bluuebunny/crossref_metadata_2025 huggingface dataset:
New Tools and Insights: Hyperhidrosis in a Community Setting
Authors: Koo Veronique , Kalaria Dipen , Wassenaar Willem
Published: June 2013

Background:

While excessive sweating is considered by many to be a benign condition, the physical and psychosocial impact it can have on hyperhidrosis sufferers is not always fully appreciated.

Methods:

A retrospective review of our pharmacy's patient records with the presenting complaint of sweating was conducted. The review covered a 2-year span and consisted of 2517 records. Using a structured questionnaire, patient information was collected via e-mail, as well as telephone and face-to-face interviews by pharmacists. Patients described their difficulties and the different coping methods they would employ to alleviate or hide their excessive sweating on different areas such as the underarms, face/scalp, hands, feet, and torso/groin.

Results:

Underarm sweating is the most frequent area for which both male and female patients seek help, followed by hands, feet, and face/neck. For males over 40, face and neck sweating is the most frequent area of concern, whereas for females over 40, underarms remain a top priority. Patients report numerous instances of feeling isolated, depressed, and a lack of self-confidence in all areas of professional and social life.

Conclusion:

It is important to recognize that for some patients, excessive sweating can be a severely debilitating condition. Appropriate action must be taken in order to improve the patient's quality of life.
The geographic accessibility of pharmacies in Nova Scotia
Authors: Law Michael R. , Heard Deborah , Fisher Judith , Douillard Jay , Muzika Greg , Sketris Ingrid S.
Published: June 2013

Introduction:

Geographic proximity is an important component of access to primary care and the pharmaceutical services of community pharmacies. Variations in access to primary care have been found between rural and urban areas in Canadian and international jurisdictions. We studied access to community pharmacies in the province of Nova Scotia.

Methods:

We used information on the locations of 297 community pharmacies operating in Nova Scotia in June 2011. Population estimates at the census block level and network analysis were used to study the number of Nova Scotia residents living within 800 m (walking) and 2 km and 5 km (driving) distances of a pharmacy. We then simulated the impact of pharmacy closures on geographic access in urban and rural areas.

Results:

We found that 40.3% of Nova Scotia residents lived within walking distance of a pharmacy; 62.6% and 78.8% lived within 2 km and 5 km, respectively. Differences between urban and rural areas were pronounced: 99.2% of urban residents lived within 5 km of a pharmacy compared with 53.3% of rural residents. Simulated pharmacy closures had a greater impact on geographic access to community pharmacies in rural areas than urban areas.

Conclusion:

The majority of Nova Scotia residents lived within walking or short driving distance of at least 1 community pharmacy. While overall geographic access appears to be lower than in the province of Ontario, the difference appears to be largely driven by the higher proportion of rural dwellers in Nova Scotia. Further studies should examine how geographic proximity to pharmacies influences patients’ access to traditional and specialized pharmacy services, as well as health outcomes and adherence to therapy. Can Pharm J 2013;146:39-46.
The willingness of community pharmacists to participate in a practice-based research network
Authors: Hébert Joanie , Laliberté Marie-Claude , Berbiche Djamal , Martin Elisabeth , Lalonde Lyne
Published: June 2013

Background:

Practice-based research networks (PBRNs) are groups of practitioners and researchers with an interest in designing, evaluating and disseminating solutions to the real-world problems of clinical practices.

Objective:

To evaluate the level of interest of community pharmacists in participating in a PBRN and to document the services such a network should offer.

Method:

In a survey of community pharmacists in Montreal, Quebec, and surrounding areas, a questionnaire was mailed to a random sample of 1250 pharmacists. Two of the 28 questions were related to PBRNs: one assessed the pharmacists’ interest in participating in a PBRN; the other sought their views on which services and activities this network should offer.

Results:

In total, 571 (45.7%) pharmacists completed the questionnaire, but 6 did not answer the questions about the PBRN. Of the respondents, 58.9% indicated they were “very interested” or “interested” in joining a PBRN, while 41.1% reported little or no interest. The most popular potential services identified were access to clinical tools developed in research projects (77.0%), access to continuing education training programs developed in research projects (75.9%), information about conferences on pharmacy practice research (64.1%) and participation in the development of new pharmaceutical practices (56.1%).

Conclusion:

This study suggests that the level of interest that community pharmacists have in PBRNs is sufficient to further evaluate how such networks may optimize and facilitate pharmacy practice research. Can Pharm J 2013;146:47-54.
The interplay between the X-DING-CD4, IFN-α and IL-8 gene activity in quiescent and mitogen- or HIV-1-exposed PBMCs from HIV-1 elite controllers, AIDS progressors and HIV-negative controls
Authors: Sachdeva Rakhee , Shilpi Rasheda Y , Simm Malgorzata
Published: June 2013

X-DING-CD4 blocks HIV-1 long terminal repeat (LTR) and pathogen induced pro-inflammatory response. Increased activity of the X-DING-CD4 gene is associated with cellular resistance to virus; therefore, HIV-1 elite controllers (ECs) should have higher X-DING-CD4 and reduced pro-inflammatory mRNA activity than viremic or uninfected individuals. Also, depending on the cell stimulating factor, expression of X-DING-CD4 mRNA in ECs might be autonomous or contingent on IFN signaling. We compared expression of X-DING-CD4, IFN-α and IL-8 mRNAs in naive, phytohemagglutinin- or HIV-1 exposed PBMCs from ECs, HIV progressors and negative controls; tested correlation between X-DING-CD4 and IFN-α expression; sensitivity of the X-DING-CD4 gene to IFN-α regulation; and evaluated interactions between innate and pro-inflammatory genes. We found that expression of X-DING-CD4 and IFN-α was up-regulated in ECs and correlated in cells stimulated with mitogen, but not HIV-1. The X-DING-CD4 gene was more sensitive to HIV-1 than rIFN-α stimulation. ECs had significantly less IL-8 mRNA when PBMCs were exposed to exogenous HIV-1. Two-way ANOVA showed that control of HIV-1 and virus-induced pro-inflammatory response by ECs stemmed from interactions between expression of innate immunity and pro-inflammatory genes, the state of cell stimulation and the status of virus control. Consequently, interaction of multiple host innate immune responses rather than a single mechanism regulates restriction of HIV-1 in ECs.
On the Nature of Automatically Triggered Approach–Avoidance Behavior
Authors: Krieglmeyer Regina , De Houwer Jan , Deutsch Roland
Published: June 2013

Theory suggests that stimulus evaluations automatically evoke approach–avoidance behavior. However, the extent to which approach–avoidance behavior is triggered automatically is not yet clear. Furthermore, the nature of automatically triggered approach–avoidance behavior is controversial. We review research on two views on the type of approach–avoidance behavior that is triggered automatically (arm flexion/extension, distance change). Present evidence supports the distance-change view and corroborates the notion of an automatic pathway from evaluation to distance-change behavior. We discuss underlying mechanisms (direct stimulus–response links, outcome anticipations, goals) as well as implications regarding the flexibility of the evaluation–behavior link.
Dodging Monsters and Dancing with Dreams: Success and Failure at Different Levels of Approach and Avoidance
Authors: Scholer Abigail A. , Higgins E. Tory
Published: June 2013

Many models of motivation suggest that goals can be arranged in a hierarchy, ranging from higher-level goals that represent desired end-states to lower-level means that operate in the service of those goals. We present a hierarchical model that distinguishes between three levels—goals, strategies, and tactics—and between approach/avoidance and regulatory focus motivations at different levels. We focus our discussion on how this hierarchical framework sheds light on the different ways that success and failure are defined within the promotion and prevention systems outlined in regulatory focus theory. Specifically, we review research that demonstrates that differences in what “counts” as success versus failure in these systems have important implications for motivational strength, emotional responses, and risky behavior.
Appetitive and Defensive Motivation: Goal-Directed or Goal-Determined?
Authors: Lang Peter J. , Bradley Margaret M.
Published: June 2013

Our view is that fundamental appetitive and defensive motivation systems evolved to mediate a complex array of adaptive behaviors that support the organism’s drive to survive—defending against threat and securing resources. Activation of these motive systems engages processes that facilitate attention allocation, information intake, sympathetic arousal, and, depending on context, will prompt tactical actions that can be directed either toward or away from the strategic goal, whether defensively or appetitively determined. Research from our laboratory that measures autonomic, central, and somatic reactions when processing emotional scenes is described which indicates that motivationally relevant cues, whether appetitive or defensive, capture attention preferentially, prompt enhanced perceptual processing and information gathering, and occasion metabolic arousal that mobilizes the organism for coping actions.
Epistaxis
Authors: Patel Anushka , Fowell Christopher
Published: June 2013

Epistaxis, or nosebleed, is a common phenomenon. It is usually self-limiting, of limited clinical significance and can often be managed in the primary care setting. However, it may also be the first presentation of more serious head and neck pathology and in some patients may lead to more significant clinical sequelae. GPs should have an understanding of the management of acute and recurrent epistaxis, and need to be able to identify aetiological factors and complications. Careful assessment and prompt intervention is required in all patients to avoid more serious outcomes.
Post-coital bleeding in pre-menopausal women
Authors: Sandhu Harpreet Kaur , Pathiraja Pubudu
Published: June 2013

Post-coital bleeding is defined as bleeding or bloody discharge occurring after intercourse, at a time separate from menstruation. The only exception is after first intercourse, when some bleeding may occur following break-down of the hymen. It is a condition experienced by 0.7–9% of women during their lives. There are a number of causes of post-coital bleeding ranging from ectropion to gynaecological malignancy. It is the role of the GP to identify and assess women with this symptom, referring patients for further gynaecological assessment where appropriate.
Postnatal care
Authors: Chatterjee Devoshree
Published: June 2013

The role of GPs in providing maternity care has changed dramatically over the past 30 years, with a trend towards declining involvement; however, recent proposals have suggested greater involvement is required. Nevertheless, the GP remains an important point of contact for postnatal advice, and it is the GP who usually carries out the 6-week postnatal maternal check. This article aims to provide an overview of the common types of problems mothers may encounter in the postnatal period and how they can be appropriately managed. It also provides a guide for the topics to be covered during the 6-week postnatal maternal check.
Cellular distribution and gene expression profile during flexor tendon graft repair: A novel tissue engineering approach*
Authors: Juneja Subhash C
Published: June 2013

To understand scar and adhesion formation during postsurgical period of intrasynovial tendon graft healing, a murine model of flexor digitorum longus tendon graft repair was developed, by utilizing flexor digitorum longus tendon allograft from donor Rosa26/+ mouse, and the healing process at days 3, 7, 14, 21, 28, and 35 post surgery of host wild-type mouse was followed. Using X-gal staining, β-galactosidase positive cells of allograft origin were detectable in tissue sections of grafted tendon post surgery. Graft healing was assessed for the cellular density, scar and adhesion formation, and their interaction with surrounding tissue. From histological analysis, it was evident that the healing of intrasynovial flexor digitorum longus tendon graft takes place in an interactive environment of donor graft, host tendon, and host surrounding tissue. A total of 32 genes, analyzed by RNA analysis, expressed during healing process. Particularly, Alk1, Postn, Tnc, Tppp3, and Mkx will be further investigated for therapeutical value in reducing scars and adhesions.
When Is “Pseudo–Ludwig’s Angina” Associated With Coagulopathy Also a “Pseudo” Hemorrhage?
Authors: Lovallo Emily , Patterson Sarah , Erickson Mitchel , Chin Cynthia , Blanc Paul , Durrani Timur S.
Published: June 2013

Sublingual hematoma secondary to short-acting anticoagulants such as warfarin has been labeled “pseudo–Ludwig’s angina” to distinguish it from the classic syndrome of localized infection and swelling involving the upper airway. Sublingual hematoma with airway compromise secondary to brodifacoum, a common long-acting anticoagulant rodenticide, has only been reported in the veterinary literature. We report a case of massive tongue swelling and impending airway compromise in the context of an intentional long-acting anticoagulant ingestion leading to coagulopathy. The swelling was initially presumed to be due either to infection or hemorrhage, but this was not supported by computed tomography scan imaging. Instead, the patient’s clinical course was consistent with corticosteroid-responsive angioedema, temporally associated with the ingested brodifacoum.
‘Van Dyck in Action’: Dressing Charles I for the Victorian Stage
Authors: Walter Helen
Published: June 2013

In 1872, the then relatively unproven young actor, Henry Irving, took to the stage of London’s Lyceum theatre to play the part of Charles I in a new play by William Gorman Wills. The play’s phenomenal popularity was Irving’s first major triumph as a tragedian, but what few historians have explored was that his success was largely predicated, not just upon his acting ability, but on the visual aspects of his performance, particularly his appearance as Charles I, and his costumes, which were characterized by his biographer Bram Stoker as akin to watching ‘Van Dyck in action’. This notion, that Irving was the incarnation of Charles I as painted by Van Dyck, came to dominate the visual and verbal rhetoric of the production. However, looking in detail at images of the king, and of Irving’s costumes, this article breaks down this myth, and questions the validity of such a metaphor, arguing that Irving was not so much portraying Van Dyck’s king as a Victorian idea of how Charles should appear, which chimed perfectly with the expectations of his audiences, and ensured his success.
The 2009 pandemic (H1N1) viruses isolated from pigs show enhanced pathogenicity in mice
Authors: Li Yongtao , Zou Wei , Jia Guangmin , Ke Jianjiang , Zhu Jiping , Lin Xian , Zhou Hongbo , Jin Meilin
Published: June 2013

Since the emergence of the 2009 pandemic (H1N1) virus (2009/H1N1) in April 2009, cases of transmission from humans to pigs have been reported frequently. In our previous studies, four 2009/H1N1 variants were isolated from pigs. To better understand the phenotypic differences of the pig isolates compared with the human isolate, in this study mice were inoculated intranasally with different 2009/H1N1 viruses, and monitored for morbidity, mortality, and viral replication, cytokine production and pathological changes in the lungs. The results show that all isolates show effective replication in lungs, but varying in their ability to cause morbidity. In particular, the strains of A/swine/Nanchang/3/2010 (H1N1) and A/swine/Nanchang/F9/2010 (H1N1) show the greatest virulence with a persisting replication in lungs and high lethality for mice, compared with the human isolate A/Liaoning /14/2009 (H1N1), which shows low virulence in mice. Furthermore, the lethal strains could induce more severe lung pathological changes and higher production of cytokines than that of other strains at an early stage. Amino acid sequence analysis illustrates prominent differences in viral surface glycoproteins and polymerase subunits between pig isolates and human strains that might correlate with their phenotypic differences. These studies demonstrate that the 2009/H1N1 pig isolates exhibit heterogeneous infectivity and pathogencity in mice, and some strains possess an enhanced pathogenicity compared with the human isolate.
Identification and analysis of MKK and MPK gene families in canola (Brassica napusL.)
Authors: Liang Wanwan , Yang Bo , Yu Bao-Jun , Zhou Zili , Li Cui , Jia Ming , Sun Yun , Zhang Yue , Wu Feifei , Zhang Hanfeng , Wang Boya , Deyholos Michael K , Jiang Yuan-Qing
Published: June 2013

Background

Eukaryotic mitogen-activated protein kinase (MAPK/MPK) signaling cascades transduce and amplify environmental signals via three types of reversibly phosphorylated kinases to activate defense gene expression. Canola (oilseed rape,Brassica napus) is a major crop in temperate regions. Identification and characterization of MAPK and MAPK kinases (MAPKK/MKK) of canola will help to elucidate their role in responses to abiotic and biotic stresses.

Results

We describe the identification and analysis of sevenMKK(BnaMKK) and 12MPK(BnaMPK) members from canola. Sequence alignments and phylogenetic analyses of the predicted amino acid sequences of BnaMKKs and BnaMPKs classified them into four different groups. We also examined the subcellular localization of four and two members of BnaMKK and BnaMPK gene families, respectively, using green fluorescent protein (GFP) and, found GFP signals in both nuclei and cytoplasm. Furthermore, we identified several interesting interaction pairs through yeast two-hybrid (Y2H) analysis of interactions between BnaMKKs and BnaMPKs, as well as BnaMPK and BnaWRKYs. We defined contiguous signaling modules including BnaMKK9-BnaMPK1/2-BnaWRKY53, BnaMKK2/4/5-BnaMPK3/6-BnaWRKY20/26 and BnaMKK9-BnaMPK5/9/19/20. Of these, several interactions had not been previously described in any species. Selected interactions were validatedin vivoby a bimolecular fluorescence complementation (BiFC) assay. Transcriptional responses of a subset of canola MKK and MPK genes to stimuli including fungal pathogens, hormones and abiotic stress treatments were analyzed through real-time RT-PCR and we identified a few ofBnaMKKsandBnaMPKsresponding to salicylic acid (SA), oxalic acid (OA),Sclerotinia sclerotiorumor other stress conditions. Comparisons of expression patterns of putative orthologs in canola and Arabidopsis showed that transcript expression patterns were generally conserved, with some differences suggestive of sub-functionalization.

Conclusions

We identified sevenMKKand 12MPKgenes from canola and examined their phylogenetic relationships, transcript expression patterns, subcellular localization, and protein-protein interactions. Not all expression patterns and interactions were conserved between canola and Arabidopsis, highlighting the limitations of drawing inferences about crops from model species. The data presented here provide the first systematic description of MKK-MPK-WRKY signaling modules in canola and will further improve our understanding of defense responses in general and provide a basis for future crop improvement.
Changes in the concentrations of biochemical indicators of diet and nutritional status of pregnant women across pregnancy trimesters in Trujillo, Peru, 2004–2005
Authors: Horton D Kevin , Adetona Olorunfemi , Aguilar-Villalobos Manuel , Cassidy Brandon E , Pfeiffer Christine M , Schleicher Rosemary L , Caldwell Kathleen L , Needham Larry L , Rathbun Stephen L , Vena John E , Naeher Luke P
Published: June 2013

Background

In developing countries, deficiencies in essential micronutrients are common, particularly in pregnant women. Although, biochemical indicators of diet and nutrition are useful to assess nutritional status, few studies have examined such indicators throughout pregnancy in women in developing countries.

Methods

The primary objective of this study was to assess the nutritional status of 78 Peruvian women throughout pregnancy for 16 different nutritional indicators including fat-soluble vitamins and carotenoids, iron-status indicators, and selenium. Venous blood samples from which serum was prepared were collected during trimesters one (n = 78), two (n = 65), three (n = 62), and at term via the umbilical cord (n = 52). Questionnaires were completed to determine the demographic characteristics of subjects. Linear mixed effects models were used to study the associations between each maternal indicator and the demographic characteristics.

Results

None of the women were vitamin A and E deficient at any stage of pregnancy and only 1/62 women (1.6%) was selenium deficient during the third trimester. However, 6.4%, 44% and 64% of women had ferritin levels indicative of iron deficiency during the first, second and third trimester, respectively. Statistically significant changes (p ≤ 0.05) throughout pregnancy were noted for 15/16 nutritional indicators for this Peruvian cohort, with little-to-no association with demographic characteristics. Three carotenoids (beta-carotene, beta-cryptoxanthin and trans-lycopene) were significantly associated with education status, while trans-lycopene was associated with age and beta-cryptoxanthin with SES (p < 0.05). Concentrations of retinol, tocopherol, beta-cryptoxanthin, lutein + zeaxanthin and selenium were lower in cord serum compared with maternal serum (p < 0.05). Conversely, levels of iron status indicators (ferritin, transferrin saturation and iron) were higher in cord serum (p < 0.05).

Conclusion

The increasing prevalence of iron deficiency throughout pregnancy in these Peruvian women was expected. It was surprising though not to find deficiencies in other nutrients. The results highlight the importance of continual monitoring of women throughout pregnancy for iron deficiency which could be caused by increasing fetal needs and/or inadequate iron intake as pregnancy progresses.
A panel study of occupational exposure to fine particulate matter and changes in DNA methylation over a single workday and years worked in boilermaker welders
Authors: Kile Molly L , Fang Shona , Baccarelli Andrea A , Tarantini Letizia , Cavallari Jennifer , Christiani David C
Published: June 2013

Background

Exposure to pollutants including metals and particulate air pollution can alter DNA methylation. Yet little is known about intra-individual changes in DNA methylation over time in relationship to environmental exposures. Therefore, we evaluated the effects of acute- and chronic metal-rich PM2.5 exposures on DNA methylation.

Methods

Thirty-eight male boilermaker welders participated in a panel study for a total of 54 person days. Whole blood was collected prior to any welding activities (pre-shift) and immediately after the exposure period (post-shift). The percentage of methylated cytosines (%mC) in LINE-1, Alu, and inducible nitric oxide synthase gene (iNOS) were quantified using pyrosequencing. Personal PM2.5 (particulate matter with an aerodynamic diameter ≤ 2.5 μm) was measured over the work-shift. A questionnaire assessed job history and years worked as a boilermaker. Linear mixed models with repeated measures evaluated associations between DNA methylation, PM2.5 concentration (acute exposure), and years worked as a boilermaker (chronic exposure).

Results

PM2.5 exposure was associated with increased methylation in the promoter region of the iNOS gene (β = 0.25, SE: 0.11, p-value = 0.04). Additionally, the number of years worked as a boilermaker was associated with increased iNOS methylation (β = 0.03, SE: 0.01, p-value = 0.03). No associations were observed for Alu or LINE-1.

Conclusions

Acute and chronic exposure to PM2.5 generated from welding activities was associated with a modest change in DNA methylation of the iNOS gene. Future studies are needed to confirm this association and determine if the observed small increase in iNOS methylation are associated with changes in NO production or any adverse health effect.
Pseudomonas aeruginosa NfsB and nitro-CBI-DEI – a promising enzyme/prodrug combination for gene directed enzyme prodrug therapy
Authors: Green Laura K , Syddall Sophie P , Carlin Kendall M , Bell Glenn D , Guise Christopher P , Mowday Alexandra M , Hay Michael P , Smaill Jeffrey B , Patterson Adam V , Ackerley David F
Published: June 2013

Background

The nitro-chloromethylbenzindoline prodrug nitro-CBI-DEI appears a promising candidate for the anti-cancer strategy gene-directed enzyme prodrug therapy, based on its ability to be converted to a highly cytotoxic cell-permeable derivative by the nitroreductase NfsB from Escherichia coli. However, relative to some other nitroaromatic prodrugs, nitro-CBI-DEI is a poor substrate for E. coli NfsB. To address this limitation we evaluated other nitroreductase candidates from E. coli and Pseudomonas aeruginosa.

Findings

Initial screens of candidate genes in the E. coli reporter strain SOS-R2 identified two additional nitroreductases, E. coli NfsA and P. aeruginosa NfsB, as being more effective activators of nitro-CBI-DEI than E. coli NfsB. In monolayer cytotoxicity assays, human colon carcinoma (HCT-116) cells transfected with P. aeruginosa NfsB were >4.5-fold more sensitive to nitro-CBI-DEI than cells expressing either E. coli enzyme, and 23.5-fold more sensitive than untransfected HCT-116. In three dimensional mixed cell cultures, not only were the P. aeruginosa NfsB expressing cells 540-fold more sensitive to nitro-CBI-DEI than pure cultures of untransfected HCT-116, the activated drug that they generated also displayed an unprecedented local bystander effect.

Conclusion

We posit that the discrepancy in the fold-sensitivity to nitro-CBI-DEI between the two and three dimensional cytotoxicity assays stems from loss of activated drug into the media in the monolayer cultures. This emphasises the importance of evaluating high-bystander GDEPT prodrugs in three dimensional models. The high cytotoxicity and bystander effect exhibited by the NfsB_Pa/nitro-CBI-DEI combination suggest that further preclinical development of this GDEPT pairing is warranted.
A generalized weak contraction principle with applications to coupled coincidence point problems
Authors: Choudhury Binayak S , Metiya Nikhilesh , Postolache Mihai
Published: June 2013

In this paper we establish some coincidence point results for generalized weak contractions with discontinuous control functions. The theorems are proved in metric spaces with a partial order. Our theorems extend several existing results in the current literature. We also discuss several corollaries and give illustrative examples. We apply our result to obtain some coupled coincidence point results which effectively generalize a number of established results.

MSC:54H10, 54H25.
Phenotype, donor age and gender affect function of human bone marrow-derived mesenchymal stromal cells
Authors: Siegel Georg , Kluba Torsten , Hermanutz-Klein Ursula , Bieback Karen , Northoff Hinnak , Schäfer Richard
Published: June 2013

Background

Mesenchymal stromal cells (MSCs) are attractive for cell-based therapies ranging from regenerative medicine and tissue engineering to immunomodulation. However, clinical efficacy is variable and it is unclear how the phenotypes defining bone marrow (BM)-derived MSCs as well as donor characteristics affect their functional properties.

Methods

BM-MSCs were isolated from 53 (25 female, 28 male; age: 13 to 80 years) donors and analyzed by: (1) phenotype using flow cytometry and cell size measurement; (2) in vitro growth kinetics using population doubling time; (3) colony formation capacity and telomerase activity; and (4) function by in vitro differentiation capacity, suppression of T cell proliferation, cytokines and trophic factors secretion, and hormone and growth factor receptor expression. Additionally, expression of Oct4, Nanog, Prdm14 and SOX2 mRNA was compared to pluripotent stem cells.

Results

BM-MSCs from younger donors showed increased expression of MCAM, VCAM-1, ALCAM, PDGFRβ, PDL-1, Thy1 and CD71, and led to lower IL-6 production when co-cultured with activated T cells. Female BM-MSCs showed increased expression of IFN-γR1 and IL-6β, and were more potent in T cell proliferation suppression. High-clonogenic BM-MSCs were smaller, divided more rapidly and were more frequent in BM-MSC preparations from younger female donors. CD10, β1integrin, HCAM, CD71, VCAM-1, IFN-γR1, MCAM, ALCAM, LNGFR and HLA ABC were correlated to BM-MSC preparations with high clonogenic potential and expression of IFN-γR1, MCAM and HLA ABC was associated with rapid growth of BM-MSCs. The mesodermal differentiation capacity of BM-MSCs was unaffected by donor age or gender but was affected by phenotype (CD10, IFN-γR1, GD2). BM-MSCs from female and male donors expressed androgen receptor and FGFR3, and secreted VEGF-A, HGF, LIF, Angiopoietin-1, basic fibroblast growth factor (bFGF) and NGFB. HGF secretion correlated negatively to the expression of CD71, CD140b and Galectin 1. The expression of Oct4, Nanog and Prdm14 mRNA in BM-MSCs was much lower compared to pluripotent stem cells and was not related to donor age or gender. Prdm14 mRNA expression correlated positively to the clonogenic potential of BM-MSCs.

Conclusions

By identifying donor-related effects and assigning phenotypes of BM-MSC preparations to functional properties, we provide useful tools for assay development and production for clinical applications of BM-MSC preparations.
Tuberculous meningitis: presentation, diagnosis and outcome in hiv-infected patients at the douala general hospital, cameroon: a cross sectional study
Authors: Luma Henry Namme , Tchaleu Benjamin Clet Nguenkam , Ngahane Bertrand Hugo Mbatchou , Temfack Elvis , Doualla Marie Solange , Halle Marie Patrice , Joko Henry Achu , Koulla-Shiro Sinata
Published: June 2013

Introduction

Tuberculous meningitis (TBM) the most fatal presentation of tuberculosis (TB) especially in HIV-infected patients is a real diagnostic and therapeutic challenge worldwide. In Cameroon where HIV and TB are amongst the leading public health problems, the magnitude of TBM has not been defined. Therefore, the objective of this cross sectional study was to describe the presentation and in-hospital outcome of TBM among HIV patients in Douala as well as its diagnostic difficulties.

Methods

We did a clinical case note analysis of all HIV-1 infected patients treated for TBM in the Internal medicine unit of the Douala General Hospital, between January 1st 2004 and December 31st 2009. The diagnosis of TBM was made using clinical, laboratory [cerebrospinal fluid (CSF) analysis] and/or brain computerised tomographic (CT) scan features.

Results

During the study period, 8% (54/672) of HIV-infected patients had TBM. Their mean age was 40.3 ± 12.7 years. The main presenting complaint was headache in 74.1% (40/54) of patients. Their median CD4 cell count was 16 cells/mm3 (IQR: 10 – 34). CSF analysis showed median protein levels of 1.7 g/l (IQR: 1.3 – 2.2), median glucose level of 0.4 g/l (IQR: 0.3 – 0.5) and median white cell count (WCC) count of 21 cells/ml (IQR: 12 – 45) of which mononuclear cells were predominant in 74% of CSF. Acid fast bacilli were found in 1.9% (1/54) of CSF samples. On CT scan hydrocephalus was the main finding in 70.6% (24/34) of patients. In hospital case fatality was 79.6% (43/54).

Conclusion

TBM is a common complication in HIV-infected patients in Douala with high case fatality. Its presumptive diagnosis reposes mostly on CSF analysis, so clinicians caring for HIV patients should not hesitate to do lumbar taps in the presence of symptoms of central nervous system disease.
Methylation kinetics and CpG-island methylator phenotyope status in colorectal cancer cell lines
Authors: Wodarz Dominik , Boland C Richard , Goel Ajay , Komarova Natalia L
Published: June 2013

Background

Hypermethylation of CpG islands is thought to contribute to carcinogenesis through the inactivation of tumor suppressor genes. Tumor cells with relatively high levels of CpG island methylation are considered CpG island methylator phenotypes (CIMP). The mechanisms that are responsible for regulating the activity ofde novomethylation are not well understood.

Results

We quantify and comparede novomethylation kinetics in CIMP and non-CIMP colon cancer cell lines in the context of different loci, following 5-aza-2’deoxycytidine (5-AZA)-mediated de-methylation of cells. In non-CIMP cells, a relatively fast rate of re-methylation is observed that starts with a certain time delay after cessation of 5-AZA treatment. CIMP cells, on the other hand, start re-methylation without a time delay but at a significantly slower rate. A mathematical model can account for these counter-intuitive results by assuming negative feedback regulation ofde novomethylation activity and by further assuming that this regulation is corrupted in CIMP cells. This model further suggests that when methylation levels have grown back to physiological levels,de novomethylation activity ceases in non-CIMP cells, while it continues at a constant low level in CIMP cells.

Conclusions

We propose that the faster rate of re-methylation observed in non-CIMP compared to CIMP cells in our study could be a consequence of feedback-mediated regulation of DNA methyl transferase activity. Testing this hypothesis will involve the search for specific feedback regulatory mechanisms involved in the activation ofde novomethylation.

Reviewers’ report

This article was reviewed by Georg Luebeck, Tomasz Lipniacki, and Anna Marciniak-Czochra
Renal sympathetic denervation versus antiarrhythmic drugs for drug-resistant hypertension and symptomatic atrial fibrillation (RSDforAF) trial: study protocol for a randomized controlled trial
Authors: Qiu Min , Yin Yuehui , Shan Qijun
Published: June 2013

Background

Recently, catheter-based renal sympathetic denervation (RSD) has been verified to be safely used to substantially reduce the levels of blood pressure, left ventricular hypertrophy, sleep apnea severity and norepinephrine spillover, and improve glucose tolerance. All these pathological changes are recognized as independent risk factors for the development and recurrence of atrial fibrillation (AF). A randomized, single-blind, parallel-control, multicenter clinical trial is being conducted to compare RSD with antiarrhythmic drugs (AAD) in patients with drug-resistant hypertension and symptomatic AF (RSDforAF trial).

Methods/design

Patients with drug-resistant hypertension and symptomatic AF will be randomized to RSD and the drug treatment groups. Patients will be followed for 12 months until study closure. Up to 200 patients may be enrolled in six medical centers in China. The primary objective is to study the effects of RSD on AF burden and blood pressure in patients with hypertension and symptomatic AF.

Discussion

RSDforAF trial will test the hypothesis that RSD is superior to AAD in reducing AF burden and blood pressure in patients with drug-resistant hypertension and symptomatic AF.

Trial registration

ClinicalTrials.gov, NCT01713270
Peripheral compound odontoma erupting in the gingiva
Authors: Hanemann João AC , Oliveira Denise T , Garcia Natália Galvão , Santos Mariana RG , Pereira Alessandro AC
Published: June 2013

Background

Peripheral odontoma arising in the extraosseous soft tissues is rare and if not removed early, may enlarge over time and eventually erupt in the oral cavity.

Case presentation

A 15-year-old girl presented with “denticles on the gingiva”. During the intraoral examination, seven small tooth-like structures were found. These were exposed in the anterior left gingiva between the permanent maxillary lateral incisor and canine teeth, and the left first premolar was absent. Radiographic examination revealed irregular tooth-like structures without evidence of bone involvement.

Conclusion

The lesion was surgically removed, and the specimens were analyzed histopathologically. The diagnosis of compound odontoma was established.

Clinical significance

This is the twelfth reported case of peripheral odontoma in the gingiva and the first one that erupted in the oral cavity.
Cultural change and loss of ethnoecological knowledge among the Isthmus Zapotecs of Mexico
Authors: Saynes-Vásquez Alfredo , Caballero Javier , Meave Jorge A , Chiang Fernando
Published: June 2013

Background

Global changes that affect local societies may cause the loss of ecological knowledge. The process of cultural change in Zapotec communities of the Oaxacan Isthmus intensified during the first years of the 20thcentury due to industrial and agro-industrial modernization projects and an increase in the level of formal schooling. Based on the case of the Oaxacan Isthmus, this study assesses the relationship between cultural change and the loss of traditional ecological knowledge (TEK).

Methods

Three hundred male heads of family were interviewed from three municipalities in the Isthmus of Tehuantepec, Oaxaca, Mexico selected to span a wide range of cultural change. Each participant was shown herbarium specimens and photographs of a sample of 30 species drawn from a pool of 94 representing local plant diversity. Visual recognition of each species, knowledge of plant form, generic name, specific name, and local uses were scored. The sum of the five scores provided an index of global knowledge which we used as a proxy for TEK. Analysis of variance revealed differences between groups of economic activities. We collected socio-demographic data from the interviewees such as age, level of schooling, and competency in the local language. With these data we ran a principal component analysis and took the first axis as an index of cultural change, and correlated it with the scores obtained each respondent.

Results

We found statistically significant differences between groups of people with different economic activities, as well as a highly significant negative relationship between the Index of cultural change and ecological knowledge at all levels, with regression coefficients between 81.2% and 88.3%, indicating that cultural change is affecting traditional botanical knowledge.

Conclusions

Our results shown that cultural change, as indicated by occupational activity, level of formal schooling, and competence in the indigenous language, is negatively associated with the loss of Zapotec ethnobotanical knowledge. Heads of family engaged in secondary economic activities and services were less culturally competent, especially regarding the knowledge of generic and specific names as well as plant uses.
Critical appraisal of the accuracy of Acuros-XB and Anisotropic Analytical Algorithm compared to measurement and calculations with the compass system in the delivery of RapidArc clinical plans
Authors: Kathirvel Murugesan , Subramanian Shanmuga , Clivio Alessandro , Arun Gandhi , Fogliata Antonella , Nicolini Giorgia , Subramani Vellaiyan , Thirumalai Swamy Shanmugam , Vanetti Eugenio , Cozzi Luca
Published: June 2013

Background

The accuracy of the two dose calculation engines available for RapidArc planning (both released for clinical use) is investigated in comparison to the COMPASS data.

Methods

Two dose calculation algorithms (Acuros-XB and Anisotropic Analytic Algorithm (AAA)) were used to calculate RA plans and compared to calculations with the Collapsed Cone Convolution algorithm (CC) from the COMPASS system (IBA Dosimetry). CC calculations, performed on patient data, are based on experimental fluence measurements with a 2D array of ion chambers mounted on the linac head. The study was conducted on clinical cases treated with RA. Five cases for each of the following groups were included: Brain, Head and Neck, Thorax, Pelvis and stereotactic body radiation therapy for hypo-fractionated treatments with small fields. COMPASS measurements were performed with the iMatrixx-2D array. RapidArc plans were optimized for delivery using 6MV photons from a Clinac-iX (Varian, Palo Alto, USA).

Accuracy of the RA calculation was appraised by means of: 1) comparison of Dose Volume histograms (DVH) metrics; 2) analysis of differential dose distributions and determination of mean dose differences per organ; 3) 3D gamma analysis with distance-to-agreement and dose difference thresholds set to 3%/3 mm or 2%/2 mm for targets, organs at risks and for the volumes encompassed by the 50 and 10% isodoses.

Results

For almost all parameters, the better agreement was between Acuros-XB and COMPASS independently from the anatomical site and fractionation. The same result was obtained from the mean dose difference per organ with Acuros-CC average differences below 0.5% while for AAA-CC data, average deviations exceeded 0.5% and in the case of the pelvis 1%. Relevance of observed differences determined with the 3D gamma analysis resulted in a pass rate exceeding 99.5% for Acuros-CC and exceeding 97.5% for AAA-CC.

Conclusions

This study demonstrated that i) a good agreement exists between COMPASS-CC calculations based on measured fluences with respect to dose distributions obtained with both Acuros-XB and AAA algorithms; ii) 3D dose distributions reconstructed from actual delivery coincide very precisely with the planned data; iii) a slight preference in favor of Acuros-XB was observed suggesting the preference for this algorithm in clinical applications.
Efficacy of platinum-based adjuvant chemotherapy in T2aN0 stage IB non-small cell lung cancer
Authors: Park Seong Yong , Lee Jin Gu , Kim Jieun , Byun Go Eun , Bae Mi Kyung , Lee Chang Young , Kim Dae Joon , Chung Kyung Young
Published: June 2013

Background

Although overall survival for non-small cell lung cancer (NSCLC) has increased, survival rate for pathologically staged T2aN0M0 stage IB NSCLC remains low. Adjuvant chemotherapy is not a standard treatment for stage IB NSCLC. Our purpose was to determine the efficacy of platinum-based adjuvant chemotherapy in stage IB NSCLC.

Methods

We retrospectively reviewed the medical records of 119 stage IB patients who underwent lobectomy and mediastinal lymph node dissection. Among these, 60 patients underwent platinum-based adjuvant chemotherapy (adjuvant group) and 59 did not receive chemotherapy (observation group).

Results

Participants had a mean age of 62.12 ± 11.51 years and 73 (61.3%) were male. The median follow-up period was 49.04 months. Mean age was higher in the observation group whereas patients in the adjuvant group had larger tumors, more dissected lymph nodes, and better performance status. The 5-year overall survival was 64.7% in the observation group and 88.2% in the adjuvant group (p = 0.010). The 5-year disease-free survival was 51.3% in the observation group and 74.0% in the adjuvant group (p = 0.011). In multivariate analysis, only platinum-based adjuvant chemotherapy was a risk factor for overall survival [hazard ratio (HR) = 0.428, p = 0.049] and disease-free survival (HR = 0.57, p = 0.043). In subset analysis, patients with a larger tumor (greater than 3.2 cm), moderate to poor differentiation, and good performance status (Eastern Cooperative Oncology Group, 0) benefitted from platinum-based adjuvant chemotherapy.

Conclusions

Platinum-based adjuvant chemotherapy for surgically treated stage IB NSCLC might offer better survival than observation alone. A large-scale randomized clinical trial is needed to validate these findings.
The presence of microcystins in fish Cyprinus carpio tissues: a histopathological study
Authors: Mitsoura Amalia , Kagalou Ifigenia , Papaioannou Nikolaos , Berillis Panagiotis , Mente Eleni , Papadimitriou Theodoti
Published: June 2013

The occurrence of heavy cyanobacterial blooms has become a worldwide problem, as a consequence of eutrophication of the aquatic ecosystems; furthermore, 60% to 75% of these blooms have been found to be toxic. Microcystins (MCYSTs), the predominant toxins of cyanobacterial blooms, are associated with mortality and illness in both animals and humans. Laboratory-controlled experiments studying the effects of different microcystins on the common carp (Cyprinus carpio) have revealed various histopathological alterations. The aim of the present study is to investigate the effect of chronic or subchronic exposure of fish to microcystins under natural environmental conditions by examining the possible histopathological changes associated with a dense cyanobacterial bloom and determining the microcystin contents of fish tissues. Common carps (C. carpio) were caught from Lake Karla (Greece), during a dense cyanobacterial bloom. The concentration of MCYSTs in the fish liver, kidney and muscle tissues was measured by enzyme-linked immunosorbent assay. The pseudogaster contents were analysed, and a histopathological examination was performed using light and electron microscopy. Severe alterations were detected in the liver and the kidney, suggesting that the toxic effects were caused by various pollutants that were particularly associated with microcystins. The histopathological findings are also discussed, taking into consideration the health conditions of the common carp as a commercial fish species. The mechanisms of expansion of the microcystins and the poisoning of aquatic organisms (e.g. fish) are not yet known in the Lake Karla ecosystem. Future research may focus on identifying the changes caused by microcystins and other factors that exert similar effects on fish tissues, as well as on establishing the overall combined effect of all these factors on fish health.
Infants’ hedonic responsiveness to food odours: a longitudinal study during and after weaning (8, 12 and 22 months)
Authors: Wagner Sandra , Issanchou Sylvie , Chabanet Claire , Marlier Luc , Schaal Benoist , Monnery-Patris Sandrine
Published: June 2013

Background

Olfaction is a highly salient sensory modality in early human life. Neonates show keen olfactory sensitivity and hedonic responsiveness. However, little is known about hedonic olfactory responsiveness between the neonatal period and 2 years of age. In an attempt to fill this gap, this longitudinal follow-up study aimed at investigating hedonic responses to food odours in infants during the first 2 years of life. The second objective was to evaluate whether gender has an influence on hedonic responses during this early period. Four control stimuli and eight odours (four rated by adults as a priori pleasant and four a priori unpleasant) were presented in bottles to 235 infants at 8, 12 and 22 months of age. The infant’s exploratory behaviour towards odorized and control bottles was measured in terms of mouthing defined as direct contact with perioral and/or perinasal areas. For each odorized bottle, duration proportions of mouthing were calculated relative to the control bottles.

Results

For the three ages, shorter duration of mouthing was found for unpleasantly scented bottles compared to pleasantly scented bottles. This contrast between pleasant and unpleasant odours was similar for girls and boys. Correlations of responses between ages were modest in number and level, and concerned mostly unpleasant odours.

Conclusion

During the first two years of life, infants discriminate the hedonic valence of odours. They avoid most of the food odours considered as unpleasant by adults, but their attraction towards food-odours judged pleasant by adults does not appear to be fully shaped at this early age. Taken as a whole, the present results highlight both the plasticity of hedonic responses to food odours, and relatively stable avoidance behaviours towards some unpleasant odours.