bluuebunny/crossref_metadata_2025 huggingface dataset:
The Cooperative Brain
Authors: Stallen Mirre , Sanfey Alan G.
Published: January 2013

Cooperation is essential for the functioning of human societies. To better understand how cooperation both succeeds and fails, recent research in cognitive neuroscience has begun to explore novel paradigms to examine how cooperative mechanisms may be encoded in the brain. By combining functional neuroimaging techniques with simple but realistic tasks adapted from experimental economics, this approach allows for the discrimination and modeling of processes that are important in cooperative behavior. Here, we review evidence demonstrating that many of the processes underlying cooperation overlap with rather fundamental brain mechanisms, such as, for example, those involved in reward, punishment and learning. In addition, we review how social expectations induced by an interactive context and the experience of social emotions may influence cooperation and its associated underlying neural circuitry, and we describe factors that appear important for generating cooperation, such as the provision of incentives. These findings illustrate how cognitive neuroscience can contribute to the development of more accurate, brain-based, models of cooperative decision making.
Study of film formation in bovine serum lubricated contacts under rolling/sliding conditions
Authors: Vrbka M , Návrat T , Křupka I , Hartl M , Šperka P , Gallo J
Published: January 2013

The aim of this study is to perform a detailed experimental analysis of lubricant film thickness of bovine serum within the contact between the artificial metal and ceramic heads (balls) and the glass disc to analyse the effect of proteins on film formation under various rolling/sliding conditions. Lubricant film observation of bovine serum solutions was carried out using an optical test rig. Chromatic interferograms were recorded with a high-speed CMOS digital camera and evaluated with thin film colorimetric interferometry. Film thickness was studied as a function of time. Under pure rolling conditions, film thickness increases with time as well as with rolling distance for all mean speeds and for both materials of the balls; however the metal ball always forms a thicker lubricating film in comparison to the ceramic ball. Under rolling/sliding conditions, when the disc is faster than the ball, the formation of lubricant film thickness is different compared to pure rolling conditions. At first, film thickness increases rapidly with a rolling/sliding distance for all mean speeds. When maximum film thickness is reached, then this effect is lost and film thickness starts to fall and finally, at the end of the measurement, film thickness drops down to a few nanometres. For the metal ball, maximum values of central film thicknesses are proportional to the mean speed; however this is not observed with the ceramic ball. An absolutely different formation of bovine serum film thickness is observed when the ball is faster than the disc. Under this condition, the protein layer is very thin for both materials of balls, and central film thickness reaches only about a few nanometres. Local protein spots are formed in a very small area of the contact zone and reach the thickness between 20 and 25 nm for the metal ball and 5 nm for the ceramic ball. From the performed experiments under rolling/sliding conditions, it is obvious that the formation of lubricant film thickness is markedly dependent on kinematic conditions acting in the contact, especially on the positive and negative slide-to-roll ratio and the mean speed. In addition, the material of the artificial head has a certain influence on the formation of bovine serum lubricating film.
The friction and wear behavior of WC coating on medical grade titanium alloys
Authors: Luo Yong , Yang Li , Tian Maocai , Ge Shirong , Wang Qingliang
Published: January 2013

The clinical success of artificial joints has provided remarkable benefit to patients with joint disorders. However, the long-term success of total joint prostheses has been frustrated by an unacceptable rate of aseptic loosening, the osteolysis induced by joint wear, metal ion release, and high risk of toxicity. In this article, a hard and wear resistance WC coating was formed on the surface of medical grade titanium alloys, using a plasma spraying system in order to solve the above clinic problems. The WC phase and micro-hardness were characterized with X-ray diffraction and Vickers hardness tester to evaluate the plasma spraying process and the mechanical properties of the coatings. Then, the friction and wear tests of WC coatings were performed on M-2000 block-on-ring tribological testing machine. After that, the tribological behavior of the modified titanium alloys was investigated by means of scanning electron microscopy. It was observed that a graded structure was formed on the surface of titanium alloy and exhibited good bonding between the coating and substrate. In addition, it was noticed that WC phase could significantly harden the surface of titanium alloys and decreased the wear factor from 38.5 × 10−11 to 1.66 × 10−11 kg/Nm. Finally, it was proved that adhesion and abrasive wear dominated the damage of titanium alloy, while the wear of WC coating was controlled by adhesion wear. All of the results indicated WC coating on titanium alloys with good bonding strength after plasma spraying was a potential candidate for the application of artificial joints from the understanding of wear resistance. Further investigation regarding biocompatibility and artificial joint simulation need to be conducted.
Generalized anxiety disorder prevalence and comorbidity with depression in coronary heart disease: A meta-analysis
Authors: Tully Phillip J , Cosh Suzanne M
Published: January 2013

Generalized anxiety disorder prevalence and comorbidity with depression in coronary heart disease patients remain unquantified. Systematic searching of Medline, Embase, SCOPUS and PsycINFO databases revealed 1025 unique citations. Aggregate generalized anxiety disorder prevalence (12 studies, N = 3485) was 10.94 per cent (95% confidence interval: 7.8–13.99) and 13.52 per cent (95% confidence interval: 8.39–18.66) employing Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria (random effects). Lifetime generalized anxiety disorder prevalence was 25.80 per cent (95% confidence interval: 20.84–30.77). In seven studies, modest correlation was evident between generalized anxiety disorder and depression, Fisher’s Z = .30 (95% confidence interval: .19–.42), suggesting that each psychiatric disorder is best conceptualized as contributing unique variance to coronary heart disease prognosis.
Doctor-certified sickness absence in first and second trimesters of pregnancy among native and immigrant women in Norway
Authors: Brekke Idunn , Berg John E. , Sletner Line , Jenum Anne Karen
Published: January 2013

Aims: The authors sought to estimate differences in doctor-certified sickness absence during pregnancy among immigrant and native women. Methods: Population-based cohort study of pregnant women attending three Child Health Clinics in Groruddalen, Oslo, and their offspring. Questionnaire data were collected at gestational weeks 10–20 and 28. The participation rate was 74%. A multivariate Poisson regression was used to analyse differences in sickness absence in pregnancy between immigrant and native women. Results: A total of 573 women who were employed prior to their pregnancies were included, 51% were immigrants. After adjusting for age, years of education, marital status, number of children, occupation, part-time/full-time work, health status, severe pregnancy-induced emesis and language proficiency, the immigrant/native differences in number of weeks with sickness absence decreased from 2.0 to 1.2 weeks. Part-time/full-time work, health status, severe pregnancy-induced emesis and language proficiency were significant predictors of sickness absence. Conclusion: Immigrant women had higher sickness absence than native women during pregnancy. The difference in average number of weeks between native and immigrant women was partly explained by poorer health status prior to pregnancy, severe pregnancy-induced emesis and poorer proficiency in the Norwegian language among the immigrant women.
Drama to promote social and personal well-being in six- and seven-year-olds with communication difficulties: the Speech Bubbles project
Authors: Barnes Jonathan
Published: January 2013

Aims:

This paper focuses on an innovative intersection between education, health and arts. Taking a broad definition of health it examines some social and psychological well-being impacts of extended collaborations between a theatre company and children with communication difficulties. It seeks to test aspects of Fredrickson’s1 broaden-and-build theory of positive emotions in a primary school curriculum context.

Methods:

The researcher participated in a project called Speech Bubbles. The programme was devised by theatre practitioners and aimed at six- and seven-year-olds with difficulties in speech, language and communication. Sessions were observed, videoed and analysed for levels of child well-being using an established scale. In addition, responses regarding perceived improvements in speech, language and communication were gathered from school records and teachers, teaching assistants, practitioners and parents. Data were captured using still images and videos, children’s recorded commentaries, conversations, written feedback and observation. Using grounded research methods, themes and categories arose directly from the collected data.

Results:

Fluency, vocabulary, inventiveness and concentration were enhanced in the large majority of referred children. The research also found significant positive developments in motivation and confidence. Teachers and their assistants credited the drama intervention with notable improvements in attitude, behaviour and relationships over the year. Aspects of many children’s psychological well-being also showed marked signs of progress when measured against original reasons for referral and normal expectations over a year. An unexpected outcome was evidence of heightened well-being of the teaching assistants involved.

Conclusions:

Findings compared well with expectations based upon Fredrickson’s theory and also the theatre company’s view that theatre-making promotes emotional awareness and empathy. Improvements in both children’s well-being and communication were at least in part related to the sustained and playful emphases on the processes and practice of drama, clear values and an inclusive environment.
Cost-Effectiveness of a Hypertension Control Intervention in Three Community Health Centers in China
Authors: Bai Yamin , Zhao Yanfang , Wang Guijing , Wang Huicheng , Liu Kejun , Zhao Wenhua
Published: January 2013

Background: Hypertension and associated chronic diseases impose enormous and growing health and economic burdens worldwide. The objective of this study was to investigate the cost-effectiveness (CE) of a hypertension control program in China. Methods: We collected information on program costs and health outcomes in three community health centers over a 1-year period. The participants were 4902 people with hypertension (systolic blood pressure [SBP] ≥140 mm Hg and/or diastolic blood pressure [DBP] ≥90 mm Hg, or on hypertension medication) aged 18 years and older. The SBP and DBP changes in the populations were estimated from a random sample of 818 participants by conducting face-to-face interviews and physical examinations. We derived CE measures based on the costs and effects on health outcomes. Findings: The total cost of implementing the intervention was Renminbi (RMB) 240 772 yuan (US$35 252), or 49 yuan (US$7.17) per participant in 2009. On average, SBP decreased from 143 to 131 mm Hg ( P < .001) and DBP decreased from 84 to 78 mm Hg ( P < .001), the SBP decreases ranged from 7.6 to 17.8 mm Hg and DBP decreases ranged from 3.9 to 8.3 mm Hg. CE ratios ranged from RMB 3.6 to 5.0 yuan (US$0.53-US$0.73) per person per mm Hg SBP decrease, and from RMB 6.3 to 9.7 yuan (US$0.92-US$1.42) per person per mm Hg DBP decrease. Interpretation: Per capita costs varied widely across the communities, as did changes in SBP and DBP, but CE was similar. The findings suggest ( a) a positive correlation between per capita costs and program effectiveness, ( b) differences in intervention levels, and ( c) differences in health status. CE results could be helpful to policy makers in making resource allocation decisions.
The Sociology of Social Inclusion
Authors: Allman Dan
Published: January 2013

This article looks at social inclusion from a sociological perspective. It argues that sociology complements biological and other natural order explanations of social stratification. The article interrogates a variety of forms of social integration, including ostracism within 5th century b.c. Greece, 19th-century solidarism, and Goffman’s mid-20th-century work on stigma. It does so to demonstrate how in each of these contexts, social inclusion and exclusion can function as apparati that problematize people on the margins, and by extension, contribute to their governance and control. The article proposes that sociology provides a valuable orientation from which to consider social inclusion because it illuminates how social integration maintains and manages the ways in which people move about and through their socially stratified worlds.
Generational Perspectives of Unprotected Sex and Sustainable Behavior Change in Nigeria
Authors: Okonkwo Amaechi D.
Published: January 2013

Despite the HIV/AIDS pandemic and over two decades of safe-sex communication and condom social marketing in Nigeria, unmarried people continue to engage in unprotected sex. Understanding their perspectives of unprotected sex will be imperative for sustainable policy and intervention design. To realize this objective, the author synthesized Giddens’s structuration theory and Rob Stones’s structurationist project research brackets to develop a long interview guide used to elicit unmarried university students’ perspectives of influences on unprotected sex, and the feasibility of sustainable behavior change in Nigeria. Participants’ constructed unprotected sex as prescripted, and the cumulative outcome of complex institutional (structural), interpersonal, and agential influences. Their narratives challenge the popular but narrow loss of control, sensation-seeking, and ignorance theses of unprotected sex. Instead, participants’ narratives implicate an interrelated web of persuasive and insidious institutional and agential influences, in a manner that privilege neither structure nor agency. To promote safer sexual practices therefore, stakeholders must concurrently engage with institutional and agential influences on unprotected sex—and not focus on unmarried people’s sexual agencies alone, as current interventions do in Nigeria.
Schwertmannite to jarosite conversion in the water column of an acidic mine pit lake
Authors: Sánchez-España J. , Yusta I. , López G. A.
Published: January 2013

Ferric precipitates in the water column at the San Telmo acidic mine pit lake in the Iberian Pyrite Belt, southwest Spain, have been studied by scanning electron microscopy, energy dispersive X-ray spectrometry, X-ray diffraction, X-ray fluorescence, inductively coupled plasma mass spectrometry and other complementary techniques. These Fe(III) precipitates were recovered from sediment traps which were left at different depths (25, 35, 40 and 100 m) in the lake for several months. Seasonal variations in the water chemistry were recorded to link the mineralogical findings to vertical and temporal changes in aqueous composition. The results indicate that schwertmannite is the first Fe(III) mineral to crystallize after the oxidation of Fe(II), in agreement with previous studies. Schwertmannite is kinetically favoured in comparison to other Fe(III) minerals, and it buffers the pH at 2.6–3.0. It is metastable, and alters to a (H3O+)- and (K+)-bearing jarosite (containing 58 mol.% H3O+ and 42 mol.% K+ on average) at lower pH (e.g. at pH 2.2–2.5 in the summer season), either in the water column (during settling) and/or in the benthic sediments, in a time period of weeks to months. The extent of hydronium substitution at the alkali site in the jarosite reflects the higher activity of free aqueous protons in solution (10–2.2 to 10–3.0) in comparison to the activities of K+ (10–4.5) and Na+ (10–3.2). Microscopic examination of mixed schwertmannite–jarosite precipitates found in the water column suggest that some textural and compositional features of metastable schwertmannite (e.g. the internal 'pincushion' arrangement and incorporation of trace amounts of Mg, Al, As and Pb) are conserved in the jarosite during the early stages of the mineralogical transformation, but many of these relics are lost in the later stages of crystal growth. Despite the hydronium-rich nature of the jarosite solid solution, this material is also an important sink for K+, which decreases in concentration with decreasing pH unlike most of the other major cations in the water column (notably Na+, Mg2+, Ca2+, Al3+, Fe3+, Cu2+, Zn2+). In addition to the release of Fe3+ to the aqueous solution, the conversion of schwertmannite to (H3O+, K+)-bearing jarosite consumes protons and thus may represent an additional pH control at San Telmo and other acidic mine pit lakes of the area.
Evidence of a water-rich silica gel state during the formation of a simple pegmatite
Authors: Thomas R. , Davidson P.
Published: January 2013

This study reports the discovery of inclusions, which are inferred to represent trapped primary silicate gels, in simple pegmatites genetically connected to the Precambrian Rønne granite of Bornholm Island, Denmark. These inclusions are randomly associated with more typical melt and alkali-carbonate-rich and bicarbonate-rich fluid inclusions. Their relationship to the latter and to the formation of the pegmatite bodies is discussed. The silicate gel inclusions become increasingly common towards the quartz cores of the pegmatites, and are considered to demonstrate increasing water and alkali carbonate concentrations in the pegmatite-forming liquid, and an accompanying tendency for sol/gel formation. This discovery may have important implications for the formation of the quartz cores of pegmatites. The possible origin of the alkali-carbonate concentrations
in pegmatite-forming fluids is also briefly discussed.
Calciodelrioite, Ca(VO3)2(H2O)4, the Ca analogue of delrioite, Sr(VO3)2(H2O)4
Authors: Kampf A. R. , Marty J. , Nash B. P. , Plášil J. , Kasatkin A. V. , Škoda R.
Published: January 2013

Calciodelrioite, ideally Ca(VO3)2(H2O)4, is a new mineral (IMA 2012-031) from the uraniumvanadium deposits of the eastern Colorado Plateau in the USA. The type locality is the West Sunday mine, Slick Rock district, San Miguel County, Colorado. The new mineral occurs on fracture surfaces in corvusite- and montroseite-impregnated sandstone and forms as a result of the oxidative alteration of these phases. At the West Sunday mine, calciodelrioite is associated with celestine, gypsum, huemulite, metarossite, pascoite and rossite. The mineral occurs as transparent colourless needles, bundles of tan to brown needles and star bursts of nearly black broad blades composed of tightly intergrown needles. Crystals are elongate and striated parallel to [100], exhibiting the prismatic forms {001} and {011} and having terminations possibly composed of the forms {100} and {61}. The mineral is transparent and has a white streak, subadamantine lustre, Mohs hardness of about 2½, brittle tenacity, irregular to splintery fracture, one perfect cleavage on {001} and possibly one or more additional cleavages parallel to [100]. Calciodelrioite is soluble in water. The calculated density is 2.451 g cm– 3. It is optically biaxial (+) with α = 1.733(3), β = 1.775(3), γ = 1.825(3) (white light), 2Vmeas = 87.3(9)° and 2Vcalc = 87°. The optical orientation is X = b; Z ≈ a. No pleochroism was observed. Electronmicroprobe analyses of two calciodelrioite samples and type delrioite provided the empirical formulae (Ca0.88Sr0.07Na0.04K0.01)Σ1.00(V1.00O3)2(H2.01O)4, (Ca0.76Sr0.21Na0.01)Σ0.98(V1.00O3)2(H2.01O)4 and (Sr0.67Ca0.32)Σ0.99(V1.00O3)2(H2.00O)4, respectively. Calciodelrioite is monoclinic, I2/a, with unit-cell parameters a = 14.6389(10), b = 6.9591(4), c = 17.052(2) Å, β = 102.568(9)°, V = 1695.5(3) Å3 and Z = 8. The seven strongest lines in the X-ray powder diffraction pattern [listed as dobs Å (I)(hkl)] are as follows: 6.450(100)(011); 4.350(16)(013); 3.489(18)(020); 3.215(17)(022); 3.027(50)(multiple); 2.560(28)(15,413); 1.786(18)(028). In the structure of calciodelrioite (refined to R1 = 3.14% for 1216 Fo > 4σF), V5+O5 polyhedra link by sharing edges to form a zigzag divanadate [VO3] chain along a, similar to that in the structure of rossite. The chains are linked via bonds to Ca atoms, which also bond to H2O groups, yielding CaO3(H2O)6 polyhedra. The Ca polyhedra form a chain along b. Each of the two symmetrically independent VO5 polyhedra has two short vanadyl bonds and three long equatorial bonds. Calciodelrioite and delrioite are isostructural and are the endmembers of the series Ca(VO3)2(H2O)4–Sr(VO3)2(H2O)4. Calciodelrioite is dimorphous with rossite, which has a similar structure; however, the smaller 8-coordinate Ca site in rossite does not accommodate Sr.
BiRd (clarithromycin, lenalidomide, dexamethasone): an update on long-term lenalidomide therapy in previously untreated patients with multiple myeloma
Authors: Rossi Adriana , Mark Tomer , Jayabalan David , Christos Paul , Zafar Faiza , Pekle Karen , Pearse Roger , Chen-Kiang Selina , Coleman Morton , Niesvizky Ruben
Published: January 2013

Key Points

Long-term lenalidomide/dexamethasone/biaxin in newly diagnosed myeloma is safe and effective. No increased incidence of second primary malignancies seen in lenalidomide without alkylators.
The anti-malarial drug Mefloquine disrupts central autonomic and respiratory control in the working heart brainstem preparation of the rat
Authors: Lall Varinder K , Dutschmann Mathias , Deuchars Jim , Deuchars Susan A
Published: January 2013

Background

Mefloquine is an anti-malarial drug that can have neurological side effects. This study examines how mefloquine (MF) influences central nervous control of autonomic and respiratory systems using the arterially perfused working heart brainstem preparation (WHBP) of the rat. Recordings of nerve activity were made from the thoracic sympathetic chain and phrenic nerve, while heart rate (HR) and perfusion pressure were also monitored in the arterially perfused, decerebrate, rat WHBP. MF was added to the perfusate at 1 μM to examine its effects on baseline parameters as well as baroreceptor and chemoreceptor reflexes.

Results

MF caused a significant, atropine resistant, bradycardia and increased phrenic nerve discharge frequency. Chemoreceptor mediated sympathoexcitation (elicited by addition of 0.1 ml of 0.03% sodium cyanide to the aortic cannula) was significantly attenuated by the application of MF to the perfusate. Furthermore MF significantly decreased rate of return to resting HR following chemoreceptor induced bradycardia. An increase in respiratory frequency and attenuated respiratory-related sympathetic nerve discharge during chemoreceptor stimulation was also elicited with MF compared to control. However, MF did not significantly alter baroreceptor reflex sensitivity.

Conclusions

These studies indicate that in the WHBP, MF causes profound alterations in autonomic and respiratory control. The possibility that these effects may be mediated through actions on connexin 36 containing gap junctions in central neurones controlling sympathetic nervous outflow is discussed.
Expression sequence tag library derived from peripheral blood mononuclear cells of the chlorocebus sabaeus
Authors: Tchitchek Nicolas , Jacquelin Béatrice , Wincker Patrick , Dossat Carole , Silva Corinne Da , Weissenbach Jean , Blancher Antoine , Müller-Trutwin Michaela , Benecke Arndt
Published: January 2013

Background

African Green Monkeys (AGM) are amongst the most frequently used nonhuman primate models in clinical and biomedical research, nevertheless only few genomic resources exist for this species. Such information would be essential for the development of dedicated new generation technologies in fundamental and pre-clinical research using this model, and would deliver new insights into primate evolution.

Results

We have exhaustively sequenced an Expression Sequence Tag (EST) library made from a pool of Peripheral Blood Mononuclear Cells from sixteen Chlorocebus sabaeus monkeys. Twelve of them were infected with the Simian Immunodeficiency Virus. The mononuclear cells were or not stimulated in vitro with Concanavalin A, with lipopolysacharrides, or through mixed lymphocyte reaction in order to generate a representative and broad library of expressed sequences in immune cells. We report here 37,787 sequences, which were assembled into 14,410 contigs representing an estimated 12% of the C. sabaeus transcriptome. Using data from primate genome databases, 9,029 assembled sequences from C. sabaeus could be annotated. Sequences have been systematically aligned with ten cDNA references of primate species including Homo sapiens, Pan troglodytes, and Macaca mulatta to identify ortholog transcripts. For 506 transcripts, sequences were quasi-complete. In addition, 6,576 transcript fragments are potentially specific to the C. sabaeus or corresponding to not yet described primate genes.

Conclusions

The EST library we provide here will prove useful in gene annotation efforts for future sequencing of the African Green Monkey genomes. Furthermore, this library, which particularly well represents immunological and hematological gene expression, will be an important resource for the comparative analysis of gene expression in clinically relevant nonhuman primate and human research.
Quantification of carbonic anhydrase gene expression in ventricle of hypertrophic and failing human heart
Authors: Alvarez Bernardo V , Quon Anita L , Mullen John , Casey Joseph R
Published: January 2013

Background

Carbonic anhydrase enzymes (CA) catalyze the reversible hydration of carbon dioxide to bicarbonate in mammalian cells. Trans-membrane transport of CA-produced bicarbonate contributes significantly to cellular pH regulation. A body of evidence implicates pH-regulatory processes in the hypertrophic growth pathway characteristic of hearts as they fail. In particular, Na+/H+ exchange (NHE) activation is pro-hypertrophic and CA activity activates NHE. Recently Cardrase (6-ethoxyzolamide), a CA inhibitor, was found to prevent and revert agonist-stimulated cardiac hypertrophy (CH) in cultured cardiomyocytes. Our goal thus was to determine whether hypertrophied human hearts have altered expression of CA isoforms.

Methods

We measured CA expression in hypertrophied human hearts to begin to examine the role of carbonic anhydrase in progression of human heart failure. Ventricular biopsies were obtained from patients undergoing cardiac surgery (CS, n = 14), or heart transplantation (HT, n = 13). CS patients presented mild/moderate concentric left ventricular hypertrophy and normal right ventricles, with preserved ventricular function; ejection fractions were ~60%. Conversely, HT patients with failing hearts presented CH or ventricular dilation accompanied by ventricular dysfunction and EF values of 20%. Non-hypertrophic, non-dilated ventricular samples served as controls.

Results

Expression of atrial and brain natriuretic peptide (ANP and BNP) were markers of CH. Hypertrophic ventricles presented increased expression of CAII, CAIV, ANP, and BNP, mRNA levels, which increased in failing hearts, measured by quantitative real-time PCR. CAII, CAIV, and ANP protein expression also increased approximately two-fold in hypertrophic/dilated ventricles.

Conclusions

These results, combined with in vitro data that CA inhibition prevents and reverts CH, suggest that increased carbonic anhydrase expression is a prognostic molecular marker of cardiac hypertrophy.
Impact of gastro-oesophageal reflux on microRNA expression, location and function
Authors: Smith Cameron M , Michael Michael Z , Watson David I , Tan Grace , Astill David St J , Hummel Richard , Hussey Damian J
Published: January 2013

Background

Ulceration of the oesophageal squamous mucosa (ulcerative oesophagitis) is a pathological manifestation of gastro-oesophageal reflux disease, and is a major risk factor for the development of Barrett’s oesophagus. Barrett’s oesophagus is characterised by replacement of reflux-damaged oesophageal squamous epithelium with a columnar intestinal-like epithelium. We previously reported discovery of microRNAs that are differentially expressed between oesophageal squamous mucosa and Barrett’s oesophagus mucosa. Now, to better understand early steps in the initiation of Barrett’s oesophagus, we assessed the expression, location and function of these microRNAs in oesophageal squamous mucosa from individuals with ulcerative oesophagitis.

Methods

Quantitative real-time PCR was used to compare miR-21, 143, 145, 194, 203, 205 and 215 expression levels in oesophageal mucosa from individuals without pathological gastro-oesophageal reflux to individuals with ulcerative oesophagitis. Correlations between microRNA expression and messenger RNA differentiation markers BMP-4, CK8 and CK14 were analyzed. The cellular localisation of microRNAs within the oesophageal mucosa was determined using in-situ hybridisation. microRNA involvement in proliferation and apoptosis was assessed following transfection of a human squamous oesophageal mucosal cell line (Het-1A).

Results

miR-143, miR-145 and miR-205 levels were significantly higher in gastro-oesophageal reflux compared with controls. Elevated miR-143 expression correlated with BMP-4 and CK8 expression, and elevated miR-205 expression correlated negatively with CK14 expression. Endogenous miR-143, miR-145 and miR-205 expression was localised to the basal layer of the oesophageal epithelium. Transfection of miR-143, 145 and 205 mimics into Het-1A cells resulted in increased apoptosis and decreased proliferation.

Conclusions

Elevated miR-143, miR-145 and miR-205 expression was observed in oesophageal squamous mucosa of individuals with ulcerative oesophagitis. These miRNAs localised to the basal layer of the oesophageal epithelium. They reduced proliferation and increased apoptosis, and may play roles in regulating epithelial restoration in response to injury caused by gastro-oesophageal reflux.
Patients receiving opioid maintenance treatment in primary care: successful chronic hepatitis C care in a real world setting
Authors: Seidenberg André , Rosemann Thomas , Senn Oliver
Published: January 2013

Background

Injection drug users (IDUs) represent a significant proportion of patients with chronic hepatitis C (CHC). The low treatment uptake among these patients results in a low treatment effectiveness and a limited public health impact. We hypothesised that a general practitioner (GP) providing an opioid maintenance treatment (OMT) for addicted patients can achieve CHC treatment and sustained virological response rates (SVR) comparable to patients without drug dependency.

Methods

Retrospective patient record analysis of 85 CHC patients who received OMT for more than 3 months in a single-handed general practice in Zurich from January 1, 2002 through May 31, 2008. CHC treatment was based on a combination with pegylated interferon and ribavirin. Treatment uptake and SVR (undetectable HCV RNA 6 months after end of treatment) were assessed. The association between treatment uptake and patient characteristics was investigated by multiple logistic regression.

Results

In 35 out of 85 CHC patients (52 males) with a median (IQR) age of 38.8 (35.0-44.4) years, antiviral therapy was started (41.2%). Median duration (IQR) of OMT in the treatment group was 55.0 (35.0-110.1) months compared to the group without therapy 24.0 (9.8-46.3) months (p<0.001). OMT duration remained a significant determinant for treatment uptake when controlled for potential confounding. SVR was achieved in 25 out of 35 patients (71%).

Conclusion

In addicted patients a high CHC treatment and viral eradication rate in a primary care setting in Switzerland is feasible. Opioid substitution seems a beneficial framework for CHC care in this “difficult to treat” population.
APC/β-catenin-rich complexes at membrane protrusions regulate mammary tumor cell migration and mesenchymal morphology
Authors: Odenwald Matthew A , Prosperi Jenifer R , Goss Kathleen H
Published: January 2013

Background

The APC tumor suppressor is mutated or downregulated in many tumor types, and is prominently localized to punctate clusters at protrusion tips in migratory cells, such as in astrocytes where it has been implicated in directed cell motility. Although APC loss is considered an initiating event in colorectal cancer, for example, it is less clear what role APC plays in tumor cell motility and whether loss of APC might be an important promoter of tumor progression in addition to initiation.

Methods

The localization of APC and β-catenin was analyzed in multiple cell lines, including non-transformed epithelial lines treated with a proteasome inhibitor or TGFβ to induce an epithelial-to-mesenchymal transition (EMT), as well as several breast cancer lines, by immunofluorescence. APC expression was knocked down in 4T07 mammary tumor cells using lentiviral-mediated delivery of APC-specific short-hairpin (sh) RNAs, and assessed using quantitative (q) reverse-transcriptase (RT)-PCR and western blotting. Tumor cell motility was analyzed by performing wound-filling assays, and morphology via immunofluorescence (IF) and phase-contrast microscopy. Additionally, proliferation was measured using BrdU incorporation, and TCF reporter assays were performed to determine β-catenin/TCF-mediated transcriptional activity.

Results

APC/β-catenin-rich complexes were observed at protrusion ends of migratory epithelial cells treated with a proteasome inhibitor or when EMT has been induced and in tumor cells with a mesenchymal, spindle-like morphology. 4T07 tumor cells with reduced APC levels were significantly less motile and had a more rounded morphology; yet, they did not differ significantly in proliferation or β-catenin/TCF transcriptional activity. Furthermore, we found that APC/β-catenin-rich complexes at protrusion ends were dependent upon an intact microtubule cytoskeleton.

Conclusions

These findings indicate that membrane protrusions with APC/β-catenin-containing puncta control the migratory potential and mesenchymal morphology of mammary tumor cells and suggest that APC loss during later stages of tumor progression might impact tumor cell dissemination or colonization.
Murraya koenigii leaf extract inhibits proteasome activity and induces cell death in breast cancer cells
Authors: Noolu Bindu , Ajumeera Rajanna , Chauhan Anitha , Nagalla Balakrishna , Manchala Raghunath , Ismail Ayesha
Published: January 2013

Background

Inhibition of the proteolytic activity of 26S proteasome, the protein-degrading machine, is now considered a novel and promising approach for cancer therapy. Interestingly, proteasome inhibitors have been demonstrated to selectively kill cancer cells and also enhance the sensitivity of tumor cells to chemotherapeutic agents. Recently, polyphenols/flavonoids have been reported to inhibit proteasome activity. Murraya koenigii Spreng, a medicinally important herb of Indian origin, has been used for centuries in the Ayurvedic system of medicine. Here we show that Murraya koenigii leaves (curry leaves), a rich source of polyphenols, inhibit the proteolytic activity of the cancer cell proteasome, and cause cell death.

Methods

Hydro-methanolic extract of curry leaves (CLE) was prepared and its total phenolic content [TPC] determined by, the Folin-Ciocalteau’s method. Two human breast carcinoma cell lines: MCF-7 and MDA-MB-231 and a normal human lung fibroblast cell line, WI-38 were used for the studies. Cytotoxicity of the CLE was assessed by the MTT assay. We studied the effect of CLE on growth kinetics using colony formation assay. Growth arrest was assessed by cell cycle analysis and apoptosis by Annexin-V binding using flow cytometry. Inhibition of the endogenous 26S proteasome was studied in intact cells and cell extracts using substrates specific to 20S proteasomal enzymes.

Results

CLE decreased cell viability and altered the growth kinetics in both the breast cancer cell lines in a dose-dependent manner. It showed a significant arrest of cells in the S phase albeit in cancer cells only. Annexin V binding data suggests that cell death was via the apoptotic pathway in both the cancer cell lines. CLE treatment significantly decreased the activity of the 26S proteasome in the cancer but not normal cells.

Conclusions

Our study suggests M. koenigii leaves to be a potent source of proteasome inhibitors that lead to cancer cell death. Therefore, identification of active component(s) from the leaf extract could lead to the development of anti-cancer agents which could be useful in the treatment of different types of cancers.
Alogliptin ameliorates postprandial lipemia and postprandial endothelial dysfunction in non- diabetic subjects: a preliminary report
Authors: Noda Yoko , Miyoshi Toru , Oe Hiroki , Ohno Yuko , Nakamura Kazufumi , Toh Norihisa , Kohno Kunihisa , Morita Hiroshi , Kusano Kengo , Ito Hiroshi
Published: January 2013

Background

Postprandial hyperlipidemia impairs endothelial function and participates in the development of atherosclerosis. We investigated the postprandial effects of a dipeptidyl peptidase IV inhibitor, alogliptin, on endothelial dysfunction and the lipid profile.

Methods

A randomized cross-over trial design in 10 healthy volunteers (8 males and 2 females, 35 ± 10 years) was performed. The postprandial effects before and after a 1-week treatment of 25 mg/day alogliptin on endothelial function were assessed with brachial artery flow-mediated dilation (FMD) and changing levels of lipids, apolipoprotein B48 (apoB-48), glucose, glucagon, insulin, and glucagon-like peptide-1 (GLP-1) during fasting and at 2, 4, 6, and 8 h after a standard meal loading test.

Results

Alogliptin treatment significantly suppressed the postprandial elevation in serum triglyceride (incremental area under the curve [AUC]; 279 ± 31 vs. 182 ± 32 mg h/dl, p = 0.01), apoB-48 (incremental AUC; 15.4 ± 1.7 vs. 11.7 ± 1.1 μg h/ml, p = 0.04), and remnant lipoprotein cholesterol (RLP-C) (incremental AUC: 29.3 ± 3.2 vs. 17.6 ± 3.3 mg h/dl, p = 0.01). GLP-1 secretion was significantly increased after alogliptin treatment. Postprandial endothelial dysfunction (maximum decrease in%FMD, from −4.2 ± 0.5% to −2.6 ± 0.4%, p = 0.03) was significantly associated with the maximum change in apoB-48 (r = −0.46, p = 0.03) and RLP-C (r = −0.45, p = 0.04).

Conclusion

Alogliptin significantly improved postprandial endothelial dysfunction and postprandial lipemia, suggesting that alogliptin may be a promising anti-atherogenic agent.
Towards the elimination of malaria in South Africa: a review of surveillance data in Mutale Municipality, Limpopo Province, 2005 to 2010
Authors: Khosa Ester , Kuonza Lazarus R , Kruger Phillip , Maimela Eric
Published: January 2013

Background

South Africa has targeted to eliminate malaria by the year 2018. Constant monitoring of malaria morbidity and mortality trends in affected subpopulations is therefore crucial in guiding and refining control interventions. Mutale Municipality in Limpopo Province is one of the areas with the highest risk of malaria in the country. This paper describes trends in malaria incidence, case fatality and household indoor residual spraying (IRS) coverage in Mutale Municipality, during the period 2005 to 2010.

Methods

A retrospective descriptive analysis was conducted on malaria data routinely collected through the Limpopo provincial malaria information system between July 2005 and June 2010. Five malaria seasons were defined. Annualized malaria incidence rates, case fatality rates (CFR) and IRS coverage rates were calculated.

Results

Cumulatively, 4,663 malaria cases and 21 malaria deaths were reported in Mutale between July 2005 and June 2010. Investigation of likely origin of the malaria in 3,517 patients revealed that 6.6% were imported cases, mostly from neighbouring Zimbabwe (222/231). Malaria incidence rates fell from 13.6 cases per 1,000 person-years in the 2005–2006 season to 2.7 cases per 1,000 person-years in the 2009–2010 season. The mean malaria CFR was stable between 0.3 and 0.6% during the first four seasons, and increased sharply to 2.1% in the 2009–2010 season. The median age of the 21 malaria deaths was 34 years (range: 16 to 60 years). CFRs were 0% in children below 15 years and above 0.5% in patients more than 24 years old. Regular IRS achieved coverage above 80% in all five seasons.

Conclusion

Malaria control interventions implemented in Mutale significantly reduced the incidence of malaria in the population. In order to accurately monitor progress towards the elimination goal, the malaria control programme should strengthen the reporting and capturing of the data in the provincial malaria information system; all patients diagnosed with malaria should be investigated to determine the likely source of the malaria, and malaria related deaths should be audited to improve case detection and management. Furthermore, the country should strengthen cross border malaria control collaborations in order to minimize malaria importation.
Primary antibiotic resistance and associated mechanisms in Helicobacter pylori isolates from Senegalese patients
Authors: Seck Abdoulaye , Burucoa Christophe , Dia Daouda , Mbengue Mouhamadou , Onambele Manuella , Raymond Josette , Breurec Sebastien
Published: January 2013

Background

Antibiotic combination therapy for Helicobacter pylori eradication must be adapted to local resistance patterns, but the epidemiology of H. pylori resistance to antibiotics is poorly documented in Africa. The aim was to determine the antibiotic resistance rates, as well as the associated molecular mechanisms, of strains isolated in Dakar, Senegal.

Methods

One hundred and eight H. pylori strains were isolated between 2007 and 2009 from 108 patients presenting with upper abdominal pain to the Gastroenterology Department of Le Dantec Hospital. Antimicrobial susceptibility testing was performed for amoxicillin, clarithromycin, metronidazole, levofloxacin and tetracyclin using the E-test method. Mutations in the 23S rRNA gene of clarithromycin-resistant strains and in gyrA and gyrB of levofloxacin-resistant strains were investigated.

Results

Isolates were characterized by no resistance to amoxicillin (0%), tetracycline (0%), and very low rate of resistance to clarithromycin (1%), but a high rate of resistance to metronidazole (85%). The clarithromycin-resistant strain displayed the A2143G mutation. A worrying rate of levofloxacin resistance was detected (15%). N87I and D91N were the most common mutations in the quinolone-resistance-determining region of gyrA.

Conclusions

The first-line empirical regimen for H. pylori eradication in Senegal should include clarithromycin. Increasing rates of fluoroquinolone resistance detected should discourage the use of levofloxacin-containing regimens without prior antimicrobial susceptibility testing.
Predicting live birth chances for women with multiple consecutive failing IVF cycles: a simple and accurate prediction for routine medical practice
Authors: Porcu Géraldine , Lehert Philippe , Colella Carolina , Giorgetti Claude
Published: January 2013

Background

Women having experienced several consecutive failing IVF cycles constitute a critical and particular subset of patients, for which growing perception of irremediable failure, increasing costs and IVF treatment related risks necessitate appropriate decision making when starting or not a new cycle. Predicting chances of LB might constitute a useful tool for discussion between the patient and the clinician. Our essential objective was to dispose of a simple and accurate prediction model for use in routine medical practice. The currently available predictive models applicable to general populations cannot be considered as accurate enough for this purpose.

Methods

Patients with at least four consecutive Failing cycles (CFCs) were selected. We constructed a predictive model of LB occurrence during the last cycle, by using a stepwise logistic regression, using all the baseline patient characteristics and intermediate stage variables during the four first cycles.

Results

On as set of 151 patients, we identified five determinant predictors: the number of previous cycles with at least one gestational sac (NGS), the mean number of good-quality embryos, age, male infertility (MI) aetiology and basal FSH. Our model was characterized by a much higher discrimination as the existing models (C-statistics=0.76), and an excellent calibration.

Conclusions

Couples having experienced multiple IVF failures need precise and appropriate information to decide to resume or interrupt their fertility project. Our essential objective was to dispose of a simple and accurate prediction model to allow a routine practice use. Our model is adapted to this purpose: It is very simple, combines five easily collected variables in a short calculation; it is more accurate than existing models, with a fair discrimination and a well calibrated prediction.
Brain damage in methylmalonic aciduria: 2-methylcitrate induces cerebral ammonium accumulation and apoptosis in 3D organotypic brain cell cultures
Authors: Jafari Paris , Braissant Olivier , Zavadakova Petra , Henry Hugues , Bonafé Luisa , Ballhausen Diana
Published: January 2013

Background

Methylmalonic aciduria is an inborn error of metabolism characterized by accumulation of methylmalonate (MMA), propionate and 2-methylcitrate (2-MCA) in body fluids. Early diagnosis and current treatment strategies aimed at limiting the production of these metabolites are only partially effective in preventing neurological damage.

Methods

To explore the metabolic consequences of methylmalonic aciduria on the brain, we used 3D organotypic brain cell cultures from rat embryos. We challenged the cultures at two different developmental stages with 1 mM MMA, propionate or 2-MCA applied 6 times every 12 h. In a dose–response experiment cultures were challenged with 0.01, 0.1, 0.33 and 1 mM 2-MCA. Immunohistochemical staining for different brain cell markers were used to assess cell viability, morphology and differentiation. Significant changes were validated by western blot analysis. Biochemical markers were analyzed in culture media. Apoptosis was studied by immunofluorescence staining and western blots for activated caspase-3.

Results

Among the three metabolites tested, 2-MCA consistently produced the most pronounced effects. Exposure to 2-MCA caused morphological changes in neuronal and glial cells already at 0.01 mM. At the biochemical level the most striking result was a significant ammonium increase in culture media with a concomitant glutamine decrease. Dose–response studies showed significant and parallel changes of ammonium and glutamine starting from 0.1 mM 2-MCA. An increased apoptosis rate was observed by activation of caspase-3 after exposure to at least 0.1 mM 2-MCA.

Conclusion

Surprisingly, 2-MCA, and not MMA, seems to be the most toxic metabolite in our in vitro model leading to delayed axonal growth, apoptosis of glial cells and to unexpected ammonium increase. Morphological changes were already observed at 2-MCA concentrations as low as 0.01 mM. Increased apoptosis and ammonium accumulation started at 0.1 mM thus suggesting that ammonium accumulation is secondary to cell suffering and/or cell death. Local accumulation of ammonium in CNS, that may remain undetected in plasma and urine, may therefore play a key role in the neuropathogenesis of methylmalonic aciduria both during acute decompensations and in chronic phases. If confirmed in vivo, this finding might shift the current paradigm and result in novel therapeutic strategies.