When prevention is dangerous: perceptions of isoniazid preventive therapy in KwaZulu-Natal, South Africa.

SETTING: In 2011, the South African government began to offer isoniazid preventive therapy (IPT) through the public health system to presumptively treat latent tuberculous infection (LTBI) among people living with human immunodeficiency virus. OBJECTIVE: To describe IPT perceptions and experiences in three Zulu communities in KwaZulu-Natal Province, South Africa. DESIGN: Using a combination of community-based research and ethnographic methods, we undertook 17 individual and group interviews between October 2014 and May 2015. Interviews transcripts were analysed using qualitative content analysis and validated with grass-roots community advisors. RESULTS: Participants reported multiple ways in which IPT was perceived as dangerous: when costs related to pill collection or consumption were unsustainable, or when daily pill consumption resulted in stigma or was seen to introduce excess dirt or toxins, 'ukungcola', in the body. Theories on dirt are evoked to describe how IPT was perceived as 'matter out of place' when given to people who believed themselves to be healthy, suggesting that under the current TB aetiological model in Zulu culture, 'prevention as tablet' may not fit. CONCLUSION: Implementing IPT without understanding the realities of community stakeholders can unintentionally undermine TB control efforts by worsening the situation for people who already encounter numerous daily problems.

Respiratory isolation for tuberculosis: the experience of Indigenous peoples on the Canadian prairies.

Setting: The Prairie provinces of Canada. Objective: To understand how Indigenous peoples with infectious pulmonary tuberculosis living in different community settings in the Prairie provinces of Canada experience respiratory isolation. Design: Using an exploratory qualitative approach, we interviewed participants living in urban centres, non-remote reserve settings and remote and isolated reserve settings. Results: Through qualitative content analysis of 48 interviews, we determined that participants experienced feelings of confinement regardless of the community setting in which they lived. Participants also experienced family and social disconnect, but the experience was more potent for the remote and isolated reserve participants, who were required to be flown out of their home communities to receive treatment, and for those urban centre and non-remote reserve participants who lacked social connections. The roles of past experiences with sanitoria and of family in providing social support are discussed. Conclusions: The conclusions of this study focus on examining isolation policies and improving the hospital isolation experience.

Contexte : Les provinces de la Prairie au Canada.Objectif : Comprendre comment les populations indigènes atteintes de tuberculose pulmonaire contagieuse, vivant dans différents contextes communautaires dans les provinces de la Prairie au Canada, ressentent l'isolement.Schéma : En utilisant une approche exploratoire qualitative, nous nous sommes entretenus avec les participants vivant dans des centres urbains, ou dans des réserves éloignées non isolées et dans des réserves éloignées et isolées.Résultat : Une analyse qualitative du contenu des 48 entretiens nous a permis de déterminer que les participants ont eu des sentiments de confinement quel que soit le contexte communautaire dans lequel ils vivaient. Les participants ont également vécu une coupure familiale et sociale, mais l'expérience a été plus dure pour les participants des réserves éloignées et isolées qui ont été obligés de quitter leurs communautés pour recevoir leur traitement, et pour les patients des centres urbains et des réserves non éloignées qui manquaient de connections sociales. Le rôle des expériences passées avec les services de santé et avec le soutien social de la famille est discuté.Conclusions: Les conclusions se concentrent sur l'examen des politiques d'isolement et l'amélioration des expériences d'isolement à l'hôpital.

Marco de referencia: Las provincias de las Praderas del Canadá.Objetivo: Comprender de qué manera perciben el aislamiento respiratorio las poblaciones indígenas con tuberculosis pulmonar contagiosa, de diferentes entornos comunitarios en las provincias de las Praderas canadienses.Método: Mediante una estrategia exploratoria cualitativa, se entrevistaron los participantes que residían en centros urbanos, en reservas no distantes y en reservas aisladas y distantes.Resultados: Tras el análisis cualitativo de contenido de 48 entrevistas, se determinó que los participantes percibían una sensación de confinamiento, con independencia en su entorno comunitario. Asimismo, los participantes percibían desconexión familiar y social, pero la experiencia fue más intensa en los participantes de ámbitos distantes y aislados que tenían que salir de sus comunidades por vía aérea con el fin de recibir el tratamiento y en los participantes de centros urbanos y reservas no distantes que carecían de conexiones sociales. En el artículo se analiza la influencia de las experiencias pasadas con sanatorios y la función de la familia en la prestación del apoyo social.Conclusión: Las conclusiones se centran en el análisis de las políticas de aislamiento y las iniciativas de mejoramiento de la experiencia hospitalaria del aislamiento respiratorio.

Biochemical evidence for gap junctions and Cx43 expression in immortalized human chondrocyte cell line: a potential model in the study of cell communication in human chondrocytes.

OBJECTIVE: The development of chondrocytic cell lines has enabled the investigation of the role of cellular phenotype and mechanisms in articular cartilage biology and physiopathology of several rheumatic diseases. Among them, the T/C-28a2 cell line has become a common tool in cartilage research. Recent results from our group have revealed that primary human chondrocytes in tissue and in monolayer culture contain high levels of connexin 43 (Cx43) and are able to directly communicate through gap junction (GJ) channels. These results challenge the existing thesis of cartilage physiology, that chondrocytes do not have the capacity to physically communicate with each other. Established cell lines offer the advantage of convenience and uniformity; however, the establishment process may cause a disruption of GJ. This study was performed to investigate if T/C-28a2 cells contain Cx43 protein and form functional channels. METHODS: Cx43 was characterized by RT-qPCR, Western blotting, and immunohistochemistry (IHC). Electrophysiology experiments, Lucifer Yellow (LY) uptake, electroporation in situ and scrape loading assay were performed to test the functionality of GJs. RESULTS: T/C-28a2 cells express Cx43. Electrophysiology experiments and LY uptake confirmed the capacity of these cells to communicate through GJ channels, although these cells contain significant levels of active c-Src kinase, presumably due to their immortalization with the Simian Virus 40 large T antigen. The results were validated using primary chondrocytes (PC). CONCLUSIONS: These results reveal that the T/C-28a2 line may provide a useful in vitro model for the study of Cx43 function and cell communication to understand the physiology of chondrocytes and cartilage.

Sulfadoxine-pyrimethamine, chlorproguanil-dapsone, or chloroquine for the treatment of Plasmodium vivax malaria in Afghanistan and Pakistan: a randomized controlled trial.

CONTEXT: In areas where Plasmodium falciparum and Plasmodium vivax coexist and treatments for the 2 species differ, misdiagnosis can lead to poor outcomes in either disease. A unified therapy effective against both species would reduce reliance on species-specific diagnosis, which in many areas is difficult to maintain. The antifolates are an important and affordable antimalarial class to which it is often assumed P vivax malaria is intrinsically resistant. OBJECTIVE: To test the relative efficacy and safety of 2 antifolate drugs against P vivax malaria and compare each with chloroquine. DESIGN, SETTING, AND PATIENTS: An open-label randomized controlled trial comparing chloroquine, sulfadoxine-pyrimethamine, and chlorproguanil-dapsone for the treatment of P vivax malaria was conducted in eastern Afghanistan and northwestern Pakistan, areas in which P vivax malaria predominates. A total of 20,410 patients older than 3 years were screened; 767 patients (315 in Pakistan and 452 in Afghanistan) with confirmed P vivax malaria were enrolled and followed up daily for 4 days, then weekly for 28 days, between March 2004 and June 2006. MAIN OUTCOME MEASURES: Complete clearance of parasites with no recrudescence by day 14. Secondary outcomes included being parasite-free by day 28, clinical failure, and anemia. RESULTS: By day 14, only 1 patient in the sulfadoxine-pyrimethamine group had parasites. By day 28, failure rates were found in 2 of 153 patients (1.3%) in the chloroquine group, 5 of 290 patients (1.7%) in the sulfadoxine-pyrimethamine group, and 27 of 272 patients (9.9%) in the chlorproguanil-dapsone group. Chlorproguanil-dapsone was less effective than sulfadoxine-pyrimethamine (adjusted odds ratio [OR], 6.4; 95% confidence interval [CI], 2.4-17.0; P<.001) and chloroquine (adjusted OR, 8.4; 95% CI, 2.0-36.5; P = .004). Chloroquine and sulfadoxine-pyrimethamine were equivalent in efficacy at day 28 (adjusted OR, 1.3; 95% CI, 0.3-7.0; P = .73). Chloroquine cleared gametocytes and asexual parasites more rapidly than sulfadoxine-pyrimethamine or chlorproguanil-dapsone did. All drugs were well tolerated. CONCLUSIONS: Although chloroquine remains the drug of choice, antifolates are effective against P vivax malaria in South Asia. These drugs may be appropriate for unified treatment where species-specific diagnosis is unavailable, most likely in combination with other drugs. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00158561.

Expression of neural cell-adhesion molecule isoforms and epithelial cadherin adhesion molecules in 47 human meningiomas: correlation with clinical and morphological data.

Meningiomas are derived from arachnoidal cells exhibiting both epithelial and mesenchymal properties. The expression of epithelial cadherin and neural cell-adhesion molecule isoforms was examined in 47 meningioma specimens and normal arachnoid villi by using immunohistochemistry and immunoblot procedures. For immunohistochemistry, the percentage of immunostained surface versus counterstained surface and the intensity of labeling were quantified by image analysis and correlated with clinical and morphological data. Neural cell-adhesion molecule, 140-kDa, was expressed by all meningiomas examined and by cap cells and the fibrous capsule forming the arachnoid villi. Neural cell-adhesion-molecule immunostaining was correlated to tumor location, histological type, and grade. The expression of polysialylated isoforms was related to tumor location and grade, with a higher expression on convexity meningiomas and high-grade tumors. Epithelial cadherin was expressed with various intensity. In arachnoid villi, its expression was restricted to cap cells, but it was found in all meningiomas, whatever their histological type or grade. However, the expression was stronger in whorls and meningiotheliomatous areas versus fibroblastic areas. No correlation was observed with the tumor location or the grade. These data suggest that neural cell-adhesion molecule and epithelial cadherin play a role in the morphogenesis and histogenesis of human meningiomas.

Changes in the distribution of sizes of ovine luteal cells during the estrous cycle.

The ovine corpus luteum is composed of two types of steroidogenic cells, which are referred to as small and large luteal cells. In this study, the size and number of steroidogenic cells were determined in corpora lutea collected on Days 4, 8, 12, and 16 of the estrous cycle. Corpora lutea were dissociated into single-cell suspensions that were stained for 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) activity, a marker for steroidogenic cells. The size of 3 beta-HSD-positive cells was measured with a Zeiss Videoplan Image Analyzer. On Day 4, most of the 3 beta-HSD-positive cells were less than 18 microns in diameter, the median being 11.2 microns. By Day 8, the number of 3 beta-HSD-positive cells increased 3-fold, and the median diameter increased to 12.8 microns. Although the number of 3 beta-HSD-positive cells was reduced by approximately 50% on Day 16, the median size on Days 12 and 16 was 14.6 and 16.8 microns, respectively. The ratio of large (greater than 18 microns) to small (less than 18 microns) luteal cells was 0.11 +/- 0.03 on Day 4; the ratio increased linearly to 0.67 +/- 0.09 by Day 16. This increase between Days 4 and 12 was attributable to an overall increase in the size of the cells; the increase between Days 12 and 16, however, was due to a loss of small luteal cells. When the experiment was conducted near the end of the breeding season, before animals became anestrous, the median size of the luteal cells did not change at different times of the estrous cycle but remained constant throughout. These data suggest that development of the corpus luteum is associated with an increase in the size and number of steroidogenic luteal cells, and that luteolysis is associated with a preferential loss of small luteal cells.

Interactions of prostaglandins with subpopulations of ovine luteal cells. II. Inhibitory effects of PGF2 alpha and protection by PGE2.

Purified preparations of ovine large luteal cells were utilized in a series of experiments to test the effects of prostaglandins (PG) E2 and F2 alpha on cell morphology, viability and secretion of progesterone. Luteal cells were allowed to attach to culture dishes overnight before experiments. In the first series of experiments incubation of large steroidogenic cells with PGF2 alpha for 6 hr resulted in morphological changes including a retraction of the cell cytoplasm and apparent extrusion of cytoplasmic components which became more pronounced after 12 hr. In a second series of experiments, PGF2 alpha decreased and PGE2 increased progesterone accumulation in media after 6 hr when media were not replaced during the incubation period, while progesterone accumulation was not different than that observed in control dishes when both prostaglandins were present. Hourly replacement of the media negated the inhibitory effects of PGF2 alpha but had no effect on the stimulated secretion of progesterone induced by PGE2. Finally, in incubations without media replacement, PGF2 alpha induced a dose-dependent decrease in progesterone accumulation while PGE2 elicited a biphasic response with progesterone secretion increasing from 0.1 ng/ml to maximal levels at 10 ng/ml followed by a dose-dependent decrease at 100 and 1000 ng/ml. These data are compatible with the hypotheses that: 1) luteolysis is initiated, at least in part, by an action of PGF2 alpha on large luteal cells; and 2) the embryonic signal from the pregnant uterus which rescues the ovine corpus luteum may be PGE2.

Observation on flock immunity to Newcastle disease after routine vaccination and experimental aerosol vaccination.

Serological responses in groups of chicks either routinely or experimentally vaccinated with Newcastle disease vaccines via various routes were compared by the micro method of HI test. The lowest serological response to vaccination was found in those groups which had been routinely vaccinated with LaSota strain in drinking water, but a better response was observed in the farm with improved environmental conditions and lower maternal antibody level. Antibody titers in experimentally vaccinated groups were higher than those of routinely vaccinated groups, and the highest antibody response was obtained by aerosol vaccination.