bluuebunny/crossref_metadata_2025 huggingface dataset:
Scale-up of home-based management of malaria based on rapid diagnostic tests and artemisinin-based combination therapy in a resource-poor country: results in Senegal
Authors: Thiam Sylla , Thwing Julie , Diallo Ibrahima , Fall Fatou B , Diouf Mame B , Perry Robert , Ndiop Medoune , Diouf Mamadou L , Cisse Moustapha M , Diaw Mamadou M , Thior Moussa
Published: September 2012

Background

Effective case management of malaria requires prompt diagnosis and treatment within 24 hours. Home-based management of malaria (HMM) improves access to treatment for populations with limited access to health facilities. In Senegal, an HMM pilot study in 2008 demonstrated the feasibility of integrated use of RDTs and ACT in remote villages by volunteer Home Care Providers (HCP). Scale-up of the strategy began in 2009, reaching 408 villages in 2009 and 861 villages in 2010. This paper reports the results of the scale-up in the targeted communities and the impact of the strategy on malaria in the formal health sector.

Methods

Data reported by the HCPs were used to assess their performance in 2009 and 2010, while routine malaria morbidity and mortality data were used to assess the impact of the HMM programme. Two high transmission regions where HMM was not implemented until 2010 were used as a comparison.

Results and discussion

From July 2009 through May 2010, 12582 suspected cases were managed by HCPs, 93% (11672) of whom were tested with an RDT. Among those tested, 37% (4270) had a positive RDT, 97% (4126) of whom were reported treated and cured. Home care providers referred 6871 patients to health posts for management: 6486 with a negative RDT, 119 infants < 2 months, 105 pregnant women, and 161 severe cases. There were no deaths among these patients. In 2009 compared to 2008, incidence of suspected and confirmed malaria cases, all hospitalizations and malaria-related hospitalizations decreased in both intervention and comparison regions. Incidence of in-hospital deaths due to malaria decreased by 62.5% (95% CI 43.8-81.2) in the intervention regions, while the decrease in comparison regions was smaller and not statistically significant.

Conclusion

Home-based management of malaria including diagnosis with RDT and treatment based on test results is a promising strategy to improve the access of remote populations to prompt and effective management of uncomplicated malaria and to decrease mortality due to malaria. When scaled-up to serve remote village communities in the regions of Senegal with the highest malaria prevalence, home care providers demonstrated excellent adherence to guidelines, potentially contributing to a decrease in hospital deaths attributed to malaria.
Three-dimensional measurement of foot arch in preschool children
Authors: Chang Hsun-Wen , Lin Chien-Ju , Kuo Li-Chieh , Tsai Ming-June , Chieh Hsiao-Feng , Su Fong-Chin
Published: September 2012

Background

The prevalence of flexible flatfoot is high among preschool-aged children, but the effects of treatment are inconclusive due to the unclear definitions of normal flatfoot. To date, a universally accepted evaluation method of the foot arch in children has not been completely established. Our aims of this study were to establish a new method to evaluate the foot arch from a three dimensional perspective and to investigate the flexibility of the foot arch among children aged from two to six.

Methods

A total of 44 children aged from two to six years of age were put into five age groups in this study. The navicular height was measured with one leg standing, and both feet were scanned separately in both sitting and one leg standing positions to compute the foot arch volume. The arch volume index, which represents the ratio of the difference in volume between sitting and one leg standing positions to the volume when sitting was calculated to demonstrate the flexibility of the foot arch. The differences of measured parameters between each aged group were analyzed by one-way ANOVA.

Results

The arch volumes when sitting and standing were highly correlated with the navicular height. The navicular height ranged from 15.75 to 27 mm, the arch volume when sitting ranged from 6,223 to 11,630 mm3, and the arch volume when standing from 3,111 to 7,848 mm3from two to six years of age. The arch volume index showed a declining trend as age increased.

Conclusion

This study is the first to describe the foot arch with volume perspective in preschool-aged children. The foot arch volume was highly correlated with the navicular height. Research results show both navicular height index and arch volume index gradually increase with age from two to six. At the same time the arch also becomes rigid with age from two to six. These results could be applied for clinical evaluation of the foot arch and post-treatment evaluation.
Lymphocyte Depletion in Experimental Hemorrhagic Shock in Swine
Authors: Hawksworth Jason S , Graybill Christopher , Brown Trevor S , Gillern Suzanne M , Wallace Shannon M , Davis Thomas A , Elster Eric A , Tadaki Doug K
Published: September 2012

Background

Hemorrhagic shock results in systemic activation of the immune system and leads to ischemia-reperfusion injury. Lymphocytes have been identified as critical mediators of the early innate immune response to ischemia-reperfusion injury, and immunomodulation of lymphocytes may prevent secondary immunologic injury in surgical and trauma patients.

Methods

Yorkshire swine were anesthetized and underwent a grade III liver injury with uncontrolled hemorrhage to induce hemorrhagic shock. Experimental groups were treated with a lymphocyte depletional agent, porcine polyclonal anti-thymocyte globulin (PATG) (n = 8) and compared to a vehicle control group (n = 9). Animals were observed over a 3 day survival period. Circulating lymphocytes were examined with FACS analysis for CD3/CD4/CD8, and central lymphocytes with mesenteric lymph node and spleen staining for CD3. Circulating and lung tissue16 infiltrating neutrophils were measured. Circulating CD3 lymphocytes in the blood and in central lymphoid organs (spleen/lymph node) were stained and evaluated using FACS analysis. Immune-related gene expression from liver tissue was quantified using RT-PCR.

Results

The overall survival was 22% (2/9) in the control and 75% (6/8) in the PATG groups, p = 0.09; during the reperfusion period (following hemorrhage) survival was 25% (2/8) in the control and 100% (6/6) in the PATG groups, p = 0.008. Mean blood loss and hemodynamic profiles were not significantly different between the experimental and control groups. Circulating CD3+CD4+ lymphocytes were significantly depleted in the PATG group compared to control. Lymphocyte depletion in the setting of hemorrhagic shock also significantly decreased circulating and lung tissue infiltrating neutrophils, and decreased expression of liver ischemia gene expression.

Conclusions

Lymphocyte manipulation with a depletional (PATG) strategy improves reperfusion survival in experimental hemorrhagic shock using a porcine liver injury model. This proof of principle study paves the way for further development of immunomodulation approaches to ameliorate secondary immune injury following hemorrhagic shock.
Copper@polypyrrole nanocables
Authors: Suárez-Guevara Jullieth , Ayyad Omar , Gómez-Romero Pedro
Published: September 2012

A simple hydrothermal redox reaction between microcrystalline CuOHCl and pyrrole leads to the isolation of striking nanostructures formed by polypyrrole-coated copper nanocables. These multicomponent cables that feature single-crystalline face-centered cubic Cu cores (ca. 300 nm wide and up to 200 μm long) are smoothly coated by conducting polypyrrole, which in addition to its functionality, offers protection against oxidation of the metal core.
Stability of the Ishikawa iteration scheme with errors for two strictly hemicontractive operators in Banach spaces
Authors: Hussain Nawab , Rafiq Arif , Ciric Ljubomir B
Published: September 2012

The main purpose of this paper is to establish the convergence, almost common-stability and common-stability of the Ishikawa iteration scheme with error terms in the sense of Xu (J. Math. Anal. Appl. 224:91-101, 1998) for two Lipschitz strictly hemicontractive operators in arbitrary Banach spaces.
Low nuclear body formation and tax SUMOylation do not prevent NF-kappaB promoter activation
Authors: Bonnet Amandine , Randrianarison-Huetz Voahangy , Nzounza Patrycja , Nedelec Martine , Chazal Maxime , Waast Laetitia , Pene Sabrina , Bazarbachi Ali , Mahieux Renaud , Bénit Laurence , Pique Claudine
Published: September 2012

Background

The Tax protein encoded by Human T-lymphotropic virus type 1 (HTLV-1) is a powerful activator of the NF-κB pathway, a property critical for HTLV-1-induced immortalization of CD4+ T lymphocytes. Tax permanently stimulates this pathway at a cytoplasmic level by activating the IκB kinase (IKK) complex and at a nuclear level by enhancing the binding of the NF-κB factor RelA to its cognate promoters and by forming nuclear bodies, believed to represent transcriptionally active structures. In previous studies, we reported that Tax ubiquitination and SUMOylation play a critical role in Tax localization and NF-κB activation. Indeed, analysis of lysine Tax mutants fused or not to ubiquitin or SUMO led us to propose a two-step model in which Tax ubiquitination first intervenes to activate IKK while Tax SUMOylation is subsequently required for promoter activation within Tax nuclear bodies. However, recent studies showing that ubiquitin or SUMO can modulate Tax activities in either the nucleus or the cytoplasm and that SUMOylated Tax can serve as substrate for ubiquitination suggested that Tax ubiquitination and SUMOylation may mediate redundant rather than successive functions.

Results

In this study, we analyzed the properties of a new Tax mutant that is properly ubiquitinated, but defective for both nuclear body formation and SUMOylation. We report that reducing Tax SUMOylation and nuclear body formation do not alter the ability of Tax to activate IKK, induce RelA nuclear translocation, and trigger gene expression from a NF-κB promoter. Importantly, potent NF-κB promoter activation by Tax despite low SUMOylation and nuclear body formation is also observed in T cells, including CD4+ primary T lymphocytes. Moreover, we show that Tax nuclear bodies are hardly observed in HTLV-1-infected T cells. Finally, we provide direct evidence that the degree of NF-κB activation by Tax correlates with the level of Tax ubiquitination, but not SUMOylation.

Conclusions

These data reveal that the formation of Tax nuclear bodies, previously associated to transcriptional activities in Tax-transfected cells, is dispensable for NF-κB promoter activation, notably in CD4+ T cells. They also provide the first evidence that Tax SUMOylation is not a key determinant for Tax-induced NF-κB activation.
Periodontal disease: the influence of metabolic syndrome
Authors: Marchetti Enrico , Monaco Annalisa , Procaccini Laura , Mummolo Stefano , Gatto Roberto , Tetè Stefano , Baldini Alberto , Tecco Simona , Marzo Giuseppe
Published: September 2012

Metabolic syndrome (MetS) is a cluster of cardiovascular risk factors that include obesity, impaired glucose tolerance or diabetes, hyperinsulinemia, hypertension, and dyslipidemia. Recently, more attention has been reserved to the correlation between periodontitis and systemic health. MetS is characterized by oxidative stress, a condition in which the equilibrium between the production and the inactivation of reactive oxygen species (ROS) becomes disrupted. ROS have an essential role in a variety of physiological systems, but under a condition of oxidative stress, they contribute to cellular dysfunction and damage. Oxidative stress may act as a common link to explain the relationship between each component of MetS and periodontitis. All those conditions show increased serum levels of products derived from oxidative damage, promoting a proinflammatory state. Moreover, adipocytokines, produced by the fat cells of fat tissue, might modulate the balance between oxidant and antioxidant activities. An increased caloric intake involves a higher metabolic activity, which results in an increased production of ROS, inducing insulin resistance. At the same time, obese patients require more insulin to maintain blood glucose homeostasis – a state known as hyperinsulinemia, a condition that can evolve into type 2 diabetes. Oxidation products can increase neutrophil adhesion and chemotaxis, thus favoring oxidative damage. Hyperglycemia and an oxidizing state promote the genesis of advanced glycation end-products, which could also be implicated in the degeneration and damage of periodontal tissue. Thus, MetS, the whole of interconnected factors, presents systemic and local manifestations, such as cardiovascular disease and periodontitis, related by a common factor known as oxidative stress.
Evasion of tumours from the control of the immune system: consequences of brief encounters
Authors: Al-Tameemi Mohannad , Chaplain Mark , d’Onofrio Alberto
Published: September 2012

Background

In this work a mathematical model describing the growth of a solid tumour in the presence of an immune system response is presented. Specifically, attention is focused on the interactions between cytotoxic T-lymphocytes (CTLs) and tumour cells in a small, avascular multicellular tumour. At this stage of the disease the CTLs and the tumour cells are considered to be in a state of dynamic equilibrium or cancer dormancy. The precise biochemical and cellular mechanisms by which CTLs can control a cancer and keep it in a dormant state are still not completely understood from a biological and immunological point of view. The mathematical model focuses on the spatio-temporal dynamics of tumour cells, immune cells, chemokines and “chemorepellents” in an immunogenic tumour. The CTLs and tumour cells are assumed to migrate and interact with each other in such a way that lymphocyte-tumour cell complexes are formed. These complexes result in either the death of the tumour cells (the normal situation) or the inactivation of the lymphocytes and consequently the survival of the tumour cells. In the latter case, we assume that each tumour cell that survives its “brief encounter” with the CTLs undergoes certain beneficial phenotypic changes.

Results

We explore the dynamics of the model under these assumptions and show that the process of immuno-evasion can arise as a consequence of these encounters. We show that the proposed mechanism not only shape the dynamics of the total number of tumor cells and of CTLs, but also the dynamics of their spatial distribution. We also briefly discuss the evolutionary features of our model, by framing them in the recent quasi-Lamarckian theories.

Conclusions

Our findings might have some interesting implication of interest for clinical practice. Indeed, immuno-editing process can be seen as an “involuntary” antagonistic process acting against immunotherapies, which aim at maintaining a tumor in a dormant state, or at suppressing it.

Reviewers

This article was reviewed by G. Bocharov (nominated by V. Kuznetsov, member of the Editorial Board of Biology Direct), M. Kimmel and A. Marciniak-Czochra.
The effect of infection order of porcine circovirus type 2 and porcine reproductive and respiratory syndrome virus on dually infected swine alveolar macrophages
Authors: Tsai Yi-Chieh , Chang Hui-Wen , Jeng Chian-Ren , Lin Tsang-Long , Lin Chun-Ming , Wan Cho-Hua , Pang Victor Fei
Published: September 2012

Background

Concurrent infection with porcine circovirus type 2 (PCV2) and porcine reproductive and respiratory syndrome virus (PRRSV) is known as one of the major causes for porcine respiratory disease complex (PRDC). Dual infection with PCV2 and PRRSV is consistently to have more severe clinical presentations and pulmonary lesions than infection with PCV2 alone or PRRSV alone. However, it is not known if dual infections with PCV2 and PRRSV in different infection order may lead to different clinical symptoms in the host. To mimic the possible field conditions, swine alveolar macrophages (AMs) were inoculated with PCV2 and PRRSV in vitro simultaneously or with one virus 18 h earlier than the other. The cell viability, cytopathic effects, antigen-containing rates, phagocytotic and microbial killing capabilities, cytokine profiles (IL-8, TNF-α, and IFN-α) and FasL transcripts were determined, analyzed, and compared to prove the hypothesis.

Results

A marked reduction in PRRSV antigen-containing rate, cytopathic effect, and TNF-α expression level was revealed in AMs inoculated with PCV2 and PRRSV simultaneously and in AMs inoculated with PCV2 first then PRRSV 18 h later, but not in AMs inoculated with PRRSV first then PCV2 18 h later. Transient decrease in phagocytosis but constant reduction in microbicidal capability in AMs in the group inoculated with PCV2 alone and constant decrease in phagocytosis and microbicidal capability in AMs in all PRRSV-inoculated groups were noted. The levels of IL-8, TNF-α, IFN-α, and FasL transcripts in AMs in all groups with dual inoculation of PCV2 and PRRSV were significantly increased regardless of the infection orders as compared with infection by PCV2 alone or PRRSV alone.

Conclusions

Swine AMs infected with PCV2 first then PRRSV later or infected with PCV2 and PRRSV simultaneously displayed marked reduction in PRRSV antigen-containing rate, cytopathic effect, and TNF-α expression level. The different inoculation orders of PCV2 and PRRSV in AMs leading to different results in viral antigen positivity, cytopathology, and cytokine profile may explain, at least partially, the underlying mechanism of the enhanced pulmonary lesions in PRDC exerted by dual infection with PCV2 and PRRSV and the variable clinical manifestations of PRDC-affected pigs in the field.
Description and outcome of a cohort of 8 patients with WHIM syndrome from the French Severe Chronic Neutropenia Registry
Authors: Beaussant Cohen Sarah , Fenneteau Odile , Plouvier Emmanuel , Rohrlich Pierre-Simon , Daltroff Gerard , Plantier Isabelle , Dupuy Alain , Kerob Delphine , Beaupain Blandine , Bordigoni Pierre , Fouyssac Fanny , Delezoide Anne-Lise , Devouassoux Gilles , Nicolas Jean François , Bensaid Philippe , Bertrand Yves , Balabanian Karl , Chantelot Christine Bellanne , Bachelerie Françoise , Donadieu Jean
Published: September 2012

Background

WHIM syndrome (WS), a rare congenital neutropenia due to mutations of the CXCR4 chemokine receptor, is associated with Human Papillomavirus (HPV)-induced Warts, Hypogammaglobulinemia, bacterial Infections and Myelokathexis. The long term follow up of eight patients highlights the clinical heterogeneity of this disease as well as the main therapeutic approaches and remaining challenges in the light of the recent development of new CXCR4 inhibitors.

Objective

This study aims to describe the natural history of WS based on a French cohort of 8 patients.

Methods

We have reviewed the clinical, biological and immunological features of patients with WS enrolled into the French Severe Chronic Neutropenia Registry.

Results

We identified four pedigrees with WS comprised of eight patients and one foetus. Estimated incidence for WS was of 0.23 per million births. Median age at the last visit was 29 years. Three pedigrees encompassing seven patients and the fetus displayed autosomal dominant heterozygous mutations of theCXCR4gene, while one patient presented a wild-typeCXCR4gene. Two subjects exhibited congenital conotruncal heart malformations. In addition to neutropenia and myelokathexis, all patients presented deep monocytopenia and lymphopenia. Seven patients presented repeated bacterial Ears Nose Throat as well as severe bacterial infections that were curable with antibiotics. Four patients with late onset prophylaxis developed chronic obstructive pulmonary disease (COPD). Two patients reported atypical mycobacteria infections which in one case may have been responsible for one patient’s death due to liver failure at the age of 40.6 years. HPV-related disease manifested in five subjects and progressed as invasive vulvar carcinoma with a fatal course in one patient at the age of 39.5 years. In addition, two patients developed T cell lymphoma skin cancer and basal cell carcinoma at the age of 38 and 65 years.

Conclusions

Continuous prophylactic anti-infective measures, when started in early childhood, seem to effectively prevent further bacterial infections and the consequent development of COPD. Long-term follow up is needed to evaluate the effect of early anti-HPV targeted prophylaxis on the development of skin and genital warts.
Metastatic pituitary carcinoma in a patient with acromegaly: a case report
Authors: Sreenan Seamus , Sengupta Elizabeth , Tormey William , Landau Richard
Published: September 2012

Introduction

Asymptomatic pituitary abnormalities occur in about 10% of cranial magnetic resonance imaging scans, but metastatic carcinoma of the pituitary gland is rare: 133 cases have been reported. Two thirds secreted either prolactin or adrenocorticotropic hormone, and another 24% were non-secreting.

Case presentation

A 42-year-old Caucasian man lived for 30 years after the diagnosis of a pituitary tumor whose clinical and biochemical features were those of acromegaly and hypogonadism. Radiotherapy, totaling 7300 rad, was administered to the sella over two courses. Growth hormone levels normalized, but he developed both thyroid and adrenal insufficiency, and replacement therapy was commenced. Fourteen years later, growth hormone levels again became elevated, and bromocriptine was commenced but led to side effects that could not be tolerated. An attempted surgical intervention failed, and octreotide and pergolide were used in succession. Twenty-seven years after the diagnosis, a mass from an excisional biopsy of below the angle of the mandible proved to be metastatic pituitary carcinoma. Immunohistochemical staining was positive for synaptophysin, growth hormone, and prolactin. One year later, an octreotide scan showed uptake at the sella, neck, and spleen. Our patient declined further active oncology treatment.

Conclusions

Metastatic pituitary carcinoma associated with acromegaly is particularly rare. To the best of our knowledge, this is the eighth such case and is the first report of growth hormone and prolactin present in the metastatic mass.
Role of Serine140 in the mode of action of Mycobacterium tuberculosis β-ketoacyl-ACP Reductase (MabA)
Authors: Rosado Leonardo A , Caceres Rafael Andrade , de Azevedo Walter Filgueira , Basso Luiz A , Santos Diógenes S
Published: September 2012

Background

Tuberculosis (TB) still remains one of the most deadly infectious diseases in the world. Mycobacterium tuberculosis β-ketoacyl-ACP Reductase (MabA) is a member of the fatty acid elongation system type II, providing precursors of mycolic acids that are essential to the bacterial cell growth and survival. MabA has been shown to be essential for M. tuberculosis survival and to play a role in intracellular signal transduction of bacilli.

Findings

Here we describe site-directed mutagenesis, recombinant protein expression and purification, steady-state kinetics, fluorescence spectroscopy, and molecular modeling for S140T and S140A mutant MabA enzymes. No enzyme activity could be detected for S140T and S140A. Although the S140T protein showed impaired NADPH binding, the S140A mutant could bind to NADPH. Computational predictions for NADPH binding affinity to WT, S140T and S140A MabA proteins were consistent with fluorescence spectroscopy data.

Conclusions

The results suggest that the main role of the S140 side chain of MabA is in catalysis. The S140 side chain appears to also play an indirect role in NADPH binding. Interestingly, NADPH titrations curves shifted from sigmoidal for WT to hyperbolic for S140A, suggesting that the S140 residue may play a role in displacing the pre-existing equilibrium between two forms of MabA in solution. The results here reported provide a better understanding of the mode of action of MabA that should be useful to guide the rational (function-based) design of inhibitors of MabA enzyme activity which, hopefully, could be used as lead compounds with anti-TB action.
Prevalence of overweight and obesity in preschool children (2–5 year-olds) in Birjand, Iran
Authors: Fatemeh Taheri , Mohammad-Mehdi Hassanzadeh-Taheri , Toba Kazemi , Afsaneh Nazari , Sharifzadeh Gholamreza ,   and Student Research committee
Published: September 2012

Background

Childhood overweight and obesity have increased progressively in developing countries and nowadays they are considered as a global epidemic.

The aim of the present study was to determine prevalence of overweight and obesity in 2–5 year-old children in kindergartens of Birjand in 2008.

Findings

This cross- sectional and descriptive- analytical study was conducted on 500 children, who were 2–5 years-old, in kindergartens of Birjand selected through census. It was found that prevalence of overweight was 10.6% (11.7% in females and 9.6% in males) and obesity 7.6% (6.3% in females and 9.6% in males). Prevalence of overweight and obesity were statistically significant regarding birth weight, mother's occupation and father's level of education.

Conclusion

Prevalence of overweight and obesity in pre-schoolchildren is more than that of 7–18 year-old group in Birjand, but it is less than the result of similar studies in Tehran and most studies in other countries. Further studies are recommended to identify risk factors in obese children. Periodic studies are necessary to compare the changes in prevalence of obesity in children in future.
Nasal cytology in children: recent advances
Authors: Gelardi Matteo , Marseglia Gian Luigi , Licari Amelia , Landi Massimo , Dell’Albani Ilaria , Incorvaia Cristoforo , Frati Franco , Quaranta Nicola
Published: September 2012

Nasal cytology is a very useful diagnostic tool in nasal disorders, being able to detect both the cellular modifications of the nasal epithelium caused by either allergen exposure or irritative stimuli (that may be physical or chemical, acute or chronic), or inflammation. Over these past few years, nasal cytology has allowed to identify new disorders, such as the non-allergic rhinitis with eosinophils (NARES), the non-allergic rhinitis with mast cells (NARMA), the non-allergic rhinitis with neutrophils (NARNE), and the non-allergic rhinitis with eosinophils and mast cells (NARESMA). The rhinocytogram is actually able to distinguish the different forms of allergic rhinitis and to suggest the appropriate treatment, such as antinflammatory drugs or allergen immunotherapy. The technique is easy to perform and nasal cytology is therefore particularly suitable even for children. Such a consideration suggests the utility of a systematic use of nasal cytology in the diagnostic work-up of nasal disorders in children, in order to reach a proper defined diagnosis and to set a rational therapeutic approach: in facts, these two elements are fundamental in order to prevent from complications and to improve the patient’s quality of life.
Engineering of acetyl-CoA metabolism for the improved production of polyhydroxybutyrate in Saccharomyces cerevisiae
Authors: Kocharin Kanokarn , Chen Yun , Siewers Verena , Nielsen Jens
Published: September 2012

Through metabolic engineering microorganisms can be engineered to produce new products and further produce these with higher yield and productivities. Here, we expressed the bacterial polyhydroxybutyrate (PHB) pathway in the yeast Saccharomyces cerevisiae and we further evaluated the effect of engineering the formation of acetyl coenzyme A (acetyl-CoA), an intermediate of the central carbon metabolism and precursor of the PHB pathway, on heterologous PHB production by yeast. We engineered the acetyl-CoA metabolism by co-transformation of a plasmid containing genes for native S. cerevisiae alcohol dehydrogenase (ADH2), acetaldehyde dehydrogenase (ALD6), acetyl-CoA acetyltransferase (ERG10) and a Salmonella enterica acetyl-CoA synthetase variant (acs
L641P), resulting in acetoacetyl-CoA overproduction, together with a plasmid containing the PHB pathway genes coding for acetyl-CoA acetyltransferase (phaA), NADPH-linked acetoacetyl-CoA reductase (phaB) and poly(3-hydroxybutyrate) polymerase (phaC) from Ralstonia eutropha H16. Introduction of the acetyl-CoA plasmid together with the PHB plasmid, improved the productivity of PHB more than 16 times compared to the reference strain used in this study, as well as it reduced the specific product formation of side products.
Cost-effectiveness of vaccination with a quadrivalent HPV vaccine in Germany using a dynamic transmission model
Authors: Schobert Deniz , Remy Vanessa , Schoeffski Oliver
Published: September 2012

Introduction

Persistent infections with human papillomavirus (HPV) are a necessary cause of cervical cancer and are responsible for important morbidity in men and women. Since 2007, HPV vaccination has been recommended and funded for all girls aged 12 to 17 in Germany. A previously published cost-effectiveness analysis, using a static model, showed that a quadrivalent HPV vaccination programme for 12-year-old girls in Germany would be cost effective. Here we present the results from a dynamic transmission model that can be used to evaluate the impact and cost-effectiveness of different vaccination schemas.

Methods

We adapted a HPV dynamic transmission model, which has been used in other countries, to the German context. The model was used to compare a cervical cancer screening only strategy with a strategy of combining vaccination of females aged 12–17 years old and cervical cancer screening, based on the current recommendations in Germany. In addition, the impact of increasing vaccination coverage in this cohort of females aged 12–17 years old was evaluated in sensitivity analysis.

Results

The results from this analysis show that the current quadrivalent HPV vaccination programme of females ages 12 to 17 in Germany is cost-effective with an ICER of 5,525€/QALY (quality adjusted life year). The incremental cost-effectiveness ratio (ICER) increased to 10,293€/QALY when the vaccine effects on HPV6/11 diseases were excluded. At steady state, the model predicted that vaccinating girls aged 12 to 17 could reduce the number of HPV 6/11/16/18-related cervical cancers by 65% and genital warts among women and men by 70% and 48%, respectively. The impact on HPV-related disease incidence and costs avoided would occur relatively soon after initiating the vaccine programme, with much of the early impact being due to the prevention of HPV6/11-related genital warts.

Conclusions

These results show that the current quadrivalent HPV vaccination and cervical cancer screening programmes in Germany will substantially reduce the incidence of cervical cancer, cervical intraepithelial neoplasia (CIN) and genital warts. The evaluated vaccination strategies were all found to be cost-effective. Future analyses should include more HPV-related diseases.
Tumor Grade Is Associated With Venous Thromboembolism in Patients With Cancer: Results From the Vienna Cancer and Thrombosis Study
Authors: Ahlbrecht Jonas , Dickmann Boris , Ay Cihan , Dunkler Daniela , Thaler Johannes , Schmidinger Manuela , Quehenberger Peter , Haitel Andrea , Zielinski Christoph , Pabinger Ingrid
Published: September 2012

Purpose

Patients with cancer are at risk of venous thromboembolism (VTE). Tumor-related factors could help estimate patients' individual risk for VTE. Currently, only scarce information on the association between tumor grade and VTE is available. We thus evaluated the role of tumor grade and its association with VTE.

Patients and Methods

The Vienna Cancer and Thrombosis Study is a prospective, observational cohort study including patients with newly diagnosed cancer or progression of disease after remission. Study end point is the occurrence of symptomatic VTE.

Results

Seven hundred forty-seven patients with solid tumors received follow-up for a median of 526 days. VTE occurred in 52 patients (7.0%). At study inclusion, 468 patients had low-grade tumors (G1 and G2) and 279 had high-grade tumors (G3 and G4). In multivariable Cox regression analysis including tumor grade, tumor histology, tumor sites, stage, sex, and age, patients with high-grade tumors had a significantly higher risk of VTE compared with those with low-grade tumors (hazard ratio, 2.0; 95% CI, 1.1 to 3.5; P = .015). The cumulative probability of developing VTE after 6 months was higher in patients with high-grade tumors than in those with low-grade tumors (8.2% v 4.0%; log-rank test P = .037). Patients with high-grade tumors had higher D-dimer levels (P = .008) and leukocyte counts (P < .001), and lower hemoglobin levels (P = .008).

Conclusion

The tumor grade may help identify patients with cancer who are at high risk of VTE. The association of tumor grade with recently identified biomarkers indicates a link between tumor differentiation and pathogenesis of cancer-associated VTE.
Deregulated Expression ofEVI1Defines a Poor Prognostic Subset ofMLL-Rearranged Acute Myeloid Leukemias: A Study of the German-Austrian Acute Myeloid Leukemia Study Group and the Dutch-Belgian-Swiss HOVON/SAKK Cooperative Group
Authors: Gröschel Stefan , Schlenk Richard F. , Engelmann Jan , Rockova Veronika , Teleanu Veronica , Kühn Michael W.M. , Eiwen Karina , Erpelinck Claudia , Havermans Marije , Lübbert Michael , Germing Ulrich , Schmidt-Wolf Ingo G.H. , Beverloo H. Berna , Schuurhuis Gerrit J. , Ossenkoppele Gert J. , Schlegelberger Brigitte , Verdonck Leo F. , Vellenga Edo , Verhoef Gregor , Vandenberghe Peter , Pabst Thomas , Bargetzi Mario , Krauter Jürgen , Ganser Arnold , Valk Peter J.M. , Löwenberg Bob , Döhner Konstanze , Döhner Hartmut , Delwel Ruud
Published: September 2012

Purpose

To evaluate the prognostic value of ecotropic viral integration 1 gene (EVI1) overexpression in acute myeloid leukemia (AML) with MLL gene rearrangements.

Patients and Methods

We identified 286 patients with AML with t(11q23) enrolled onto German-Austrian Acute Myeloid Leukemia Study Group and Dutch-Belgian-Swiss Hemato-Oncology Cooperative Group prospective treatment trials. Material was available from 177 AML patients for EVI1 expression analysis.

Results

We divided 286 MLL-rearranged AMLs into three subgroups: t(9;11)(p22;q23) (44.8%), t(6;11)(q27;q23) (14.7%), and t(v;11q23) (40.5%). EVI1 overexpression (EVI1+) was found in 45.8% of all patients with t(11q23), with t(6;11) showing the highest frequency (83.9%), followed by t(9;11) at 40.0%, and t(v;11q23) at 34.8%. Concurrent gene mutations were rare or absent in all three subgroups. Within all t(11q23) AMLs, EVI1+was the sole prognostic factor, predicting for inferior overall survival (OS; hazard ratio [HR], 2.06; P = .003), relapse-free survival (HR, 2.28; P = .002), and event-free survival (HR, 1.79; P = .009). EVI1+AMLs with t(11q23) in first complete remission (CR) had a significantly better outcome after allogeneic transplantation compared with other consolidation therapies (5-year OS, 54.7% v 0%; Mantel-Byar, P = .0006). EVI1−t(9;11) AMLs had lower WBC counts, more commonly FAB M5 morphology, and frequently had additional trisomy 8 (39.6%; P < .001). Among t(9;11) AMLs, EVI1+again was the sole independent adverse prognostic factor for survival.

Conclusion

Deregulated EVI1 expression defines poor prognostic subsets among AML with t(11q23) and AML with t(9;11)(p22;q23). Patients with EVI1+MLL-rearranged AML seem to benefit from allogeneic transplantation in first CR.
Cancer Survivorship Care: Don't Let the Perfect Be the Enemy of the Good
Authors: Earle Craig C. , Ganz Patricia A.
Published: September 2012

It has now been more than 5 years since the Institute of Medicine (IOM) laid out its bold vision of comprehensive survivorship care. Although there is clearly more attention paid to this phase of the cancer journey than previously, implementation of the IOM recommendations has proved difficult. In this article, we review some of the challenges to providing survivorship care and discuss efforts to prioritize the most essential elements.
Delivering Care to Long-Term Adult Survivors of Hematopoietic Cell Transplantation
Authors: Syrjala Karen L. , Martin Paul J. , Lee Stephanie J.
Published: September 2012

This review highlights long-term and late consequences of hematopoietic cell transplantation (HCT) as well as strategies to manage or prevent complications that are more prevalent after HCT than most other cancer treatments. Chronic graft-versus-host disease stands out as a unique late effect of allogeneic HCT that is not seen after other types of cancer treatment. However, many other complications seen after solid tumor treatments are also common after HCT, including infections, second cancers, bone loss, and cardiovascular, pulmonary, renal, and endocrine dysfunction. Symptoms and syndromes that are reported after HCT include sexual dysfunction, cognitive problems, fatigue, insomnia, musculoskeletal symptoms, emotional distress, anger, and depression. Addressing these complex potential or actual complications requires diligent routine health care to intervene early or, when possible, to prevent late complications. To accomplish early detection and prevention of life-threatening complications, HCT survivors should undergo an annual comprehensive physical examination that includes screening for functional and psychosocial consequences of treatment and encouraging healthy lifestyle behaviors. Clinicians can link survivors to numerous online, print, and video resources to help them advocate for their health needs.
Cancer- and Cancer Treatment–Associated Cognitive Change: An Update on the State of the Science
Authors: Ahles Tim A. , Root James C. , Ryan Elizabeth L.
Published: September 2012

Cognitive changes associated with cancer and cancer treatments have become an increasing concern. Using breast cancer as the prototype, we reviewed the research from neuropsychological, imaging, genetic, and animal studies that have examined pre- and post-treatment cognitive change. An impressive body of research supports the contention that a subgroup of patients is vulnerable to post-treatment cognitive problems. We also propose that models of aging may be a useful conceptual framework for guiding research in this area and suggest that a useful perspective may be viewing cognitive change in patients with cancer within the context of factors that influence the trajectory of normal aging.
Late Cardiac Effects of Cancer Treatment
Authors: Lenihan Daniel J. , Cardinale Daniela M.
Published: September 2012

Cardiac toxicities from cancer therapy can become evident many years after treatment, and these late cardiac effects can have a profound impact on cancer survivors. There are a myriad of potential cardiovascular complications from cancer therapy, but these can be grouped into three main categories. First, vascular conditions including atherosclerosis, thrombosis, and hypertension predominate. Second, cardiac structural problems, especially valvular degeneration, can have a dramatic impact long term. Lastly, and most importantly, cardiac dysfunction and heart failure are potentially common late cardiac effects and can certainly be prevented or detected early during active cancer therapy to result in optimal outcomes. Future research on late cardiac effects in cancer survivors needs to include advanced cardiac imaging techniques, novel cardiac biomarkers, and genetic determinants of response to cancer treatment.
Disruptions of Global and Jagged1-Mediated Notch Signaling Affect Thyroid Morphogenesis in the Zebrafish
Authors: Porazzi Patrizia , Marelli Federica , Benato Francesca , de Filippis Tiziana , Calebiro Davide , Argenton Francesco , Tiso Natascia , Persani Luca
Published: September 2012

The mechanisms underlying the early steps of thyroid development are largely unknown. In search for novel candidate genes implicated in thyroid function, we performed a gene expression analysis on thyroid cells revealing that TSH regulates the expression of several elements of the Notch pathway, including the ligand Jagged1. Because the Notch pathway is involved in cell-fate determination of several foregut-derived endocrine tissues, we tested its contribution in thyroid development using the zebrafish, a teleost model recapitulating the mammalian molecular events during thyroid development. Perturbing the Notch signaling (e.g. mib mutants, γ-secretase inhibition, or Notch intracellular domain overexpression), we obtained evidence that this pathway has a biological role during the earlier phases of thyroid primordium induction, limiting the number of cells that proceed to a specialized fate and probably involving actions from surrounding tissues. Moreover, we were able to confirm the expression of Jagged1 during different phases of zebrafish thyroid development, as well as in mouse and human thyroid tissues. The two orthologues to the single jagged1 gene (JAG1) in humans, jag1a and jag1b, are expressed with different spatiotemporal patterns in the developing zebrafish thyroid. Both jag1a and jag1b morphants, as well as jag1b mutant fish line, display thyroid hypoplasia and impaired T4 production; this thyroid phenotype was rescued by coinjection of human JAG1 mRNA. In conclusion, Notch pathway is involved in the early steps of thyroid morphogenesis, and Jagged1-Notch signal is required for zebrafish thyroid development and function. Thus, genetic alterations affecting the Notch pathway may confer susceptibility for thyroid dysgenesis.
Myths of health care decentralization
Authors: Costa-I-Font Joan
Published: September 2012

There are several myths about the impact of decentralization of health care governance. These include a worsening of regional inequalities, greater privatization of health care, greater inefficiency resulting from duplication of managerial activities such as human resource policies, and lower productivity. These myths have partly arisen from a lack of rigorous assessments of the effects of decentralization.
Asthma in pregnancy: a review
Authors: Giles Warwick , Murphy Vanessa
Published: September 2012

Asthma is one of the most common medical conditions in women of childbearing age. There are now data to show that asthma is not a benign condition with respect to maternal and fetal health. Despite this there are several problems encountered in the management of such women. There is a tendency to cease or reduce optimal asthma treatments because pregnant women and/or their clinicians may believe they pose a risk to the fetus. There is also a lack of clinician awareness of the complications of asthma in pregnancy.
A new model for quality improvement in acute inpatient psychiatry: observational data from an acute assessment unit
Authors: Hayes Joseph , Gibbons Rachel , Outim Faizal , Tang Sylvia , Chakraborty Apu
Published: September 2012

Objectives

There is little research into the constituents of effective psychiatric inpatient care. The aim of this study was to assess the effectiveness of a newly adopted model of inpatient care; the acute assessment ward.

Design

Review of data collected over a year-long period.

Setting

Acute assessment ward in North London.

Participants

All Admissions between 8 October 2009 and 7 October 2010.

Main outcome measures

Duration of stay, need for readmission, patient satisfaction and frequency of conflict behaviours.

Results

A total of 485 admissions over the yearlong study period. The median stay to discharge from the assessment ward was 6 days, whereas in those transferred it was 19 days. Readmission within 28 days following discharge from the assessment ward was 13.9%, whereas those discharged from other wards was 9.2% ( P = 0.1). Patient satisfaction was no lower, for all domains, than for other wards in the trust. Frequency of conflict behaviour was equal to previous studies, 1 but self harm was significantly less common ( P = 0.01).

Conclusions

Our data show that focusing on the ‘point of entry’ to inpatient services means that some admission times can be reduced without an increase in 28-day readmission rates or conflict behaviours. The acute assessment model attempts to address the need for the NHS to deliver more for less, whilst remaining focused on service-user and staff satisfaction. Research into which areas of this complex intervention are effective is challenging, but we would urge others who run services with novel structures to publish data about their functioning.
Intravenous fluid prescribing practices by foundation year one doctors – a questionnaire study
Authors: Lim Chung Thong , Dunlop Michael , Lim Chung Sim
Published: September 2012

Objectives

Foundation Year Ones (FY1s) are the most junior doctors in the UK who are often required to prescribe intravenous fluid to patients not under their regular care, during on-call or out-of-hours ward cover. This study aimed to investigate FY1s’ practice and decision-making process of intravenous fluid prescribing to these patients.

Design

Questionnaire survey.

Setting

Survey on Practices during on-calls and out-of-hours ward covers.

Participants

FY1s of five National Health Service (NHS) hospitals in England and Scotland.

Results

All 149 FY1s responded to survey. Eighty-six percent have been taught intravenous fluid prescribing during medical school, compared with only 48% in FY1 induction. More than half always/often checked the patient's urea and electrolytes (U&Es) (72%), read the fluid balance (58%) and observation charts (80%), discussed the case with nursing staff (75%), enquired about oral status (82%), identified the main diagnosis/operation (75%) and indication for intravenous fluid (72%) of the patient when prescribing intravenous fluid. However, less than half often/always read the medical notes (43%) or performed clinical examinations on patients (16%). Most FY1s (94%) always/often checked patient's U&Es when prescribing potassium.

Conclusions

The questionnaire study demonstrated variations among FY1s in the practice and decision-making process of intravenous fluid prescribing to patients unknown to them, during on-calls or out-of-hours ward covers. Such variations in practice should be addressed especially by medical and foundation schools, and NHS hospitals to improve patient care.
Cas5d processes pre-crRNA and is a member of a larger family of CRISPR RNA endonucleases
Authors: Garside Erin L. , Schellenberg Matthew J. , Gesner Emily M. , Bonanno Jeffrey B. , Sauder J. Michael , Burley Stephen K. , Almo Steven C. , Mehta Garima , MacMillan Andrew M.
Published: September 2012

Small RNAs derived from clustered, regularly interspaced, short palindromic repeat (CRISPR) loci in bacteria and archaea are involved in an adaptable and heritable gene-silencing pathway. Resistance to invasive genetic material is conferred by the incorporation of short DNA sequences derived from this material into the genome as CRISPR spacer elements separated by short repeat sequences. Processing of long primary transcripts (pre-crRNAs) containing these repeats by a CRISPR-associated (Cas) RNA endonuclease generates the mature effector RNAs that target foreign nucleic acid for degradation. Here we describe functional studies of a Cas5d ortholog, and high-resolution structural studies of a second Cas5d family member, demonstrating that Cas5d is a sequence-specific RNA endonuclease that cleaves CRISPR repeats and is thus responsible for processing of pre-crRNA. Analysis of the structural homology of Cas5d with the previously characterized Cse3 protein allows us to model the interaction of Cas5d with its RNA substrate and conclude that it is a member of a larger family of CRISPR RNA endonucleases.
Advances in non-surgical facial aesthetics
Authors: Pickett Andy
Published: September 2012

Non-surgical facial aesthetics procedures are now commonplace treatments provided by dentists across the UK. These have evolved over the years as new products, new ways of giving the products and new approaches to treatments have been identified and brought into use. Now, botulinum toxin, dermal fillers and combinations of these are the staple products for routine use in the clinic.
The role of forensic dentistry in forensic science: issues and validity?
Authors: Adams Cath
Published: September 2012

Recently, the scientific foundation of forensic disciplines has been called into question and the subject of bite mark comparison in particular has been recognised as being particularly troubling.