bluuebunny/crossref_metadata_2025 huggingface dataset:
The study design and characteristics of the Danish national health interview surveys
Authors: Ekholm Ola , Hesse Ulrik , Davidsen Michael , Kjøller Mette
Published: July 2009

Aims: The Danish National Institute of Public Health, University of Southern Denmark has carried out national representative health interview surveys among adult Danes in 1987, 1994, 2000 and 2005. The aim of this study is to describe the characteristics of the design, including the response rates of the four surveys. Methods: The samples in 1987 and 1994 are based on simple random sampling. The samples in 2000 and 2005 are based on stratified random sampling. In addition, all invited to the survey in 1994 were re-invited in both 2000 and 2005. Data were collected via face-to-face interview at the respondent’s home. Following the interview in 1994, 2000 and 2005, all respondents were asked to complete a self-administered questionnaire. Results: The response rate for the face-to-face interview fell from 79.9% in 1987 to 66.7% in 2005 and the response rate for the self-administered questionnaire from 68.1% in 1994 to 51.5% in 2005. The decrease is particularly marked among the young. The mean interview length has increased from 33.3 minutes in 1987 to 50.2 minutes in 2005. Conclusions: The declining response rate in the surveys is a major concern and can pose problems in generalizing data from the surveys to the Danish population. However, these surveys are essential, as the information collected cannot be gathered by means of official statistical registers. Hence, efforts to increase the response rate will be important in the forthcoming surveys.
Not Quite Crisp, Not Yet Fuzzy? Assessing the Potentials and Pitfalls of Multi-value QCA
Authors: Vink Maarten P. , Van Vliet Olaf
Published: July 2009

This article assesses the strengths and shortcomings of multi-value qualitative comparative analysis (mvQCA), a comparative technique for small- to medium-sized data sets that has been integrated in the TOSMANA software developed by Lasse Cronqvist. The main difference with “crisp-set” QCA is that in mvQCA, the conditions can have more values than just the Boolean values 0 and 1, whereas the main difference with “fuzzy-set” QCA is that mvQCA conditions remain discrete. The major advantage of nondichotomous categorization, according to its proponents, is that it reduces the likelihood of contradictory configurations because of a more homogeneous grouping of cases. We give an overview of existing mvQCA applications, with a detailed discussion of two recent publications, and argue that crisp-set and fuzzy-set alternatives should be less easily discarded, as the mvQCA solution comes with substantial set-theoretical costs.
Implications of Emotional Eating Beliefs and Reactance to Dietary Advice for the Treatment of Emotional Eating and Outcome Following Roux-en-Y Gastric Bypass
Authors: Chesler Betty E. , Harris Bernadette G. , Oestreicher Pamela H.
Published: July 2009

This case describes cognitive—behavioral treatment for emotional eating, preceding and following Roux-en-Y gastric bypass, which is associated with 84.52% excess BMI (body mass index) loss 53 months after surgery. It explores the relevance of emotional eating beliefs (EEB; that is, equating food with both alleviation of negative feelings and friendship) and reactance to dietary advice (RDA; that is, rebelling against prescribed nutrition) for the deliberate use of food to feel both better and befriended. EEB and RDA motivate and justify, respectively, the conscious consumption of rich or “forbidden” foods. Simultaneous treatment of EEB and RDA is associated with the utilization of rational thinking and problem solving to cope with emotional discomfort. Remediation of equations of food with friendship engenders amelioration of distress through spousal support. Unrecognized emotional distress fueling reflexive eating and accompanying external eating are found. External eating is decreased coincident with therapy for emotional eating. Implications are discussed.
Endovascular Therapy for Symptomatic Mobile Thrombus of Infrarenal Abdominal Aorta
Authors: Luckeroth Patricia , Steppacher Robert , Rohrer Michael J. , Eslami Mohammad H.
Published: July 2009

Mobile thrombus is a rare cause of distal arterial embolization. We report 2 cases of mobile thrombus of the abdominal aorta leading to distal embolization. Both patients were successfully treated with endovascular exclusion of the thrombus and distal embolectomy. Endovascular exclusion of a mobile thrombus of the abdominal aorta is a significantly less invasive alternative to open abdominal aorta thrombectomy.
Distinct spatio-temporal Ca2+ signaling elicited by integrin α2β1 and glycoprotein VI under flow
Authors: Mazzucato Mario , Cozzi Maria Rita , Battiston Monica , Jandrot-Perrus Martine , Mongiat Maurizio , Marchese Patrizia , Kunicki Thomas J. , Ruggeri Zaverio M. , De Marco Luigi
Published: July 2009

We studied how integrin α2β1 and glycoprotein VI (GPVI) contribute to collagen-induced platelet activation under flow conditions by evaluating stable adhesion and intracellular Ca2+ concentration ([Ca2+]i) of FLUO 3-AM–labeled platelets perfused over acid-soluble type I or microfibrillar type VI collagen. Adhering platelets displayed 2 kinds of [Ca2+]i oscillations. Rapid α-like peaks were unaffected by the membrane-impermeable Ca2+ chelator ethyleneglycoltetraacetic acid but abolished by membrane-permeable BAPTA-AM. Longer-lasting γ-like peaks were always preceded by at least one α-like peak and abolished by intracellular or extracellular Ca2+ chelation. Inhibition of phosphatidylinositol 3-kinase or phospholipase C and modulation of cyclic nucleotides, but not blockage of adenosine diphosphate receptors, prevented both Ca2+ responses. Human or mouse platelets lacking GPVI function exhibited α-like but not γ-like Ca2+ peaks, whereas those lacking α2β1 showed markedly reduced to absent α-like and no γ-like Ca2+ peaks. Specific α2β1 ligation induced α-like but not γ-like peaks. Thus, α2β1 may generate Ca2+ signals that are reinforced by GPVI and required for subsequent longer-lasting Ca2+ oscillation mediated by GPVI through transmembrane ion flux. Our results delineate a GPVI-independent signaling role of α2β1 in response to collagen stimulation.
Risk factors for inadequate prenatal care use in the metropolitan area of Aracaju, Northeast Brazil
Authors: Ribeiro Eleonora RO , Guimarães Alzira Maria DN , Bettiol Heloísa , Lima Danilo DF , Almeida Maria Luiza D , de Souza Luiz , Silva Antônio Augusto M , Gurgel Ricardo Q
Published: July 2009

Background

The aim of prenatal care is to promote good maternal and foetal health and to identify risk factors for adverse pregnancy outcomes in an attempt to promptly manage and solve them. Although high prenatal care attendance is reported in most areas in Brazil, perinatal and neonatal mortalities are disproportionally high, raising doubts about the quality and performance of the care provided. The objective of the present study was to evaluate the adequacy of prenatal care use and the risk factors involved in inadequate prenatal care utilization in the metropolitan area of Aracaju, Northeast Brazil.

Methods

A survey was carried out with puerperal women who delivered singleton liveborns in all four maternity hospitals of Aracaju. A total of 4552 singleton liveborns were studied. The Adequacy of Prenatal Care Utilization Index, modified according to the guidelines of the Prenatal Care and Birth Humanization Programme, was applied. Socioeconomic, demographic, biological, life style and health service factors were evaluated by multiple logistic regression. Results: Prenatal care coverage in Aracaju was high (98.3%), with a mean number of 6.24 visits. Prenatal care was considered to be adequate or intensive in 66.1% of cases, while 33.9% were considered to have inadequate usage. Age < 18 to 34 years at delivery, low maternal schooling, low family income, two or more previous deliveries, maternal smoking during pregnancy, having no partner and prenatal care obtained outside Aracaju were associated with inadequate prenatal care use. In contrast, private service attendance protected from inadequate prenatal care use.

Conclusion

Prenatal care coverage was high. However, a significant number of women still had inadequate prenatal care use. Socioeconomic inequalities, demographic factors and behavioural risk factors are still important factors associated with inadequate prenatal care use.
"Good idea but not feasible" – the views of decision makers and stakeholders towards strategies for better palliative care in Germany: a representative survey
Authors: Lueckmann Sara Lena , Behmann Mareike , Bisson Susanne , Schneider Nils
Published: July 2009

Background

Statements on potential measures to improve palliative care in Germany predominantly reflect the points of view of experts from specialized palliative care organizations. By contrast, relatively little is known about the views of representatives of organizations and institutions that do not explicitly specialize in palliative care, but are involved to a relevant extent in the decision-making and policy-making processes. Therefore, for the first time in Germany, we carried out a representative study of the attitudes of a broad range of different stakeholders acting at the national or state level of the health care system.

Methods

442 organizations and institutions were included and grouped as follows: patient organizations, nursing organizations, medical associations, specialized palliative care organizations, political institutions, health insurance funds and others. Using a standardized questionnaire, the participants were asked to rate their agreement with the World Health Organization's definition of palliative care (five-point scale: 1 = completely agree, 5 = completely disagree) and to evaluate 18 pre-selected improvement measures with regard to their general meaningfulness and the feasibility of their introduction into the German health care system (two-point scale: 1 = good, 2 = poor).

Results

The response rate was 67%. Overall, the acceptance of the aims of palliative care in the WHO definition was strong. However, the level of agreement among health insurance funds' representatives was significantly less than that among representatives of the palliative care organizations. All the improvement measures selected for evaluation were rated significantly higher in respect of their meaningfulness than of their feasibility in Germany. In detail, the meaningfulness of 16 measures was evaluated positively (70–100% participants chose the answer "good"); for six of these measures feasibility was evaluated negatively (0–30% "good"), while for the remaining ten measures feasibility was evaluated inconsistently (31–69% "good").

Conclusion

The reason why potentially meaningful improvement measures are considered to be not very feasible in Germany may be the existence of barriers resulting from the high degree of fragmentation of health care provision and responsibilities. In overcoming these barriers and further improving palliative care it may be helpful that the basic understanding of the palliative care approach seems to be quite homogenous among the different groups.
Use of dried blood for measurement of trans fatty acids
Authors: Gupta Ruby , Abraham Ransi Ann , Dhatwalia Savita , Ramakrishnan Lakshmy , Prabhakaran Dorairaj , Reddy Kolli Srinath
Published: July 2009

Background

Fatty acid measurements especially trans fatty acid has gained interest in recent times. Among the various available biomarkers, adipose tissue is considered to be the best for the long term dietary intake but the invasive nature of tissue aspiration reduces its utility. Phlebotomy is a much less invasive method of sample collection when a large number of participants are involved in the study and therefore is an alternative, most suitable for large population based studies. In the present study fatty acid (with special emphasis on trans fatty acid) extraction from blood spotted and dried on filter paper was carried out to simplify the sample collection procedure and transportation.

Methods

Blood samples were collected from 19 healthy volunteers. The blood was spotted (30 spots of 10 μl each) on filter paper, dried at room temperature and stored at 4°C in zip-lock poly bags. For comparison whole blood stored at -70°C was simultaneously analyzed.

Results

A good agreement was seen between trans fatty acid values obtained in dried blood and whole blood as evident from the pearson correlation coefficients ('r' for monounsaturated (trans) 0.70 and for polyunsaturated (trans) 0.692 respectively). The intraclass correlation coefficient for monounsaturated trans was 0.805 and for polyunsarurated trans was 0.776.

Conclusion

Dried blood spots can be used for trans fatty acid analysis.
DOMINO-AD protocol: donepezil and memantine in moderate to severe Alzheimer's disease – a multicentre RCT
Authors: Jones Rob , Sheehan Bart , Phillips Patrick , Juszczak Ed , Adams Jessica , Baldwin Ashley , Ballard Clive , Banerjee Sube , Barber Bob , Bentham Peter , Brown Richard , Burns Alistair , Dening Tom , Findlay David , Gray Richard , Griffin Mary , Holmes Clive , Hughes Alan , Jacoby Robin , Johnson Tony , Jones Roy , Knapp Martin , Lindesay James , McKeith Ian , McShane Rupert , Macharouthu Ajay , O'Brien John , Onions Caroline , Passmore Peter , Raftery James , Ritchie Craig , Howard Rob ,   the DOMINO-AD team
Published: July 2009

Background

Alzheimer's disease (AD) is the commonest cause of dementia. Cholinesterase inhibitors, such as donepezil, are the drug class with the best evidence of efficacy, licensed for mild to moderate AD, while the glutamate antagonist memantine has been widely prescribed, often in the later stages of AD. Memantine is licensed for moderate to severe dementia in AD but is not recommended by the England and Wales National Institute for Health and Clinical Excellence. However, there is little evidence to guide clinicians as to what to prescribe as AD advances; in particular, what to do as the condition progresses from moderate to severe. Options include continuing cholinesterase inhibitors irrespective of decline, adding memantine to cholinesterase inhibitors, or prescribing memantine instead of cholinesterase inhibitors. The aim of this trial is to establish the most effective drug option for people with AD who are progressing from moderate to severe dementia despite treatment with donepezil.

Method

DOMINO-AD is a pragmatic, 15 centre, double-blind, randomized, placebo controlled trial. Patients with AD, currently living at home, receiving donepezil 10 mg daily, and with Standardized Mini-Mental State Examination (SMMSE) scores between 5 and 13 are being recruited. Each is randomized to one of four treatment options: continuation of donepezil with memantine placebo added; switch to memantine with donepezil placebo added; donepezil and memantine together; or donepezil placebo with memantine placebo. 800 participants are being recruited and treatment continues for one year. Primary outcome measures are cognition (SMMSE) and activities of daily living (Bristol Activities of Daily Living Scale). Secondary outcomes are non-cognitive dementia symptoms (Neuropsychiatric Inventory), health related quality of life (EQ-5D and DEMQOL-proxy), carer burden (General Health Questionnaire-12), cost effectiveness (using Client Service Receipt Inventory) and institutionalization. These outcomes are assessed at baseline, 6, 18, 30 and 52 weeks. All participants will be subsequently followed for 3 years by telephone interview to record institutionalization.

Discussion

There is considerable debate about the clinical and cost effectiveness of anti-dementia drugs. DOMINO-AD seeks to provide clear evidence on the best treatment strategies for those managing patients at a particularly important clinical transition point.

Trial registration

Current controlled trials ISRCTN49545035
Quasi-MSn identification of flavanone 7-glycoside isomers in Da Chengqi Tang by high performance liquid chromatography-tandem mass spectrometry
Authors: Xu Fengguo , Liu Ying , Zhang Zunjian , Yang Cheng , Tian Yuan
Published: July 2009

Background

Da Chengqi Tang (DCT) is a common purgative formula in Chinese medicine. Flavanones are its major active compounds derived from Fructus Aurantii Immaturus. The present study developed an LC-MS/MS method to characterize two pairs of flavanone 7-glycoside isomers, i.e., hesperidin versus neohesperidin and naringin versus isonaringin.

Methods

After solid phase purification, components in sample were separated on a Agilent zorbax SB-C18 (5 μm, 250 mm × 4.6 mm) analytical column. ESI-MS and quasi-MSn were performed in negative ion mode to obtain structural data of these two pairs of flavanone 7-glycoside isomers. Moreover, UV absorption was measured.

Results

There was no intra-pairs difference in the UV-Vis and MS/MS spectra of the two pairs of 7-glycoside isomers, whereas the mass spectrometry fragmentation pathways between pairs were different.

Conclusion

The present study developed a LC-MS/MS method to explore the inter- and intra-pair difference of two pairs of flavanone 7-glycoside isomers.
Pulmonary nocardiosis in the acquired immunodeficiency syndrome, computed tomographic findings: a case report
Authors: Sarcinelli-Luz Branca , Marchiori Edson , Zanetti Gláucia , Mano Claudia Mauro , Abdalla Flávia , Carvalho Juliana França , Assed Carla , Santos Isabella Guedes
Published: July 2009

The authors describe a case of pulmonary nocardiosis in a 37-year-old man with acquired immunodeficiency syndrome in treatment with antiretroviral drugs. Clinical symptoms were productive cough, hemoptysis and progressive weight loss. A chest x-ray showed a right upper lobe consolidation while the computed tomography demonstrated consolidation with air bronchogram and airspace nodules. The radiologic findings were unspecific. Consequently, a bronchoscopy with bronchoalveolar lavage was performed, revealing filamentous Gram-positive bacteria (Nocardia species). Treatment with trimethoprim-sulfamethoxazole resulted in complete remission of the respiratory symptoms.
Hourglass urinary bladder in a spinal cord injury patient - unusual late complication of suprapubic cystostomy: a case report
Authors: Vaidyanathan Subramanian , Hughes Peter L , Soni Bakul M , Singh Gurpreet , Mansour Paul
Published: July 2009

Introduction

Suprapubic cystostomy is performed in spinal cord injury patients in order to prevent complications associated with long-term urethral catheter drainage. We report a patient in whom suprapubic catheter did not drain urine satisfactorily and imaging studies revealed hourglass bladder.

Case presentation

A female patient sustained paraplegia in a traffic accident in 1994 at the age of seventeen years. When she was discharged from spinal unit, she was performing self- catheterisations. In 1995, indwelling urethral catheter drainage was instituted, as she was not able to cope up with self-catheterisations. Intravenous urography, performed in 1994, 1997, 2000 and 2003 showed urinary bladder of normal shape. In 2004, this patient developed frequent blockages and bypassing of catheter; therefore, suprapubic cystostomy was performed. In 2005, she was leaking urine per urethra; therefore, an indwelling catheter was inserted; both suprapubic and urethral catheters drained urine. In 2008, suprapubic catheter failed to drain any urine. Cystogram revealed hourglass bladder. The balloon of suprapubic Foley catheter was located in the upper compartment of hourglass bladder whereas the urethral catheter was placed in the inferior compartment. Ultrasound examination of urinary bladder showed two compartments of hourglass bladder separated by a narrow waist. Computed tomography cystogram delineated smaller superior and larger inferior compartment of the hourglass bladder. At present this patient is happy to manage her bladder with suprapubic and urethral catheters.

Conclusion

When prompt replacement of a mal-functioning suprapubic catheter fails to rectify the problem, computer tomography cystography should be performed to check precise location of suprapubic catheter and structural abnormalities of urinary bladder. In this patient, cystogram revealed hourglass bladder. Possible reasons for development of hourglass bladder in spinal cord injury patients are: traction applied to dome of urinary bladder by Foley balloon when suprapubic catheter is taped tightly to anterior abdominal wall for several months; uncoordinated contractions of detrusor muscle; chronic cystitis leading to hypertrophy of bladder wall.
Isolated common femoral artery aneurysm: a case report
Authors: Sharma Saurabh , Nalachandran Sanjay
Published: July 2009

Introduction

Isolated aneurysm of common femoral artery is a rare occurrence. They may mimic other common conditions like groin lymph nodes or groin hernia.

Case presentation

Here we present a case of 61-years-old Chinese gentleman who presented with a right groin lump, which was suspected to be groin hernia but turned out common femoral artery aneurysm. The aneurysm was surgically excised and a prosthetic vascular repair was done.

Conclusion

Isolated common femoral artery aneurysms are rare and can mimic groin hernias, so one must be careful. Color Doppler is the investigation of choice. Best treatment modality is surgical excision with repair with or without graft for aneurysms > 2.5 cm.
Rigid fibrescope Bonfils: use in simulated difficult airway by novices
Authors: Piepho Tim , Noppens Rüdiger R , Heid Florian , Werner Christian , Thierbach Andreas R
Published: July 2009

Background

The Bonfils intubation fibrescope is a promising alternative device for securing the airway. We examined the success rate of intubation and the ease of use in standardized simulated difficult airway scenarios by physicians. We compared the Bonfils to a classical laryngoscope with Macintosh blade.

Methods

30 physicians untrained in the use of rigid fibrescopes but experienced in airway management performed endotracheal intubation in an airway manikin (SimMan, Laerdal, Kent, UK) with three different airway conditions. We evaluated the success rate using the Bonfils (Karl Storz, Tuttlingen, Germany) or the Macintosh laryngoscope, the time needed for securing the airway, and subjective rating of both techniques.

Results

In normal airway all intubations were successful using laryngoscope (100%) vs. 82% using the Bonfils (p < 0.05). In the scenario "tongue oedema" success rate using the Macintosh laryngoscope was 67% and 83% using the Bonfils. In the scenario "decreased cervical range of motion with jaw trismus", success rate using the Macintosh laryngoscope was 84% vs. 76%. In difficult airway scenarios time until airway was secured did not differ between the two devices. Use of Bonfils was rated "easier" in both difficult airway scenarios.

Conclusion

The Bonfils can be successfully used by physicians unfamiliar with this technique in an airway manikin. The airway could be secured with at least the same success rate as using a Macintosh laryngoscope in difficult airway scenarios. Use of the Bonfils did not delay intubation in the presence of a difficult airway. These results indicate that intensive special training is advised to use the Bonfils effectively in airway management.
Uric acid is a strong independent predictor of renal dysfunction in patients with rheumatoid arthritis
Authors: Daoussis Dimitrios , Panoulas Vasileios , Toms Tracey , John Holly , Antonopoulos Ioannis , Nightingale Peter , Douglas Karen MJ , Klocke Rainer , Kitas George D
Published: July 2009

Introduction

Recent evidence suggests that uric acid (UA), regardless of crystal deposition, may play a direct pathogenic role in renal disease. We have shown that UA is an independent predictor of hypertension and cardiovascular disease (CVD), and that CVD risk factors associate with renal dysfunction, in patients with rheumatoid arthritis (RA). In this study we investigated whether UA associates with renal dysfunction in patients with RA and whether such an association is independent or mediated through other comorbidities or risk factors for renal impairment.

Methods

Renal function was assessed in 350 consecutive RA patients by estimated glomerular filtration rate (GFR) using the six-variable Modification of Diet in Renal Disease equation. Risk factors for renal dysfunction were recorded or measured in all participants. Linear regression was used to test the independence of the association between GFR and UA.

Results

Univariable analysis revealed significant associations between GFR and age, systolic blood pressure, total cholesterol, triglycerides, RA duration and UA. UA had the most powerful association with renal dysfunction (r = -0.45, P < 0.001). A basic model was created, incorporating all of the above parameters along with body mass index and gender. UA ranked as the first correlate of GFR (P < 0.001) followed by age. Adjustments for the use of medications (diuretics, low-dose aspirin, cyclooxygenase II inhibitors and nonsteroidal anti-inflammatory drugs) and further adjustment for markers of inflammation and insulin resistance did not change the results.

Conclusions

UA is a strong correlate of renal dysfunction in RA patients. Further studies are needed to address the exact causes and clinical implications of this new finding. RA patients with elevated UA may require screening for renal dysfunction and appropriate management.
A novel role for signal transducer and activator of transcription 5b (STAT5b) in β1-integrin-mediated human breast cancer cell migration
Authors: Bernaciak Teresa M , Zareno Jessica , Parsons J Thomas , Silva Corinne M
Published: July 2009

Introduction

Signal transducer and activator of transcription (STAT) 5b is a transcription factor involved in pro-proliferative and pro-survival signaling in a number of solid tumors, including breast cancer. The contribution of STAT5b to breast cancer cell motility has not been explored. This work aims to elucidate the role of STAT5b in breast cancer cell migration.

Methods

STAT5b was knocked down by using siRNA in two aggressive, highly migratory breast cancer cell lines (BT-549 and MDA-MB-231), and transwell migration assays were performed to determine the importance of STAT5b for their migration. Knockdown-rescue experiments were used to validate the specificity of STAT5b knockdown and to determine which regions/functions of STAT5b are necessary for its role in migration. Live-cell imaging of wound healing and spreading was carried out to examine cell morphology and motility after STAT5b knockdown.

Results

Knockdown of STAT5b, but not STAT5a, inhibited migration of BT-549 and MDA-MB-231 breast cancer cells to serum by 60% to 80%, and inhibited migration equally over a range of serum concentrations (0.1% to 10% serum). Migratory inhibition upon STAT5b knockdown could be rescued by reintroduction of wild-type STAT5b, as well as Y699F- and dominant-negative STAT5b mutants, but not an SH2 domain defective R618K-STAT5b mutant. β1- integrin-mediated migration of breast cancer cells to fibronectin was inhibited with STAT5b knockdown, and loss of STAT5b correlated with loss of directional migration and formation of multiple, highly contractile protrusions upon attachment to fibronectin.

Conclusions

The data presented here demonstrate that STAT5b is integral to breast cancer cell migration and identify a novel, SH2-dependent function of STAT5b in regulating β1-integrin-mediated migration of highly aggressive breast cancer cells.
Differential Endothelin Receptor Expression and Function in Rat Myometrial Cells and Leiomyoma ELT3 Cells
Authors: Raymond Marie-Noëlle , Robin Philippe , De Zen Federica , Vilain Ginette , Tanfin Zahra
Published: July 2009

Uterine leiomyoma are the most common benign tumors of the myometrium. We previously identified endothelin (ET)-1 as a proliferative and antiapoptotic factor in Eker rat-derived leiomyoma (ELT3) cells. A major role of ETB receptor in the prosurvival effect was revealed. Here we investigated, in ELT3 and myometrial cells, the respective contribution of ETA and ETB in the proliferative effect of ET-1. In myometrial cells, binding experiments show that ETA is almost exclusively expressed and stimulates phospholipase C (PLC) activity and ERK1/2 phosphorylation and proliferation. In ELT3 cells, ETB is expressed at about the same level as ETA, and the two receptors are differently coupled to Gi protein. The ETB agonist, sarafotoxin S6c, stimulates PLC activity 60% less than ET-1 but is as potent as ET-1 to increase ERK1/2 phosphorylation and induce proliferation. However, the ability of ETA to activate ERK1/2 is observed after ETB desensitization. Although ETA and ETB antagonists partially reduce ET-1 stimulated PLC activity, they are without effect on ET-1-induced ERK1/2 phosphorylation and proliferation. Only the simultaneous use of ETA and ETB antagonists reduces ET-1-triggered ERK1/2 activation. These unconventional properties of ETRs may reveal the existence of functional ETA-ETB heterodimers. Finally, treatment of ELT3 cells with ETB but not ETA-directed small interfering RNA reduces the proliferative effect of ET-1. All the data obtained in ELT3 cells strengthen the relation between ETB overexpression, which decreases the ETA to ETB ratio, and the ability of leiomyoma cells to highly proliferate and resist apoptosis.
Low- and High-Density Lipoproteins Modulate Function, Apoptosis, and Proliferation of Primary Human and Murine Pancreatic β-Cells
Authors: Rütti Sabine , Ehses Jan A. , Sibler Rahel A. , Prazak Richard , Rohrer Lucia , Georgopoulos Spiros , Meier Daniel T. , Niclauss Nadja , Berney Thierry , Donath Marc Y. , von Eckardstein Arnold
Published: July 2009

A low high-density lipoprotein (HDL) plasma concentration and the abundance of small dense low-density lipoproteins (LDL) are risk factors for developing type 2 diabetes. We therefore investigated whether HDL and LDL play a role in the regulation of pancreatic islet cell apoptosis, proliferation, and secretory function. Isolated mouse and human islets were exposed to plasma lipoproteins of healthy human donors. In murine and human β-cells, LDL decreased both proliferation and maximal glucose-stimulated insulin secretion. The comparative analysis of β-cells from wild-type and LDL receptor-deficient mice revealed that the inhibitory effect of LDL on insulin secretion but not proliferation requires the LDL receptor. HDL was found to modulate the survival of both human and murine islets by decreasing basal as well as IL-1β and glucose-induced apoptosis. IL-1β-induced β-cell apoptosis was also inhibited in the presence of either the delipidated protein or the deproteinated lipid moieties of HDL, apolipoprotein A1 (the main protein component of HDL), or sphingosine-1-phosphate (a bioactive sphingolipid mostly carried by HDL). In murine β-cells, the protective effect of HDL against IL-1β-induced apoptosis was also observed in the absence of the HDL receptor scavenger receptor class B type 1. Our data show that both LDL and HDL affect function or survival of β-cells and raise the question whether dyslipidemia contributes to β-cell failure and hence the manifestation and progression of type 2 diabetes mellitus.
Complex Regulation of Mammalian Target of Rapamycin Complex 1 in the Basomedial Hypothalamus by Leptin and Nutritional Status
Authors: Villanueva Eneida C. , Münzberg Heike , Cota Daniela , Leshan Rebecca L. , Kopp Keely , Ishida-Takahashi Ryoko , Jones Justin C. , Fingar Diane C. , Seeley Randy J. , Myers Martin G.
Published: July 2009

The medial basal hypothalamus, including the arcuate nucleus (ARC) and the ventromedial hypothalamic nucleus (VMH), integrates signals of energy status to modulate metabolism and energy balance. Leptin and feeding regulate the mammalian target of rapamycin complex 1 (mTORC1) in the hypothalamus, and hypothalamic mTORC1 contributes to the control of feeding and energy balance. To determine the mechanisms by which leptin modulates mTORC1 in specific hypothalamic neurons, we immunohistochemically assessed the mTORC1-dependent phosphorylation of ribosomal protein S6 (pS6). In addition to confirming the modulation of ARC mTORC1 activity by acute leptin treatment, this analysis revealed the robust activation of mTORC1-dependent ARC pS6 in response to fasting and leptin deficiency in leptin receptor-expressing Agouti-related protein neurons. In contrast, fasting and leptin deficiency suppress VMH mTORC1 signaling. The appropriate regulation of ARC mTORC1 by mutant leptin receptor isoforms correlated with their ability to suppress the activity of Agouti-related protein neurons, suggesting the potential stimulation of mTORC1 by the neuronal activity. Indeed, fasting- and leptin deficiency-induced pS6-immunoreactivity (IR) extensively colocalized with c-Fos-IR in ARC and VMH neurons. Furthermore, ghrelin, which activates orexigenic ARC neurons, increased ARC mTORC1 activity and induced colocalized pS6- and c-Fos-IR. Thus, neuronal activity promotes mTORC1/pS6 in response to signals of energy deficit. In contrast, insulin, which activates mTORC1 via the phosphatidylinositol 3-kinase pathway, increased ARC and VMH pS6-IR in the absence of neuronal activation. The regulation of mTORC1 in the basomedial hypothalamus thus varies by cell and stimulus type, as opposed to responding in a uniform manner to nutritional and hormonal perturbations.
Lower Zinc-α2-Glycoprotein Production by Adipose Tissue and Liver in Obese Patients Unrelated to Insulin Resistance
Authors: Selva David M. , Lecube Albert , Hernández Cristina , Baena Juan A. , Fort José M. , Simó Rafael
Published: July 2009

Context: Zinc-α2 glycoprotein (ZAG) has been proposed as a new candidate in the pathogenesis of obesity, but most of the information stems from studies performed in rodents and in vitro assays.

Objective: The main aim of the study was to compare serum levels of ZAG and its expression (mRNA levels and protein) in adipose tissue and the liver between obese and nonobese subjects. The relationship between ZAG and insulin resistance was also explored.

Design: This was a case-control study.

Setting: The study was conducted at a university referral center.

Patients and Methods: Samples of serum, sc adipose tissue (SAT), visceral adipose tissue (VAT), and liver were obtained from 20 obese subjects during bariatric surgery. Samples from 10 nonobese patients matched by age and gender were used as a control group. Serum ZAG levels were determined by ELISA. ZAG mRNA levels were measured by real-time PCR and protein content by Western blot. The effect of insulin on liver production of ZAG was assessed using HepG2 cultures.

Results: Serum concentration of ZAG (micrograms per milliliter) was significantly lower in obese subjects (40.87 ± 10.45 vs. 63.26 ± 16.40; P = 0.002). ZAG expression was significantly lower in the adipose tissue (SAT and VAT) and liver of obese patients than in control subjects. Significant negative correlations between body mass index and circulating ZAG (r = −0.65, P < 0.001) as well as between body mass index and mRNA ZAG levels in SAT (r = −0.68, P < 0.001) and VAT were detected (r = −0.64, P < 0.001). No relationship was found between ZAG and homeostasis model assessment for insulin resistance and insulin had no effect on ZAG production in vitro.

Conclusion: A down-regulation of ZAG in SAT, VAT, and liver exists in obese patients but seems unrelated to insulin resistance.

A downregulation of zinc-α2 glycoprotein in adipose tissue and liver exists in obese patients, and it is unrelated to insulin resistance.
Single Payers, Multiple Systems: The Scope and Limits of Subnational Variation Under a Federal Health Policy Framework
Authors: Tuohy Carolyn Hughes
Published: July 2009

In political discourse, the term “single-payer system” originated in an attempt to stake out a middle ground between the public and private sectors in providing universal access to health care. In this view, a single-payer system is one in which health care is financed by government and delivered by privately owned and operated health care providers. The term appears to have been coined in U.S. policy debates to provide a rhetorical reference point for universal health insurance other than the “socialized medicine” of state-owned and -operated health care providers. This article, like others in this special issue, is meant to provide a more nuanced view of singe-payer systems. In particular, it reviews experience in the prototypical single-payer system for physician and hospital services: the Canadian case. Given Canada's federal governance structure, this example also aptly illuminates the scope and limits of subnational variation within this single model of health care finance. And what it demonstrates in essence is that the very feature that defines the single-payer prototype—the maintenance of independent providers remunerated by a single public payer in each province—also leads to a set of profession-state bargains that define the limits of variation.
Gap and Parallel Insurance in Health Care Systems with Mandatory Contributions to a Single Funding Pool for Core Medical and Hospital Benefits for All Citizens in Any Given Geographic Area
Authors: White Joseph
Published: July 2009

Single-pool systems as defined in this article may be accompanied by two forms of voluntary health insurance (VHI): gap coverage for benefits not included in the statutory arrangement and parallel coverage through which individuals pay extra for ostensibly superior versions of the statutory benefits. In all cases the markets for this coverage are much smaller than the market for private insurance in the United States. In each case, the market for VHI depends on perceived inadequacy in the statutory system. With gap coverage, the extent of the statutory benefit package is a more basic issue than the gap coverage itself. Parallel coverage raises more significant independent issues. It is particularly related to the dynamics and politics of waiting lists in the statutory system. Waiting lists appear to be a greater concern in single-pool systems than in social insurance systems due to the effects of having spending on a government's budget and some perverse incentives for physicians. Single-pool approaches are less politically plausible in the United States than adaptation of social insurance models because they leave less room for private insurance and thus will be less attractive to advocates of the private sector; yet leaving any room at all requires that the statutory system be less attractive than advocates of national health insurance could probably justify politically.
The apicobasal polarity kinase aPKC functions as a nuclear determinant and regulates cell proliferation and fate duringXenopusprimary neurogenesis
Authors: Sabherwal Nitin , Tsutsui Akiko , Hodge Sarah , Wei Jun , Chalmers Andrew D. , Papalopulu Nancy
Published: July 2009

During neurogenesis in Xenopus, apicobasally polarised superficial and non-polar deep cells take up different fates: deep cells become primary neurons while superficial cells stay as progenitors. It is not known whether the proteins that affect cell polarity also affect cell fate and how membrane polarity information may be transmitted to the nucleus. Here, we examine the role of the polarity components, apically enriched aPKC and basolateral Lgl2,in primary neurogenesis. We report that a membrane-tethered form of aPKC(aPKC-CAAX) suppresses primary neurogenesis and promotes cell proliferation. Unexpectedly, both endogenous aPKC and aPKC-CAAX show some nuclear localisation. A constitutively active aPKC fused to a nuclear localisation signal has the same phenotypic effect as aPKC-CAAX in that it suppresses neurogenesis and enhances proliferation. Conversely, inhibiting endogenous aPKC with a dominant-negative form that is restricted to the nucleus enhances primary neurogenesis. These observations suggest that aPKC has a function in the nucleus that is important for cell fate specification during primary neurogenesis. In a complementary experiment, overexpressing basolateral Lgl2 causes depolarisation and internalisation of superficial cells, which form ectopic neurons when supplemented with a proneural factor. These findings suggest that both aPKC and Lgl2 affect cell fate, but that aPKC is a nuclear determinant itself that might shuttle from the membrane to the nucleus to control cell proliferation and fate; loss of epithelial cell polarity by Lgl2 overexpression changes the position of the cells and is permissive for a change in cell fate.
The Crumbs complex: from epithelial-cell polarity to retinal degeneration
Authors: Bulgakova Natalia A. , Knust Elisabeth
Published: July 2009

The evolutionarily conserved Crumbs protein complex is a key regulator of cell polarity and cell shape in both invertebrates and vertebrates. The important role of this complex in normal cell function is illustrated by the finding that mutations in one of its components, Crumbs, are associated with retinal degeneration in humans, mice and flies. Recent results suggest that the Crumbs complex plays a role in the development of other disease processes that are based on epithelial dysfunction, such as tumorigenesis or the formation of cystic kidneys. Localisation of the complex is restricted to a distinct region of the apical plasma membrane that abuts the zonula adherens in epithelia and photoreceptor cells of invertebrates and vertebrates, including humans. In addition to the core components, a variety of other proteins can be recruited to the complex, depending on the cell type and/or developmental stage. Together with diverse post-transcriptional and post-translational mechanisms that regulate the individual components, this provides an enormous functional diversity and flexibility of the complex. In this Commentary, we summarise findings concerning the organisation and modification of the Crumbs complex, and the conservation of its constituents from flies to mammals. In addition, we discuss recent results that suggest its participation in various human diseases, including blindness and tumour formation.
Phosphorylation of histone H3 at Thr3 is part of a combinatorial pattern that marks and configures mitotic chromatin
Authors: Markaki Yolanda , Christogianni Anastasia , Politou Anastasia S. , Georgatos Spyros D.
Published: July 2009

We have previously shown that histone H3 is transiently phosphorylated at Thr3 during mitosis. Extending these studies, we now report that phosphorylated Thr3 is always in cis to trimethylated Lys4 and dimethylated Arg8, forming a new type of combinatorial modification, which we have termed PMM. PMM-marked chromatin emerges at multiple, peripheral sites of the prophase nucleus, then forms distinct clusters at the centric regions of metaphase chromosomes, and finally spreads (as it wanes) to the distal areas of segregating chromatids. The characteristic prophase pattern can be reproduced by expressing ectopically the kinase haspin at interphase, suggesting that the formation of the PMM signature does not require a pre-existing mitotic environment. On the other hand, the `dissolution' and displacement of PMM clusters from a centric to distal position can be induced by partial dephosphorylation or chromosome unravelling, indicating that these changes reflect the regulated grouping and scrambling of PMM subdomains during cell division. Formation of PMM is prevented by haspin knockdown and leads to delayed exit from mitosis. However, PMM-negative cells do not exhibit major chromosomal defects, suggesting that the local structures formed by PMM chromatin may serve as a `licensing system' that allows quick clearance through the metaphase-anaphase checkpoint.
Rhenium-catalyzed Regio- and Stereoselective Dimerization and Cyclotrimerization of Terminal Alkynes
Authors: Kawata Atsushi , Kuninobu Yoichiro , Takai Kazuhiko
Published: July 2009

A combination of catalytic amounts of [ReBr(CO)3(thf)]2 and tetrabutylammonium fluoride (TBAF) promoted the dimerization of aryl- and alkenyl-substituted alkynes with high regio- and stereoselectivities, and gave only (E)-enynes. When terminal alkynes having a carbonyl group were employed as substrates, regioselective cyclotrimerization of the alkynes occurred to give 1,3,5-trisubstituted aromatic compounds.
First-line antituberculosis drug resistance prevalence and its pattern among HIV-infected patients in the national referral tuberculosis centre, Iran
Authors: Tabarsi P , Chitsaz E , Moradi A , Baghaei P , Farnia P , Marjani M , Irannejad P , Mansouri D , Masjedi M
Published: July 2009

The objective of this study was to determine the drug resistance prevalence and its pattern among tuberculosis (TB)–HIV patients in Iran. In this retrospective study, all admitted TB/HIV patients presenting to our tertiary centre during 2005–2007 were considered. After confirmation for TB–HIV, first-line DST was performed for culture-positive patients. The drug resistance patterns and the treatment outcomes were analysed. Of the total 92 TB/HIV patients, 27 were culture negative, and DST were available in 65. Intravenous drug abuse was seen in 59 (90.8%). Thirty-seven (57%) were ‘sensitive’ cases and 28 (43%) were ‘any drug resistance’ cases. Twenty-one (32.3%) were mono-drug, three (4.6%) poly-drug and four (6.1%) were multidrug-resistant TB patients. Previous anti-TB medication was significantly associated with any drug resistance ( P = 0.041; 95% confidence interval =0.086–0.984); however, having any drug resistance did not affect the treatment outcome ( P = 0.56). Streptomycin showed the highest resistance rate (27%) followed by isoniazid (20%), pyrazinamide (9.8%), rifampin (9.2%) and ethambutol (3%). Drug resistance to antitubercular agents in TB–HIV co-infected patients in Iran is high compared with other reports. Drug resistance is higher among those who have had prior anti-TB medication.
Audit of hepatitis B vaccination of men who have sex with men attending Scottish genitourinary medicine clinics
Authors: Ramasami S , Abu-Rajab K , Sarkar P , Baguley S
Published: July 2009

Practice related to hepatitis B vaccination of men who have sex with men (MSM) in Scottish genitourinary medicine clinics was audited against targets based on the offer and completion of vaccination set by the British Association of Sexual Health and HIV. Of 521cases audited from 11 clinics, 215 (41%) were eligible for vaccination and 175 (81%) of eligible MSM were offered vaccination. Of those, 144 (82%) accepted vaccination. The super-accelerated schedule was most commonly prescribed but only 29% of those starting this schedule completed it, compared with 57% of those receiving the standard course. The overall vaccination completion rate was 31% and 82% of those completing vaccination had antisurface antibodies measured. A more robust recall system and uniformity in vaccination policies addressing the balance of patient compliance and immunogenicity of vaccine schedule are needed to improve completion rates.
Conjunctival intraepithelial neoplasia in an HIV-positive patient
Authors: Serisha B , Shenoy R , Evans J
Published: July 2009

We describe the case of a 37-year-old African woman with an asymptomatic lesion on her right conjunctiva; histology of the lesion revealed the presence of conjunctival intraepithelial neoplasia. HIV-positive patients from Africa are at increased risk of developing conjunctival malignancies, and early diagnosis and treatment can prevent serious consequences.