bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pilus Gene Pool Variation and the Virulence of Corynebacterium diphtheriae Clinical Isolates during Infection of a Nematode
Authors: Broadway Melissa M. , Rogers Elizabeth A. , Chang Chungyu , Huang I-Hsiu , Dwivedi Prabhat , Yildirim Suleyman , Schmitt Michael P. , Das Asis , Ton-That Hung 
Published: June 2013

ABSTRACT

Toxigenic
Corynebacterium diphtheriae
strains cause diphtheria in humans. The toxigenic
C. diphtheriae
isolate NCTC13129 produces three distinct heterotrimeric pili that contain SpaA, SpaD, and SpaH, making up the shaft structure. The SpaA pili are known to mediate bacterial adherence to pharyngeal epithelial cells. However, to date little is known about the expression of different pili in various clinical isolates and their importance in bacterial pathogenesis. Here, we characterized a large collection of
C. diphtheriae
clinical isolates for their pilin gene pool by PCR and for the expression of the respective pilins by immunoblotting with antibodies against Spa pilins. Consistent with the role of a virulence factor, the SpaA-type pili were found to be prevalent among the isolates, and most significantly, corynebacterial adherence to pharyngeal epithelial cells was strictly correlated with isolates that were positive for the SpaA pili. By comparison, the isolates were heterogeneous for the presence of SpaD- and SpaH-type pili. Importantly, using
Caenorhabditis elegans
as a model host for infection, we show here that strain NCTC13129 rapidly killed the nematodes, the phenotype similar to isolates that were positive for toxin and all pilus types. In contrast, isogenic mutants of NCTC13129 lacking SpaA-type pili or devoid of toxin and SpaA pili exhibited delayed killing of nematodes with similar kinetics. Consistently, nontoxigenic or toxigenic isolates that lack one, two, or all three pilus types were also attenuated in virulence. This work signifies the important role of pili in corynebacterial pathogenesis and provides a simple host model to identify additional virulence factors.
A Multicopper Oxidase Is Required for Copper Resistance in Mycobacterium tuberculosis
Authors: Rowland Jennifer L. , Niederweis Michael 
Published: June 2013

ABSTRACT

Mycobacterium tuberculosis
, the causative agent of tuberculosis, is one of the most important bacterial pathogens. Recent work has revealed that the natural bactericidal properties of copper are utilized by the host immune system to combat infections with bacteria, including
M. tuberculosis
. However,
M. tuberculosis
employs multiple mechanisms to reduce the internal copper amount by efflux and sequestration, which are required for virulence of
M. tuberculosis
. Here, we describe an alternative mechanism of copper resistance by
M. tuberculosis
. Deletion of the
rv0846c
gene increased the susceptibility of
M. tuberculosis
to copper at least 10-fold, establishing Rv0846c as a major component of copper resistance in
M. tuberculosis
.
In vitro
assays showed that Rv0846c oxidized organic substrates and Fe(II). Importantly, mutation of the predicted copper-coordinating cysteine 486 resulted in inactive Rv0846c protein which did not protect
M. tuberculosis
against copper stress. Hence, Rv0846c is a multicopper oxidase of
M. tuberculosis
and was renamed
m
ycobacterial
m
ulti
c
opper
o
xidase (MmcO). MmcO is membrane associated, probably by lipidation after export across the inner membrane by the twin-arginine translocation system. However, mutation of the lipidation site did not affect the oxidase activity or the copper protective function of MmcO. Our study revealed MmcO as an important copper resistance mechanism of
M. tuberculosis
, which possibly acts by oxidation of toxic Cu(I) in the periplasm.
Doctors’ self-reported physical activity, their counselling practices and their correlates in urban Trivandrum, South India: should a full-service doctor be a physically active doctor?
Authors: Patra Lipika , Mini G K , Mathews Elezebeth , Thankappan K R 
Published: June 2013

BackgroundDoctors’ self-reported physical activity (PA) is associated with their propensity for prescribing PA.MethodsWe surveyed 146 doctors (median age 42 years; men 58.9%), selected by multistage random sampling. Information on demographic details, self-reported PA and counselling offered to their patients was collected using a pretested, structured, self-administered questionnaire. Multivariate logistic regression analysis was carried out to find the predictors of PA and PA counselling offered to the patients.ResultsModerate PA was reported by 37.7% (95% CI 29.8 to 45.5) of the doctors and the remaining 62.3%reported being inactive. Doctors who were motivated to perform PA (OR 4.01, 95% CI 1.82 to 8.86), who used exercise equipment at home (OR 3.97, CI 1.68 to 9.36) and who used a neighbourhood facility for PA (OR 2.36, CI 1.11 to 5.02) were more likely to perform moderate PA compared with their counterparts. 25% of the doctors always asked and advised their patients on PA. Doctors who believed that their own healthy lifestyle influenced advice practices (OR 9.13, CI 2.49 to 33.41), who consulted less than 30 patients/day (OR 5.35, CI 1.41 to 20.25) and who reported previous participation in sports activities (OR 4.22, CI 1.77 to 10.04) were more likely to always ask and advise their patients on PA compared with their counterparts.ConclusionsA majority of the doctors in our study were inactive and did not ask or advise their patients on PA. Measures are warranted to enhance doctors’ own PA and their counselling practices.
What physical activity surveillance needs: validity of a single-item questionnaire
Authors: Wanner Miriam , Probst-Hensch Nicole , Kriemler Susi , Meier Flurina , Bauman Adrian , Martin Brian W 
Published: June 2013

BackgroundSelf-report instruments to assess physical activity are still the most feasible option in many population-wide surveys, and often need to be very short owing to resource constraints. The aim of this study was to test the criterion validity of a single-item physical activity measure using accelerometers and to compare its measurement properties by gender, age group (including older adults) and language region.MethodsA validation study was carried out within the second follow-up of a large Swiss cohort study (Swiss Cohort Study on Air Pollution and Lung and Heart Disease in Adults, SAPALDIA, n=208) and included an additional convenient sample (n=110). Participants wore an accelerometer over eight consecutive days and then completed the single-item measure. Spearman's rank-order correlations were used to assess the criterion validity.ResultsPhysical activity levels were higher in men, younger individuals and those from the German-speaking part of Switzerland. Correlation coefficients for the number of days with at least 30 min of moderate-to-vigorous physical activity according to the single item and different accelerometer activity outcomes ranged from 0.40 to 0.54. Correlations were higher for women, younger individuals and participants from the French-speaking and the Italian-speaking parts.ConclusionsThe single-item physical activity measure performed at least as well as other physical activity questionnaires. The differences in criterion validity between sub groups indicate that factors such as gender and age should be taken into account when developing physical activity questionnaires and in future validation studies.
Recurrence of Achilles tendon injuries in elite male football players is more common after early return to play: an 11-year follow-up of the UEFA Champions League injury study
Authors: Gajhede-Knudsen Mariann , Ekstrand Jan , Magnusson Henrik , Maffulli Nicola 
Published: June 2013

BackgroundThere is limited information about Achilles tendon disorders in professional football.AimsTo investigate the incidence, injury circumstances, lay-off times and reinjury rates of Achilles tendon disorders in male professional football.MethodsA total of 27 clubs from 10 countries and 1743 players have been followed prospectively during 11 seasons between 2001 and 2012. The team medical staff recorded individual player exposure and time-loss injuries.ResultsA total of 203 (2.5% of all injuries) Achilles tendon disorders were registered. A majority (96%) of the disorders were tendinopathies, and nine were partial or total ruptures. A higher injury rate was found during the preseason compared with the competitive season, 0.25 vs 0.18/1000 h (rate ratio (RR) 1.4, 95% CI 1.1 to 2.0; p=0.027). The mean lay-off time for Achilles tendinopathies was 23±37 (median=10, Q1=4 and Q3=24) days, while a rupture of the Achilles tendon, on average, caused 161±65 (median=169, Q1=110 and Q3=189) days of absence. Players with Achilles tendon disorders were significantly older than the rest of the cohort, with a mean age of 27.2±4 years vs 25.6±4.6 years (p<0.001). 27% of all Achilles tendinopathies were reinjuries. A higher reinjury risk was found after short recovery periods (31%) compared with longer recovery periods (13%) (RR 2.4, 95% CI 2.1 to 2.8; p<0.001).ConclusionsAchilles tendon disorders account for 3.8% of the total lay-off time and are more common in older players. Recurrence is common after Achilles tendinopathies and the reinjury risk is higher after short recovery periods.
Unravelling the grey zone: cardiac MRI volume to wall mass ratio to differentiate hypertrophic cardiomyopathy and the athlete's heart
Authors: Luijkx Tim , Cramer Maarten J , Buckens Constantinus F , Zaidi Abbas , Rienks Rienk , Mosterd Arend , Prakken Niek HJ , Dijkman Barbara , Mali Willem PThM , Velthuis Birgitta K 
Published: June 2013

BackgroundDifferentiating physiological left ventricular hypertrophy (LVH) in athletes from pathological hypertrophic cardiomyopathy (HCM) can be challenging. This study assesses the ability of cardiac MRI (CMR) to distinguish between physiological LVH (so-called athlete's heart) and HCM.Methods45 patients with HCM (71% men and 20% athletic) and 734 healthy control participants (60% men and 75% athletic) underwent CMR. Quantitative ventricular parameters were used for multivariate logistic regression with age, gender, sport status and left ventricular (LV) end-diastolic volume (EDV) to ED ventricular wall mass (EDM) ratio as covariates. A second model added the LV EDV : right ventricular (RV) EDV ratio. The performance of the model was subsequently tested.ResultsLV EDM was greater in patients with HCM (74 g/m2) compared with healthy athletes/non-athletes (53/41 g/m2), while LV EDV was largest in athletes (114 ml/m2) as compared with non-athletes (94 ml/m2) and patients with HCM (88 ml/m2). The LV EDV : EDM ratio was significantly lower in patients with HCM compared with healthy controls and athletes (1.30/2.39/2.25, p<0.05). The LV EDV : RV EDV ratio was significantly greater in patients with HCM (1.10) than in healthy participants (non-athletes/athletes 0.94/0.93). The regression model resulted in high sensitivity and specificity levels in all and borderline-LVH participants (as defined by septal wall thickness). Corresponding areas under the receiver operator characteristic (ROC) curves were 0.995 (all participants) and 0.992 (borderline-LVH participants only). Adding the LV EDV : RV EDV ratio yielded no additional improvement.ConclusionsA model incorporating the LV EDV : EDM ratio can help distinguish HCM from physiological hypertrophy in athletes. This also applies to cases with borderline LVH, which present the greatest diagnostic challenge in clinical practice.
Safety and efficacy of ticagrelor for neuroendovascular procedures. A single center initial experience
Authors: Hanel Ricardo A , Taussky Philipp , Dixon Tanya , Miller David A , Sapin Merlie , Nordeen Jerah D , Tawk Rabih G , Navarro Ramon , Johns Gretchen , Freeman William D 
Published: June 2013

IntroductionAlthough platelet response testing is controversial, up to one-third of neuroendovascular patients are ‘resistant’ to clopidogrel and are at risk for in stent thrombotic complications and may require alternative antiplatelet therapy. Ticagrelor is a new reversible ADP P2Y12 platelet receptor inhibitor with no known resistance. We describe the clinical experience with ticagrelor for neuroendovascular procedures as an alternative in clopidogrel P2Y12 platelet resistant patients.MethodsWe reviewed our cerebrovascular database for all patients who were non-responders to clopidogrel, defined as P2Y12% inhibition <30%, despite repeat clopidogrel loading dose of at least 600 mg, and who were then administered ticagrelor.Results18 patients were non-responders to clopidogrel; 10 (56%) were men, eight (44%) were women, with a median age of 61 years (range 38–84). All patients received loading doses of at least 600 mg of clopidogrel and showed P2Y12 levels below 20% prior to ticagrelor administration. Patients were loaded with 180 mg of ticagrelor, and all but one patient showed an initial P2Y12 response above 60%. 11 patients underwent stenting, two underwent coiling, and five underwent treatment by pipeline embolization device. No patient experienced any adverse effects in the postoperative period related to the use of ticagrelor.ConclusionsTicagrelor offers an effective alternative to clopidogrel non-responders. All of our patients showed immediate platelet inhibition after a loading dose of 180 mg of ticagrelor, with no adverse effects. The cost of medication, patient compliance (twice a day doses), and reversible inhibition should be taken into consideration when using ticagrelor.
The organisation, operational dynamics and structure of female sex work in Pakistan
Authors: Emmanuel Faran , Thompson Laura H , Athar Uzma , Salim Momina , Sonia Altaf , Akhtar Naeem , Blanchard James F 
Published: June 2013

BackgroundPakistan is known to have large populations of female sex workers (FSWs) with considerable geographic heterogeneity in their characteristics. In this paper, we describe the social organisation and structural patterns of female sex work in different geographic regions of Pakistan.MethodsWe report geographic and network mapping data collected among FSWs in 15 cities across Pakistan in 2011 as part of the Canada-Pakistan HIV/AIDS Surveillance Project.ResultsA total number of 89 178 FSWs were estimated in the target cities for an average of 7.2 FSWs per 1000 adult males. 55% of the estimated number of FSWs concentrated in Karachi and Lahore. Based on the operations of female sex work, two major typologies of FSWs were identified: establishment-based and non-establishment-based. FSWs were further subtyped into those operating through brothels, homes, kothikhanas, streets and by cell phone. Cities varied considerably in terms of predominance of different FSW typologies.ConclusionsThere is considerable heterogeneity among FSWs in Pakistan, geographically and in terms of operational typology. Understanding the social organisation of sex work and the influence of social-cultural and legal factors in Pakistan is essential for the design of HIV prevention programmes and other services for FSWs.
An Approximation Method for Convolution Calderón-Zygmund Operators
Authors: Yu Yunxia , Yang Zhanying 
Published: June 2013

We present an approximation method for convolution Calderón-Zygmund operators. We give a uniform approximation accuracy of the operators on the endpoint Triebel-Lizorkin spaceF˙1 0;q   (2<q<∞). Our proof mainly relies on then-dimensional Daubechies wavelet bases and the atomic-molecular approach.
The Distance Matrices of Some Graphs Related to Wheel Graphs
Authors: Zhang Xiaoling , Song Chengyuan 
Published: June 2013

LetDdenote the distance matrix of a connected graphG. The inertia ofDis the triple of integers (n+(D), n0(D), n-(D)), wheren+(D),n0(D), andn-(D)denote the number of positive, 0, and negative eigenvalues ofD, respectively. In this paper, we mainly study the inertia of distance matrices of some graphs related to wheel graphs and give a construction for graphs whose distance matrices have exactly one positive eigenvalue.
BRAF in Melanoma: Current Strategies and Future Directions
Authors: Salama April K.S. , Flaherty Keith T. 
Published: June 2013

Abstract
Selective BRAF inhibitors have now been established as a standard of care option for patients diagnosed with metastatic melanoma whose tumors carry a BRAF mutation. Their successful development represents a milestone in the treatment of this disease, and has the potential to impact therapy for other malignancies as well. The use of these agents, however, has introduced a number of critical questions about the optimal use and selection of patients for BRAF inhibitor therapy. This review discusses the current status of BRAF inhibitor clinical development, the clinicopathologic features of BRAF-mutated melanoma, as well as strategies for overcoming resistance. Clin Cancer Res; 19(16); 4326–34. ©2013 AACR.
Inhibition of Lung Tumorigenesis by Metformin Is Associated with Decreased Plasma IGF-I and Diminished Receptor Tyrosine Kinase Signaling
Authors: Quinn Brendan J. , Dallos Matthew , Kitagawa Hiroshi , Kunnumakkara Ajaikumar B. , Memmott Regan M. , Hollander M. Christine , Gills Joell J. , Dennis Phillip A. 
Published: June 2013

Abstract
Metformin is the most commonly prescribed drug for type II diabetes and is associated with decreased cancer risk. Previously, we showed that metformin prevented tobacco carcinogen (NNK)–induced lung tumorigenesis in a non-diabetic mouse model, which was associated with decreased IGF-I/insulin receptor signaling but not activation of AMPK in lung tissues, as well as decreased circulating levels of IGF-I and insulin. Here, we used liver IGF-I–deficient (LID) mice to determine the importance of IGF-I in NNK-induced lung tumorigenesis and chemoprevention by metformin. LID mice had decreased lung tumor multiplicity and burden compared with wild-type (WT) mice. Metformin further decreased lung tumorigenesis in LID mice without affecting IGF-I levels, suggesting that metformin can act through IGF-I–independent mechanisms. In lung tissues, metformin decreased phosphorylation of multiple receptor tyrosine kinases (RTK) as well as levels of GTP-bound Ras independently of AMPK. Metformin also diminished plasma levels of several cognate ligands for these RTKs. Tissue distribution studies using [14C]-metformin showed that uptake of metformin was high in liver but four-fold lower in lungs, suggesting that the suppression of RTK activation by metformin occurs predominantly via systemic, indirect effects. Systemic inhibition of circulating growth factors and local RTK signaling are new AMPK-independent mechanisms of action of metformin that could underlie its ability to prevent tobacco carcinogen–induced lung tumorigenesis. Cancer Prev Res; 6(8); 801–10. ©2013 AACR.
Dietary Soy Effects on Mammary Gland Development during the Pubertal Transition in Nonhuman Primates
Authors: Dewi Fitriya N. , Wood Charles E. , Lees Cynthia J. , Willson Cynthia J. , Register Thomas C. , Tooze Janet A. , Franke Adrian A. , Cline J. Mark 
Published: June 2013

AbstractWhile epidemiologic studies suggest that soy intake early in life may reduce breast cancer risk, there are also concerns that exposure to soy isoflavones during childhood may alter pubertal development and hormonal profiles. Here, we assessed the effect of a high-soy diet on pubertal breast development, sex hormones, and growth in a nonhuman primate model. Pubertal female cynomolgus monkeys were randomized to receive a diet modeled on a typical North American diet with one of two protein sources for approximately 4.5 years: (i) casein/lactalbumin (CL, n = 12, as control) or (ii) soy protein isolate with a human equivalent dose of 120 mg/d isoflavones (SOY, n = 17), which is comparable to approximately four servings of soy foods. Pubertal exposure to the SOY diet did not alter onset of menarche, indicators of growth and pubertal progression, or circulating estradiol and progesterone concentrations. Greater endometrial area was seen in the SOY group on the first of four postmenarchal ultrasound measurements (P &lt; 0.05). There was a subtle effect of diet on breast differentiation whereby the SOY group showed higher numbers of differentiated large-sized lobular units and a lower proportion with immature ducts following menarche (P &lt; 0.05). Numbers of small lobules and terminal end buds and mammary epithelial cell proliferation did not differ by diet. Expression of progesterone receptor was lower in immature lobules of soy-fed animals (P &lt; 0.05). Our findings suggest that consumption of soy starting before menarche may result in modest effects consistent with a more differentiated breast phenotype in adulthood. Cancer Prev Res; 6(8); 832–42. ©2013 AACR.
Grape Seeds: Ripe for Cancer Chemoprevention
Authors: Katiyar Santosh K. , Athar Mohammad 
Published: June 2013

Abstract
A wide variety of phytochemicals, mostly flavonoids or polyphenolics, have been shown to possess anticarcinogenic activities. Among these are the grape seed proanthocyanidins (GSPs), which are the active ingredients of grape seed extract (GSE). Substantial in vitro and preclinical in vivo studies have shown the chemopreventive efficacy of GSPs against various forms of cancers in different tumor models. In this issue of the journal, Derry and colleagues show that administration of GSE in the diet reduces azoxymethane-induced colon carcinogenesis in an A/J mouse model. The results of this innovative and comprehensive study indicate that inhibition of azoxymethane-induced colon cancer by dietary GSE is mediated through the induction of apoptosis that is associated with alterations in microRNA (miRNA) and cytokine expression profiles as well as β-catenin signaling. Notably, the demonstration that miRNA expression is affected by dietary GSE suggests a novel underlying mechanism for the chemopreventive action of GSE in colon cancer and, potentially, other cancers. Cancer Prev Res; 6(7); 617–21. ©2013 AACR.
Unbiased Metabolite Profiling Indicates That a Diminished Thymidine Pool Is the Underlying Mechanism of Colon Cancer Chemoprevention by Alpha-Difluoromethylornithine
Authors: Witherspoon Mavee , Chen Qiuying , Kopelovich Levy , Gross Steven S. , Lipkin Steven M. 
Published: June 2013

Abstract
The ornithine decarboxylase inhibitor α-difluoromethylornithine (DFMO) is a highly effective chemopreventive agent for colorectal cancer thought to act via polyamine depletion. However, in DFMO-treated patients, mucosal polyamine levels do not directly correlate with colorectal cancer risk. Untargeted metabolite profiling was used to broadly survey DFMO actions on colon cancer cell metabolism. We found that DFMO treatment of ApcMin intestinal tumors and human colorectal cancer cells is associated with reduced levels of folate-dependent metabolites, including S-adenosylmethionine (SAM), thymidine pools, and related pathway intermediates. We hypothesized that unrestrained SAM consumption/regeneration constitutes a futile DFMO-triggered cascade that can steal tetrahydrofolate from thymidylate synthase and thereby diminish thymidine pools. In accord with this hypothesis, DFMO treatment altered the folate cofactor balance and thymidine supplementation prevented DFMO-elicited cytostasis without restoring polyamine levels. These findings suggest that thymidine metabolite pool insufficiency is a fundamental mechanism of DFMO cytostatic activity.
Significance: A previously unappreciated metabolic linkage between polyamine and thymidine biosynthesis is revealed, based on the competing requirement of these pathways for a limited pool of tetrahydrofolate cofactor. This study identifies the first shared mechanism for colorectal cancer chemoprevention and chemotherapy, suggesting a common metabolic target for both premalignant and malignant colon cells. Cancer Discov; 3(9); 1072–81. ©2013 AACR.
See related commentary by Casero, p. 975
This article is highlighted in the In This Issue feature, p. 953