bluuebunny/crossref_metadata_2025 huggingface dataset:
Ventilatory and ECMO treatment of H1N1-induced severe respiratory failure: results of an Italian referral ECMO center
Authors: Cianchi Giovanni , Bonizzoli Manuela , Pasquini Andrea , Bonacchi Massimo , Zagli Giovanni , Ciapetti Marco , Sani Guido , Batacchi Stefano , Biondi Simona , Bernardo Pasquale , Lazzeri Chiara , Giovannini Valtere , Azzi Alberta , Abbate Rosanna , Gensini Gianfranco , Peris Adriano
Published: February 2011

Background

Since the first outbreak of a respiratory illness caused by H1N1 virus in Mexico, several reports have described the need of intensive care or extracorporeal membrane oxygenation (ECMO) assistance in young and often healthy patients. Here we describe our experience in H1N1-induced ARDS using both ventilation strategy and ECMO assistance.

Methods

Following Italian Ministry of Health instructions, an Emergency Service was established at the Careggi Teaching Hospital (Florence, Italy) for the novel pandemic influenza. From Sept 09 to Jan 10, all patients admitted to our Intensive Care Unit (ICU) of the Emergency Department with ARDS due to H1N1 infection were studied. All ECMO treatments were veno-venous. H1N1 infection was confirmed by PCR assayed on pharyngeal swab, subglottic aspiration and bronchoalveolar lavage. Lung pathology was evaluated daily by lung ultrasound (LUS) examination.

Results

A total of 12 patients were studied: 7 underwent ECMO treatment, and 5 responded to protective mechanical ventilation. Two patients had co-infection by Legionella Pneumophila. One woman was pregnant. In our series, PCR from bronchoalveolar lavage had a 100% sensitivity compared to 75% from pharyngeal swab samples. The routine use of LUS limited the number of chest X-ray examinations and decreased transportation to radiology for CT-scan, increasing patient safety and avoiding the transitory disconnection from ventilator. No major complications occurred during ECMO treatments. In three cases, bleeding from vascular access sites due to heparin infusion required blood transfusions. Overall mortality rate was 8.3%.

Conclusions

In our experience, early ECMO assistance resulted safe and feasible, considering the life threatening condition, in H1N1-induced ARDS. Lung ultrasound is an effective mean for daily assessment of ARDS patients.
Consequences of spinal pain: Do age and gender matter? A Danish cross-sectional population-based study of 34,902 individuals 20-71 years of age
Authors: Leboeuf-Yde Charlotte , Fejer René , Nielsen Jan , Kyvik Kirsten O , Hartvigsen Jan
Published: February 2011

Background

While low back pain (LBP) and neck pain (NP) have been extensively studied, knowledge on mid back pain (MBP) is still lacking. Furthermore, pain from these three spinal areas is typically studied or reported separately and in depth understanding of pain from the entire spine and its consequences is still needed.

Objectives

To describe self-reported consequences of pain in the three spinal regions in relation to age and gender.

Methods

This was a cross-sectional postal survey, comprising 34,902 twin individuals, representative of the general Danish adult population. The variables of interest in relation to consequences of spinal pain were: Care-seeking, reduced physical activity, sick-leave, change in work situation, and disability pension.

Results

Almost two-thirds of individuals with spinal pain did not report any consequence. Generally, consequences due to LBP were more frequently reported than those due to NP or MBP. Regardless of area of complaint, care seeking and reduced physical activities were the most commonly reported consequences, followed by sick-leave, change of work, and disability pension. There was a small mid-life peak for care-seeking and a slow general increase in reduced activities with increasing age. Increasing age was not associated with a higher reporting of sick-leave but the duration of the sick-leave increased somewhat with age. Disability pension due to spinal pain was reported exceedingly rare before the age of 50. Typically, women slightly more often than men reported some kind of consequences due to spinal pain.

Conclusions

Most people reporting spinal pain manage without any serious consequences. Low back pain more commonly results in some kind of consequence when compared to NP and MBP. Few age-related trends in consequences were seen with a slight predominance of women reporting consequences.
Diffusion patterns of new anti-diabetic drugs into hospitals in Taiwan: the case of Thiazolidinediones for diabetes
Authors: Wen Yu-Wen , Huang Weng-Foung , Lee Yue-Chune , Kuo Ken N , Tsai Chia-Rung , Tsai Yi-Wen
Published: February 2011

Background

Diffusion of new drugs in the health care market affects patients' access to new treatment options and health care expenditures. We examined how a new drug class for diabetes mellitus, thiazolidinediones (TZDs), diffused in the health care market in Taiwan.

Methods

Assuming that monthly hospital prescriptions of TZDs could serve as a micro-market to perform drug penetration studies, we retrieved monthly TZD prescription data for 580 hospitals in Taiwan from Taiwan's National Health Insurance Research Database for the period between March 1, 2001 and December 31, 2005. Three diffusion parameters, time to adoption, speed of penetration (monthly growth on prescriptions), and peak penetration (maximum monthly prescription) were evaluated. Cox proportional hazards model and quantile regressions were estimated for analyses on the diffusion parameters.

Results

Prior hospital-level pharmaceutical prescription concentration significantly deterred the adoption of the new drug class (HR: 0.02, 95%CI = 0.01 to 0.04). Adoption of TZDs was slower in district hospitals (HR = 0.43, 95%CI = 0.24 to 0.75) than medical centers and faster in non-profit hospitals than public hospitals (HR = 1.79, 95%CI = 1.23 to 2.61). Quantile regression showed that penetration speed was associated with a hospital's prior anti-diabetic prescriptions (25%Q: 18.29; 50%Q: 25.57; 75%Q: 30.97). Higher peaks were found in hospitals that had adopted TZD early (25%Q: -40.33; 50%Q: -38.65; 75%Q: -32.29) and in hospitals in which the drugs penetrated more quickly (25%Q: 16.53; 50%Q: 24.91; 75%Q: 31.50).

Conclusions

Medical centers began to prescribe TZDs earlier, and they prescribed more TZDs at a faster pace. The TZD diffusion patterns varied among hospitals depending accreditation level, ownership type, and prescription volume of Anti-diabetic drugs.
var gene transcription and PfEMP1 expression in the rosetting and cytoadhesive Plasmodium falciparum clone FCR3S1.2
Authors: Albrecht Letusa , Moll Kirsten , Blomqvist Karin , Normark Johan , Chen Qijun , Wahlgren Mats
Published: February 2011

Background

The pathogenicity of Plasmodium falciparum is in part due to the ability of the parasitized red blood cell (pRBC) to adhere to intra-vascular host cell receptors and serum-proteins. Binding of the pRBC is mediated by Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), a large multi-variant molecule encoded by a family of ≈60 var genes.

Methods

The study of var gene transcription in the parasite clone FCR3S1.2 was performed by semi-quantitative PCR and quantitative PCR (qPCR). The expression of the major PfEMP1 in FCR3S1.2 pRBC was analysed with polyclonal sera in rosette disruption assays and immunofluorecence.

Results

Transcripts from var 1 (FCR3S1.2
var

1; IT4var 21) and other var genes were detected by semi-quantitative PCR but results from qPCR showed that one var gene transcript dominated over the others (FCR3S1.2
var

2; IT4var 60). Antibodies raised in rats to the recombinant NTS-DBL1α of var 2 produced in E. coli completely and dose-dependently disrupted rosettes (≈95% at a dilution of 1/5). The sera reacted with the Maurer's clefts in trophozoite stages (IFA) and to the infected erythrocyte surface (FACS) indicating that FCR3S1.2
var2
encodes the dominant PfEMP1 expressed in this parasite.

Conclusion

The major transcript in the rosetting model parasite FCR3S1.2 is FCR3S1.2
var

2 (IT4var 60). The results suggest that this gene encodes the PfEMP1-species responsible for the rosetting phenotype of this parasite. The activity of previously raised antibodies to the NTS-DBL1α of FCR3S1.2
var

1 is likely due to cross-reactivity with NTS-DBL1α of the var 2 encoded PfEMP1.
Automated haematology analysis to diagnose malaria
Authors: Campuzano-Zuluaga Germán , Hänscheid Thomas , Grobusch Martin P
Published: February 2011

For more than a decade, flow cytometry-based automated haematology analysers have been studied for malaria diagnosis. Although current haematology analysers are not specifically designed to detect malaria-related abnormalities, most studies have found sensitivities that comply with WHO malaria-diagnostic guidelines, i.e. ≥ 95% in samples with > 100 parasites/μl. Establishing a correct and early malaria diagnosis is a prerequisite for an adequate treatment and to minimizing adverse outcomes. Expert light microscopy remains the 'gold standard' for malaria diagnosis in most clinical settings. However, it requires an explicit request from clinicians and has variable accuracy. Malaria diagnosis with flow cytometry-based haematology analysers could become an important adjuvant diagnostic tool in the routine laboratory work-up of febrile patients in or returning from malaria-endemic regions. Haematology analysers so far studied for malaria diagnosis are the Cell-Dyn®, Coulter®GEN·S and LH 750, and the Sysmex XE-2100®analysers. For Cell-Dyn analysers, abnormal depolarization events mainly in the lobularity/granularity and other scatter-plots, and various reticulocyte abnormalities have shown overall sensitivities and specificities of 49% to 97% and 61% to 100%, respectively. For the Coulter analysers, a 'malaria factor' using the monocyte and lymphocyte size standard deviations obtained by impedance detection has shown overall sensitivities and specificities of 82% to 98% and 72% to 94%, respectively. For the XE-2100, abnormal patterns in the DIFF, WBC/BASO, and RET-EXT scatter-plots, and pseudoeosinophilia and other abnormal haematological variables have been described, and multivariate diagnostic models have been designed with overall sensitivities and specificities of 86% to 97% and 81% to 98%, respectively. The accuracy for malaria diagnosis may vary according to species, parasite load, immunity and clinical context where the method is applied. Future developments in new haematology analysers such as considerably simplified, robust and inexpensive devices for malaria detection fitted with an automatically generated alert could improve the detection capacity of these instruments and potentially expand their clinical utility in malaria diagnosis.
Socioeconomic status and mortality after acute myocardial infarction: a study from Iran
Authors: Donyavi Tahereh , Naieni Kourosh Holakouie , Nedjat Saharnaz , Vahdaninia Mariam , Najafi Mahdi , Montazeri Ali
Published: February 2011

Background

Studies have shown an inverse relationship between socioeconomic status (SES) and mortality due to coronary heart disease (CHD). Little is known about this association in Iran. This study aimed to investigate whether mortality after myocardial infarction (MI) varies by SES.

Methods

In a retrospective study, 1283 MI patients who hospitalized in Tehran Heart Center from March 2005 to March 2006 were followed up in March 2008. Demographic, clinical and SES data were collected from case records and by telephone interviews. Multiple logistic regression analysis was performed to estimate the predictive effect of socioeconomic factors on outcome.

Results

In all 664 patients were studied. Of these, 500 patients were alive and 164 were dead due to MI (64 died at hospital and 100 died at home). The results of regression analysis showed that in addition to treatment (OR = 9.52, 95%CI 4.84-18.7), having diabetes (OR = 1.78, 95% CI 1.12-2.81) or hyperlipidemia (OR = 1.82, 95% CI 1.14-2.90), socioeconomic variables including living area in square per person (lowest level vs. upper level OR = 4.92, 95% CI 2.11-11.4), unemployment (OR = 3.50, 95% CI 1.50-8.13) and education (OR for illiterate patients = 2.51, 95% CI 1.00-6.31) were the most significant contributing factors to increased mortality after MI.

Conclusion

Although the findings should be interpreted with caution, the study results indicated that socioeconomic variables were significant contributing factors to increased mortality after myocardial infarction. The underlying role of socioeconomic status on increased mortality after MI deserves further investigation.
Gravity models to classify commuting vs. resident workers. An application to the analysis of residential risk in a contaminated area
Authors: Signorino Guido , Pasetto Roberto , Gatto Elisa , Mucciardi Massimo , La Rocca Marina , Mudu Pierpaolo
Published: February 2011

Background

The analysis of risk for the population residing and/or working in contaminated areas raises the topic of commuting. In fact, especially in contaminated areas, commuting groups are likely to be subject to lower exposure than residents. Only very recently environmental epidemiology has started considering the role of commuting as a differential source of exposure in contaminated areas. In order to improve the categorization of groups, this paper applies a gravitational model to the analysis of residential risk for workers in the Gela petrochemical complex, which began life in the early 60s in the municipality of Gela (Sicily, Italy) and is the main source of industrial pollution in the local area.

Results

A logistic regression model is implemented to measure the capacity of Gela "central location" to attract commuting flows from other sites. Drawing from gravity models, the proposed methodology: a) defines the probability of finding commuters from municipalities outside Gela as a function of the origin's "economic mass" and of its distance from each destination; b) establishes "commuting thresholds" relative to the origin's mass. The analysis includes 367 out of the 390 Sicilian municipalities. Results are applied to define "commuters" and "residents" within the cohort of petrochemical workers. The study population is composed of 5,627 workers. Different categories of residence in Gela are compared calculating Mortality Rate Ratios for lung cancer through a Poisson regression model, controlling for age and calendar period. The mobility model correctly classifies almost 90% of observations. Its application to the mortality analysis confirms a major risk for lung cancer associated with residence in Gela.

Conclusions

Commuting is a critical aspect of the health-environment relationship in contaminated areas. The proposed methodology can be replicated to different contexts when residential information is lacking or unreliable; however, a careful consideration of the territorial characteristics ("insularity" and its impact on transportation time and costs, in our case) is suggested when specifying the area of application for the mobility analysis.
Curcumin: A review of anti-cancer properties and therapeutic activity in head and neck squamous cell carcinoma
Authors: Wilken Reason , Veena Mysore S , Wang Marilene B , Srivatsan Eri S
Published: February 2011

Curcumin (diferuloylmethane) is a polyphenol derived from theCurcuma longaplant, commonly known as turmeric. Curcumin has been used extensively in Ayurvedic medicine for centuries, as it is nontoxic and has a variety of therapeutic properties including anti-oxidant, analgesic, anti-inflammatory and antiseptic activity. More recently curcumin has been found to possess anti-cancer activities via its effect on a variety of biological pathways involved in mutagenesis, oncogene expression, cell cycle regulation, apoptosis, tumorigenesis and metastasis. Curcumin has shown anti-proliferative effect in multiple cancers, and is an inhibitor of the transcription factor NF-κB and downstream gene products (including c-myc, Bcl-2, COX-2, NOS, Cyclin D1, TNF-α, interleukins and MMP-9). In addition, curcumin affects a variety of growth factor receptors and cell adhesion molecules involved in tumor growth, angiogenesis and metastasis. Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and treatment protocols include disfiguring surgery, platinum-based chemotherapy and radiation, all of which may result in tremendous patient morbidity. As a result, there is significant interest in developing adjuvant chemotherapies to augment currently available treatment protocols, which may allow decreased side effects and toxicity without compromising therapeutic efficacy. Curcumin is one such potential candidate, and this review presents an overview of the current in vitro and in vivo data supporting its therapeutic activity in head and neck cancer as well as some of the challenges concerning its development as an adjuvant chemotherapeutic agent.
Synthesis of three-dimensional calcium carbonate nanofibrous structure from eggshell using femtosecond laser ablation
Authors: Tavangar Amirhossein , Tan Bo , Venkatakrishnan Krishnan
Published: February 2011

Background

Natural biomaterials from bone-like minerals derived from avian eggshells have been considered as promising bone substitutes owing to their biodegradability, abundance, and lower price in comparison with synthetic biomaterials. However, cell adhesion to bulk biomaterials is poor and surface modifications are required to improve biomaterial-cell interaction. Three-dimensional (3D) nanostructures are preferred to act as growth support platforms for bone and stem cells. Although there have been several studies on generating nanoparticles from eggshells, no research has been reported on synthesizing 3D nanofibrous structures.

Results

In this study, we propose a novel technique to synthesize 3D calcium carbonate interwoven nanofibrous platforms from eggshells using high repetition femtosecond laser irradiation. The eggshell waste is value engineered to calcium carbonate nanofibrous layer in a single step under ambient conditions. Our striking results demonstrate that by controlling the laser pulse repetition, nanostructures with different nanofiber density can be achieved. This approach presents an important step towards synthesizing 3D interwoven nanofibrous platforms from natural biomaterials.

Conclusion

The synthesized 3D nanofibrous structures can promote biomaterial interfacial properties to improve cell-platform surface interaction and develop new functional biomaterials for a variety of biomedical applications.
Effect of liver growth factor on both testicular regeneration and recovery of spermatogenesis in busulfan-treated mice
Authors: Pérez-Crespo Miriam , Pericuesta Eva , Pérez-Cerezales Serafín , Arenas Maria I , Lobo Maria VT , Díaz-Gil Juan J , Gutierrez-Adan Alfonso
Published: February 2011

Background

Some adult stem cells persist in adult tissue; however, we do not know how to stimulate stem cells in adults to heal injuries. Liver growth factor (LGF) is a biliprotein with hepatic mitogen activity. Its concentration increases markedly in the presence of any type of liver injury, and it shows in vivo therapeutic biological activity at extrahepatic sites.

Methods

We have analyzed the effect of LGF on the replenishment of germinal cells in the testes of mice injected with busulfan, a common cancer drug that also specifically affects germ line stem cells and spermatogonia. We determined the testicular and epididymal weight, spermatozoal concentration in the epididymis and sperm motility, and performed a histological analysis.

Results

Intraperitoneal administration of LGF was able to partially restore spermatogenesis, as well as sperm production and motility, in mice sterilized with busulfan. LGF treatment in busulfan-treated animals that have suffered a disruption of spermatogenesis can accelerate the reactivation of this process in most of the tubules, as shown in the histological analysis.

Conclusions

Our results suggest a potential use of LGF in the mobilization of testicular stem cells and in the restoration of spermatogenesis after busulfan-induced damage to the testicular germinal epithelium.
Selective transmission of R5 HIV-1 variants: where is the gatekeeper?
Authors: Grivel Jean-Charles , Shattock Robin J , Margolis Leonid B
Published: February 2011

To enter target cells HIV-1 uses CD4 and a coreceptor.In vivothe coreceptor function is provided either by CCR5 (for R5) or CXCR4 (for X4 HIV-1). Although both R5 and X4 HIV-1 variants are present in body fluids (semen, blood, cervicovaginal and rectal secretions), R5 HIV-1 appears to transmit infection and dominates early stages of HIV disease. Moreover, recent sequence analysis of virus in acute infection shows that, in the majority of cases of transmission, infection is initiated by a single virus. Therefore, the existence of a “gatekeeper” that selects R5 over X4 HIV-1 and that operates among R5 HIV-1 variants has been suggested. In the present review we consider various routes of HIV-transmission and discuss potential gatekeeping mechanisms associated with each of these routes. Although many mechanisms have been identified none of them explains the almost perfect selection of R5 over X4 in HIV-1 transmission. We suggest that instead of one strong gatekeeper there are multiple functional gatekeepers and that their superimposition is sufficient to protect against X4 HIV-1 infection and potentially select among R5 HIV-1 variants. In conclusion, we propose that the principle of multiple barriers is more general and not restricted to protection against X4 HIV-1 but rather can be applied to other phenomena when one factor has a selective advantage over the other(s). In the case of gatekeepers for HIV-1 transmission, the task is to identify them and to decipher their molecular mechanisms. Knowledge of the gatekeepers‘ localization and function may enable us to enhance existing barriers against R5 transmission and to erect the new ones against all HIV-1 variants.
Clinical use of CCR5 inhibitors in HIV and beyond
Authors: Gilliam Bruce L , Riedel David J , Redfield Robert R
Published: February 2011

Since the discovery of CCR5 as a coreceptor for HIV entry, there has been interest in blockade of the receptor for treatment and prevention of HIV infection. Although several CCR5 antagonists have been evaluated in clinical trials, only maraviroc has been approved for clinical use in the treatment of HIV-infected patients. The efficacy, safety and resistance profile of CCR5 antagonists with a focus on maraviroc are reviewed here along with their usage in special and emerging clinical situations. Despite being approved for use since 2007, the optimal use of maraviroc has yet to be well-defined in HIV and potentially in other diseases. Maraviroc and other CCR5 antagonists have the potential for use in a variety of other clinical situations such as the prevention of HIV transmission, intensification of HIV treatment and prevention of rejection in organ transplantation. The use of CCR5 antagonists may be potentiated by other agents such as rapamycin which downregulate CCR5 receptors thus decreasing CCR5 density. There may even be a role for their use in combination with other entry inhibitors. However, clinical use of CCR5 antagonists may have negative consequences in diseases such as West Nile and Tick-borne encephalitis virus infections. In summary, CCR5 antagonists have great therapeutic potential in the treatment and prevention of HIV as well as future use in novel situations such as organ transplantation. Their optimal use either alone or in combination with other agents will be defined by further investigation.
Synthesis of long group IV semiconductor nanowires by molecular beam epitaxy
Authors: Xu Tao , Sulerzycki Julien , Nys Jean Philippe , Patriarche Gilles , Grandidier Bruno , Stiévenard Didier
Published: February 2011

We report the growth of Si and Ge nanowires (NWs) on a Si(111) surface by molecular beam epitaxy. While Si NWs grow perpendicular to the surface, two types of growth axes are found for the Ge NWs. Structural studies of both types of NWs performed with electron microscopies reveal a marked difference between the roughnesses of their respective sidewalls. As the investigation of their length dependence on their diameter indicates that the growth of the NWs predominantly proceeds through the diffusion of adatoms from the substrate up along the sidewalls, difference in the sidewall roughness qualitatively explains the length variation measured between both types of NWs. The formation of atomically flat {111} sidewalls on the <110>-oriented Ge NWs accounts for a larger diffusion length.
Blood lipid profiles and peripheral blood mononuclear cell cholesterol metabolism gene expression in patients with and without methotrexate treatment
Authors: Chen Der-Yuan , Chih Hui-Min , Lan Joung-Liang , Chang Hsin-Yueh , Chen Wei-Wen , Chiang En-Pei Isabel
Published: February 2011

Background

Methotrexate (MTX) is the most commonly prescribed disease-modifying antirheumatic drug (DMARD) in rheumatoid arthritis. ATP-binding cassette transporter-A1 (ABCA1) and 27-Hydroxylase (HY27) are known antiatherogenic proteins that promote cellular cholesterol efflux. In THP-1 macrophages, MTX can promote the reversal of cholesterol transport, limit foam cell formation and also reverse COX-2 inhibitor-mediated downregulation of ABCA1. Despite its antiatherogenic potential in vitro, the impact of clinical use of low-dose MTX on cholesterol metabolism in humans is unknown. Objective of the study was to examine whether clinical MTX use is associated with altered blood lipids and/or ABCA1/HY27 expressions.

Methods

In all, 100 rheumatoid arthritis subjects were recruited from a medical center in central Taiwan. Plasma lipid profiles and peripheral blood mononuclear cell HY27 and ABCA1 expressions were compared between subjects taking MTX (MTX+) and other disease-modifying antirheumatic drugs (DMARDs) (MTX-). Dietary intake was assessed by a registered dietician.

Results

Though no difference observed in the blood lipids between MTX+ and MTX- subjects, the expressions of ABCA1 and HY27 were significantly elevated in MTX+ subjects (n = 67) compared to MTX- subjects (n = 32, p < 0.05). ABCA expression correlated with MTX doses (r = 0.205, p = 0.042), and MTX+ subjects are more likely to have increased HY27 compared to MTX- subjects (OR = 2.5, p = 0.038). Prevalence of dyslipidemia and overweight, and dietary fat/cholesterol intake were lower than that of the age-matched population. Although no differences were observed in the blood lipids, the potential impacts of MTX on cholesterol metabolism should not be overlooked and the atheroprotective effects from MTX induced HY27 and ABCA1 expressions may still be present in those persons with pre-existing dyslipidemia.

Conclusions

We demonstrated novel findings on the increased gene expressions of atheroprotective protein HY27 and ABCA1 in human peripheral blood mononuclear cells (PBMCs) with clinical use of low-dose MTX. Whether MTX induced HY27 and ABCA1 expressions can protect against cardiovascular disease in patients with chronic inflammation through the facilitation of cholesterol export remains to be established. Further studies on the impacts of low-dose MTX on hypercholesterolemic patients are underway.
Immune response of macrophages from young and aged mice to the oral pathogenic bacterium Porphyromonas gingivalis
Authors: Shaik-Dasthagirisaheb Yazdani B , Kantarci Alpdogan , Gibson Frank C
Published: February 2011

Periodontal disease is a chronic inflammatory gum disease that in severe cases leads to tooth loss.Porphyromonas gingivalis(Pg) is a bacterium closely associated with generalized forms of periodontal disease. Clinical onset of generalized periodontal disease commonly presents in individuals over the age of 40. Little is known regarding the effect of aging on inflammation associated with periodontal disease. In the present study we examined the immune response of bone marrow derived macrophages (BMM) from young (2-months) and aged (1-year and 2-years) mice to Pg strain 381. Pg induced robust expression of cytokines; tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10, chemokines; neutrophil chemoattractant protein (KC), macrophage colony stimulating factor (MCP)-1, macrophage inflammatory protein (MIP)-1α and regulated upon activation normal T cell expressed and secreted (RANTES), as well as nitric oxide (NO, measured as nitrite), and prostaglandin E2 (PGE2) from BMM of young mice. BMM from the 2-year age group produced significantly less TNF-α, IL-6 and NO in response to Pg as compared with BMM from 2-months and 1-year of age. We did not observe any difference in the levels of IL-1β, IL-10 and PGE2 produced by BMM in response to Pg. BMM from 2-months and 1-year of age produced similar levels of all chemokines measured with the exception of MCP-1, which was reduced in BMM from 1-year of age. BMM from the 2-year group produced significantly less MCP-1 and MIP-1α compared with 2-months and 1-year age groups. No difference in RANTES production was observed between age groups. Employing a Pg attenuated mutant, deficient in major fimbriae (Pg DPG3), we observed reduced ability of the mutant to stimulate inflammatory mediator expression from BMMs as compared to Pg 381, irrespective of age. Taken together these results support senescence as an important facet of the reduced immunological response observed by BMM of aged host to the periodontal pathogen Pg.
WINPEPI updated: computer programs for epidemiologists, and their teaching potential
Authors: Abramson Joseph H
Published: February 2011

Background

The WINPEPI computer programs for epidemiologists are designed for use in practice and research in the health field and as learning or teaching aids. The programs are free, and can be downloaded from the Internet. Numerous additions have been made in recent years.

Implementation

There are now seven WINPEPI programs: DESCRIBE, for use in descriptive epidemiology; COMPARE2, for use in comparisons of two independent groups or samples; PAIRSetc, for use in comparisons of paired and other matched observations; LOGISTIC, for logistic regression analysis; POISSON, for Poisson regression analysis; WHATIS, a "ready reckoner" utility program; and ETCETERA, for miscellaneous other procedures. The programs now contain 122 modules, each of which provides a number, sometimes a large number, of statistical procedures. The programs are accompanied by a Finder that indicates which modules are appropriate for different purposes. The manuals explain the uses, limitations and applicability of the procedures, and furnish formulae and references.

Conclusions

WINPEPI is a handy resource for a wide variety of statistical routines used by epidemiologists. Because of its ready availability, portability, ease of use, and versatility, WINPEPI has a considerable potential as a learning and teaching aid, both with respect to practical procedures in the planning and analysis of epidemiological studies, and with respect to important epidemiological concepts. It can also be used as an aid in the teaching of general basic statistics.
The porcine circovirus type 1 capsid gene promoter improves antigen expression and immunogenicity in a HIV-1 plasmid vaccine
Authors: Tanzer Fiona L , Shephard Enid G , Palmer Kenneth E , Burger Marieta , Williamson Anna-Lise , Rybicki Edward P
Published: February 2011

Background

One of the promising avenues for development of vaccines against Human immunodeficiency virus type 1 (HIV-1) and other human pathogens is the use of plasmid-based DNA vaccines. However, relatively large doses of plasmid must be injected for a relatively weak response. We investigated whether genome elements from Porcine circovirus type 1 (PCV-1), an apathogenic small ssDNA-containing virus, had useful expression-enhancing properties that could allow dose-sparing in a plasmid vaccine.

Results

The linearised PCV-1 genome inserted 5' of the CMV promoter in the well-characterised HIV-1 plasmid vaccine pTHgrttnC increased expression of the polyantigen up to 2-fold, and elicited 3-fold higher CTL responses in mice at 10-fold lower doses than unmodified pTHgrttnC. The PCV-1 capsid gene promoter (Pcap) alone was equally effective. Enhancing activity was traced to a putative composite host transcription factor binding site and a "Conserved Late Element" transcription-enhancing sequence previously unidentified in circoviruses.

Conclusions

We identified a novel PCV-1 genome-derived enhancer sequence that significantly increased antigen expression from plasmids in in vitro assays, and improved immunogenicity in mice of the HIV-1 subtype C vaccine plasmid, pTHgrttnC. This should allow significant dose sparing of, or increased responses to, this and other plasmid-based vaccines. We also report investigations of the potential of other circovirus-derived sequences to be similarly used.
Age-related sensitivity and pathological differences in infections by 2009 pandemic influenza A (H1N1) virus
Authors: Sun Shihui , Zhao Guangyu , Xiao Wenjun , Hu Jingya , Guo Yan , Yu Hong , Wu Xiaohong , Tan Yadi , Zhou Yusen
Published: February 2011

Background

The highly pandemic 2009 influenza A H1N1 virus infection showed distinguished skewed age distribution with majority of infection and death in children and young adults. Although previous exposure to related antigen has been proposed as an explanation, the mechanism of age protection is still unknown.

Methods

In this study, murine model of different ages were inoculated intranasally with H1N1 (A/Beijing/501/09) virus and the susceptibility and pathological response to 2009 H1N1 infection were investigated.

Results

Our results showed that the younger mice had higher mortality rate when infected with the same dose of virus and the lethal dose increased with age. Immunohistochemical staining of H1N1 antigens in mice lung indicated infection was in the lower respiratory tract. Most bronchial and bronchiolar epithelial cells in 4-week mice were infected while only a minor percentage of those cells in 6-month and 1-year old mice did. The young mice developed much more severe lung lesions and had higher virus load in lung than the two older groups of mice while older mice formed more inducible bronchus-associated lymphoid tissue in their lungs and more severe damage in spleen.

Conclusions

These results suggest that young individuals are more sensitive to H1N1 infection and have less protective immune responses than older adults. The age factor should be considered when studying the pathogenesis and transmission of influenza virus and formulating strategies on vaccination and treatment.
A brief review on molecular, genetic and imaging techniques for HCV fibrosis evaluation
Authors: Ahmad Waqar , Ijaz Bushra , Gull Sana , Asad Sultan , Khaliq Saba , Jahan Shah , Sarwar Muhammad T , Kausar Humera , Sumrin Aleena , Shahid Imran , Hassan Sajida
Published: February 2011

Background

Chronic HCV is one of the major causes of morbidity and mortality in the present day world. The assessment of disease progression not only provides useful information for diagnosis and therapeutic supervision judgment but also for monitoring disease. Different invasive and non invasive methods are applied to diagnose the disease from initial to end stage (mild fibrosis to cirrhosis). Although, liver biopsy is still considered as gold standard to identify liver histological stages, an assessment of the disease development based on non-invasive clinical findings is also emerging and this may replace the need of biopsy in near future. This review gives brief insight on non-invasive methods currently available for predicting liver fibrosis in HCV with their current pros and cons to make easier for a clinician to choose better marker to assess liver fibrosis in HCV infected patients.

Methods

More than 200 studies regarding invasive and noninvasive markers available for HCV liver disease diagnosis were thoroughly reviewed. We examined year wise results of these markers based on their sensitivity, specificity, PPV, NPV and AUROCs.

Results

We found that in all non-invasive serum markers for HCV, FibroTest, Forn's Index, Fibrometer and HepaScore have high five-year predictive value but with low AUROCs (0.60~0.85) and are not comparable to liver biopsy (AUROC = 0.97). Even though from its beginning, Fibroscan is proved to be best with high AUROCs (> 0.90) in all studies, no single noninvasive marker is able to differentiate all fibrosis stages from end stage cirrhosis. Meanwhile, specific genetic markers may not only discriminate fibrotic and cirrhotic liver but also differentiate individual fibrosis stages.

Conclusions

There is a need of marker which accurately determines the stage based on simplest routine laboratory test. Genetic marker in combination of imaging technique may be the better non invasive diagnostic method in future.
Evaluating the effects of sevelamer carbonate on cardiovascular structure and function in chronic renal impairment in Birmingham: the CRIB-PHOS randomised controlled trial
Authors: Chue Colin D , Townend Jonathan N , Steeds Richard P , Ferro Charles J
Published: February 2011

Background

Serum phosphate is an independent predictor of cardiovascular morbidity and mortality in patients with chronic kidney disease and the general population. There is accumulating evidence that phosphate promotes arterial stiffening through structural vascular alterations such as medial calcification, which are already apparent in the early stages of chronic kidney disease.

Aim

To determine the effects of phosphate binding with sevelamer carbonate on left ventricular mass and function together with arterial stiffness in patients with stage 3 chronic kidney disease.

Methods/Design

A single-centre, prospective, randomised, double-blind, placebo-controlled trial of 120 subjects with stage 3 chronic kidney disease recruited from University Hospitals Birmingham NHS Foundation Trust. Baseline investigations include transthoracic echocardiography and cardiac magnetic resonance imaging to assess ventricular mass, volumes and function, applanation tonometry to determine pulse wave velocity and pulse wave analysis as surrogate measures of arterial stiffness and dual energy x-ray absorptiometry scanning to determine bone density. During an open-label run in phase, subjects will receive 1600 mg sevelamer carbonate with meals for four weeks. They will then be randomised to either continue sevelamer carbonate or receive an identical placebo (60 subjects per arm) for the remaining 36 weeks. Four-weekly monitoring of serum electrolytes and bone biochemistry will be performed. All baseline investigations will be repeated at the end of the treatment period. The primary endpoint of the study is a reduction in left ventricular mass after 40 weeks of treatment. Secondary endpoints are: i) change in aortic compliance; ii) change in arterial stiffness; iii) change in arterial elastance; iv) change in left ventricular systolic and diastolic elastance; v) change in left ventricular function; and vi) change in bone density.

Trial Registration

This trial is registered at ClinicalTrials.gov: NCT00806481 and Current Controlled Trials: ISRCTN35254279.
Defined plant extracts can protect human cells against combined xenobiotic effects
Authors: Gasnier Céline , Laurant Claire , Decroix-Laporte Cécile , Mesnage Robin , Clair Emilie , Travert Carine , Séralini Gilles-Eric
Published: February 2011

Background

Pollutants representative of common environmental contaminants induce intracellular toxicity in human cells, which is generally amplified in combinations. We wanted to test the common pathways of intoxication and detoxification in human embryonic and liver cell lines. We used various pollutants such as Roundup residues, Bisphenol-A and Atrazine, and five precise medicinal plant extracts called Circ1, Dig1, Dig2, Sp1, and Uro1 in order to understand whether specific molecular actions took place or not.

Methods

Kidney and liver are major detoxification organs. We have studied embryonic kidney and hepatic human cell lines E293 and HepG2. The intoxication was induced on the one hand by a formulation of one of the most common herbicides worldwide, Roundup 450 GT+ (glyphosate and specific adjuvants), and on the other hand by a mixture of Bisphenol-A and Atrazine, all found in surface waters, feed and food. The prevention and curative effects of plant extracts were also measured on mitochondrial succinate dehydrogenase activity, on the entry of radiolabelled glyphosate (in Roundup) in cells, and on cytochromes P450 1A2 and 3A4 as well as glutathione-S-transferase.

Results

Clear toxicities of pollutants were observed on both cell lines at very low sub-agricultural dilutions. The prevention of such phenomena took place within 48 h with the plant extracts tested, with success rates ranging between 25-34% for the E293 intoxicated by Roundup, and surprisingly up to 71% for the HepG2. By contrast, after intoxication, no plant extract was capable of restoring E293 viability within 48 h, however, two medicinal plant combinations did restore the Bisphenol-A/Atrazine intoxicated HepG2 up to 24-28%. The analysis of underlying mechanisms revealed that plant extracts were not capable of preventing radiolabelled glyphosate from entering cells; however Dig2 did restore the CYP1A2 activity disrupted by Roundup, and had only a mild preventive effect on the CYP3A4, and no effect on the glutathione S-transferase.

Conclusions

Environmental pollutants have intracellular effects that can be prevented, or cured in part, by precise medicinal plant extracts in two human cell lines. This appears to be mediated at least in part by the cytochromes P450 modulation.
Characterization of BoHV-5 field strains circulation and report of transient specific subtype of bovine herpesvirus 5 in Argentina
Authors: Maidana Silvina S , Ladelfa María F , Pérez Sandra E , Lomónaco Patricia M , Del Médico Zajac María P , Odeón Anselmo , Viera Javier Blanco , Combessies Gustavo , Fondevila Norberto , Palacios María , Thiry Julien , Muylkens Benoît , Thiry Etienne , Romera Sonia A
Published: February 2011

Background

Bovine herpesvirus 5 (BoHV-5) is a member of the subfamilyAlphaherpesvirinaeresponsible for meningo-encephalitis in young cattle. The first case of bovine meningo-encephalitis associated with a herpesvirus infection was reported in Australia. The current geographical distribution of BoHV-5 infection is mainly restricted to South America, especially Brazil and Argentina. Outbreaks of BoHV-5 are regularly observed in Argentina suggesting the circulation of the virus in the bovine population.

Results

Seventeen field strains of BoHV-5 isolated from 1984 to now were confirmed by differential PCR and subjected to restriction endonuclease analysis (REA). Viral DNA was cleaved with BstEII which allows the differentiation among subtypes a, b and non a, non b. According to the REA with BstEII, only one field strain showed a pattern similar to the Argentinean A663 strain (prototype of BoHV-5b). All other isolates showed a clear pattern similar to the Australian N569 strain (prototype of BoHV-5a) consistent with the subtypes observed in Brazil, the other South-American country where BoHV-5 is known to be prevalent. The genomic region of subtype b responsible for the distinct pattern was determined and amplified by PCR; specifically a point mutation was identified in glycoprotein B gene, on the BstEII restriction site, which generates the profile specific of BoHV-5b.

Conclusions

This is the first report of circulation of BoHV-5a in Argentina as the prevailing subtype. Therefore the circulation of BoHV-5b was restricted to a few years in Argentina, speculating that this subtype was not able to be maintained in the bovine population. The mutation in the gB gene is associated with the difference in the restriction patterns between subtypes "a" and "b".
Carney-Complex: Multiple resections of recurrent cardiac myxoma
Authors: Bireta Christian , Popov Aron F , Schotola Hanna , Trethowan Brian , Friedrich Martin , El-Mehsen Mohamed , Schoendube Friedrich A , Tirilomis Theodor
Published: February 2011

We report a case of a female patient who was operated at the third relapse of an atrial myxoma caused by Carney complex. The difficult operation was performed without any complications despite extensive adhesions caused by the previous operations. The further inpatient course went without complications and the patient was discharged to the consecutive treatment on the 9th postoperative day. The echocardiographic finding postoperative showed no abnormalities.
Identification of BACE1 cleavage sites in human voltage-gated sodium channel beta 2 subunit
Authors: Gersbacher Manuel T , Kim Doo Yeon , Bhattacharyya Raja , Kovacs Dora M
Published: February 2011

Background

The voltage-gated sodium channel β2 subunit (Navβ2) is a physiological substrate of BACE1 (β-site APP cleaving enzyme) and γ-secretase, two proteolytic enzymes central to Alzheimer's disease pathogenesis. Previously, we have found that the processing of Navβ2 by BACE1 and γ-secretase regulates sodium channel metabolism in neuronal cells. In the current study we identified the BACE1 cleavage sites in human Navβ2.

Results

We found a major (147-148 L↓M, where ↓ indicates the cleavage site) and a minor (144145 L↓Q) BACE1 cleavage site in the extracellular domain of human Navβ2 using a cell-free BACE1 cleavage assay followed by mass spectrometry. Next, we introduced two different double mutations into the identified major BACE1 cleavage site in human Navβ2: 147LM/VI and 147LM/AA. Both mutations dramatically decreased the cleavage of human Navβ2 by endogenous BACE1 in cell-free BACE1 cleavage assays. Neither of the two mutations affected subcellular localization of Navβ2 as confirmed by confocal fluorescence microscopy and subcellular fractionation of cholesterol-rich domains. Finally, wildtype and mutated Navβ2 were expressed along BACE1 in B104 rat neuroblastoma cells. In spite of α-secretase still actively cleaving the mutant proteins, Navβ2 cleavage products decreased by ~50% in cells expressing Navβ2 (147LM/VI) and ~75% in cells expressing Navβ2 (147LM/AA) as compared to cells expressing wildtype Navβ2.

Conclusion

We identified a major (147-148 L↓M) and a minor (144-145 L↓Q) BACE1 cleavage site in human Navβ2. Our in vitro and cell-based results clearly show that the 147-148 L↓M is the major BACE1 cleavage site in human Navβ2. These findings expand our understanding of the role of BACE1 in voltage-gated sodium channel metabolism.
6-OHDA generated ROS induces DNA damage and p53- and PUMA-dependent cell death
Authors: Bernstein Alison I , Garrison Sean P , Zambetti Gerard P , O'Malley Karen L
Published: February 2011

Background

Parkinson's disease (PD) is characterized by the selective loss of dopaminergic neurons in the substantia nigra (SN), resulting in tremor, rigidity, and bradykinesia. Although the etiology is unknown, insight into the disease process comes from the dopamine (DA) derivative, 6-hydroxydopamine (6-OHDA), which produces PD-like symptoms. Studies show that 6-OHDA activates stress pathways, such as the unfolded protein response (UPR), triggers mitochondrial release of cytochrome-c, and activates caspases, such as caspase-3. Because the BH3-only protein, Puma (p53-upregulated mediator of apoptosis), is activated in response to UPR, it is thought to be a link between cell stress and apoptosis.

Results

To test the hypothesis that Puma serves such a role in 6-OHDA-mediated cell death, we compared the response of dopaminergic neurons from wild-type and Puma-null mice to 6-OHDA. Results indicate that Puma is required for 6-OHDA-induced cell death, in primary dissociated midbrain cultures as well as in vivo. In these cultures, 6-OHDA-induced DNA damage and p53 were required for 6-OHDA-induced cell death. In contrast, while 6-OHDA led to upregulation of UPR markers, loss of ATF3 did not protect against 6-OHDA.

Conclusions

Together, our results indicate that 6-OHDA-induced upregulation of Puma and cell death are independent of UPR. Instead, p53 and DNA damage repair pathways mediate 6-OHDA-induced toxicity.