Active transforming growth factor-β is associated with phenotypic changes in granulomas after drug treatment in pulmonary tuberculosis

Background: Tuberculosis (TB) chemotherapy clears bacterial burden in the lungs of patients and allows the tuberculous lesions to heal through a fibrotic process. The healing process leaves pulmonary scar tissue that can impair lung function. The goal of this study was to identify fibrotic mediators as a stepping-stone to begin exploring mechanisms of tissue repair in TB. Methods: Hematoxylin and eosin staining and Masson's trichrome stain were utilized to determine levels of collagenization in tuberculous granulomas from non-human primates. Immunohistochemistry was then employed to further interrogate these granulomas for markers associated with fibrogenesis, including transforming growth factor-β (TGFβ), α-smooth muscle actin (αSMA), phosphorylated SMAD-2/3, and CD163. These markers were compared across states of drug treatment using one-way ANOVA, and Pearson's test was used to determine the association of these markers with one another. Results: TGFβ and αSMA were present in granulomas from primates with active TB disease. These molecules were reduced in abundance after TB chemotherapy. Phosphorylated SMAD-2/3, a signaling intermediate of TGFβ, was observed in greater amounts after 1 month of drug treatment than in active disease, suggesting that this particular pathway is blocked in active disease. Collagen production during tissue repair is strongly associated with TGFβ in this model, but not with CD163+ macrophages. Conclusions: Tissue repair and fibrosis in TB that occurs during drug treatment is associated with active TGFβ that is produced during active disease. Further work will identify mechanisms of fibrosis and work towards mitigating lung impairment with treatments that target those mechanisms

Preserving Madagascar's Natural Heritage: The Importance of Keeping the Island's Vertebrate Fossils in the Public Domain

No Abstrac

Facilitators and barriers to hypertension self-management in urban African Americans: perspectives of patients and family members.

INTRODUCTION: We aimed to inform the design of behavioral interventions by identifying patients' and their family members' perceived facilitators and barriers to hypertension self-management. MATERIALS AND METHODS: We conducted focus groups of African American patients with hypertension and their family members to elicit their views about factors influencing patients' hypertension self-management. We recruited African American patients with hypertension (n = 18) and their family members (n = 12) from an urban, community-based clinical practice in Baltimore, Maryland. We conducted four separate 90-minute focus groups among patients with controlled (one group) and uncontrolled (one group) hypertension, as well as their family members (two groups). Trained moderators used open-ended questions to assess participants' perceptions regarding patient, family, clinic, and community-level factors influencing patients' effective hypertension self-management. RESULTS: Patient participants identified several facilitators (including family members' support and positive relationships with doctors) and barriers (including competing health priorities, lack of knowledge about hypertension, and poor access to community resources) that influence their hypertension self-management. Family members also identified several facilitators (including their participation in patients' doctor's visits and discussions with patients' doctors outside of visits) and barriers (including their own limited health knowledge and patients' lack of motivation to sustain hypertension self-management behaviors) that affect their efforts to support patients' hypertension self-management. CONCLUSION: African American patients with hypertension and their family members reported numerous patient, family, clinic, and community-level facilitators and barriers to patients' hypertension self-management. Patients' and their family members' views may help guide efforts to tailor behavioral interventions designed to improve hypertension self-management behaviors and hypertension control in minority populations

Delivery of Complex Organic Compounds from Evolved Stars to the Solar System

Stars in the late stages of evolution are able to synthesize complex organic compounds with aromatic and aliphatic structures over very short time scales. These compounds are ejected into the interstellar medium and distributed throughout the Galaxy. The structures of these compounds are similar to the insoluble organic matter found in meteorites. In this paper, we discuss to what extent stellar organics has enriched the primordial Solar System and possibly the early Earth

Impact of comorbid psychiatric disorders on the outcome of substance abusers: a six year prospective follow-up in two Norwegian counties

BACKGROUND: Most help-seeking substance abusers have comorbid psychiatric disorders. The importance of such disorders for the long-term course of substance abuse is, however, still unclear. The aim of this paper is to describe six-year outcomes regarding death and relapse among alcoholics and poly-substance abusers and to analyse the predictive value of lifetime psychiatric disorders on relapse. METHODS: A consecutive sample of substance-dependent patients who received treatment in two counties in Norway (n = 287) was followed up after approximately six years. Information on socio-demographics, Axis I (CIDI) and II disorders (MCMI-II) and mental distress (HSCL-25) was gathered at baseline. At follow-up, detailed information regarding socio-demographics, use of substances (AUDIT and DUDIT) and mental distress (HSCL-25) was recorded (response rate: 63%). RESULTS: At six-year follow-up, 11% had died, most often male alcoholics (18%). Among the surviving patients, 70% had drug or alcohol related problems the year prior to follow-up. These patients were, classified as "relapsers". There were no significant differences in the relapse rate between women and men and among poly-substance abusers and alcoholics. The relapsers had an earlier onset of a substance use disorder, and more frequently major depression and agoraphobia. Multivariate analysis indicated that both psychiatric disorders (major depression) and substance use factors (early onset of a substance use disorder) were independent predictors of relapse. CONCLUSION: For reducing the risk of long-term relapse, assessment and treatment of major depression (and agoraphobia) are important. In addition, we are in need of a comprehensive treatment and rehabilitation program that also focuses on the addictive behaviour

Animal abuse and intimate partner violence: researching the link and its significance in Ireland - a veterinary perspective

Research on domestic violence has established a substantial association between intimate partner abuse and the abuse of children within the home. It is only recently however, that researchers have demonstrated the correlation between non-accidental injury in animals, and abuse of women by their intimate male partners. A growing body of evidence suggests that animal abuse can be an early indicator for other forms of violent behaviour. This research includes the responses of a sample of 23 women using refuge services in the Republic of Ireland. It investigates the connection between domestic violence and animal abuse, and ascertains if there is sufficient support service for animals and people relevant to domestic abuse. In the survey population, 57% of women reported witnessing one or more forms of abuse, or threats of abuse, of their pets. Five of which were reported to have resulted in the death of the pet. Eighty seven per cent of women felt a facility to accommodate pets would have made their decision to leave the family home easier. Four women disclosed that lack of such a service and concern for the welfare of their companion animals caused them to remain in their abusive relationships for longer than they felt appropriate. Nine families placed pets in the care of family or friends, one woman is unaware of the fate of her pet, while the pets of six families remained with the abusive male after his partner entered a refuge. The majority of women felt unable to talk to anyone about their fears for their pets' welfare. Many felt that there is no service which can provide temporary accommodation for womens' pets while they are in refuge. The results obtained support those found elsewhere in larger studies in the USA and UK, and demonstrate an association of animal abuse in households where there is reported domestic violence

Ghana's evolving protein economy

This paper provides an initial analysis of Ghana's protein economy in the light on current debates about nutritional transition and livestock revolution. Ghana's strong economic growth and reducing levels of poverty make it a particularly interesting case. Protein-rich foods, including fish and livestock products, supply 20-40 percent of protein consumed. Overall fish is becoming less important and poultry more important; but there also are large difference in household expenditure on protein-rich foods across wealth categories, regions and areas. Specifically, the protein element of the nutritional transition and the consumption side of the livestock revolution would appear to be unfolding at different speeds and in different ways, along an axis that is urban-south-non-poor at one end, and rural-north-poor at the other. We explore the policy and political economy dimensions of these change

Community ecology of the Middle Miocene primates of La Venta, Colombia: the relationship between ecological diversity, divergence time, and phylogenetic richness

It has been suggested that the degree of ecological diversity that characterizes a primate community correlates positively with both its phylogenetic richness and the time since the members of that community diverged (Fleagle and Reed in Primate communities. Cambridge University Press, New York, pp 92–115, 1999). It is therefore questionable whether or not a community with a relatively recent divergence time but high phylogenetic richness would be as ecologically variable as a community with similar phylogenetic richness but a more distant divergence time. To address this question, the ecological diversity of a fossil primate community from La Venta, Colombia, a Middle Miocene platyrrhine community with phylogenetic diversity comparable with extant platyrrhine communities but a relatively short time since divergence, was compared with that of modern Neotropical primate communities. Shearing quotients and molar lengths, which together are reliable indicators of diet, for both fossil and extant species were plotted against each other to describe the dietary “ecospace” occupied by each community. Community diversity was calculated as the area of the minimum convex polygon encompassing all community members. The diversity of the fossil community was then compared with that of extant communities to test whether the fossil community was less diverse than extant communities while taking phylogenetic richness into account. Results indicate that the La Ventan community was not significantly less ecologically diverse than modern communities, supporting the idea that ecological diversification occurred along with phylogenetic diversification early in platyrrhine evolution

The stellar and sub-stellar IMF of simple and composite populations

The current knowledge on the stellar IMF is documented. It appears to become top-heavy when the star-formation rate density surpasses about 0.1Msun/(yr pc^3) on a pc scale and it may become increasingly bottom-heavy with increasing metallicity and in increasingly massive early-type galaxies. It declines quite steeply below about 0.07Msun with brown dwarfs (BDs) and very low mass stars having their own IMF. The most massive star of mass mmax formed in an embedded cluster with stellar mass Mecl correlates strongly with Mecl being a result of gravitation-driven but resource-limited growth and fragmentation induced starvation. There is no convincing evidence whatsoever that massive stars do form in isolation. Various methods of discretising a stellar population are introduced: optimal sampling leads to a mass distribution that perfectly represents the exact form of the desired IMF and the mmax-to-Mecl relation, while random sampling results in statistical variations of the shape of the IMF. The observed mmax-to-Mecl correlation and the small spread of IMF power-law indices together suggest that optimally sampling the IMF may be the more realistic description of star formation than random sampling from a universal IMF with a constant upper mass limit. Composite populations on galaxy scales, which are formed from many pc scale star formation events, need to be described by the integrated galactic IMF. This IGIMF varies systematically from top-light to top-heavy in dependence of galaxy type and star formation rate, with dramatic implications for theories of galaxy formation and evolution.Comment: 167 pages, 37 figures, 3 tables, published in Stellar Systems and Galactic Structure, Vol.5, Springer. This revised version is consistent with the published version and includes additional references and minor additions to the text as well as a recomputed Table 1. ISBN 978-90-481-8817-

Dosimetric evaluation and radioimmunotherapy of anti-tumour multivalent Fab́ fragments

We have been investigating the use of cross-linked divalent (DFM) and trivalent (TFM) versions of the anti-carcinoembryonic antigen (CEA) monoclonal antibody A5B7 as possible alternatives to the parent forms (IgG and F(ab́)2) which have been used previously in clinical radioimmunotherapy (RIT) studies in colorectal carcinoma. Comparative biodistribution studies of similar sized DFM and F(ab́)2 and TFM and IgG, radiolabelled with both 131I and 90Y have been described previously using the human colorectal tumour LS174T nude mouse xenograft model (Casey et al (1996) Br J Cancer 74: 1397–1405). In this study quantitative estimates of radiation distribution and RIT in the xenograft model provided more insight into selecting the most suitable combination for future RIT. Radiation doses were significantly higher in all tissues when antibodies were labelled with 90Y. Major contributing organs were the kidneys, liver and spleen. The extremely high absorbed dose to the kidneys on injection of 90Y-labelled DFM and F(ab́)2 as a result of accumulation of the radiometal would result in extremely high toxicity. These combinations are clearly unsuitable for RIT. Cumulative dose of 90Y-TFM to the kidney was 3 times lower than the divalent forms but still twice as high as for 90Y-IgG. TFM clears faster from the blood than IgG, producing higher tumour to blood ratios. Therefore when considering only the tumour to blood ratios of the total absorbed dose, the data suggests that TFM would be the most suitable candidate. However, when corrected for equitoxic blood levels, doses to normal tissues for TFM were approximately twice the level of IgG, producing a two-fold increase in the overall tumour to normal tissue ratio. In addition RIT revealed that for a similar level of toxicity and half the administered activity, 90Y-IgG produced a greater therapeutic response. This suggests that the most promising A5B7 antibody form with the radionuclide 90Y may be IgG. Dosimetry analysis revealed that the tumour to normal tissue ratios were greater for all 131I-labelled antibodies. This suggests that 131I may be a more suitable radionuclide for RIT, in terms of lower toxicity to normal tissues. The highest tumour to blood dose and tumour to normal tissue ratio at equitoxic blood levels was 131I-labelled DFM, suggesting that 131I-DFM may be best combination of antibody and radionuclide for A5B7. The dosimetry estimates were in agreement with RIT results in that twice the activity of 131I-DFM must be administered to produce a similar therapeutic effect as 131I-TFM. The toxicity in this therapy experiment was minimal and further experiments at higher doses are required to observe if there would be any advantage of a higher initial dose rate for 131I-DFM. © 1999 Cancer Research Campaig