province of West Kalimantan, the FLCU invents unique types of social capital and financial organization that bolster its unparallel financial performance. In recognition of this achievement, the Indonesian government presented the FLCU with the 2005 Award for Small-Medium Corporate Excellence. Decades of inter-ethnic hostility inspired school teachers to establish the FLCU in 1987. They dreamt of creating a big microfinance institution and promoting the economic well-being of the Dayak ethnic group. The Dayak, one of Kalimantan's two largest ethnic groups, defines itself as disadvantaged. A sense of grievance evolving around these issues culminated in a series of ethnic conflicts. Today, after more than two decades of operations, the FLCU has not only won the trust of most Dayak people but also inspires other ethnic groups to establish microfinance institutions. This environment has allowed unique types of social capital and financial organization to flourish. The Fountain of Love Foundation (FLF), the parent organization of the FLCU, has set up a variety of social and economic organizations. They work in partnership with the FLCU in all aspects of its business, from recruiting, disciplining, and empowering clients to weaving organizational networks with other microfinance institutions. The latter plays a vital role in curbing the penetration of modern micro banking in the province. The FLF, therefore, has become an ethnic-based conglomerate in which the FLCU functions as one of its driving forces. However, the FLCU faces a number of hurdles. Almost all FLCU clients, in rural and urban areas, are of the Dayak ethnic group. From organizational and policy points of view, the legal status of the FLCU is vulnerable as its assets grow beyond the mandatory requirement of the current banking law.
Associations between Testosterone Levels and Incident Prostate, Lung, and Colorectal Cancer. A Population-Based Study
Authors: Hyde Zoë , Flicker Leon , McCaul Kieran A. , Almeida Osvaldo P. , Hankey Graeme J. , Chubb S.A. Paul , Yeap Bu B. 
Published: August 2012

Abstract
Background: The relationship between testosterone and cancer is relatively unexplored. We sought to examine whether testosterone and related hormones are associated with incident prostate, lung, and colorectal cancer.
Methods: This was a population-based cohort study. Demographic and clinical predictors of cancer, and testosterone, sex hormone-binding globulin (SHBG), and luteinizing hormone (LH) were measured between 2001 and 2004 in 3,635 community-dwelling men aged 70 to 88 years (mean 77 years). Cancer notifications were obtained via electronic record linkage until December 31, 2010.
Results: During a mean follow-up period of 6.7 ± 1.8 years, there were 297, 104, and 82 cases of prostate, colorectal, and lung cancer. In adjusted competing risks proportional hazards models, each one SD increase in free testosterone was associated with a 9% increase in prostate cancer risk (95% confidence interval [CI], 1.00–1.18), but other hormones were not significantly associated. No significant associations were observed between hormonal parameters and colorectal cancer. Higher total testosterone was associated with lung cancer. Compared with the mean of 15 nmol/L, men with levels of 20 nmol/L were 1.38 times more likely to be cases (95% CI, 1.21–1.57), whereas those with levels of 30 nmol/L were 3.62 times more likely to be cases (95% CI, 2.53–5.18). Higher free testosterone was also associated with lung cancer, though SHBG and LH were not. Associations were maintained after exclusion of current smokers.
Conclusions: Higher free testosterone was associated with incident prostate cancer. Higher testosterone levels may also be associated with lung cancer.
Impact: Further studies should investigate whether these risks apply to men receiving testosterone therapy. Cancer Epidemiol Biomarkers Prev; 21(8); 1319–29. ©2012 AACR.
The Oncogenic Role of miR-155 in Breast Cancer
Authors: Mattiske Sam , Suetani Rachel J. , Neilsen Paul M. , Callen David F. 
Published: August 2012

AbstractmiR-155 is an oncogenic miRNA with well described roles in leukemia. However, additional roles of miR-155 in breast cancer progression have recently been described. A thorough literature search was conducted to review all published data to date, examining the role of miR-155 in breast cancer. Data on all validated miR-155 target genes was collated to identify biologic pathways relevant to miR-155 and breast cancer progression. Publications describing the clinical relevance, functional characterization, and regulation of expression of miR-155 in the context of breast cancer are reviewed. A total of 147 validated miR-155 target genes were identified from the literature. Pathway analysis of these genes identified likely roles in apoptosis, differentiation, angiogenesis, proliferation, and epithelial–mesenchymal transition. The large number of validated miR-155 targets presented here provide many avenues of interest as to the clinical potential of miR-155. Further investigation of these target genes will be required to elucidate the specific mechanisms and functions of miR-155 in breast cancer. This is the first review examining the role of miR-155 in breast cancer progression. The collated data of target genes and biologic pathways of miR-155 identified in this review suggest new avenues of research for this oncogenic miRNA. Cancer Epidemiol Biomarkers Prev; 21(8); 1236–43. ©2012 AACR.
Weight Change and Survival after Breast Cancer in the After Breast Cancer Pooling Project
Authors: Caan Bette J. , Kwan Marilyn L. , Shu Xiao Ou , Pierce John P. , Patterson Ruth E. , Nechuta Sarah J. , Poole Elizabeth M. , Kroenke Candyce H. , Weltzien Erin K. , Flatt Shirley W. , Quesenberry Charles P. , Holmes Michelle D. , Chen Wendy Y. 
Published: August 2012

Abstract
Background: Weight change after a breast cancer diagnosis has been linked to lower survival. To further understand effects of postdiagnostic weight variation on survival, we examined the relationship by comorbid status and initial body mass index (BMI).
Methods: The current analysis included 12,915 patients with breast cancer diagnosed between 1990 and 2006 with stage I–III tumors from four prospective cohorts in the United States and China. HRs and 95% confidence intervals (CI) representing the associations of five weight change categories [within &lt;5% (reference); 5%–&lt;10% and ≥10% loss and gain] with mortality were estimated using Cox proportional hazards models.
Results: Mean weight change was 1.6 kg. About 14.7% women lost and 34.7% gained weight. Weight stability in the early years postdiagnosis was associated with the lowest overall mortality risk. Weight loss ≥10% was related to a 40% increased risk of death (HR, 1.41; 95% CI, 1.14–1.75) in the United States and over three times the risk of death (HR, 3.25; 95% CI: 2.24, 4.73) in Shanghai. This association varied by prediagnosis BMI, and in the United States, lower survival was seen for women who lost weight and had comorbid conditions. Weight gain ≥10% was associated with a nonsignificant increased risk of death.
Conclusions: Prevention of excessive weight gain is a valid public health goal for breast cancer survivors. Although intentionality of weight loss could not be determined, women with comorbid conditions may be particularly at risk of weight loss and mortality.
Impact: Weight control strategies for breast cancer survivors should be personalized to the individual's medical history. Cancer Epidemiol Biomarkers Prev; 21(8); 1260–71. ©2012 AACR.