554 research outputs found

    Effects of long-term organophosphate exposures on neurological symptoms, vibration sense and tremor amongst South African farm workers

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    OBJECTIVES: This study assessed the relationship between long-term exposure to organophosphate insecticides and neurological symptoms, vibration sense, and motor tremor after control for the effect of past poisoning and acute exposure. METHODS: This cross-sectional study included 164 pesticide applicators and 83 nonspraying reference workers on deciduous fruit farms. The workers were tested on the Vibratron II, on tests of dynamic and static tremor, and for a set of neurological and "dummy" symptoms. Exposure was derived with the use of a job-exposure matrix for pesticides in agriculture. RESULTS: Compared with nonapplicators, current applicators reported significantly more dizziness, sleepiness, and headache and had a higher overall neurological symptom score. This association remained statistically significant after multiple logistic regression analyses controlling for a range of confounders and effect modifiers [odds ratio (OR) 2.25, for current applicators having high neurological score, 95% confidence interval (95% CI) 1.15-4.39]. The average lifetime intensity of organophosphate exposure was nonsignificantly associated with both neurological (OR 1.98, 95% CI 0.49-7.94) and "dummy" symptoms (OR 2.37, 95% CI 0.54-10.35). Previous pesticide poisoning was significantly associated with the neurological scores (OR 4.08, 95% CI 1.48-11.22) but not with the "dummy" symptoms. Vibration sense outcomes were associated with age and height, but not with the organophosphate exposure measures. In the multiple linear regression modeling for tremor intensity in the dominant hand, recent organophosphate exposure in the past 10 days was a significant predictor (partial correlation coefficient = 0.04), but none of the long-term organophosphate exposure measures were significant. CONCLUSIONS: Strong evidence was found for an association between symptom outcomes and past organophosphate poisoning and between symptom outcomes and current spray activity. In contrast to symptoms, there was no association between either past poisoning or current spray activity and vibration sense or tremor outcome. Long-term organophosphate exposure did not appear to predict symptoms, vibration sense, or tremor outcome

    Epide·miology of non-fatal injuries due to external causes in Johannesburg-Soweto Part I. Methodology and materials

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    In this, the first of two articles examining the epidemiology of non-fatal trauma in Johannesburg-Soweto, we define case inclusion criteria, and discuss the methodology and materials used in this low-cost, hospital-based survey. The survey was conducted between 8 June 1989 and 24 August 1990. Sampling of both inpatient trauma cases and those seen in casualty departments took place in 6 state and 5 private hospitals located within or nearby the Johannesburg magisterial district. Demographic details about each patient, as well as information concerning spatial and temporal details of the incident, involvement of alcohol or drugs, diagnosis, severity of injury, and placement after casualty treatment, were collected by interviewing each patient. Data concerning the age, sex and racial composition of the background population were assembled from a number of sources. After discussing the internal limitations of this methodology, it is concluded that its findings may be of limited use for improving secondary interventions, but are of definite value for trauma prevention programmes

    Epidemiology of non-fatal injuries due to external causes in Johannesburg-Soweto Part 11. Incidence and determinants

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    A total of 3535 trauma cases were enumerated in Johannesburg- Soweto between 1989 and 1990 in the course of 271 hospital ward rounds and 43 casualty watches. The overall trauma incidence was 2886 new cases per annum per 100000 population, rising to 19872 for coloured males aged 20 - 24 years and to 8761 for black males aged 20 - 24 years. Overall the malelfemale ratio was 2,9 rising to 6 or more in adolescence (15 - 19) for blacks andcoloureds. There were some 156 new resident cases of trauma daily; half these were victims of interpersonal violence, and coloureds constituted 22% of this group, although forming only 8% of the denominator population. Witluegards to cause, most trauma among blacks and coloureds arose from interpersonal violence and significantly less from transport accidents. Among blacks injured in transport accidents (the majority of which involved motor vehicles) most were pedestrians, whereas most whites injured in such accidents were occupants of vehicles. For all groups trauma was most likely to be incurred 'in the street' although for white and coloured women the home was most dangerous. The implications of these and related findings for treatment and prevention and briefly reviewed

    Targeting triple-negative breast cancer cells with the histone deacetylase inhibitor panobinostat

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    INTRODUCTION: Of the more than one million global cases of breast cancer diagnosed each year, approximately fifteen percent are characterized as triple-negative, lacking the estrogen, progesterone, and Her2/neu receptors. Lack of effective therapies, younger age at onset, and early metastatic spread have contributed to the poor prognoses and outcomes associated with these malignancies. Here, we investigate the ability of the histone deacetylase inhibitor panobinostat (LBH589) to selectively target triple-negative breast cancer (TNBC) cell proliferation and survival in vitro and tumorigenesis in vivo. METHODS: TNBC cell lines MDA-MB-157, MDA-MB-231, MDA-MB-468, and BT-549 were treated with nanomolar (nM) quantities of panobinostat. Relevant histone acetylation was verified by flow cytometry and immunofluorescent imaging. Assays for trypan blue viability, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) proliferation, and DNA fragmentation were used to evaluate overall cellular toxicity. Changes in cell cycle progression were assessed with propidium iodide flow cytometry. Additionally, qPCR arrays were used to probe MDA-MB-231 cells for panobinostat-induced changes in cancer biomarkers and signaling pathways. Orthotopic MDA-MB-231 and BT-549 mouse xenograft models were used to assess the effects of panobinostat on tumorigenesis. Lastly, flow cytometry, ELISA, and immunohistochemical staining were applied to detect changes in cadherin-1, E-cadherin (CDH1) protein expression and the results paired with confocal microscopy in order to examine changes in cell morphology. RESULTS: Panobinostat treatment increased histone acetylation, decreased cell proliferation and survival, and blocked cell cycle progression at G2/M with a concurrent decrease in S phase in all TNBC cell lines. Treatment also resulted in apoptosis induction at 24 hours in all lines except the MDA-MB-468 cell line. MDA-MB-231 and BT-549 tumor formation was significantly inhibited by panobinostat (10 mg/kg/day) in mice. Additionally, panobinostat up-regulated CDH1 protein in vitro and in vivo and induced cell morphology changes in MDA-MB-231 cells consistent with reversal of the mesenchymal phenotype. CONCLUSIONS: This study revealed that panobinostat is overtly toxic to TNBC cells in vitro and decreases tumorigenesis in vivo. Additionally, treatment up-regulated anti-proliferative, tumor suppressor, and epithelial marker genes in MDA-MB-231 cells and initiated a partial reversal of the epithelial-to-mesenchymal transition. Our results demonstrate a potential therapeutic role of panobinostat in targeting aggressive triple-negative breast cancer cell types

    Die Bedeutung einer Ausfallbedrohtheit von Versicherungskontrakten - ein Beitrag zur Behavioral Insurance

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    Kahneman/Tversky 1979 haben das theoretische Konstrukt der Probabilistic Insurance Kontrakte in die Literatur eingeführt. Hiermit werden Versicherungsverträge bezeichnet, deren Erfüllung im Leistungsfalle aufgrund einer möglichen Insolvenz des Versicherungsunternehmens nicht gewährleistet ist. In Ausweitung einer Studie von Wakker/Thaler/Tversky 1997 wird in der vorliegenden Arbeit eine experimentelle Untersuchung durchgeführt, wobei die Zahlungsbereitschaft potentieller Versicherungsnehmer in Abhängigkeit des Ratings des den Versicherungskontrakt anbietenden Unternehmens festgestellt wird. Dabei zeigt sich, daß diese ausfallbedrohte Versicherungsprodukte relativ zu ausfallfreien Verträgen mit erheblichen Prämienabschlägen sanktionieren. Der Preisabschlag nimmt dabei mit sinkender Unternehmensbonität (erhöhter Ausfallgefahr) zu. Die Befragungsergebnisse zeigen zudem das neuartige Phänomen, daß mit zunehmender Ausfallbedrohtheit immer weniger Personen bereit sind, ausfallbedrohte Versicherungsprodukte überhaupt zu akzeptieren. Schließlich werden Schlußfolgerungen für die Steuerung von Versicherungsunternehmen diskutiert

    Recent acquisition of Helicobacter pylori by Baka Pygmies

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    Both anatomically modern humans and the gastric pathogen Helicobacter pylori originated in Africa, and both species have been associated for at least 100,000 years. Seven geographically distinct H. pylori populations exist, three of which are indigenous to Africa: hpAfrica1, hpAfrica2, and hpNEAfrica. The oldest and most divergent population, hpAfrica2, evolved within San hunter-gatherers, who represent one of the deepest branches of the human population tree. Anticipating the presence of ancient H. pylori lineages within all hunter-gatherer populations, we investigated the prevalence and population structure of H. pylori within Baka Pygmies in Cameroon. Gastric biopsies were obtained by esophagogastroduodenoscopy from 77 Baka from two geographically separated populations, and from 101 non-Baka individuals from neighboring agriculturalist populations, and subsequently cultured for H. pylori. Unexpectedly, Baka Pygmies showed a significantly lower H. pylori infection rate (20.8%) than non-Baka (80.2%). We generated multilocus haplotypes for each H. pylori isolate by DNA sequencing, but were not able to identify Baka-specific lineages, and most isolates in our sample were assigned to hpNEAfrica or hpAfrica1. The population hpNEAfrica, a marker for the expansion of the Nilo-Saharan language family, was divided into East African and Central West African subpopulations. Similarly, a new hpAfrica1 subpopulation, identified mainly among Cameroonians, supports eastern and western expansions of Bantu languages. An age-structured transmission model shows that the low H. pylori prevalence among Baka Pygmies is achievable within the timeframe of a few hundred years and suggests that demographic factors such as small population size and unusually low life expectancy can lead to the eradication of H. pylori from individual human populations. The Baka were thus either H. pylori-free or lost their ancient lineages during past demographic fluctuations. Using coalescent simulations and phylogenetic inference, we show that Baka almost certainly acquired their extant H. pylori through secondary contact with their agriculturalist neighbors
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