bluuebunny/crossref_metadata_2025 huggingface dataset:
Serotonin Transporter Polymorphism Interacts With Childhood Adversity to Predict Aspects of Impulsivity
Authors: Carver Charles S. , Johnson Sheri L. , Joormann Jutta , Kim Youngmee , Nam Jennifer Y.
Published: April 2011

The serotonin transporter polymorphism has been linked—often in interaction with environmental adversity—to a variety of outcomes, including affective disorders. This polymorphism is widely viewed as relating to anxiety traits. A different view is that it relates instead to impulsivity (vs. control) in reacting to emotions. In a test of the latter view, 303 students were genotyped on this polymorphism and completed self-reports bearing on impulsive reactions to emotions (including both negative and positive emotions in separate measures), impulsive tendencies that do not stem from emotions, and childhood adversity. The impulsivity measures reflected three latent variables: pervasive influence of feelings, feelings (including positive feelings) triggering action, and failure to carry through on intentions (with no mention of emotion). Interactions between genotype and adversity emerged for both emotion-related aspects of impulsivity. Theoretical implications of the findings are discussed.
What Implies the Good Work for Registered Nurses in Municipal Elderly Care in Sweden?
Authors: Josefsson Karin , Åling Jenny , Östin Britt-Louise
Published: April 2011

The aim was to describe registered nurses’ perceptions of what the good work implies to them in municipal elderly care. A descriptive design and a structured questionnaire specifically designed for this study were used. Sixty housing units for older people and 213 nurses participated, with a response rate of 62%. The good work included the following aspects: intellectually stimulating without guilt feelings; freedom and independence with the possibility to influence; having appreciative and pleasant fellow workers and a fair and understanding manager; a good physical and risk-free environment; work security and a steady income with the possibility of improving salary through work effort; work effort should be beneficial to others; innovative thinking and initiative should be highly valued; and pride in work without compromising personal values. Employers must take this into consideration to retain those nurses already employed and recruit nurses to municipal elderly care.
Efficiency and Cost-Effectiveness of Recruitment Methods for Male Latino Smokers
Authors: Graham Amanda L. , Lopez-Class Maria , Mueller Noel T. , Mota Guadalupe , Mandelblatt Jeanne
Published: April 2011

Little is known about the most effective strategies to recruit male Latino smokers to cessation research studies. The purpose of this study was to identify efficient and cost-effective research recruitment strategies for this priority population.
Community Participation and Psychological Empowerment
Authors: Christens Brian D. , Peterson N. Andrew , Speer Paul W.
Published: April 2011

Empowerment theory provides both a value orientation for community-based research and practice, and a conceptual framework for understanding and evaluating interventions. One critical question in empowerment theory involves whether a reciprocal (bidirectional) relationship exists between community participation (CP) and psychological empowerment (PE). This study applied structural equation modeling (SEM) with two waves of survey data from a cross-lagged panel design to test reciprocal and unidirectional causal relations between latent variables representing CP and PE. Participants ( n = 474) were randomly selected neighborhood residents and organizational members from the United States. Four models were tested using SEM: (a) a baseline model with autoregressive paths, (b) a model with autoregressive effects and CP predicting future PE, (c) a model with autoregressive effects and PE predicting future CP, and (d) a fully cross-lagged model. Results indicated that CP influenced future PE; however, reciprocal causality was not found to occur between the variables. Implications of the study for empowerment theory and community-based practice are described, and directions for future research discussed.
Differences in Smokers and Nonsmokers’ Assessments of an Educational Campaign About Tobacco Use
Authors: Harris Jenine K. , Cohen Elisia L. , Wyrwich Kathleen W. , Luke Douglas A.
Published: April 2011

The authors surveyed 1,998 Missourians to evaluate (a) awareness and (b) understanding of messages about the impact of tobacco use in Missouri, (c) belief in the accuracy of the messages, and (d) intention to vote for a tobacco tax increase on the basis of the messages. Using structural equation modeling, the relationships among these four constructs were evaluated. A comparison of smokers and nonsmokers indicated that these two groups were influenced by the messages in different ways, χ2(8) = 20.89, p < .05, and should be modeled separately. The nonsmokers’ model demonstrated significant ( p < .05) relationships between understanding the messages and belief in message accuracy ( b = .41; R2 = .17) and between belief in message accuracy and intention to vote in favor of the tobacco tax ( b = .54; R2 = .29). In the smokers’ model, understanding the messages was not a statistically significant predictor of belief in message accuracy. However, belief in message accuracy had a significant and positive relationship with intention to vote in favor of the tax ( b = .45; R2 = .21). These findings indicate that media campaigns about tobacco use should approach smokers and nonsmokers differently.
Immunosuppression with FTY720 is insufficient to prevent secondary progressive neurodegeneration in experimental autoimmune encephalomyelitis
Authors: Al-Izki Sarah , Pryce Gareth , Jackson Samuel J , Giovannoni Gavin , Baker David
Published: April 2011

Background: There has been poor translation for the use of immunosuppressive agents from experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), into the treatment of MS. This may be due to the fact that most EAE studies examine prophylactic, pre-treatment regimes that prove to be therapeutically-ineffective in long-established, often progressive, MS. FTY720 (fingolimod/Gilenya) is a sphingosine-1-phosphate receptor modulator. This is a new oral agent that markedly reduces the number of relapses in people with MS, compared with currently licensed injectable agents such as the beta interferons. FTY720 has activity against lymphocytes but may also influence oligodendroglia and could therefore have the potential to influence progressive MS, by promoting remyelination.

Methods: The effect of FTY720 was assessed in relapsing-progressive EAE in mice.

Results: Early intervention during relapsing EAE could completely inhibit subsequent relapses, inhibited the accumulation of neurodegeneration, and facilitated motor recovery. However, when examined in secondary progressive EAE, that develops after the accumulation of deficit from relapsing disease, long-term treatment with FTY720 failed to slow deterioration when initiated late (4 months) into the disease course.

Conclusions: This study indicates that early intervention with immunosuppressive agents may inhibit the generation of the neurodegenerative microenvironment, which is no longer responsive to potent immunosuppression. However, if treatment is initiated too late, progressive, neurological-disease continues unabated. This suggests that immunosuppression is insufficient to control secondary progression in animals, as has been found so far to be the case in MS, and may warrant early intervention with FTY720 for optimal treatment benefit.
High nationwide prevalence of multiple sclerosis in Sweden
Authors: Ahlgren C , Odén A , Lycke J
Published: April 2011

Background: Few nationwide multiple sclerosis (MS) prevalence studies have been published. In Scandinavia, the nationwide MS prevalence was 173/100,000 in Denmark 2005 and 100/100,000 in Iceland 1990.

Objective: Our aim with the present study was to determine the first population-based nationwide MS prevalence in Sweden, based on observed, registered patients and to investigate the presence of a north–south gradient of MS prevalence.

Methods: By linking the Swedish National Patient Register, the Swedish Multiple Sclerosis Registry and the Swedish Total Population Register we obtained the number of patients who were diagnosed with MS before 2009, and who were registered, alive and resident in Sweden on the prevalence date 31 December 2008. We calculated the gender-specific nationwide MS prevalence in 1-year age intervals. The relationship between MS risk and latitude was studied in a logistic regression model including all individuals in the population of Sweden.

Results: The number of registered MS patients in 2008 was 17,485 out of the Swedish population of 9,256,347. The overall MS prevalence was 188.9/100,000 (95% CI 186.1–191.7), 113.4 (95% CI 110.3–116.5) for men and 263.6 (95% CI 258.9–268.3) for women. The female to male ratio was 2.35:1. The prevalence of MS significantly increased for each degree of north latitude with 1.5% in men ( p = 0.013) and 1% in women ( p = 0.015).

Conclusions: The MS prevalence of 188.9/100,000 in Sweden is among the highest nationwide prevalence estimates in the world. In Sweden, the risk of MS increases with increasing north latitude for both men and women.
A situated-Information Motivation Behavioral Skills Model of Care Initiation and Maintenance (sIMB-CIM): An IMB Model Based Approach to Understanding and Intervening in Engagement in Care for Chronic Medical Conditions
Authors: Rivet Amico K.
Published: April 2011

A sizable portion of adults living with chronic medical conditions (CMCs) delay initiation of care or maintain it inconsistently, which has tremendous personal and public costs. However, few explanatory models with high yield for intervention development and implementation have been proposed to date that would help to characterize and support care use for CMCs. A situated Information, Motivation, Behavioral Skills model of Care Initiation and Maintenance (sIMB-CIM) is presented here as an application of the IMB model to medical care use for CMCs. An example of a sIMB model for characterizing and intervening to support maintenance in HIV-care is provided.
‘I’m better off now’: The role of temporal comparisons and exposure evaluations in smoking cessation
Authors: Menninga Karin , Dijkstra Arie , Gebhardt Winifred A. , Siero Frans
Published: April 2011

Two new psychological concepts related to relapse in smoking cessation were tested. ‘Temporal comparisons’ are ex-smokers’ evaluations of their present situation compared to their situation as a smoker. ‘Exposure evaluations’ are evaluations of situations ex-smokers encountered when they used to smoke. In a cohort study among 323 ex-smokers, both concepts significantly predicted relapse after six months. Moreover, the relationship between temporal comparisons and relapse was mediated by exposure evaluations. In addition, this relationship also depended on self-efficacy; particularly when self-efficacy was low, temporal comparisons predicted relapse. These data provide new theoretical and practical perspectives to relapse.
Body image, weight loss and muscle building among Tongan adolescents in Tonga and New Zealand
Authors: McCabe Marita P , Fotu Kalasita , Dewes Ofa
Published: April 2011

This study examined body image and associated behaviours among 48 adolescents (24 males, 24 females) in Tonga, as well as 48 Tongan adolescents (24 males, 24 females) living in New Zealand (NZ). There was a lack of focus on body weight and shape among adolescents in both countries. Males evidenced a high focus on muscles. Females wanted to lose weight and obtain a soft round body. There were very few differences in the body image or body change strategies of Tongan adolescents in Tonga or NZ. Sociocultural messages need to be explored further in order to better understand these findings.
Internet use among patients with psychosomatic disorders: What are the health-related demands and needs?
Authors: Teufel Martin , Schäffeler Norbert , de Zwaan Martina , Graap Holmer , Zipfel Stephan , Giel Katrin Elisabeth
Published: April 2011

While Internet-based health-related offers for various disorders are increasing, little is known about the way patients with psychosomatic disorders use the Internet. We conducted a questionnaire survey in outpatient clinics at two university hospitals’ Departments of Psychosomatic Medicine. Seventy-four percent of N = 274 patients had Internet home access and 60 percent of those patients reported health-related Internet use. Patients expressed the wish for more professional, evidence-based online information and expert-guided treatment. The survey results support the Internet’s high potential in future treatment strategies for patients with psychosomatic disorders.
Influence of dietary therapy appraisal on future perceived control of type 2 diabetes
Authors: Shibayama Taiga , Sato Eiko , Nishigaki Masakazu , Ochiai Ryota , Kazuma Keiko
Published: April 2011

We sought to elucidate the causal effect of patients’ self-appraisal of their dietary regimen on their control beliefs among adults with type 2 diabetes. Data from 176 outpatients were assessed using a two-wave cross-lagged panel model. We found that a cross-lagged path connecting dietary appraisal at baseline to perceived control at one year (β = .30, p = .003) was larger than a path connecting perceived control at baseline to dietary appraisal at one year (β = —.16, p = .07). We conclude that dietary appraisal has a feedback effect on the future perceived control of type 2 diabetes.
‘Don’t mention obesity’: Contradictions and tensions in the UK Change4Life health promotion campaign
Authors: Piggin Joe , Lee Jessica
Published: April 2011

The emphasis on body weight and the terms ‘fat’, ‘overweight’ and ‘obese’ are increasingly political in public health promotion. The UK government’s 2009—2011 social marketing campaign, Change4Life explicitly avoids the term ‘obesity’ and imagery that connotes it, despite the emphasis on obesity in the preceding research, policy and strategy. Using a critical health psychology perspective, this research explores the tensions arising from the omission of ‘obesity’ in the Change4Life campaign. We argue the justifications for omitting obesity are at times contrary to evidence that informed the campaign. Considerations are offered for the construction of future health promotion campaigns.
Angiotensin II profile and mRNA encoding RAS proteins during bovine follicular wave
Authors: Ferreira Rogério , Gasperin Bernardo , Santos Joabel , Rovani Monique , Santos Robson AS , Gutierrez Karina , Oliveira João Francisco , Reis Adelina M , Gonçalves Paulo Bayard
Published: April 2011

Angiotensin II (AngII) has a role in ovarian follicle development, ovulation, and oocyte meiotic resumption. The objective of the present study was to characterise the AngII profile and the mRNA encoding RAS proteins in a bovine follicular wave. Cows were ovariectomised when the size between the largest (F1) and the second largest follicle (F2) was not statistically different (day 2), slightly different (day 3), or markedly different (day 4). AngII was measured in the follicular fluid and the mRNA abundance of genes encoding angiotensin-converting enzyme (ACE), (pro)renin receptor, and renin-binding protein (RnBP) was evaluated in the follicular cells from F1 and F2. The AngII levels increased at the expected time of the follicular deviation in F1 but did not change in F2. However, the expression of the genes encoding ACE, (pro)renin receptor, and RnBP was not regulated in F1 but was upregulated during or after the follicular deviation in F2. Moreover, RnBP gene expression increased when the F1 was treated with the oestrogen receptor-antagonist in vivo. In conclusion, the AngII concentration increased in the follicular fluid of the dominant follicle during and after deviation and further supports our finding that RAS is present in the ovary regulating follicular dominance.
Concurrent Cryptococcal and Pneumocystis Pneumonia along with Pulmonary Tuberculosis in an HIV-Positive Patient: Lessons Learned for Early Management
Authors: Kaur Ravinder , Gautam Hitender , Maheshwari Megha , Goyal Ritu , Bhalla Preena , Dewan Richa
Published: April 2011

Case: We are presenting a 50-year-old patient of pulmonary tuberculosis, on anti-tuberculosis therapy (ATT) for last 2 months who presented with fever, cough, breathlessness, anorexia, and weight loss. The case was found to be HIV reactive. His sputum sample showed Candida albicans and Pneumocystis jirovecii. Fluconazole and cotrimoxazole + sulphamethoxazole were added. The index case did not respond to the treatment and his clinical condition started to deteriorate and he developed headache, vomiting, and dysphagia. Repeat sputum sample and cerebrospinal fluid (CSF) showed Cryptococcus neoformans which was found to be sensitive to Amphotericin B. Amphotericin B was added to the treatment and patient clinically responded to treatment. In conclusion, emphasis should be given to correct etiological identification, allowing appropriate treatment and decreasing the morbidity and mortality in these patients as concomitant opportunistic infections may cause diagnostic problems.
Comparison of an Automated and a Manual Method of Viral Load Determination in HIV-Infected Persons in Yaounde, Cameroon
Authors: Ndumbe Peter M. , Efuetnkeng Bechem , Ikomey George M. , Atashili Julius
Published: April 2011

Objectives: Although access to antiretroviral therapy is being improved in the resource-limited settings most affected by the HIV pandemic, the assessment of treatment success or failure remains a challenge. Methods of viral load determination that are inexpensive, easy to use, and practicable at peripheral health centers are required. This study aimed at evaluating the validity and relative cost of a manual method compared to an automated method of viral load quantification. Methods: HIV-1 viral load was determined by both the COBAS Amplicor HIV-1 Monitor and the Amplicor HIV-1 Monitor assays in 18 patients in Yaounde, Cameroon. Results: There was a strong correlation between values of viral load obtained by the automated method and the manual method ( r = .83, P value < .0001). Also, both methods were not statistically different from each other (Wilcoxon rank-sum statistic P value .99). Conclusions: The manual method of determining HIV viral load was correlated with the automated method and should be considered as a viable alternative.
Long-Term Resolution of Viral Breakthrough after Changing HIV Viral Load Assay
Authors: Obeid Karam M. , Sural Preethi , Szpunar Susan , Johnson Leonard B.
Published: April 2011

Background: Viral load (VL) measurement assays differ in their sensitivity with polymerase chain reaction assays (PCR) being more sensitive than branched DNA (bDNA) assays. We evaluated virologic outcomes of patients and physicians' response to increased VL after a switch from bDNA to PCR assay. Method: Retrospective, case-control study on 65 HIV+ patients receiving highly active antiretroviral therapy (HAART). Cases included patients with undetectable VL by bDNA that became detectable after the switch; controls were patients that remained undetectable. Records were reviewed up to 1 year after the switch. Results: A total of 58.5% patients had detectable VL after the switch. Repeat VL testing and resistance testing were ordered in 15.4% and 23.1% of these patients, respectively. By 1 year, VL was undetectable in 82.8% of cases and 92% of controls ( P = .30), without change in HAART. Conclusion: Transient viremia after changing VL assay reflects the different sensitivity of these assays with no impact on patients' outcomes compared to controls.
Home Fires in America
Authors: Diekman Shane , Ballesteros Michael F. , Ahrens Marty
Published: April 2011

Fires are the third leading cause of unintentional home injury deaths. Young children and older adults are especially at risk for home fire deaths. Other high-risk groups include males, people with physical disabilities, people impaired by alcohol or other drugs, and people living in rural communities or in poverty. Lifestyle decisions (eg, choosing products) and behaviors (eg, maintaining working smoke alarms or smoking) can influence the risk of being in and surviving a home fire. Fortunately, medical practitioners can foster safer home environments for their patients by promoting effective fire prevention and protection strategies to reduce home fire risks. This review highlights the association between lifestyle and home fires with a focus on achievable lifestyle changes that can prevent fires and fire-related injuries and deaths.
Prescribing high-dose lipid-lowering therapy early to avoid subsequent cardiovascular events: is this a cost-effective strategy?
Authors: Ara R , Pandor A , Stevens J , Rafia R , Ward SE , Rees A , Durrington PN , Reynolds TM , Wierzbicki AS , Stevenson M
Published: April 2011

Background: While evidence shows high-dose statins reduce cardiovascular events compared with moderate doses in individuals with acute coronary syndrome (ACS), many primary care trusts (PCT) advocate the use of generic simvastatin 40 mg/day for these patients. Methods and results: Data from 28 RCTs were synthesized using a mixed treatment comparison model. A Markov model was used to evaluate the cost-effectiveness of treatments taking into account adherence and the likely reduction in cost for atorvastatin when the patent expires. There is a clear dose–response: rosuvastatin 40 mg/day produces the greatest reduction in low-density lipoprotein cholesterol (56%) followed by atorvastatin 80 mg/day (52%), and simvastatin 40 mg/day (37%). Using a threshold of £20,000 per QALY, if adherence levels in general practice are similar to those observed in RCTs, all three higher dose statins would be considered cost-effective compared to simvastatin 40 mg/day. Using the net benefits of the treatments, rosuvastatin 40 mg/day is estimated to be the most cost-effective alternative. If the cost of atorvastatin reduces in line with that observed for simvastatin, atorvastatin 80 mg/day is estimated to be the most cost-effective alternative. Conclusion: Our analyses show that current PCT policies intended to minimize primary care drug acquisition costs result in suboptimal care.
Flt-1 regulates vascular endothelial cell migration via a protein tyrosine kinase-7–dependent pathway
Authors: Lee Hyung Keun , Chauhan Sunil K. , Kay EunDuk , Dana Reza
Published: April 2011

Protein tyrosine kinase 7 (PTK7) is a pseudokinase whose precise function in regulating angiogenesis remains unknown. The purpose of this study was to define the mechanisms by which PTK7 promotes vascular endothelial growth factor-A (VEGF-A)–induced angiogenesis in vivo and in vitro. Immunoblotting was used to measure PTK7 expression in several types of vascular endothelial cells. Using both immunoprecipitation and immunoblotting, PTK7 was found to join a receptor complex with Flt-1 (VEGFR1), but not with KDR/Flk-1 (VEGFR2) or with Flt-4 (VEGFR3). By surface plasmon resonance analysis, the interaction between Flt-1 and PTK7 was confirmed and found to be intensified by VEGF-A. Flt-1 phosphorylation and downstream signals of Akt, and focal adhesion kinase (FAK) thus induced were down-regulated by inhibition of PTK7 expression using siRNA. Moreover, PTK7 overexpression in endothelial cells resulted in enhanced angiogenesis in vitro. In contrast, neovascularization induced in vivo by VEGF-A pellets was significantly decreased by injection of siRNA targeting PTK7. These data suggest that PTK7 serves an essential role in Flt-1–mediated angiogenesis.
Myc-mediated repression of microRNA-34a promotes high-grade transformation of B-cell lymphoma by dysregulation of FoxP1
Authors: Craig Vanessa J. , Cogliatti Sergio B. , Imig Jochen , Renner Christoph , Neuenschwander Stefan , Rehrauer Hubert , Schlapbach Ralph , Dirnhofer Stephan , Tzankov Alexander , Müller Anne
Published: April 2011

Gastric marginal zone B-cell lymphoma of MALT type (MALT lymphoma) arises in the context of chronic inflammation induced by the bacterial pathogen Helicobacter pylori. Although generally considered an indolent disease, MALT lymphoma may transform to gastric diffuse large B-cell lymphoma (gDLBCL) through mechanisms that remain poorly understood. By comparing microRNA expression profiles of gastric MALT lymphoma and gDLBCL, we have identified a signature of 27 deregulated microRNAs(miRNAs) that share the characteristic of being transcriptionally repressed by Myc. Myc overexpression was consequently detected in 80% of gDLBCL but only 20% of MALT lymphomas spotted on a tissue microarray. A highly similar signature of Myc-repressed miRNAs was further detected in nodal DLBCL. Small interfering RNA–mediated knock-down of Myc blocked proliferation of DLBCL cell lines. Of the Myc-repressed miRNAs down-regulated in malignant lymphoma, miR-34a showed the strongest antiproliferative properties when overexpressed in DLBCL cells. We could further attribute miR-34a's tumor-suppressive effects to deregulation of its target FoxP1. FoxP1 overexpression was detected in gDLBCL but not in gastric MALT lymphoma; FoxP1 knock-down efficiently blocked DLBCL proliferation. In conclusion, our results elucidate a novel Myc- and FoxP1-dependent pathway of malignant transformation and suggest miR-34a replacement therapy as a promising strategy in lymphoma treatment.
Host fibrinogen stably bound to hemozoin rapidly activates monocytes via TLR-4 and CD11b/CD18-integrin: a new paradigm of hemozoin action
Authors: Barrera Valentina , Skorokhod Oleksii A. , Baci Denisa , Gremo Giuliana , Arese Paolo , Schwarzer Evelin
Published: April 2011

Natural hemozoin (nHZ), prepared after schizogony, consists of crystalline ferriprotoporphyrin-IX dimers from undigested heme bound to host and parasite proteins and lipids. Phagocytosed nHZ alters important functions of host phagocytes. Most alterations are long-term effects. We show that host fibrinogen (FG) was constantly present (at ∼ 1 FG per 25 000 HZ-heme molecules) and stably bound to nHZ from plasma-cultured parasites. FG was responsible for the rapid 100-fold stimulation of reactive oxygen species production and 50-fold increase of TNF and monocyte chemotactic protein 1 by human monocytes. Those effects, starting within minutes after nHZ cell contact, were because of interaction of FG with FG-receptors TLR4 and integrin CD11b/CD18. Receptor blockage by specific mAbs or removal of FG from nHZ abrogated the effects. nHZ-opsonizing IgGs contribute to the stimulatory response but are not essential for FG effects. Immediate increase in reactive oxygen species and TNF may switch on previously described long-term effects of nHZ, largely because of HZ-generated lipo-peroxidation products 15(S,R)-hydroxy-6,8,11,13-eicosatetraenoic acid and 4-hydroxynonenal. The FG/HZ effects mediated by TLR4/integrins represent a novel paradigm of nHZ activity and allow expansion of nHZ effects to nonphagocytic cells, such as endothelia and airway epithelia, and lead to a better understanding of organ pathology in malaria.
Twenty-five years of peripheral blood stem cell transplantation
Authors: Körbling Martin , Freireich Emil J
Published: April 2011

Peripheral blood stem cell transplantation (PBSCT) is the most common transplantation procedure performed in medicine. Its clinical introduction in 1986 replaced BM as a stem-cell source to approximately 100% in the autologous and to approximately 75% in the allogeneic transplantation setting. This historical overview provides a brief insight into the discovery of circulating hematopoietic stem cells in the early 1960s, the development of apheresis technology, the discovery of hematopoietic growth factors and small molecule CXCR4 antagonist for stem- cell mobilization, and in vivo experimental transplantation studies that eventually led to clinical PBSCT. Also mentioned are the controversies surrounding the engraftment potential of circulating stem cells before acceptance as a clinical modality. Clinical trials comparing the outcome of PBSCT with BM transplantation, registry data analyses, and the role of the National Marrow Donor Program (NMDP) in promoting unrelated blood stem-cell donation are addressed.
Long-term treatment with eculizumab in paroxysmal nocturnal hemoglobinuria: sustained efficacy and improved survival
Authors: Kelly Richard J. , Hill Anita , Arnold Louise M. , Brooksbank Gemma L. , Richards Stephen J. , Cullen Matthew , Mitchell Lindsay D. , Cohen Dena R. , Gregory Walter M. , Hillmen Peter
Published: April 2011

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic disorder with increased mortality and morbidity resulting from intravascular hemolysis. Eculizumab, a monoclonal antibody against the complement protein 5, stops the intravascular hemolysis in PNH. We evaluated 79 consecutive patients treated with eculizumab in Leeds between May 2002 and July 2010. The survival of patients treated with eculizumab was not different from age- and sex-matched normal controls (P = .46) but was significantly better than 30 similar patients managed before eculizumab (P = .030). Three patients on eculizumab, all over 50 years old, died of causes unrelated to PNH. Twenty-one patients (27%) had a thrombosis before starting eculizumab (5.6 events per 100 patient-years) compared with 2 thromboses on eculizumab (0.8 events per 100 patient-years; P < .001). Twenty-one patients with no previous thrombosis discontinued warfarin on eculizumab with no thrombotic sequelae. Forty of 61 (66%) patients on eculizumab for more than 12 months achieved transfusion independence. The 12-month mean transfusion requirement reduced from 19.3 units before eculizumab to 5.0 units in the most recent 12 months on eculizumab (P < .001). Eculizumab dramatically alters the natural course of PNH, reducing symptoms and disease complications as well as improving survival to a similar level to that of the general population.
Circulating Heat Shock Protein 70 in Health, Aging and Disease
Authors: Njemini Rose , Bautmans Ivan , Onyema Oscar O , Van Puyvelde Katrien , Demanet Christian , Mets Tony
Published: April 2011

Background

Heat shock proteins (Hsp) are ubiquitously synthesised in virtually all species and it is hypothesised that they might have beneficial health effects. Recent studies have identified circulating Hsp as an important mediator in inflammation - the effects of low-grade inflammation in the aging process are overwhelming. While much is known about intracellular Hsp70, scant data exist on circulating Hsp70 in the aging context. Therefore, the objectives of this study were to investigate the effect of age and disease on circulating Hsp70 and, in particular, to evaluate the association between circulating Hsp70 and inflammatory parameters.

Results

Serum Hsp70, Interleukin (IL) -10, IL-6 and Tumor Necrosis Factor (TNF) alpha concentrations were determined in 90 hospitalised geriatric patients (aged 83 ± 6 years) and in 200 community-dwelling control subjects (100 elderly, aged 74 ± 5 years, and 100 young, aged 23 ± 3 years). In the community-dwelling elderly, serum Hsp70 and IL-10 concentrations were significantly lower and IL-6 was significantly higher when compared to healthy young control subjects. Elderly patients presenting inflammation (CRP serum levels ≥5 mg/L) showed significantly (p = 0.007) higher Hsp70 values; and Hsp70 correlated positively (p < 0.001) with IL-6 and CRP, but not with TNF-alpha or IL-10. A significant association was also noted between Hsp70 levels and the degree of dependency and cognitive decline in geriatric patients.

Conclusions

The present data provide new evidence that serum concentration of Hsp70 decreases with age in a normal population. Our study also shows that higher levels of Hsp70 are associated with inflammation and frailty in elderly patients.
The constancy of global regulation across a species: the concentrations of ppGpp and RpoS are strain-specific in Escherichia coli
Authors: Ferenci Thomas , Galbiati Heloisa Filus , Betteridge Thu , Phan Katherine , Spira Beny
Published: April 2011

Background

Sigma factors and the alarmone ppGpp control the allocation of RNA polymerase to promoters under stressful conditions. Both ppGpp and the sigma factor σS (RpoS) are potentially subject to variability across the species Escherichia coli. To find out the extent of strain variation we measured the level of RpoS and ppGpp using 31 E. coli strains from the ECOR collection and one reference K-12 strain.

Results

Nine ECORs had highly deleterious mutations in rpoS, 12 had RpoS protein up to 7-fold above that of the reference strain MG1655 and the remainder had comparable or lower levels. Strain variation was also evident in ppGpp accumulation under carbon starvation and spoT mutations were present in several low-ppGpp strains. Three relationships between RpoS and ppGpp levels were found: isolates with zero RpoS but various ppGpp levels, strains where RpoS levels were proportional to ppGpp and a third unexpected class in which RpoS was present but not proportional to ppGpp concentration. High-RpoS and high-ppGpp strains accumulated rpoS mutations under nutrient limitation, providing a source of polymorphisms.

Conclusions

The ppGpp and σS variance means that the expression of genes involved in translation, stress and other traits affected by ppGpp and/or RpoS are likely to be strain-specific and suggest that influential components of regulatory networks are frequently reset by microevolution. Different strains of E. coli have different relationships between ppGpp and RpoS levels and only some exhibit a proportionality between increasing ppGpp and RpoS levels as demonstrated for E. coli K-12.
Differential miRNA expression in Rehmannia glutinosaplants subjected to continuous cropping
Authors: Yang Yanhui , Chen Xinjian , Chen Junying , Xu Haixia , Li Juan , Zhang Zhongyi
Published: April 2011

Background

The productivity of the medicinally significant perennial herb Rehmannia glutinosa is severely affected after the first year of cropping. While there is some information available describing the physiological and environmental causes of this yield decline, there is as yet no data regarding the changes in gene expression which occur when the species is continuously cropped.

Results

Using a massively parallel (Solexa) DNA sequencing platform, it was possible to identify and quantify the abundance of a large number of R. glutinosa miRNAs. We contrasted the miRNA content of first year crop plants with that of second year crop ones, and were able to show that of 89 conserved (belonging to 25 families) and six novel miRNAs (six families), 29 of the former and three of the latter were differentially expressed. The three novel miRNAs were predicted to target seven genes, and the 29 conserved ones 308 genes. The potential targets of 32 of these differentially expressed miRNAs involved in the main transcription regulation, plant development and signal transduction. A functional analysis of the differentially expressed miRNAs suggested that several of the proposed targets could be directly or indirectly responsible for the development of the tuberous root.

Conclusion

We have compared differential miRNAs expression in the first year crop (FP) R. glutinosa plants and second year crop (SP) ones. The outcome identifies some potential leads for understanding the molecular basis of the processes underlying the difficulty of maintaining the productivity of continuously cropped R. glutinosa.
Differences in cerebral response to esophageal acid stimuli and psychological anticipation in GERD subtypes - An fMRI study
Authors: Wang Kun , Duan Li-Ping , Zeng Xiang-Zhu , Liu Jian-Yu , Xu-Chu Weng
Published: April 2011

Background

To evaluate whether there are differences in the cerebral response to intraesophageal acid and psychological anticipation stimuli among subtypes of gastroesophageal reflux disease (GERD).

Methods

Thirty nine patients with GERD and 11 healthy controls were enrolled in this study after gastroscopy and 24 hr pH monitoring. GERD subjects were divided into four subgroups: RE (reflux esophagitis), NERD+ (non-erosive reflux disease with excessive acid reflux), NERD-SI+ (normal acid exposure and positive symptom index) and NERD-SI+ (normal acid exposure and negative symptom index, but responded to proton pump inhibitor trial). Cerebral responses to intraesophageal acid and psychological anticipation were evaluated with fMRI.

Results

During intraesophageal acid stimulation, the prefrontal cortex (PFC) region was significantly activated in all subgroups of GERD; the insular cortex (IC) region was also activated in RE, NERD+ and NERD-SI- groups; the anterior cingulated cortex (ACC) region was activated only in RE and NERD-SI- groups. The RE subgroup had the shortest peak time in the PFC region after acid was infused, and presented the greatest change in fMRI signals in the PFC and ACC region (P = 0.008 and P = 0.001, respectively). During psychological anticipation, the PFC was significantly activated in both the control and GERD groups. Activation of the IC region was found in the RE, NERD-SI+ and NERD-SI- subgroups. The ACC was activated only in the NERD-SI+ and NERD-SI- subgroups. In the PFC region, the NERD-SI- subgroup had the shortest onset time (P = 0.008) and peak time (P < 0.001). Compared with actual acid infusion, ACC in RE and IC in NERD+ were deactivated while additional areas including the IC and ACC were activated in the NERD-SI+ group; and in NERD-SI- group, onset-time and peak time in the PFC and IC areas were obviously shorter in induced anticipation than in actual acid infusion.

Conclusions

The four subgroups of GERD patients and controls showed distinctly different activation patterns and we therefore conclude GERD patients have different patterns of visceral perception and psychological anticipation. Psychological factors play a more important role in NERD-SI+ and NERD-SI- groups than in RE and NERD+ groups.
Clinical characteristics of Pneumocystis pneumonia in non-HIV patients and prognostic factors including microbiological genotypes
Authors: Matsumura Yasufumi , Shindo Yuichiro , Iinuma Yoshitsugu , Yamamoto Masaki , Shirano Michinori , Matsushima Aki , Nagao Miki , Ito Yutaka , Takakura Shunji , Hasegawa Yoshinori , Ichiyama Satoshi
Published: April 2011

Background

The number of patients with non-HIV Pneumocystis pneumonia (PCP) is increasing with widespread immunosuppressive treatment. We investigated the clinical characteristics of non-HIV PCP and its association with microbiological genotypes.

Methods

Between January 2005 and March 2010, all patients in 2 university hospitals who had been diagnosed with PCP by PCR were enrolled in this study. Retrospective chart review of patients, microbiological genotypes, and association with 30-day mortality were examined.

Results

Of the 82 adult patients investigated, 50 patients (61%) had inflammatory diseases, 17 (21%) had solid malignancies, 12 (15%) had hematological malignancies, and 6 (7%) had received transplantations. All patients received immunosuppressive agents or antitumor chemotherapeutic drugs. Plasma (1→3) β-D-glucan levels were elevated in 80% of patients, and were significantly reduced after treatment in both survivors and non-survivors. However, β-D-glucan increased in 18% of survivors and was normal in only 33% after treatment. Concomitant invasive pulmonary aspergillosis was detected in 5 patients. Fifty-six respiratory samples were stored for genotyping. A dihydropteroate synthase mutation associated with trimethoprim-sulfamethoxazole resistance was found in only 1 of the 53 patients. The most prevalent genotype of mitochondrial large-subunit rRNA was genotype 1, followed by genotype 4. The most prevalent genotype of internal transcribed spacers of the nuclear rRNA operon was Eb, followed by Eg and Bi. Thirty-day mortality was 24%, in which logistic regression analysis revealed association with serum albumin and mechanical ventilation, but no association with genotypes.

Conclusions

In non-HIV PCP, poorer general and respiratory conditions at diagnosis were independent predictors of mortality. β-D-glucan may not be useful for monitoring the response to treatment, and genotypes were not associated with mortality.
Human PTCHD3 nulls: rare copy number and sequence variants suggest a non-essential gene
Authors: Ghahramani Seno Mohammad M , Kwan Benjamin YM , Lee-Ng Ka Ki M , Moessner Rainald , Lionel Anath C , Marshall Christian R , Scherer Stephen W
Published: April 2011

Background

Copy number variations (CNVs) can contribute to variable degrees of fitness and/or disease predisposition. Recent studies show that at least 1% of any given genome is copy number variable when compared to the human reference sequence assembly. Homozygous deletions (or CNV nulls) that are found in the normal population are of particular interest because they may serve to define non-essential genes in human biology.

Results

In a genomic screen investigating CNV in Autism Spectrum Disorders (ASDs) we detected a heterozygous deletion on chromosome 10p12.1, spanning the Patched-domain containing 3 (PTCHD3) gene, at a frequency of ~1.4% (6/427). This finding seemed interesting, given recent discoveries on the role of another Patched-domain containing gene (PTCHD1) in ASD. Screening of another 177 ASD probands yielded two additional heterozygous deletions bringing the frequency to 1.3% (8/604). The deletion was found at a frequency of ~0.73% (27/3,695) in combined control population from North America and Northern Europe predominately of European ancestry. Screening of the human genome diversity panel (HGDP-CEPH) covering worldwide populations yielded deletions in 7/1,043 unrelated individuals and those detected were confined to individuals of European/Mediterranean/Middle Eastern ancestry. Breakpoint mapping yielded an identical 102,624 bp deletion in all cases and controls tested, suggesting a common ancestral event. Interestingly, this CNV occurs at a break of synteny between humans and mouse. Considering all data, however, no significant association of these rare PTCHD3 deletions with ASD was observed. Notwithstanding, our RNA expression studies detected PTCHD3 in several tissues, and a novel shorter isoform for PTCHD3 was characterized. Expression in transfected COS-7 cells showed PTCHD3 isoforms colocalize with calnexin in the endoplasmic reticulum. The presence of a patched (Ptc) domain suggested a role for PTCHD3 in various biological processes mediated through the Hedgehog (Hh) signaling pathway. However, further investigation yielded one individual harboring a homozygous deletion (PTCHD3 null) without ASD or any other overt abnormal phenotype. Exon sequencing of PTCHD3 in other individuals with deletions revealed compound point mutations also resulting in a null state.

Conclusion

Our data suggests that PTCHD3 may be a non-essential gene in some humans and characterization of this novel CNV at 10p12.1 will facilitate population and disease studies.
Interaction and uptake of exosomes by ovarian cancer cells
Authors: Escrevente Cristina , Keller Sascha , Altevogt Peter , Costa Júlia
Published: April 2011

Background

Exosomes consist of membrane vesicles that are secreted by several cell types, including tumors and have been found in biological fluids. Exosomes interact with other cells and may serve as vehicles for the transfer of protein and RNA among cells.

Methods

SKOV3 exosomes were labelled with carboxyfluoresceine diacetate succinimidyl-ester and collected by ultracentrifugation. Uptake of these vesicles, under different conditions, by the same cells from where they originated was monitored by immunofluorescence microscopy and flow cytometry analysis. Lectin analysis was performed to investigate the glycosylation properties of proteins from exosomes and cellular extracts.

Results

In this work, the ovarian carcinoma SKOV3 cell line has been shown to internalize exosomes from the same cells via several endocytic pathways that were strongly inhibited at 4°C, indicating their energy dependence. Partial colocalization with the endosome marker EEA1 and inhibition by chlorpromazine suggested the involvement of clathrin-dependent endocytosis. Furthermore, uptake inhibition in the presence of 5-ethyl-N-isopropyl amiloride, cytochalasin D and methyl-beta-cyclodextrin suggested the involvement of additional endocytic pathways. The uptake required proteins from the exosomes and from the cells since it was inhibited after proteinase K treatments. The exosomes were found to be enriched in specific mannose- and sialic acid-containing glycoproteins. Sialic acid removal caused a small but non-significant increase in uptake. Furthermore, the monosaccharides D-galactose, α-L-fucose, α-D-mannose, D-N-acetylglucosamine and the disaccharide β-lactose reduced exosomes uptake to a comparable extent as the control D-glucose.

Conclusions

In conclusion, exosomes are internalized by ovarian tumor cells via various endocytic pathways and proteins from exosomes and cells are required for uptake. On the other hand, exosomes are enriched in specific glycoproteins that may constitute exosome markers. This work contributes to the knowledge about the properties and dynamics of exosomes in cancer.
Replicase-based plasmid DNA shows anti-tumor activity
Authors: Rodriguez B Leticia , Yu Zhen , Chung Woon-Gye , Weiss Richard , Cui Zhengrong
Published: April 2011

Background

Double stranded RNA (dsRNA) has multiple anti-tumor mechanisms. Over the past several decades, there have been numerous attempts to utilize synthetic dsRNA to control tumor growth in animal models and clinical trials. Recently, it became clear that intracellular dsRNA is more effective than extracellular dsRNA on promoting apoptosis and orchestrating adaptive immune responses. To overcome the difficulty in delivering a large dose of synthetic dsRNA into tumors, we propose to deliver a RNA replicase-based plasmid DNA, hypothesizing that the dsRNA generated by the replicase-based plasmid in tumor cells will inhibit tumor growth.

Methods

The anti-tumor activity of a plasmid (pSIN-β) that encodes the sindbis RNA replicase genes (nsp1-4) was evaluated in mice with model tumors (TC-1 lung cancer cells or B16 melanoma cells) and compared to a traditional pCMV-β plasmid.

Results

In cell culture, transfection of tumor cells with pSIN-β generated dsRNA. In mice with model tumors, pSIN-β more effectively delayed tumor growth than pCMV-β, and in some cases, eradicated the tumors.

Conclusion

RNA replicase-based plasmid may be exploited to generate intracellular dsRNA to control tumor growth.
Number of casual male sexual partners and associated factors among men who have sex with men: Results from the National HIV Behavioral Surveillance system
Authors: Rosenberg Eli S , Sullivan Patrick S , DiNenno Elizabeth A , Salazar Laura F , Sanchez Travis H
Published: April 2011

Background

In 2006, the majority of new HIV infections were in MSM. We sought to describe numbers of casual sex partners among US MSM.

Methods

Data are from the first MSM cycle of the National HIV Behavioral Surveillance system, conducted from 2003 to 2005. Relationships between number of casual male sex partners within the previous year and demographic information, self-reported HIV status, and risk behaviors were determined through regression models.

Results

Among 11,191 sexually active MSM, 76% reported a casual male partner. The median casual partner number was three. Lower number of casual partners was associated with black race, Hispanic ethnicity, and having a main sex partner in the previous year. Factors associated with a higher number included gay identity, exchange sex, both injection and non-injection drug use. Being HIV-positive was associated with more partners among non-blacks only. Age differences in partner number were seen only among chat room users.

Conclusions

MSM who were black, Hispanic or had a main sex partner reported fewer casual sex partners. Our results suggest specific populations of MSM who may benefit most from interventions to reduce casual partner numbers.