Carrier-bound Methotrexate. III.‡ Antiproliferative Activity of Macromolecular MTX Conjugates Against the Human HeLa and Colo Carcinoma Cell Lines

In continuation of studies in these laboratories aiming at the bioevaluation of macromolecular anticancer drug models, in vitro cytotoxicity screens are performed on several series of water-soluble polymer-methotrexate  conjugates. The methotrexate drug in these conjugates is bound through amide or ester linkages to water- soluble polyamide- or polyamidoamine-type carriers by previously developed anchoring techniques.Tests were  conducted against the HeLahumancervical carcinoma cell line generally considered to be drug-sensitive, and  against two variants of the rather refractory Colo 320 DM, a human colon adenocarcinoma line.KEYWORDS: Drug conjugation, Colo cell line, HeLa cell line, methotrexate, polyaspartamide,  polyamidoamine

Use of a porous membrane for gas bubble removal in microfluidic channels: physical mechanisms and design criteria

We demonstrate and explain a simple and efficient way to remove gas bubbles from liquid-filled microchannels, by integrating a hydrophobic porous membrane on top of the microchannel. A prototype chip is manufactured in hard, transparent polymer with the ability to completely filter gas plugs out of a segmented flow at rates up to 7.4 microliter/s per mm2 of membrane area. The device involves a bubble generation section and a gas removal section. In the bubble generation section, a T-junction is used to generate a train of gas plugs into a water stream. These gas plugs are then transported towards the gas removal section, where they slide along a hydrophobic membrane until complete removal. The system has been successfully modeled and four necessary operating criteria have been determined to achieve a complete separation of the gas from the liquid. The first criterion is that the bubble length needs to be larger than the channel diameter. The second criterion is that the gas plug should stay on the membrane for a time sufficient to transport all the gas through the membrane. The third criterion is that the gas plug travel speed should be lower than a critical value: otherwise a stable liquid film between the bubble and the membrane prevents mass transfer. The fourth criterion is that the pressure difference across the membrane should not be larger than the Laplace pressure to prevent water from leaking through the membrane

From regional pulse vaccination to global disease eradication: insights from a mathematical model of Poliomyelitis

Mass-vaccination campaigns are an important strategy in the global fight against poliomyelitis and measles. The large-scale logistics required for these mass immunisation campaigns magnifies the need for research into the effectiveness and optimal deployment of pulse vaccination. In order to better understand this control strategy, we propose a mathematical model accounting for the disease dynamics in connected regions, incorporating seasonality, environmental reservoirs and independent periodic pulse vaccination schedules in each region. The effective reproduction number, $R_e$, is defined and proved to be a global threshold for persistence of the disease. Analytical and numerical calculations show the importance of synchronising the pulse vaccinations in connected regions and the timing of the pulses with respect to the pathogen circulation seasonality. Our results indicate that it may be crucial for mass-vaccination programs, such as national immunisation days, to be synchronised across different regions. In addition, simulations show that a migration imbalance can increase $R_e$ and alter how pulse vaccination should be optimally distributed among the patches, similar to results found with constant-rate vaccination. Furthermore, contrary to the case of constant-rate vaccination, the fraction of environmental transmission affects the value of $R_e$ when pulse vaccination is present.Comment: Added section 6.1, made other revisions, changed titl

Family Belongingness Attenuates Entrapment and Buffers Its Association with Suicidal Ideation in a Sample of Dutch Sexual Minority Emerging Adults

Sexual minority emerging adults are more likely to engage in suicidal ideation than their heterosexual counterparts. Experiences of homophobic violence are associated with suicidal ideation. Yet, the specific mechanisms linking homophobic violence to suicidal ideation remain unclear. Entrapment and social belongingness were tested to determine their relevance for understanding the link between homophobic violence and suicidal ideation. A sample of sexual minority Dutch emerging adults (N = 675; ages 18–29, M = 21.93 years, SD = 3.20) were recruited through online platforms and flyers. Homophobic violence was expected to be positively associated with suicidal ideation and entrapment. The association between homophobic violence and suicidal ideation was expected to be indirectly linked through entrapment. We explored whether various sources of social belongingness moderated the path between entrapment and suicidal ideation and whether those sources of social belongingness moderated the indirect effect of homophobic violence on suicidal ideation through entrapment. Results showed that homophobic violence and entrapment were positively associated with suicidal ideation and that family belongingness was negatively associated with suicidal ideation. Homophobic violence and suicidal ideation were not indirectly linked through entrapment. The interaction effect between entrapment and family belongingness was significant, suggesting that, on average, the effect of entrapment on suicidal ideation decreased when family belongingness was high. These results suggest that family belongingness may reduce the association between entrapment and suicidal ideation while adjusting for homophonic violence. Reducing entrapment and improving family belongingness may be useful targets for programs aimed at preventing suicidal ideation among sexual minority emerging adults

Local host response following an intramammary challenge with Staphylococcus fleurettii and different strains of Staphylococcus chromogenes in dairy heifers

Coagulase-negative staphylococci (CNS) are a common cause of subclinical mastitis in dairy cattle. The CNS inhabit various ecological habitats, ranging between the environment and the host. In order to obtain a better insight into the host response, an experimental infection was carried out in eight healthy heifers in mid-lactation with three different CNS strains: a Staphylococcus fleurettii strain originating from sawdust bedding, an intramammary Staphylococcus chromogenes strain originating from a persistent intramammary infection (S. chromogenes IM) and a S. chromogenes strain isolated from a heifer's teat apex (S. chromogenes TA). Each heifer was inoculated in the mammary gland with 1.0 x 10(6) colony forming units of each bacterial strain (one strain per udder quarter), whereas the remaining quarter was infused with phosphate-buffered saline. Overall, the CNS evoked a mild local host response. The somatic cell count increased in all S. fleurettii-inoculated quarters, although the strain was eliminated within 12 h. The two S. chromogenes strains were shed in larger numbers for a longer period. Bacterial and somatic cell counts, as well as neutrophil responses, were higher after inoculation with S. chromogenes IM than with S. chromogenes TA. In conclusion, these results suggest that S. chromogenes might be better adapted to the mammary gland than S. fleurettii. Furthermore, not all S. chromogenes strains induce the same local host response

Exponential dichotomies of evolution operators in Banach spaces

This paper considers three dichotomy concepts (exponential dichotomy, uniform exponential dichotomy and strong exponential dichotomy) in the general context of non-invertible evolution operators in Banach spaces. Connections between these concepts are illustrated. Using the notion of Green function, we give necessary conditions and sufficient ones for strong exponential dichotomy. Some illustrative examples are presented to prove that the converse of some implication type theorems are not valid

A latent trait approach to measuring HIV/AIDS related stigma in healthcare professionals: application of mokken scaling technique

The attitudes of healthcare professionals towards HIV positive patients and high risk groups are central to the quality of care and therefore to the management of HIV/AIDS related stigma in health settings. Extant HIV/AIDS stigma scales that measure stigmatising attitudes towards people living with HIV/AIDS have been developed using scaling techniques such as principal component analysis. This approach has resulted in instruments that are often long. Mokken scale analysis is a nonparametric hierarchical scaling technique that can be used to develop unidimensional cumulative scales. This technique is advantageous over the other approaches; as the scales are usually shorter, while retaining acceptable psychometric properties. Moreover, Mokken scales also make no distributional assumptions about the underlying data, other than that the data are capable of being ordered by item and by person. In this study we aimed at developing a precise and concise measure of HIV/AIDS related stigma among health care professionals, using Mokken scale analysis

HIV Infection among Men Who Have Sex with Men in Kampala, Uganda–A Respondent Driven Sampling Survey

Uganda's generalized HIV epidemic is well described, including an estimated adult male HIV prevalence in Kampala of 4.5%, but no data are available on the prevalence of and risk factors for HIV infection among men who have sex with men (MSM).From May 2008 to February 2009, we used respondent-driven sampling to recruit MSM ≥18 years old in Kampala who reported anal sex with another man in the previous three months. We collected demographic and HIV-related behavioral data through audio computer-assisted self-administered interviews. Laboratory testing included biomarkers for HIV and other sexually transmitted infections. We obtained population estimates adjusted for the non-random sampling frame using RDSAT and STATA. 300 MSM were surveyed over 11 waves; median age was 25 years (interquartile range, 21-29 years). Overall HIV prevalence was 13.7% (95% confidence interval [CI] 7.9%-20.1%), and was higher among MSM ≥25 years (22.4%) than among MSM aged 18-24 years (3.9%, odds ratio [OR] 5.69, 95% CI 2.02-16.02). In multivariate analysis, MSM ≥25 years (adjusted OR [aOR] 4.32, 95% CI 1.33-13.98) and those reporting ever having been exposed to homophobic abuse (verbal, moral, sexual, or physical abuse; aOR 5.38, 95% CI 1.95-14.79) were significantly more likely to be HIV infected.MSM in Kampala are at substantially higher risk for HIV than the general adult male population. MSM reporting a lifetime history of homophobic abuse are at increased risk of being HIV infected. Legal challenges and stigma must be overcome to provide access to tailored HIV prevention and care services

Definitions, Criteria and Global Classification of Mast Cell Disorders with Special Reference to Mast Cell Activation Syndromes: A Consensus Proposal

Activation of tissue mast cells (MCs) and their abnormal growth and accumulation in various organs are typically found in primary MC disorders also referred to as mastocytosis. However, increasing numbers of patients are now being informed that their clinical findings are due to MC activation (MCA) that is neither associated with mastocytosis nor with a defined allergic or inflammatory reaction. In other patients with MCA, MCs appear to be clonal cells, but criteria for diagnosing mastocytosis are not met. A working conference was organized in 2010 with the aim to define criteria for diagnosing MCA and related disorders, and to propose a global unifying classification of all MC disorders and pathologic MC reactions. This classification includes three types of `MCA syndromes' (MCASs), namely primary MCAS, secondary MCAS and idiopathic MCAS. MCA is now defined by robust and generally applicable criteria, including (1) typical clinical symptoms, (2) a substantial transient increase in serum total tryptase level or an increase in other MC-derived mediators, such as histamine or prostaglandin D 2, or their urinary metabolites, and (3) a response of clinical symptoms to agents that attenuate the production or activities of MC mediators. These criteria should assist in the identification and diagnosis of patients with MCAS, and in avoiding misdiagnoses or overinterpretation of clinical symptoms in daily practice. Moreover, the MCAS concept should stimulate research in order to identify and exploit new molecular mechanisms and therapeutic targets. Copyright (C) 2011 S. Karger AG, Base