bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of in vivo T cell kinetics: use of heavy isotope labelling in type 1 diabetes
Authors: Bollyky J B , Long S A , Fitch M , Bollyky P L , Rieck M , Rogers R , Samuels P L , Sanda S , Buckner J H , Hellerstein M K , Greenbaum C J
Published: January 2013

CD4+ memory cell development is dependent upon T cell receptor (TCR) signal strength, antigen dose and the cytokine milieu, all of which are altered in type 1 diabetes (T1D). We hypothesized that CD4+ T cell turnover would be greater in type 1 diabetes subjects compared to controls. In vitro studies of T cell function are unable to evaluate dynamic aspects of immune cell homoeostasis. Therefore, we used deuterium oxide (2H2O) to assess in vivo turnover of CD4+ T cell subsets in T1D (n = 10) and control subjects (n = 10). Serial samples of naive, memory and regulatory (Treg) CD4+ T cell subsets were collected and enrichment of deoxyribose was determined by gas chromatography–mass spectrometry (GC–MS). Quantification of T cell turnover was performed using mathematical models to estimate fractional enrichment (f, n = 20), turnover rate (k, n = 20), proliferation (p, n = 10) and disappearance (d*, n = 10). Although turnover of Tregs was greater than memory and naive cells in both controls and T1D subjects, no differences were seen between T1D and controls in Treg or naive kinetics. However, turnover of CD4+ memory T cells was faster in those with T1D compared to control subjects. Measurement and modelling of incorporated deuterium is useful for evaluating the in vivo kinetics of immune cells in T1D and could be incorporated into studies of the natural history of disease or clinical trials designed to alter the disease course. The enhanced CD4+ memory T cell turnover in T1D may be important in understanding the pathophysiology and potential treatments of autoimmune diabetes.
Perceptual Metrics for Static and Dynamic Triangle Meshes
Authors: Corsini M. , Larabi M. C. , Lavoué G. , Petřík O. , Váša L. , Wang K.
Published: January 2013

Almost all mesh processing procedures cause some more or less visible changes in the appearance of objects represented by polygonal meshes. In many cases, such as mesh watermarking, simplification or lossy compression, the objective is to make the change in appearance negligible, or as small as possible, given some other constraints. Measuring the amount of distortion requires taking into account the final purpose of the data. In many applications, the final consumer of the data is a human observer, and therefore the perceptibility of the introduced appearance change by a human observer should be the criterion that is taken into account when designing and configuring the processing algorithms. In this review, we discuss the existing comparison metrics for static and dynamic (animated) triangle meshes. We describe the concepts used in perception‐oriented metrics used for 2D image comparison, and we show how these concepts are employed in existing 3D mesh metrics. We describe the character of subjective data used for evaluation of mesh metrics and provide comparison results identifying the advantages and drawbacks of each method. Finally, we also discuss employing the perception‐correlated metrics in perception‐oriented mesh processing algorithms.
Efficacy of LIFT for recurrent anal fistula
Authors: Lehmann J.‐P. , Graf W.
Published: January 2013

Aim

Ligation of the intersphincteric fistula tract (LIFT) is a novel sphincter‐preserving technique for anal fistula. This pilot study was designed to evaluate the results in patients with a recurrent fistula.

Method

Seventeen patients [nine men; median age 49 (range, 30–76) years] with a recurrent trans‐sphincteric fistula were treated with a LIFT procedure between June 2008 and February 2011. All were followed prospectively for a median of 16 (range, 5–27) weeks with clinical examination. Fifteen followed for 13.5 (range, 8–26) months by clinical examination also had three‐dimensional (3D) anal ultrasound.

Results

The duration of the procedure was 35 (range, 18–70) min. One patient developed a small local haematoma and one had a subcutaneous infection, but otherwise there was no morbidity. At follow up, 11 (65%) patients had a successful closure, two (12%) had a remaining sinus and four (23%) had a persistent fistula. The incidence of persistent or recurrent fistulae at 13.5 months was six (40%) of 15 patients. No de novo faecal incontinence was reported.

Conclusion

LIFT is a safe procedure for patients with recurrent anal fistula, with healing at short‐term and medium‐term follow‐up comparable with or superior to that of other sphincter‐preserving techniques. Larger studies with a longer follow up are needed to define the ultimate role of LIFT in patients with recurrence.
Clinical variants of lichen planus
Authors: Wagner Gunnar , Rose Christian , Sachse Michael Max
Published: January 2013

Lichen planus is characterized by lichenoid, polygonal papules with fine white lines, called Wickham striae. Lesions most commonly occur on the limbs and on the dorsal aspect of the trunk. At the same time often leukoplakia of mucous membranes as well as nail disorders are seen.

There are numerous variants of lichen planus which can be distinguished from the classical form on the basis of morphology and distribution of the lesions. The typical primary lesion of lichen planus may be replaced by other forms, such as patches, hyperkeratoses, ulcerations, or bullous lesions. Moreover, distribution patterns of these lesions may vary and include erythrodermic, inverse or linear arrangements. In contrast to these numerous clinical features, histologic findings remain characteristic in the variants, so that the diagnosis can be made securely. Differential diagnoses of lichen planus include diverse dermatoses such as bullous pemphigoid or paronychia.
Population response to information on reversibility of Type 2 diabetes
Authors: Steven S. , Lim E. L. , Taylor R.
Published: January 2013

Aims

Following publication of the Counterpoint Study (on the reversibility of Type 2 diabetes using a very low energy diet), the extent of public interest prompted the authors to make available, on a website, general information about reversing diabetes. Shortly thereafter, individuals began to feed back their personal experiences of attempting to reverse their diabetes. We have collated this information on the effects of energy restriction in motivated individuals with Type 2 diabetes that has been achieved outside a research setting.

Methods

Emails, letters and telephone communications received between July 2011 and September 2012 were evaluated (n = 77: 66 men, 11 women). Median diabetes duration was 5.5 years (3 months–28 years). Reversal of diabetes was defined as achieving fasting capillary blood glucose < 6.1 mmol/l and/or, if available, HbA1c less than 43 mmol/mol (6.1%) off treatment.

Results

Self‐reported weight fell from 96.7 ± 17.5 kg at baseline to 81.9 ± 14.8 kg after weight loss (P < 0.001). Self‐reported fasting blood glucose levels fell from 8.3 mmol/l (5.9–33.0) to 5.5 mmol/l (4.0–10.0) after the weight loss period (P < 0.001). Diabetes reversal was considered to have occurred in 61% of the population. Reversal of diabetes was observed in 80, 63 and 53% of those with > 20, 10–20 and < 10 kg weight loss, respectively. There was a significant correlation between degree of weight loss and reported fasting glucose levels (Rs –0.38, P = 0.006). Reversal rates according to diabetes duration were: short (< 4 years) = 73%, medium (4–8 years) = 56% and long (> 8 years) = 43%.

Conclusion

These data demonstrate that intentional weight loss achieved at home by health‐motivated individuals can reverse Type 2 diabetes. Diabetes reversal should be a goal in the management of Type 2 diabetes.
Sfrp5 correlates with insulin resistance and oxidative stress
Authors: Carstensen Maren , Herder Christian , Kempf Kerstin , Erlund Iris , Martin Stephan , Koenig Wolfgang , Sundvall Jouko , Bidel Siamak , Kuha Suvi , Roden Michael , Tuomilehto Jaakko
Published: January 2013

Background

Secreted frizzled‐related protein 5 (Sfrp5) has been described as novel adipokine in mice with insulin‐sensitising and anti‐inflammatory properties similar to adiponectin. The aim of this study was to compare serum concentrations and determinants of Sfrp5, its pro‐inflammatory antagonist wingless‐type MMTV integration site family member (Wnt)5a and adiponectin in humans and their regulation by coffee.

Material and methods

Serum concentrations of Sfrp5, Wnt5a and adiponectin were measured in 47 individuals who participated in a coffee intervention study. Associations with demographic, metabolic and immunological variables and regulation of serum levels by different amounts of daily coffee intake were analysed.

Results

At baseline, fasting serum Sfrp5 levels ranged between 96 and 4056 ng/mL. Sfrp5 was directly correlated with a surrogate of insulin resistance (homeostasis model assessment of insulin resistance/HOMA‐IR; r = 0·32, P < 0·05) and with the oxidative stress markers 8‐isoprostane (r = 0·44, P < 0·01) and nitrotyrosine (r = 0·52, P < 0·001). Adiponectin showed inverse correlations with several indices of insulin resistance (e.g. HOMA‐IR, Stumvoll index; all P < 0·05) and a direct correlation with the anti‐atherogenic apolipoprotein A‐I (r = 0·56, P < 0·001). Coffee did not affect serum concentrations of Sfrp5. Serum Wnt5a concentrations were below the detection limit (0·02 ng/mL) in 81% of the study participants.

Conclusions

In contrast to obese mouse models, serum Sfrp5 was directly related to HOMA‐IR and oxidative stress in humans, but not with apolipoproteins, and thus, associations differed from those found for circulating adiponectin. These differences between Sfrp5 and adiponectin might be explained by differences in the investigated species.
Silver eel (Anguilla anguilla) population dynamics and production in the River Shannon, Ireland
Authors: MacNamara Ruairí , McCarthy T. Kieran
Published: January 2013

The European eel (Anguilla anguilla) is in decline throughout its distribution and accurate regional information, particularly on the silver eel life‐stage, is an essential component of stock recovery plans. Therefore, silver eel population dynamics and production were investigated on the Irish River Shannon. Size frequency analysis during the annual seaward migration showed that between 2008 and 2011, seasonal trends in both sex ratio and female size occurred. Catch analysis and mark‐recapture experiments were undertaken during the same period to determine silver eel production. Due to extreme discharge in 2009, no catch data was available for 17 nights, and a novel protocol was developed using a Dual Frequency Identification Sonar (DIDSON) to quantify silver eel migration. In 2008, silver eel production was estimated at 57.3 t (1.35 kg·ha−1), but an additional 18.3 t of potential migrants were estimated to have been removed by the summer yellow eel fishery. In 2009, following closure of the yellow eel fishery, silver eel production increased to 68.6 t (1.62 kg·ha−1), before declining to 62.7 t (1.47 kg·ha−1) in 2010 and 61.6 t (1.45 kg·ha−1) in 2011. Modelling, based on long‐term stocking data (1959–2011) and retrospectively estimated silver eel production (1992–2007) suggests that despite commercial fishery closure on the river, the decline in River Shannon silver eel production will continue for at least the coming decade.
Timing of brown trout spawning in Alpine rivers with special consideration of egg burial depth
Authors: Riedl Christina , Peter Armin
Published: January 2013

Timing of spawning, habitat use and egg burial depths of brown trout were studied in seven Swiss (alpine and prealpine) rivers, which differed in size, altitude and flow regime. In general, we observed brown trout spawning activity between the end of October and the beginning of January. The spawning duration differed significantly, however, between rivers, ranging from 28 to 72 days. Analysis of environmental parameters for their influence on spawning activity revealed mean water temperature and altitude as the most explanatory variables. Detailed investigation of redd characteristics based on water velocity, water depth and substrate size clearly showed differences between positions on the redd. Brown trout in Alpine rivers preferred to use velocities of 30–40 cm·s−1, water depths of 10–20 cm and substrates of 16–32 mm for spawning. It has to be noted, however, that recorded values cover almost the whole range of data on spawning habitats that has been reported in literature so far. A special focus of this study was on egg burial depths, which were surprisingly not found to differ significantly between the rivers despite their different flow regimes. Recorded egg burial depths were, however, found to be distinctly lower (mean burial depth: 3.8 cm) than reported by almost any study so far. We see this observation of low burial depths in Alpine rivers as useful in the context of scouring effects, especially when evaluating the influence of scouring on fish populations.
NIETZSCHE'S ‘THIER MIT ROTHEN BACKEN’: THE BIRTH OF CULTURE OUT OF THE SPIRIT OF SHAME
Authors: Speirs Ronald
Published: January 2013

The article explores the topic of shame in Nietzsche with particular reference to the role it played in his conception of culture from Die Geburt der Tragödie onwards. It argues that two elements were central to his thinking about these questions throughout. One was the concept of the adyton, originally an element in religious practice, but extended by Nietzsche into other fields. The other was the dialectical principle of opposing forces.

Der Aufsatz untersucht das Thema der Scham bei Nietzsche unter besonderer Berücksichtigung ihrer kulturprägenden Rolle sowohl in Die Geburt der Tragödie als auch in seinen späteren Überlegungen zur Erneuerung der Kultur in der Moderne. Dabei werden zwei Momente hervorgehoben. Das eine ist der über das Gebiet der Religion hinausgehende Begriff des adyton. Das andere ist das durchgehend eingesetzte dialektische Prinzip entgegengesetzter Kräfte.
Changes in liver gluconeogenesis during the development of Walker‐256 tumour in rats
Authors: Moreira Carolina Campos Lima , Cassolla Priscila , Dornellas Ana Paula Segantini , de Morais Hely , de Souza Camila Oliveira , Borba‐Murad Glaucia Regina , Bazotte Roberto Barbosa , de Souza Helenir Medri
Published: January 2013

Few studies have investigated liver gluconeogenesis in cancer and there is no agreement as to whether the activity of this pathway is increased or decreased in this disease. The aim of this study was to evaluate gluconeogenesis from alanine, pyruvate and glycerol, and related metabolic parameters in perfused liver from Walker‐256 tumour‐bearing rats on days 5 (WK5 group), 8 (WK8 group) and 12 (WK12 group) of tumour development. There was reduction (P < 0.05) of liver glucose production from alanine and pyruvate in WK5, WK8 and WK12 groups, which was accompanied by a decrease (P < 0.05) in oxygen consumption. Moreover, there was higher (P < 0.05) pyruvate and lactate production from alanine in the WK5 group and a marked reduction (P < 0.05) of pyruvate and urea production from alanine in the WK12 group. In addition, liver glucose production and oxygen consumption from glycerol were not reduced in WK5, WK8 and WK12 groups. Thus the, the results show inhibition of hepatic gluconeogenesis from alanine and pyruvate, but not from glycerol, on days 5, 8 and 12 of Walker‐256 tumour development, which can be attributed to the metabolic step in which the substrate enters the gluconeogenic pathway.
Lymphangiogenesis and Prognostic Significance of Vascular Endothelial Growth Factor C in Gastro‐oesophageal Junction Adenocarcinoma
Authors: Xie Liang‐Xi , Zhai Tian‐Tian , Yang Li‐Ping , Yang Eleanor , Zhang Xiao‐Hui , Chen Jiong‐Yu , Zhang Hao
Published: January 2013

Vascular endothelial growth factor C (VEGF‐C) is a crucial regulator of the development of lymphatic vessels and is involved in the lymph node metastasis of cancer. The levels of VEGF‐C expression and lymphatic vessel density (LVD) in 128 gastro‐oesophageal junction adenocarcinoma (GEJA) tissues were examined by immunohistochemistry and analysed for their association with clinicopathological features and disease‐free survival. We found that 75.0% of tumour samples displayed strong immunoreactivity to VEGF‐C. The levels of VEGF‐C expression in the tumour tissues were associated with the stages of the clinical tumours and the lymph node metastasis status, but not with the age, gender and the size and type of tumours in the cohort. Similarly, LVD, as evaluated by anti‐D2‐40 staining, was also associated with the clinical stages of GEJA. The values of LVD were positively correlated with the levels of VEGF‐C expression in these samples (r = 0.3760, P = 0.0001). High levels of VEGF‐C expression and high values of LVD were associated with shorter periods of disease‐free survival (DFS) in patients with GEJA (P < 0.001). In addition, GEJA at N1 and N2 stages, at T4 stage, chemotherapy after surgery, high levels of VEGF‐C expression and lower marginal resection were independent factors for the prognosis of DFS in patients with GEJA. Our data indicate that VEGF‐C may promote the lymphangiogenesis and lymphatic metastasis of GEJA and that VEGF‐C may be a valuable biomarker for the diagnosis of lymphatic metastasis and a prognostic factor of the survival of patients with GEJA.
The transcription factor Fli‐1 regulates monocyte, macrophage and dendritic cell development in mice
Authors: Suzuki Eiji , Williams Sarah , Sato Shuzo , Gilkeson Gary , Watson Dennis K. , Zhang Xian K.
Published: January 2013

Fli‐1 belongs to the Ets transcription factor family and is expressed in haematopoietic cells, including most of the cells that are active in immunity. The mononuclear phagocytes, i.e. monocytes, macrophages and dendritic cells, originate in haematopoietic stem cells and play an important role in immunity. To assess the role of Fli‐1 in mononuclear phagocyte development in vivo, we generated mice that express a truncated Fli‐1 protein, lacking the C‐terminal transcriptional activation domain (Fli‐1ΔCTA). Fli‐1ΔCTA/ΔCTA mice had significantly increased populations of haematopoietic stem cells and common dendritic cell precursors in bone marrow compared with wild‐type littermates. Significantly increased classical dendritic cells, plasmacytoid dendritic cells, and macrophage populations were found in spleens from Fli‐1∆CTA/∆CTA mice compared with wild‐type littermates. Fli‐1ΔCTA/ΔCTA mice also had increased pre‐classical dendritic cell and monocyte populations in peripheral blood mononuclear cells. Furthermore, bone marrow reconstitution studies demonstrated that expression of Fli‐1 in both haematopoietic cells and stromal cells affected mononuclear phagocyte development in mice. Expression of Fms‐like tyrosine kinase 3 ligand (Flt3L), a haematopoietic growth factor, in multipotent progenitors was statistically significantly increased from Fli‐1∆CTA/∆CTA mice compared with wild‐type littermates. Fli‐1 protein binds directly to the promoter region of the Flt3L gene. Hence, Fli‐1 plays an important role in the mononuclear phagocyte development, and the C‐terminal transcriptional activation domain of Fli‐1 negatively modulates mononuclear phagocyte development.
The effectiveness of socially sustainable sourcing mechanisms: Assessing the prospects of a new form of joint regulation
Authors: Wright Chris F. , Brown William
Published: January 2013

The traditional mechanisms for improving and protecting labour standards in advanced economies are failing. In Britain, the effectiveness of collective bargaining has diminished substantially over the past quarter century. Legally enforceable minimum labour standards have been an inadequate substitute. A new form of ‘joint regulation’ is emerging that may be better attuned to the contemporary structure of product market competition. It involves employers and unions coordinating action on labour standards across the supply chains of firms that contribute to the production of a particular good or service. This article explores the circumstances in which these ‘socially sustainable sourcing’ mechanisms develop and examines their impact on labour standards, by means of two case studies.
3D pseudo‐seismic imaging of transient electromagnetic data – a feasibility study
Authors: Xue G.Q. , Gelius L.‐J. , Xiu L. , Qi Z.P. , Chen W.Y.
Published: January 2013

We investigate a pseudo‐seismic approach based on the so‐called inverse Q‐transform as an alternative way of processing transient electromagnetic (TEM) data. This technique transforms the diffusive TEM response into that of propagating waves obeying the standard wave‐equation. These transformed data can be input into standard seismic migration schemes with the potential of giving higher resolution subsurface images. Such images contain geometrical and qualitative information about the medium but no quantitative results are obtained as in model‐based inversion techniques. These reconstructed images can be used directly for geological interpretation or in further constraining possible inversions. We extend the original Q‐transform based on an electrical‐source formulation to the case of a large‐loop TEM source. Moreover, an efficient discrete version of the inverse of this modified Q‐transform is presented using a regularization method. Application of this inverse transform to the measured TEM responses gives the corresponding pseudo‐seismic data, which are input into a 3D migration scheme. We then use a 3D boundary element type of Kirchhoff migration to ensure high computational efficiency. This proposed method was applied to both synthetic data as well as field measurements taken from an engineering geology survey. The results indicate that the resolution of the TEM data is significantly improved when compared with standard apparent‐resistivity plots, demonstrating that higher resolution 3D transient electromagnetic imaging is feasible using this method.
A Bayesian approach for estimating detection times in horses: exploring the pharmacokinetics of a urinary acepromazine metabolite
Authors: Mcgree J. M. , Noble G. , Schneiders F. , Dunstan A. J. , Mckinney A. R. , Boston R. , Sillence M.
Published: January 2013

We describe the population pharmacokinetics of an acepromazine (ACP) metabolite (2‐(1‐hydroxyethyl)promazine) (HEPS) in horses for the estimation of likely detection times in plasma and urine.ACP(30 mg) was administered to 12 horses, and blood and urine samples were taken at frequent intervals for chemical analysis. A Bayesian hierarchical model was fitted to describe concentration–time data and cumulative urine amounts forHEPS. The metaboliteHEPSwas modelled separately from the parentACPas the half‐life of the parent was considerably less than that of the metabolite. The clearance (Cl/FPM) and volume of distribution (V/FPM), scaled by the fraction of parent converted to metabolite, were estimated as 769 L/h and 6874 L, respectively. For a typical horse in the study, after receiving 30 mg ofACP, the upper limit of the detection time was 35 h in plasma and 100 h in urine, assuming an arbitrary limit of detection of 1 lg/L and a small (≈0.01) probability of detection. The model derived allowed the probability of detection to be estimated at the population level. This analysis was conducted on data collected from only 12 horses, but we assume that this is representative of the wider population.
Pathological and biochemical outcomes after radical prostatectomy in men with low‐risk prostate cancer meeting the Prostate Cancer International: Active Surveillance criteria
Authors: Mitsuzuka Koji , Narita Shintaro , Koie Takuya , Kaiho Yasuhiro , Tsuchiya Norihiko , Yoneyama Takahiro , Kakoi Narihiko , Kawamura Sadafumi , Tochigi Tatsuo , Habuchi Tomonori , Ohyama Chikara , Arai Yoichi
Published: January 2013

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

Active surveillance has been widely accepted as a treatment tool for low‐risk prostate cancer, and use of the Prostate Cancer Research International: Active Surveillance (PRIAS) criteria can select smaller and less aggressive tumours in low‐risk disease.

The study shows the pathological outcomes of radical prostatectomy for patients with low‐risk disease who met the PRIAS criteria. It found that ∼20% had unfavourable pathological features and only 30% satisfied insignificant cancer criteria with pT2 stage, a Gleason score ≤6 and tumour volume <2.5 mL. It concludes that close follow‐up including repeat biopsy or MRI is necessary to minimize unexpected progression of disease.

Objective

To assess the effectiveness of the Prostate Cancer Research International Active Surveillance (PRIAS) criteria in identifying indolent cancer.

Patients and Methods

Data from 1268 patients undergoing radical prostatectomy without neoadjuvant therapy were retrospectively reviewed.

Within this cohort, patients with low‐risk disease (n = 211) were classified according to whether they met (Group A, n = 87) or did not meet (Group B, n = 124) the PRIAS criteria.

Pathological upstaging, upgrading, tumour volume and 5‐year prostate‐specific antigen (PSA) recurrence‐free survival were compared between the two groups, and factors that predicted upstaging, upgrading and PSA recurrence were analysed by univariate and multivariate methods.

Results

Pathological T3 stage was present in 10.3% of patients in Group A and in 18.5% of patients in Group B (P = 0.08). Gleason score upgrading to 4+3 or greater was seen in 19.5% of Group A and in 29.9% of Group B (P = 0.01).

The mean (range) tumour volume was 0.81 (0.03–5.09) mL in Group A and 1.40 (0.04–8.21) mL in Group B (P < 0.01). The rates of insignificant cancer with total tumour volume <2.5 mL, Gleason score ≤6 and stage pT2 were 30.6% in Group A and 15.4% in Group B (P = 0.07).

With a median follow‐up of 44 months, the 5‐year PSA recurrence‐free survival rates were 91.2% in Group A and 86.4% in Group B (P = 0.47).

In multivariate analysis, PSA density and the PRIAS criteria were independent factors that predicted upstaging.

Conclusions

Although use of the PRIAS criteria could select more favourable tumours even in low‐risk prostate cancer, about one in five men had unfavourable pathological outcomes and only three in ten had insignificant cancer.

Close and careful follow‐up is necessary to avoid misclassification or progression of disease, especially during the first few years of active surveillance.
Ethanol‐Induced Mast Cell‐Mediated Inflammation Leads to Increased Susceptibility of Intestinal Tumorigenesis in the APCΔ468 Min Mouse Model of Colon Cancer
Authors: Wimberly Andre L. , Forsyth Christopher B. , Khan Mohammad W. , Pemberton Alan , Khazaie Khashayarsha , Keshavarzian Ali
Published: January 2013

Background

Chronic and frequent alcohol (ethanol [EtOH]) intake has been associated with an increased incidence of several types of cancers including breast, mouth, throat, esophageal, stomach, and colorectal (CRC). The underlying mechanism of this deleterious carcinogenic effect of alcohol has not been clearly established but inflammation may be 1 unifying feature of these cancers. We have recently shown that intestinal mast cells play a central role in intestinal carcinogenesis. In this study, we tested our hypothesis that mast cell‐mediated inflammation is 1 underlying mechanism by which chronic alcohol promotes intestinal tumorigenesis.

Methods

APCΔ468 mice were fed either an alcohol‐containing Nanji liquid diet or isocaloric dextrose‐containing Nanji diet for 10 weeks and then sacrificed to collect small and large intestine samples. Assessments of tumor number and size as well as mast cell number and mast cell activity and histology score for invasion were compared between Control (dextrose‐fed) and alcohol‐fed APC∆468 mice. The effect of alcohol on mast cell‐mediated tumor migration was also assessed using an in vitro migration assay.

Results

Alcohol feeding increased both polyp number and size within both the small and the large intestines of APC∆468 mice. Only alcohol‐fed mice showed evidence of tumor invasion. Chronic alcohol feeding also resulted in an increased mast cell number and activity in tumor stroma and invading borders. In vitro migration assay showed that alcohol significantly increases mast cell‐mediated tumor migration in vitro.

Conclusions

Our data show that chronic alcohol intake promotes: (i) intestinal tumorigenesis and tumor invasion in genetically susceptible mice; (ii) increases in polyp‐associated mast cells; and (iii) mast cell‐mediated tumor migration in vitro. Both our in vivo and in vitro studies suggest that mast cell‐mediated inflammation could be 1 mechanism by which alcohol promotes carcinogenesis.
Collaborative Care Management Reduces Disparities in Dementia Care Quality for Caregivers with Less Education
Authors: Brown Arleen F. , Vassar Stefanie D. , Connor Karen I. , Vickrey Barbara G.
Published: January 2013

Objectives

To examine educational gradients in dementia care and whether the effect of a dementia collaborative care management intervention varied according to the educational attainment of the informal caregiver.

Design

Analysis of data from a cluster‐randomized controlled trial.

Setting

Eighteen clinics in three healthcare organizations in southern California.

Participants

Dyads of Medicare recipients aged 65 and older with a diagnosis of dementia and an eligible caregiver.

Intervention

Collaborative care management for dementia.

Measurements

Caregiver educational attainment, adherence to four dimensions of guideline‐recommended processes of dementia care (assessment, treatment, education and support, and safety) before and after the intervention, and the adjusted intervention effect (IE) for each dimension stratified according to caregiver education. Each IE was estimated by subtracting the difference between pre‐ and postintervention scores for the usual care participants from the difference between pre‐ and postintervention scores in the intervention participants.

Results

At baseline, caregivers with lower educational attainment provided poorer quality of dementia care for the Treatment and Education dimensions than those with more education, but less‐educated caregivers had significantly more improvement after the intervention on the assessment, treatment, and safety dimensions. The IEs for those who had not graduated from high school were 44.4 for the assessment dimension, 36.9 for the treatment dimension, and 52.7 for the safety dimension, versus 29.5, 15.7, and 40.9 respectively, for college graduates (P < .001 for all three).

Conclusions

Collaborative care management was associated with smaller disparities in dementia care quality between caregivers with lower educational attainment and those with more education.
Racial Differences in the Incidence of and Risk Factors for Atrial Fibrillation in Older Adults: The Cardiovascular Health Study
Authors: Jensen Paul N. , Thacker Evan L. , Dublin Sascha , Psaty Bruce M. , Heckbert Susan R.
Published: January 2013

This study examined whether different associations between risk factors and atrial fibrillation (AF) according to race could explain the lower incidence of AF in blacks. Baseline risk factor information was obtained from interviews, clinical examinations, and echocardiography in 4,774 white and 911 black Cardiovascular Health Study participants aged 65 and older without a history of AF at baseline in 1989/90 or 1992/93. Incident AF was determined according to hospital discharge diagnosis or annual study electrocardiogram. Cox regression was used to assess associations between risk factors and race and incident AF. During a mean 11.2 years of follow‐up, 1,403 whites and 182 blacks had incident AF. Associations between all examined risk factors were similar in both races, except left ventricular posterior wall thickness, which was more strongly associated with AF in blacks (per 0.2 cm, blacks: hazard ratio (HR) = 1.72, 95% confidence interval (CI) = 1.44–2.06; whites: HR = 1.30, 95% CI = 1.18–1.43). Overall, the relative risk of AF was 25% lower in blacks than whites after adjustment for age and sex (HR = 0.75, 95% CI = 0.64–0.87) and 45% lower after adjustment for all considered risk factors (HR = 0.55, 95% CI = 0.35–0.88). Different associations of the considered risk factors and incident AF by race do not explain the lower incidence of AF in blacks.
Ten‐Year Trajectory of Potentially Inappropriate Medications in Very Old Women: Importance of Cognitive Status
Authors: Koyama Alain , Steinman Michael , Ensrud Kristine , Hillier Teresa A. , Yaffe Kristine
Published: January 2013

Objectives

To determine which older adults tend to receive potentially inappropriate medications (PIMs), how this may differ according to cognitive status, and how the trajectories of PIM use change over time.

Design

Ten‐year longitudinal cohort study.

Setting

Three clinical sites in the United States.

Participants

One thousand four hundred eighty‐four community‐dwelling women aged 75 and older.

Measurements

At follow‐up, cognitive status was ascertained and classified as normal, mild cognitive impairment (MCI), or dementia. Beers 2003 criteria and other literature were used to identify PIMs from detailed medication inventory performed at three time points. Anticholinergic load was measured using the Anticholinergic Cognitive Burden Scale (ACB), which assigns medications a value from 0 to 3 depending on anticholinergic properties.

Results

At baseline, 23.9% of women were taking at least one PIM and the mean ± SD ACB score was 1.41 ± 1.69. The most frequently reported PIMs were anticholinergics (15.2%), benzodiazepines (8.6%), and antispasmodics (8.0%). Over 10 years, PIM use increased for women with dementia (24.9–33.1%; P = .02) but remained fairly constant for women with MCI (23.9–23.0%; P = .84) and normal cognitive status (22.2–19.8%; P = .17). Mean ACB score increased significantly (P < .001) over time for all groups (dementia: 1.28–2.05; MCI: 0.98–1.66; normal: 0.99–1.48).

Conclusion

PIM use and anticholinergic load in a community‐dwelling population of older women was high, especially in women who later developed dementia. Future guidelines should limit PIM use and seek safer alternatives.
Stress‐induced changes in gene expression of urocortin 2 and other CRH peptides in rat adrenal medulla: involvement of glucocorticoids
Authors: Tillinger Andrej , Nostramo Regina , Kvetnansky Richard , Serova Lidia , Sabban Esther L.
Published: January 2013

The corticotropin‐releasing hormone (CRH) family regulates the endocrine stress response. Here, we examined the effect of immobilization stress (IMO) on gene expression of adrenomedullary CRH family members. Urocortin 2 (Ucn2) has the highest basal gene expression and is increased by > 30‐fold in response to single IMO and about 10‐fold after six daily repeated IMO. IMO also induced a smaller rise in CRH (six‐fold) and CRH receptor type 1 (CRHR1; two‐fold with single IMO). The influence of glucocorticoids was examined. Dexamethasone (DEX) or corticosterone greatly increased Ucn2 mRNA levels in PC12 cells in a dose‐dependent manner. The DEX elicited rise in Ucn2 was abolished by actinomycin D pre‐treatment, indicating a transcriptionally mediated response. DEX also triggered a rise in CRHR1 and lowered CRH mRNA levels. In CRH‐knockout mice, where the IMO‐induced rise in corticosterone was attenuated, the response of IMO on Ucn2, as well as CRHR2 mRNAs was absent. Overall, the results suggest that the stress‐triggered rise in glucocorticoids is involved in the large induction of Ucn2 mRNA levels by IMO, which may allow Ucn2 to act in an autocrine/paracrine fashion to modulate adrenomedullary function, or act as an endocrine hormone.
The pattern of the coronary arterial orifices in hearts with congenital malformations of the outflow tracts: a marker of rotation of the outflow tract during cardiac development?
Authors: Houyel Lucile , Bajolle Fanny , Capderou André , Laux Daniela , Parisot Pauline , Bonnet Damien
Published: January 2013

Outflow tract defects, including cardiac neural crest defects (so‐called conotruncal defects) and transposition of the great arteries, are due to an abnormal rotation of the outflow tract during cardiac development. Coronary orifices are often abnormal in outflow tract defects, particularly in common arterial trunk (CAT). A recent study indicates that abnormal coronary artery pattern in a mouse model with common arterial outlet (Tbx1−/− mouse mutant) could be due to a reduced and malpositioned subpulmonary coronary‐refractory myocardial domain. The aim of our study was to demonstrate the relation between coronary orifices pattern in outflow tract defects in human and the abnormal embryonic rotation of the outflow tract. We analyzed 101 heart specimens with outflow tract defects: 46 CAT, 15 tetralogy of Fallot (TOF), 29 TOF with pulmonary atresia (TOF‐PA), 11 double‐outlet right ventricle with subaortic ventricular septal defect (DORV) and 17 controls. The position of left and right coronary orifices (LCO, RCO) was measured in degrees on the aortic/truncal circumference. The anterior angle between LCO and RCO (α) was calculated. The LCO was more posterior in TOF (31 °), TOF‐PA (47 °), DORV (44 °), CAT (63 °), compared with controls (0 °, P < 0.05), and more posterior in CAT than in other outflow tract defects (P < 0.05). The RCO was more anterior in TOF (242 °), TOF‐PA (245 °) and DORV (271 °) than in controls (213 °, P < 0.05), but not in CAT (195 °). The α angle was similar in TOF, TOF‐PA, DORV and controls (149 °, 162 °, 133 °, 147 °), but significantly larger in CAT (229 °, P < 0.0001). In all outflow tract defects but CAT, the displacement of LCO (anterior) and RCO (posterior), while the α angle remains constant, might be due to incomplete rotation of the myocardium at the base of the outflow tract, leading to an abnormally positioned subpulmonary coronary‐refractory myocardial domain. The larger α angle in CAT could reflect its dual identity, aortic and pulmonary.
Stability studies of binary and ternary mixtures containing morphine, midazolam, levomepromazine and hyoscine butylbromide for parenteral administration
Authors: Fernandez-Campos Francisco , Mallandrich Mireia , Calpena Ana C , Ayestarán Ana , Lacasa Carmen
Published: January 2013

Objetives

Parenteral (intravenous or subcutaneous) administration is routinely used in palliative medicine because patients are not able to take drugs orally. To avoid excessive injections, several drugs are usually given in the same dose, but the stability of these drugs when mixed is not always known. The aim of this study was to evaluate the stability of several mixtures of drugs (morphine, midazolam, levomepromazine and hyoscine butylbromide) kept under different storage conditions.

Methods

Stability was evaluated on the basis of percentage of drug remaining, pH, change of colour and gas or precipitate formation.

Key findings

The most notable results of the study showed that levomepromazine is rapidly degraded in 0.9% NaCl in all cases, and at high concentrations, morphine can precipitate when stored at 4°C.

Conclusions

Mixtures containing levomepromazine are rapidly degraded under experimental conditions.
Habituation of Sexual Responses in Men and Women: A Test of the Preparation Hypothesis of Women's Genital Responses
Authors: Dawson Samantha J. , Suschinsky Kelly D. , Lalumière Martin L.
Published: January 2013

Introduction

Laboratory studies have revealed two well-replicated sex differences in sexual arousal patterns: category specificity and sexual concordance. Men's genital responses are dependent on specific sexual cues and are concordant with subjective reports of arousal. Women's genital responses are much less dependent on specific sexual cues and are much less concordant with their subjective reports. The preparation hypothesis provides a functional explanation for these sex differences and posits that women's genital responses are not tied to sexual preferences but rather occur automatically in the presence of any sexual cue to protect the genital tissues from injuries incurred through sexual activity. This hypothesis leads to the expectation that women's genital responses may not habituate as quickly or as completely as men's.

Aim

To determine whether there is a sex difference in the habituation of genital responses and to further test the preparation hypothesis of women's genital responses.

Methods

Twenty men and 20 women had their genital responses measured while they were exposed to nine consecutive presentations of the same erotic film clip (habituation), followed by two presentations of different erotic film clips (novelty), and followed by two presentations of the original erotic film clip (dishabituation).

Main Outcome Measures

Genital responses were measured continuously using penile strain gauges (assessing penile circumference) and vaginal probes (assessing vaginal pulse amplitude). Participants reported subjective sexual arousal, perceived genital arousal, and attention after each film clip presentation.

Results

Men and women displayed very similar patterns of genital responses, consistent with habituation and novelty effects. Effects of habituation and novelty were eliminated once subjective reports of attention were covaried.

Conclusion

Contrary to the prediction from the preparation hypothesis of women's genital responses, men's and women's responses showed similar patterns of habituation upon repeated exposure. Future research should attempt to maintain participants' attention in order to further test the preparation hypothesis.
A qualitative study exploring parental accounts of feeding pre‐school children in two low‐income populations in the UK
Authors: Hayter Arabella K.M. , Draper Alizon K. , Ohly Heather R. , Rees Gail A. , Pettinger Clare , McGlone Pauline , Watt Richard G.
Published: January 2013

Good nutrition in the early years of life is essential, yet the diets of many pre‐school children in the UK are known to be poor. Understanding the decisions parents make when feeding young children is very important in determining what type and nature of interventional support may be developed to promote good nutrition. The aim of this study was to explore using qualitative methods, parental perceptions of feeding their children in order to inform the development of a nutrition intervention. Focus groups (n = 33) and individual interviews (n = 6) were undertaken with parents, most of whom were attending children's centres in two deprived populations from one urban (Islington, north London) and one rural (Cornwall) location in England. Accounts of feeding pre‐school children were primarily concerned with dealing with the practicalities of modern life, in particular the cost of food and the need to manage on a restricted household budget. Time pressures, a lack of perceived knowledge and confidence in preparing food and managing conflict over food choices between family members were also strong themes. Parents commonly reported differences between how they would like to feed their children and the reality of what they were able to do in their circumstances. These findings suggest that the poor eating habits of many pre‐school children may be less a case of parental ignorance but rather the product of a range of coping strategies. Designing an intervention, which helps parents to build their confidence and self‐efficacy, may enable them to make positive changes to their children's diets.
Development and validation of a food frequency questionnaire for consumption of polyphenol‐rich foods in pregnant women
Authors: Vian Izabele , Zielinsky Paulo , Zilio Ana Maria , Mello Anne , Lazzeri Bruna , Oliveira Andressa , Lampert Kenya Venusa , Piccoli Antônio , Nicoloso Luis Henrique , Bubols Guilherme Borges , Garcia Solange Cristina
Published: January 2013

Previous studies have shown that maternal consumption of polyphenol‐rich foods after the third trimester of pregnancy may interfere with the anatomical and functional activity of the fetal heart as, to our knowledge, there are no validated instruments to quantify total polyphenols in pregnant women. The aim of this study was evaluate the reproducibility and validity of a food frequency questionnaire (FFQ), with 52 items, to assess the intake of polyphenol‐rich foods in pregnant women in Brazil. This cross‐sectional study included 120 pregnant women who participated in nutritional interviews in two moments. The intake of polyphenols estimated by the developed FFQ was compared with the average of two 24‐h recalls (24HR), with the average intake measured by a 3‐day food diary (D3days) and with the urinary excretion of total polyphenols. The triangular method was applied to calculate Pearson's correlation coefficients, intraclass correlation and Bland–Altman plots for the FFQ, using an independent biochemical marker, in addition to classification by quarters of consumption. The questionnaires were log transformed, adjusted for body mass index and gestational age. The adjustment for energy was applied only of 24HR and D3days. Analysis of the reproducibility between the FFQ showed a very high correlation (r = 0.72; P < 0.05). A low but significant association was observed between the FFQ and urinary excretion (0.23; P = 0.01). The association between the dietary survey methods was moderate to very high (r = 0.36 to r = 0.72; P < 0.001). In conclusion, this questionnaire showed reproducibility and validity for the quantification of consumption of total polyphenols in pregnant women.
The transcriptional regulator TamR from Streptomyces coelicolor controls a key step in central metabolism during oxidative stress
Authors: Huang Hao , Grove Anne
Published: January 2013

Multiple antibiotic resistance regulator (MarR) family transcriptional regulators usually regulate gene activity by responding to specific ligands. Here we show that TamR (trans‐aconitate methyltransferase regulator), a MarR homologue from Streptomyces coelicolor, functions in oxidative stress responses to regulate a key step in central metabolism. The gene encoding TamR is oriented divergently from the tam gene, which encodes trans‐aconitate methyltransferase. Trans‐aconitate methyltransferase methylates trans‐aconitate, which is formed when cis‐aconitate is released during aconitase‐mediated isomerization of citrate to isocitrate; trans‐aconitate, but not its methyl ester, is a potent inhibitor of aconitase. We show that TamR binds with high affinity to the intergenic region between the tamR and tam genes. Notably, trans‐aconitate attenuates DNA‐binding by TamR, as do citrate, cis‐aconitate and isocitrate, which are the substrate, intermediate and product of aconitase respectively. In vivo, hydrogen peroxide and citrate induce significant upregulation of the tam (SCO3132), tamR (SCO3133) and aconitase (SCO5999) genes. Since oxidative stress leads to disassembly of the [4Fe‐4S] cluster that is essential for aconitase activity, resulting in accumulation of citrate and release of cis‐aconitate and its subsequent conversion to trans‐aconitate, we propose that TamR mediates a novel regulatory function in which the inhibitory effects of trans‐aconitate and accumulated citrate are alleviated.