bluuebunny/crossref_metadata_2025 huggingface dataset:
Interferon-Γ Release Assays for the Diagnosis and Mycobacterium Tuberculosis Infection in Children: A Systematic Review and Meta-Analysis
Authors: Chiappini E. , Accetta G. , Bonsignori F. , Boddi V. , Galli L. , Biggeri A. , De Martino M.
Published: January 2017

Data regarding the use of Interferon-gamma release assays (IGRAs) for tuberculosis diagnosis are accumulating. We systematically searched PubMed, EMBASE and Cochrane and performed pooled estimates of sensitivity and specificity of QuantiFERON-TB Gold In Tube (QFT-G-IT) and T-SPOT. TB compared to tuberculin skin test (TST). For studies assessing sensitivity, children had to have active tuberculosis. Specificity data were derived from children classified as non-infected. Eleven studies were included in the sensitivity analysis for TST, 10 for QFT-G-IT, and 9 for T-SPOT.TB. Eight studies were included in specificity analysis for TST, 8 for QFT-G-IT, and 7 for T-SPOT.TB. Pooled QFT-G-IT sensitivity was 0.79 (95%CI:0.70–0.89) pooled T-SPOT.TB sensitivity was 0.74 (95%CI:0.59–0.90) and pooled TST sensitivity was 0.82 (95%CI:0.72–0.93). Pooled QFT-G-IT and T-SPOT.TB specificities were 0.95 (95%CI:0.93–0.97) and 0.96 (95%CI:0.93–1.00), respectively. Pooled TST specificity was significantly lower 0.83 (95%CI:0.74–0.92). IGRA performance in children showed no better sensitivity than TST, but higher specificity.
Nutrition and Cancer Prevention
Authors: Tetè S. , Nicoletti M. , Saggini A. , Maccauro G. , Rosati M. , Conti F. , Cianchetti E. , Tripodi D. , Toniato E. , Fulcheri M. , Salini V. , Caraffa A. , Antinolfi P. , Frydas S. , Pandolfi F. , Conti P. , Potalivo G. , Theoharides T.C.
Published: January 2017

Cancer cells invade surrounding tissues and metastasize to distant sites. Diet high in fat is a strong link to, and perhaps causes, a high incidence of tumours. Trans-fatty acid might impair the function and it could be involved in the development of cancer. Cholesterol is also strongly suspected to be involved in the development of tumours, therefore it is important for everyone to eat well, especially for people with cancer to prevent the body tissues from breaking down and helping to rebuild the normal tissue that may have been affected by the treatments. Factors secreted by adipocytes and macrophages such as TNF-alpha and other inflammatory proteins are involved in inflammation in cancer. In addition, MCSF which up-regulates adipocyte tissue is also important for the stimulation of fat cell proliferation and is expressed by human adipocytes. Many cytokines, such as IL-1, IL-6, IL-8, IL-32, IL-33 and MCP-1, are biomarkers for cancer and chronic diseases along with transcription factors NFkB and AP-1; these last two factors are important bioactive substances on the molecular mechanism of the control of genes which in turn affect cellular metabolism. In this paper we revisit the interrelationship between cancer and metabolism.
Melatonin Protection against Burn-Induced Hepatic Injury by Down-Regulation and Nuclear Factor Kappa B Activation
Authors: Bekyarova G. , Apostolova M. , Kotzev I.
Published: January 2017

Melatonin exhibits a wide variety of biological activity including antioxidant and anti-inflammatory effects. We have previously reported its protective effect on hepatic oxidative hepatic injury in burns. In this study, we investigated the role of nuclear factor kappa B (NF-kB) in melatonin-mediated protection against liver injury by using the burned-rat model. Melatonin (N-acetyl-5-methoxytriptamin, 10mg/kg (-1), i.p.) was administered immediately and 12 hours after thermal skin injury. Hepatic NF-kB expression was determined by Western blotting. TNF-α level in liver homogenate was quantified using enzyme-linked immunosorbent assay (ELISA) kit. Plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were determined to assess liver injury at the 24th hour after burns. Thermal skin injury caused significant elevation of hepatic NF-kB expression by 48%, TNF-α level by 55% and plasma AST and ALT activities by 2- and 3-fold, respectively, in comparison with normal control rats. Treatment with melatonin decreased significantly elevated hepatic NF-kB activity and TNF-α, maintaining the levels close to the control values Melatonin suppressed the elevation of plasma AST and ALT activities (p<0.001), which remained significantly increased compared to controls. In conclusion, thermal skin injury causes hepatic NF-kB activation that may mediate the release of hepatic TNF-α and contribute to liver damage. Melatonin protects against burn-induced hepatic injury as to a certain extent this effect may result from the suppression of NF-kB-mediated inflammatory response.
Exression and PI3K/AKT Pathway in Gastric Cancer and its Blockade Suppresses Tumor Growth and Metastasis
Authors: Ye B. , Jiang L-L. , Xu H-T. , Zhou D-W. , Li Z-S.
Published: January 2017

Phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway plays a crucial role in the formation and progression of many malignancies, and has been shown to be an important therapeutic target for cancer. In the present study, human gastric adenocarcinoma tissues of different grades (N=45) were collected. The protein expression of PI3Kp85α and phosphorylated AKT (p-AKT) was evaluated immunohistochemically in the biopsy samples. PI3K/AKT pathway was blocked by constructed recombinant small hairpin RNA adenovirus vector rAd5-PI3Kp85α (rAd5-P) used to transfect into human gastric cancer SGC-7901cell line. The transfection efficiency of rAd5-P in SGC-7901 cells was observed under fluorescent microscope. The expression of PI3Kp85α, p-AKT, Ki-67 and matrix metallopeptidase-2 (MMP-2) was detected by Real-time PCR and Western blot assays. Cell proliferative activities and metastatic capabilities were determined by MTT and Transwell assays. As a consequence, the protein expression of PI3Kp85α and p-AKT was respectively observed in 80.0% and 82.2% gastric adenocarcinoma tissues, elevating with the ascending order of tumor malignancy. Targeted blockade of PI3K pathway decreased the expression of PI3Kp85α, p-AKT, Ki-67 and MMP-2, and inhibited the proliferative activities and metastatic capabilities of gastric cancer cells. In conclusion, PI3Kp85a and p-AKT were strongly expressed in gastric adenocarcinoma tissues, and targeted blockade of PI3K pathway may inhibit gastric cancer growth and metastasis through down-regulation of Ki-67 and MMP-2 expression. PI3K/AKT pathway may represent an important therapeutic target for gastric cancer.
Uptake and Silica and Carbon Nanotubes by Human Macrophages/Monocytes Induces Activation of Fibroblasts in vitro — Potential Implication for Pathogenesis of Inflammation and Fibrotic Diseases
Authors: Guo X. , Jagannath C. , Espitia M.G. , Zhou X.
Published: January 2017

The potential pathogenic effects of silica and carbon nanotubes (CNTs) on fibroblasts, macrophages/monocytes, and T cells were investigated. Human macrophage/monocytes were cultured and stimulated with silica, CNTs, or titanium particles. After adding human T cells to the stimulated macrophages/monocytes, the cells were added to cultured human fibroblasts. Upon microscopic examination, CNT stimulation after 24 hours showed centralization of macrophages/monocytes around the CNTs. Silica stimulation showed a significant increase of IL-1α and IL-1β in cultured medium, and an increased gene expression of CTGF in cultured fibroblasts at 1 hour, as well as an up-regulation of the COL1A2 gene at 24-hour time point. In addition to the same changes of IL-1α, IL-1β and the COL1A2 by silica, CNT stimulation showed an increase of IL-8 in cultured medium at 1-hour time point. Titanium stimulation yielded no significant changes. The results indicate a proinflammatory and/or profibrotic effect of silica and CNTs to cultured human cells including macrophages/monocyte, T cells and fibroblasts.
Food Allergy and the Development of Asthma Symptoms
Authors: Zicari A.M. , Indinnimeo L. , De Castro G. , Zappalà D. , Tancredi G. , Bonci E. , Celani C. , Duse M.
Published: January 2017

Allergies are multifactorial diseases the onset of which depends also on genetic and environmental factors in early life. Thus, environmental factors can affect the immune response and modify lung development, thereby leading to asthma. The role of the factors used to date to predict asthma development is modest, and clinical criteria should always be considered in association with familiarity for atopy. The aim of this study is to evaluate the risk of asthma in a population with positive Skin Prick Test (SPT) (which is a reliable marker of atopy) to food allergens, regardless of clinical manifestations in the early years of life. The cohort of children enrolled in our study who had a positive SPT to food in the first three years of life had a prevalence of asthma after 7–14 years, double that of the general pediatric population. This prevalence increased significantly in patients with SPT positivity for food and inhalant allergens. We identified a correlation between the sensitization profile in children under the age of 36 months and the development of asthma during a period of 7–14 years. This study confirms that early sensitization is an important risk factor for the development of asthma, particularly in association with sensitization to inhalants, and that the persistence of food sensitization in school-age children and adolescents is associated to more severe asthma.
Potpourri: Reflections from Husband/Wife Academic Editors
Authors: Becker William E. , Becker Suzanne R.
Published: January 2017

The authors provide a review of some of the more notable experiences they have had editing an academic journal and dealing with other editors of journals and books over the past thirty-five years. They address the use of the English language, poor scholarship, the refereeing process and the possible demise of economic education as a scholarly activity.
Kerry Farmers and the European Community: Capital Transitions in a Rural Irish Parish
Authors: Shutes Mark T.
Published: January 2017

Rural communities within the European Community (EC) will be dramatically affected by the removal of most of the remaining economic barriers at the end of 1992. Of critical importance in understanding the nature and consequences of these changes is the identification of the ways in which local farmers' productive decisions are affected by different kinds of capital input. This work examines the changes in production strategy in an Irish farming community both before and after EC membership, and shows that the differences are attributable to different forms of capital input within the farming sector of that community.
Informalization of Metropolitan Labour Forces: The Case of Irish Immigrants in the New York Construction Industry
Authors: Corcoran Mary P.
Published: January 2017

This paper discusses Sassen's model of informalization in advanced urban economies, and in particular, its application to the construction industry in New York City. The validity of the model is assessed in light of the ethnographic accounts of Irish construction workers, which deal with both the formal and informal economies within the construction sector. While the findings are generally compatible with Sassen's model, the paper concludes that greater attention needs to be paid to the role of ethnicity as an independent variable operating in the labour market.
Problems of North-South Economic Integration and Politics in Ireland: Southern Perspectives
Authors: Anderson James , Goodman James
Published: January 2017

North-South economic integration across the border in Ireland is being stimulated by wider transnational processes and European Union integration. But its meanings and extent, as elsewhere in the EU, are defined by state-centred structures and political ideologies. In Ireland, economic integration, and the lack of it, has been shaped by political Partition and the national conflict over Northern Ireland. This article discusses economic integration and politics from a Southern perspective, drawing on interviews with Dublin-based representatives of business organisations, professional associations and semi-state bodies. It mirrors earlier research in Belfast on the motivations and problems of cross-border integration, its institutional forms and future potential. Private firms, associations and other bodies have generally tried to circumvent rather than supersede North-South and national divisions. But the end result of trying to keep ‘economics’ separate from ‘politics’ is a very uneven and stunted form of integration which is sorely lacking in coherence, coordination, and accountability. It is concluded that overcoming these problems requires North-South political institutions and democratic involvement.
‘Messers, Visionaries and Organobureaucrats’: Dilemmas of Institutionalisation in the Irish Organic Farming Movement
Authors: Tovey Hilary
Published: January 2017

This paper asks what happens to ‘alternative’ social movements like the Irish organic farming movement, which try to promote sustainable forms of rural development, when they begin to be incorporated into state policy for farming and the countryside. Does this provide a context in which farming and the food industry can begin to be ‘restructured from below’, or does it lead instead to ‘deradicalisation’ of the movement and its ideas? The European literature on ‘new’ or alternative social movements has focused more on mobilisation of such movements than on processes of institutionalisation and their effects. Yet institutionalisation is often experienced by movement members themselves as a critical, even highly divisive development, which can result in severe damage to the movement's core ideology and values. The Irish case discussed here is a starting point from which we may develop a more general understanding of the increasing institutionalisation of environmentalism in the contemporary developed world.
Mycoplasma Genitalium in Non-Gonococcal Urethritis — A Study in Swedish Male STD Patients
Authors: Björnelius Eva , Lidbrink Peter , Jensen Jørgen Skov
Published: January 2017

Urethral swab specimens obtained from 101 men attending an STD clinic were examined for the presence of Mycoplasma genitalium by polymerase chain reaction (PCR) amplification. Fifty patients had non-gonococcal urethritis (NGU), and 51 patients were included as controls without urethritis. M. genitalium DNA was detected in 13 (26%) of the urethritis patients and in 5 (10%) of the control patients ( P=0.06). No patient positive for M. genitalium had a simultaneous chlamydial infection. Thus, in the 36 patients with non-chlamydial NGU, the prevalence of M. genitalium infection was 36% ( P=0.007 compared with controls). All patients with M. genitalium positive urethritis had a high grade urethritis defined as >10 polymorphonuclear cells per high power microscopical field. Compared with the control group, those with M. genitalium positive urethritis had more often had a history of urethritis than had those with chlamydial NGU or those with M. genitalium negative, non-chlamydial NGU.
Genivir (DIP-253) 1% Cream versus Placebo Cream in the Treatment of Recurrent Genital Herpes: A Double-Blind Study
Authors: Lassus A , Dahlgren A , Linnavuori K
Published: January 2017

A total of 100 heterosexual adults of either sex with frequent episodes of recurrent genital herpes were allocated to treatment with either Genivir (DIP-253) 1% cream or placebo cream. All patients had genital herpes previously verified by a positive viral culture. The study was carried out as a double-blind parallel group trial. Fifty patients were allocated to each of the two treatment groups. The treatment was initiated within 24 hours after the first sign of a recurrence, and at the pre-treatment examination all patients had developed typical lesions with blisters and/or sores. At baseline a sample for herpes virus culture and typing was obtained. The creams were applied four times daily for five days. Follow-up examinations were carried out on days 1, 2, 4 and if needed on days 7, 10 and 14. The major factor used for assessment of efficacy was the time to complete healing of all lesions. Duration of pruritus and pain were also recorded.

In the group of patients treated with Genivir cream the time to complete healing was 3.3 days and in the placebo group 6.1 days. The difference was statistically significant ( P<0.001). The mean duration of pain was 1.3 days in the Genivir group and 2.5 days in the placebo group: this difference also reached significance ( P<0.01). The duration of pruritus was about the same in both groups. The active agent in Genivir, DIP-253, is a heterocyclic aromatic complex with confirmed anti-herpetic activity and with evidence of a local immunomodulatory effect. It was concluded that the efficacy of topical application of DIP-253 may be due to combined antiviral and immunomodulatory activities.
Long-Term Preservation of Whole Blood Samples for Flow Cytometry Analysis in Normal and HIV-Infected Individuals from Africa
Authors: Lal Renu B , Hira Subhash K , Dhawan Rita R , Perine Peter L
Published: January 2017

A whole blood method requiring less than 4 ml of heparinized blood was developed to assess the practicality of preparing whole blood samples that could be easily stored, transported and readily used to determine the lymphocyte phenotypes and proliferation responses of individuals from remote areas who are infected with the human immunodeficiency virus. Minor modifications in standard whole blood procedure for lymphocyte phenotyping have significantly increased the stability of light scatter and fluorescence intensity of the cells for subsequent flow cytometry (FC) analysis. These changes include removal of lysis solution prior to fixation, fixation of monoclonal antibody-stained cells in 1% paraformaldehyde for 30 minutes and storage of fixed samples in medium containing 1% bovine serum albumin. Lymphocyte subsets and their functional subsets could reliably be determined on samples stored for up to 4 weeks. Further, blood samples could be kept at room temperature for up to 96 hours or at ambient temperature during transportation from Africa before staining for FC without affecting their quantitation. While samples could be processed for FC analysis under field-laboratory conditions, proliferation assays could only be performed on samples that were transported within 48 hours of their collection. The whole blood method saves time and expense and decreases the volumes of blood required to perform phenotypic analysis and functional assays on specimens collected in remote areas.
AIDS Education in Rural Uganda—A Way Forward
Authors: Anderson S R , Bainbridge J W B , Shah A , El-Jassar P , Schofield G , Brook H D D , Kapila M
Published: January 2017

A survey of acquired immunodeficiency syndrome (AIDS)-related knowledge and attitudes was conducted during July and August 1988 in rural SW Uganda. The aim was to assess the impact of Uganda's AIDS education programme and to consider how future programmes could be more effectively implemented. Four hundred and seventy-six individuals aged 12–45 years were selected by a quota method, to form a sample stratified by age and sex.

Mass AIDS education has successfully raised levels of knowledge but misconceptions persist. However, it has failed, firstly, to stress the urgency of AIDS as a personal issue, and secondly, to change negative attitudes toward people with AIDS: 57% would avoid or stigmatise an individual with AIDS. Unexpectedly findings show that a correlation exists ( P<0.05) between high levels of ‘correct’ beliefs and negative attitudes toward people with AIDS. To achieve future behavioural and attitude changes, possible ways forward for Ugandan AIDS education include involvement of HIV carriers in education, small-scale targetted approaches developed by active participation of the target group and through role playing of people with AIDS.
Is Coexisting Chlamydial Infection More Common in Gonococcal Infections with Serogroup WI?
Authors: McKenna J G , Young H , Moyes A , Smith I W
Published: January 2017

Over a 4-year period a total of 8974 women were screened for Neisseria gonorrhoeae and Chlamydia trachomatis. There were 489 cases of cervical gonorrhoea, 261 serogroup WI and 228 serogroup WII/III. A total of 169 (34.6%) cases had a dual infection with C. trachomatis, 92 from the WI serogroup and 77 from the WII/III. Using Fisher's exact test, no statistically significant difference was observed in the rates of chlamydial carriage between the two serogroups ( P=0.39). These findings are at odds with previously reported data, which suggested a biological interaction resulting in a positive correlation between colonization with serogroup WI and C. trachomatis. Possible reasons for the difference between the findings are discussed.
CD4 Lymphocyte Numbers after Splenectomy in Patients Infected with the Human Immunodeficiency virus
Authors: Fairley Christopher K , Spelman Denis , Street Alison , Jennens Ian D , Spicer W John , Crowe Suzanne
Published: January 2017

Splenectomy has been reported to alter inconsistently the CD4 lymphocyte numbers in patients infected with the human immunodeficiency virus (HIV). To further assess the effect of splenectomy we have retrospectively examined the charts of 10 patients who were infected with HIV and who had undergone splenectomy. There was a significant increase in the mean CD4 numbers following splenectomy (mean increase of 326/μl, or 2.1-fold, P = 0.0009), the total lymphocyte numbers (mean increase of 1.55/ml, or 2.2-fold, P = 0.001) and in the CD8 lymphocyte count (mean increase of 968/μl, or 2.3–fold, P = 0.014). No significant difference was observed in the percentage CD4 lymphocytes ( P = 0.95) or in the CD4:CD8 lymphocyte ratio ( P = 0.76).

In two patients, symptoms suggestive of impaired immune function developed post-splenectomy, at a time when their CD4 lymphocyte numbers were markedly higher than their pre-splenectomy values. One developed oral candidiasis (CD4 960/μl, percentage CD4 32%), and in one patient a 7 kg weight loss was associated with recurrent mouth ulcers (CD4 680/μl, percentage CD4 7%).

We conclude that the total CD4 count increases significantly after splenectomy while the percentage CD4 lymphocyte count and CD4:CD8 lymphocyte ratio do not. Our data suggest that the CD4 lymphocyte count overestimates the immune function in these patients, although our findings are not conclusive.
Cervical Intraepithelial Neoplasia and Human Papillomavirus Infection among Senegalese Women Seropositive for HIV-1 or HIV-2 or Seronegative for HIV
Authors: Seek Awa Coll , Faye Mama Awa , Critchlow Cathy W , Mbaye Adia Diack , Kuypers Jane , Woto-Gaye Giselle , Langley Carol , De Elisabeth Benga , Holmes King K , Kiviat Nancy B
Published: January 2017

Studies in various regions of the world have shown that women infected with HIV-1 are at increased risk for cervical human papillomavirus (HPV) infection as well as for cervical cancer precursor lesions. HIV infection and cervical cancer are both widespread in West Africa, but little is known about the relationship between HPV and HIV-2, which is the predominant type of HIV in the general population of many West African countries. To address this issue, we collected cervical samples for cytology and HPV analysis from 93 women presenting to the University of Dakar Infectious Disease Service (18 women with HIV-1 infection, 17 with HIV-2 infection, and 58 HIV seronegative controls). Compared to those without HIV infection, HIV seropositive women were 13.1 (95% CI = 2.4, 128) and 11.0 (95% CI = 3.5, 35.8) times more likely to have HPV detected using Southern transfer hybridization (STH) and the polymerase chain reaction (PCR) respectively. Detection of high and intermediate risk HPV types were significantly associated with HIV-1 and HIV-2 infection. Among HPV positive women, those with, as compared to those without HIV infection were more likely to harbour high risk HPV types (OR = 9.2, 95% CI = 0.97, 433). HIV-1 and HIV-2 seropositive women were 23.3 (95% CI = 2.9, 209) and 9.3 (95% CI = 1.1, 79) times more likely to have a cytological diagnosis of dysplasia, respectively, than were HIV seronegative women. Biopsy-proven CIN 3 was found in one woman with HIV-1 and invasive cancer was found in one woman with HIV-2. It remains to be seen whether HIV-1 and HIV-2 will confer similar risks of development of CIN 2–3 and potentially of invasive cervical cancer.
Evaluation of a Safe-Sex Intervention Programme among Sex Workers in Singapore
Authors: Archibald C P , Chan R K W , Wong M L , Goh A , Goh C L
Published: January 2017

The purpose of this study was to evaluate the effects of a brief intervention programme on STD knowledge, condom use and gonorrhoea incidence among sex workers in Singapore. A controlled before-and-after study design with non-random assignment of sex workers was used, supplemented by multivariate analysis to adjust for baseline differences. Control ( n = 221, denoted C1) and experimental ( n = 221, denoted E1) groups were interviewed on 2 occasions 3 months apart. Two supplementary groups were interviewed once each at the end of the 3-month period ( n = 145 who had received the intervention and n = 151 who had not). Basic knowledge of STD symptoms and HIV transmission was high in all groups. There were misconceptions about casual transmission of HIV which improved dramatically at the second interview for group El (from 37–56% correct responses to 82–90%). Overall condom use was high (about 75%) and did not change after the intervention. Gonorrhoea rates were correspondingly low (0.4 episodes/worker/year) and also did not change. This brief intervention improved the STD knowledge of sex workers. However, behaviour as measured by reported condom use and gonorrhoea incidence did not change. Implications for future intervention programmes are discussed.
Prostanoid production in endothelial and Kupffer liver cells from monocrotaline intoxicated rats
Authors: Lemberg Abraham , Calabrese Graciela , Majowicz Mónica , Peredo Horacio , Scorticati Camila , Filinger Esther , Perazzo Juan Carlos
Published: January 2017

A single dose of monocrotaline, a pyrrolizidine alkaloid, was injected into rats in order to produce 25 (Group I) and 45 (Group II) days later a progressive and so called delayed liver injury. The present study investigated the prostanoid production of Kupffer cells and endothelial cells separated from Monocrotaline and saline (Group III) injected rat livers. Kupffer cells: formation of 6 keto Prostaglandin F1a, the major prostacyclin metabolite, gradually decreased in Groups I vs II (P50.01) and in both Groups I and II vs Controls (P50.01). In addition Prostaglandin F2a showed a significant increase in Groups I and II when compared to Group III, (P50.001), and Thromboxane B2 was present in both Groups of Monocrotaline treated animals, while it was not detectable in the control Group III. Endothelial cells:6ketoProstaglandin F1a decreased in Groups I vs II. This differences was significant when compared, and compared to controls (Group III, P50.001). Prostaglandin E2 was detected only in Groups I and II. Prostaglandin F2a and Thromboxane B2 could not be detected in any Group. Ultramicroscopy showed morphological cell damage in nonparenchymal cells in Monocrotaline intoxication in Group II, rats sacrified 45 days after the injection, while it shows normal features in those treated animals sacrified 25 days after the injection, as well as in control group. Conclusion: Asingle Monocrotaline injection produces, 25 and 45 days later, severe and progressive alterations in the prostanoid production in Kupffer and Endothelial cells, while ultramicroscopic alterations was only observed 45 days after the injection of Monocrotaline. A decreased production of vasodilators and the presence of vasoconstrictor prostanoids that can participate in the production of the circulatory derangements enhancing liver injury and portal hypertension were also observed.
Aspirin® and heparin prevent hepatic blood stasis and thrombosis induced by the toxic glycoprotein Bolesatine in mice
Authors: Ennamany R , Bingen A , Creppy E E , Kretz O , Gut J P , Dubuisson L , Balabaud C , Sage P Bioulac , Kirn A
Published: January 2017

Bolesatine is a toxic glycoprotein isolated from Boletus satanas Lenz, which inhibits protein synthesis in vivo and in vitro. The LD50 (24 h) is 1 mg /kg bw (i.p.), in mice and rats. When given i.p. to mice (0.1 - 1.0 mg/kg bw) bolesatine induced thrombi and blood stasis in the liver, 5 - 21 h after injection, and modifications of the number of blood corpuscles in peripheral blood. These effects were efficiently reversed by aspirin, ticlopidin and heparin (as attested by histology and electron microscopy) which however failed to prevent death in animals given lethal doses. Together, these results showed that the death of bolesatine poisoned animals given high doses, was rather due to a combination of thrombosis and other toxic effects. In addition, they suggest that these antithrombotic drugs may overcome cases of human poisoning, with low exposures of this boletus, showing a hypertension probably due to mechanical obstruction which resists normal therapy.
Statistical research needs in mechanistic modelling for carcinogenic risk assessment
Authors: Portier Christopher , El Masri Hisham
Published: January 2017

If the broad spectrum of mechanistic research conducted on an environmental carcinogen is to be used in quantifying cancer risks, statisticians must play a key role. Statistical methods are critically needed for a scientifically valid analysis of a complicated series of linked experimental findings. This will require a greater understanding of the underlying biology than is common in statistical consulting, aiding in the development of complicated mechanistically based mathematical descriptions of mean response and in the creation of statistical methods for the estimation of model parameters (e.g. likelihoods) able to use both the underlying model and much of the available data.
Optimal statistical design for toxicokinetic studies
Authors: Beatty D A , Piegorsch W W
Published: January 2017

Optimal statistical design strategies are applied to toxicokinetic experiments, for determining proper allocations of subjects and/or spacings of sampling times under a variety of nonlinear concentration-time models. The strategies include: (i) optimal allocations of subjects assuming the placement of time points is fixed, (ii) optimal spacing of design time points while assuming an equal allocation of subjects per time points and (iii) allocations/time-point spacings optimized jointly. Emphasis is placed on the first case, where a variance-minimization method is illustrated for optimizing the allocations when estimating specific toxicokinetic parameters. Appeals to forms of D -optimality are also considered, for cases when no specific toxicokinetic parameter is of specialized interest.
Sound-Propagation Curves in Industrial Workrooms: Statistical Trends and Empirical Prediction Models
Authors: Hodgson Murray
Published: January 2017

Predictions of workroom noise levels are based on predictions of the workroom sound-propagation curve, SP( r) – the variation with distance r from an omnidirectional point source of the sound-pressure level Lp ( r) minus the source sound-power level Lw SP( r) = Lp ( r)- Lw. While more accurate approaches such as ray tracing exist, from a practical point of view there is considerable scope for developing simple empirical prediction methods. In fact, several such models exist. However, these have short-comings which warrant the development of a new model. The approach taken here was to predict the slope(s) and absolute level(s) of the sound-propagation curve, approximated by one or more straight-line segments. With this in mind, octave-band sound-propagation measurements were made in a number of empty and fitted workrooms. The curves were approximated by one or two straight-line segments. The intercepts and slopes of the segments were then determined, and their averages and standard deviations calculated. The statistical trends provide information on the behaviour of sound in industrial workrooms. The results are used to develop simple empirical prediction models.
Combinations of drugs
Authors: Kappos Ludwig
Published: January 2017

As a result of recent therapeutic trials, recombinant Interferon beta (r/FNβ)-1b and-1a as well as Copolymer 1 (COP 1) and to some extent unspecific immunosuppressants have been accepted as partially efficient treatments of relapsing-remitting MS. In view of partially effective single treatments, the question arises if combination of two or even more agents could improve efficacy without increasing side effects. The theoretical background of possible combinations is discussed. The selection of combination partners should be based on their proven efficacy as Singh treatment, on their mode of action and their distinct target in the pathogenetic cascade of events and on their specific side effect prof ile. Combination regimens selected in this way should undergo evaluation in short term early phase II studies and if the results are positive enter phase III studies. The use of surrogate markers (especially MRI-findings) may help to accelerate this process. Combinations that could enter phase II and III studies in the near future are r/FNβ with unspecific immunosuppressants, e.g. Azathioprine or Methotrexate and r/FNβ with COP I. Combinations including agents just entering phase I and II studies as a single treatment may be more promising for the future.
Telemedicine in Rural Areas. Experience with Medical Desktop-Conferencing via Satellite
Authors: Ricke J , Kleinholz L , Hosten N , Zendel W , Lemke A , Wielgus W , Vöge K H , Fleck E , Marciniak R , Felix R
Published: January 2017

Cooperation between physicians in hospitals in rural areas can be assisted by desktop-conferencing using a satellite link. For six weeks, medical desktop-conferencing was tested during daily clinical conferences between the Virchow-Klinikum, Berlin, and the Medical Academy, Wroclaw. The communications link was provided by the German Telekom satellite system MCS, which allowed temporary connections to be established on demand by manual dialling. Standard hardware and software were used for videoconferencing, as well as software for medical communication developed in the BERMED project. Digital data, such as computed tomography or magnetic resonance images, were transmitted by a digital data channel in parallel to the transmission of analogue video and audio signals. For conferences involving large groups of people, hardware modifications were required. These included the installation of a video projector, adaptation of the audio system with improved echo cancellation, and installation of extra microphones. Learning to use an unfamiliar communication medium proved to be uncomplicated for the participating physicians.
Genetically Modified Crops in the United States: Federal Regulation and State Tort Liability
Authors: Grossman Margaret Rosso
Published: January 2017

This article first discusses some benefits and risks of agricultural crops developed through biotechnology and then outlines the complex US regulatory scheme for genetically modified crops. The article then analyses nuisance, trespass, negligence, and strict liability as possible tort law remedies for damage caused by these crops.
Behind Closed Doors: The Use of Agreements in the UK to Protect the Environment
Authors: Ross Andrea , Rowan-Robinson Jeremy
Published: January 2017

The wider use of consensual rather than regulatory instruments for securing environmental protection and the wider use of public access to information and public participation in decision-making are both aspects of the drive to promote shared responsibility for the environment. The question addressed here is whether these different approaches to promoting shared responsibility are compatible with each other. The question is tested by reference to the use of agreements to secure environmental goals. The authors conclude that both legislation and practice with regard to the use of agreements make no more than limited provision for access to information and public participation. They argue that this need not be so and indicate how the position could be improved.
Successful Coil Embolization for a “Three-Hump” Internal Carotid Artery Anterior Wall Aneurysm
Authors: Fukushima Y. , Miyasaka Y. , Takagi H. , Kurata A. , Suzuki S. , Fujii K.
Published: January 2017

We describe an unusually shaped aneurysm arising from the anterior wall of the internal carotid artery (ICA) that was treated successfully with Guglielmi detachable coils (GDCs). A 38-year-old woman presented with sudden onset of headache and was transferred to our hospital. Computed tomography revealed thin subarachnoid hemorrhage in the basal cisterns. Three-dimensional rotational angiography clearly showed a “three-hump” anterior wall aneurysm of the ICA. The two distal humps of the aneurysm were successfully obliterated with GDCs, but the proximal hump was too small to treat by coil embolization. The patient was discharged without neurological deficit. Anterior wall (blister-like) aneurysms of the ICA have a high risk of rupture due to fragility of the wall. These aneurysms are considered difficult to manage by traditional surgical approaches. Our experience suggests that endovascular GDC embolization is a good alternative treatment modality for patients with such an aneurysm.
Inflammatory Markers: Serum Amyloid A, Fibrinogen and C-Reactive Protein — A Revisited Study
Authors: Salini V. , Saggini A. , Maccauro G. , Caraffa A. , Shaik-Dasthagirisaheb Y.B. , Conti P.
Published: January 2017

The acute phase response is the part of the innate defence system of an animal against trauma, inflammation or infection. During this response, there is increased production and release of certain plasma proteins known as acute phase proteins, which include C-reactive protein (CRP), serum amyloid A (SAA) and fibrinogen (Fg). CRP consists of five identical subunits of 206 amino acids with a molecular weight of approximately 23 kDa. There is strong evidence from numerous studies that CRP is a predictor of inflammation. The acute-phase protein serum amyloid A (SAA) is a clinically useful marker of inflammation. SAA plays not only an important role in the development of AA amyloidosis (an important complication of rheumatoid arthritis) but also interacts with events closely involved in the metabolic syndrome as a high- and low-grade inflammatory modulator. Fibrinogen (Fg) is a high molecular weight plasma adhesion protein and is a biomarker of inflammation. It is synthesized and assembled in hepatocytes and fibroblasts and when secreted into the circulation, its plasma half-life ranges from 3 to 4 days. Several cytokines, are involved in the induction of acute phase protein synthesis, but the mutual importance of these cytokines seems to be cell-type specific and to vary in various experimental settings. Here we revisited the classic acute phase proteins SAA, C-Reactive protein and fibrinogen in their role in inflammation and their interrelationship with some cytokines.
What You Should Know about Escherichia Coli Infection
Authors: Saggini A. , Anogeianaki A. , Maccauro G. , Teté S. , Salini V. , Caraffa A. , Conti P. , Shaik-Dasthagirisaheb Y.B.
Published: January 2017

As in Northern Germany there have recently been several deaths caused by Escherichia coli (E.coli), we decided to revisit the effects of E.coli infection. Since this bacteria is the most numerous facultative and aerobic germ in the human intestine, we would like to warn the population of its pathogenicity. In fact, E.coli can be pathogenic both in humans and in animals and can start an inflammatory process, activating some factors of the cell nucleus such as NFkB, with the consequent production of cytokines. E.coli can appear in several strains and can be very aggressive and can contaminate food, water and the environment, causing severe disease, and in some cases death.
In Vitro Studies of the Immunomodulatory Effects of Statins Alone and in Combination with Immunosuppressive Drugs
Authors: Guillén D. , Millán O. , Brunet M.
Published: January 2017

The effects of statins go beyond their lipid-lowering properties and include immunomodulatory and anti-inflammatory effects. Unfortunately, there is a lack of in vitro assays that study the immunomodulatory effect of statins at therapeutic concentrations and the possible synergism with immunosuppressive drugs. Besides, they are mostly evaluated on isolated peripheral blood mononuclear cells instead of using whole blood as a matrix. The aim of this study is to perform in vitro experiments to evaluate the effect of atorvastatin, simvastatin and fluvastatin at therapeutic concentrations alone and in combination with everolimus or tacrolimus on immunosuppressive response, using whole blood as a matrix by investigating lymphocyte proliferation and production of the soluble cytokines interleukin (IL)-2, IL-10 and interferon (IFN)-γ. Statins (0.1 μM) inhibited T cell proliferation by 12–16% in a dose-dependent manner and when statins at 0.1 μM were combined with each immunosuppressive drug at 8 ng/ml, inhibition increased by 6–9% (p<0.05) for everolimus and 8–15% (p<0.05) for tacrolimus, but not for atorvastatin. At a dose of 0.1 μM, all three statins inhibited soluble IFN-γ production by approximately 5–9% (p<0.02). IL-2 and IL-10 production were unaltered by the presence of statins. These findings suggest that statins seem to exert a mild anti-inflammatory effect that might potentially be used to treat autoimmune diseases.
The Effects of Interferon-α2b on Intestinal Flora in Peritoneal Fibrosis
Authors: Binici D.N. , Güneş N. , Kayataş K. , Pişkinpaşa N.
Published: January 2017

Peritonitis is an important cause of the mortality and morbidity of peritoneal dialysis patients. The present study aims to investigate the effects of ýnterferon (IFN)-α2b on intestinal flora in peritoneal fibrosis. Twenty-four Wistar albino rats were divided into three groups. The control group received 0.9% saline (3 ml/d) intraperitoneally; the Chlorhexidine gluconate (CH) group received 3 ml daily injections of 0.1% CH intraperitoneally; the CH+IFN group received 3 ml daily injections of 0.1% CH intraperitoneally and pegylated IFN-α2b 1.5 μg/kg per week subcutaneously on days 0, 7, 14. On the twenty-first day rats were sacrificed and visseral peritoneum samples were obtained from the liver. Blood samples were obtained from the abdominal aorta and intestinal flora samples were obtained from distal small intestine and transverse colon. Histopathologic control of CH, CH+IFN groups peritoneal thickness were 6.04±2.32, 135.4±22.24, and 42.56±11.6 um, respectively. The decrease in thickness of parietal peritoneum in the CH+IFN group was statistically significant when compared to the CH group. Escherechia coli (E. Coli) had grown in cultures of the small intestine and colon samples of all the rats in the control group, whereas Proteus species (spp) had grown in one and Enterobacter spp. in seven cultures of the CH group. E. Coli had grown in four cultures, Proteus spp in three culture and Enterobacter spp. in one culture obtained from small intestine and transverse colon of the control group. The intestinal flora changed as the peritoneal thickness increased. The intestinal flora in the CH group completely changed compared with the control group (p<0.001). There was no correlation between visceral peritoneal thickness and intestinal flora change in the IFN group (p>0.05). IFN-α2b recovers the intestinal flora and the intestinal motility, thus reducing the experimental peritoneal fibrosis.
Prediction of Allergy by Total Serum IgE Measurements in Infancy: A 10-Year Follow-up
Authors: Ciprandi G. , De Amici M. , Quaglini S. , Concaro S. , Cerra C. , Carugno B. , Bosio M. , Marseglia G.L. , Spinillo A. , Stronati M. , Moratti R. ,   Workgroup “Allergy Project”
Published: January 2017

Asthma, allergic rhinitis and atopic dermatitis are multifactorial disorders influenced by various familial and environmental factors. Cord blood IgE levels may be predictive for subsequent allergy onset. Serum IgE assessment has been rarely investigated. This study is aimed at evaluating serum IgE levels during the first year of life and relating to subsequent allergies. Total serum IgE levels were assessed in 102 newborns in the first days of life (2–3) and then again at 3, 5, 6, 11 and 12 months of age. After ten years, paediatricians and general practitioners caring for these children were tracked through the Local Healthcare Agency (LHA) database and asked about possible allergy of their patients, including transient ones. F Serum IgE increased in allergic infants at 1 year of life. The predictive model was significant. In conclusion, this study demonstrates that serum IgE may be predictive of subsequent allergy onset, preferably if assessed at 1 year of age.
Who is blinded in randomized clinical trials? A study of 200 trials and a survey of authors
Authors: Haahr Mette Thorlund , Hróbjartsson Asbjørn
Published: January 2017

Background Insufficient blinding of persons involved in randomized clinical trials is associated with bias. The appraisal of the risk of bias is difficult without adequate information in trial reports.

Purpose We wanted to study how blinding is reported in clinical trials and how lack of reporting relate to lack of blinding.

Methods A cohort study of 200 blinded randomized clinical trials published in 2001 randomly sampled from the Cochrane Central Register of Controlled Trials, and a questionnaire survey of the trial authors.

Results One-hundred and fifty-six (78%) articles described trials as ‘double blind’. In three (2%) of such articles the blinding status of patients, health care providers and data collectors was explicitly described. Eighty-eight (56%) articles did not describe the blinding status of any trial person, and 41 articles (26%) reported no blinding relevant information at all beyond the trial being ‘double blind’. One-hundred and thirty (65%) surveyed authors responded. Patients were blinded in 101 (97%) ‘double blind’ trials, and health care providers in 93 (89%). Twenty (19%) ‘double blind’ trials had not blinded either patients, health care providers or data collectors. Survey responders provided 15 different operational meanings of the term ‘double blind’, and typically felt that their preferred definition was the most widely used.

Limitations The proportions in the author survey may be too optimistic due to reporting bias. It is not known how the increased use of the CONSORT guidelines may have afffected reporting in years after 2001.

Conclusions The blinding status of key trial persons was incompletely reported in most randomized clinical trials. Unreported blinding may be frequent, but one of five ‘double blind’ trials did not blind either patients, treatment providers or data collectors. Authors, referees, and journal editors could improve the completeness of reporting of blinding, eg, by adhering to the CONSORT statement. It is inappropriate to presume blinding of key trial persons based only on the ambiguous term ‘double blind’.