Adverse Outcome of Early Recurrent Ischemic Stroke Secondary to Atrial Fibrillation after Repeated Systemic Thrombolysis

Background. Recurrent ischemic stroke is associated with adverse neurological outcome in patients with atrial fibrillation. There is very scarce information regarding the neurological outcome of atrial fibrillation patients undergoing repeated systemic thrombolysis after early recurrent ischemic stroke. Clinical Case and Discussion. We describe a case of a 76-year-old woman with known paroxysmal atrial fibrillation who was admitted because of an acute right middle cerebral artery ischemic stroke and who underwent repeated systemic thrombolysis within 110 hours. The patient underwent systemic thrombolysis after the first ischemic stroke with almost complete neurological recovery. On the fourth day after treatment, an acute left middle cerebral artery ischemic stroke was diagnosed and she was treated with full-dose intravenous recombinant tissue plasminogen activator. A hemorrhagic transformation of the left middle cerebral artery infarction was noted on follow-up cranial computed tomographic scans. The patient did not recover from the second cerebrovascular event and died 25 days after admission. Conclusion. To the best of our knowledge, this is the second case reporting the adverse neurological outcome of a patient with diagnosis of atrial fibrillation undergoing repeated systemic thrombolysis after early recurrent ischemic stroke. Our report represents a contribution to the scarce available evidence suggesting that repeated systemic thrombolysis for recurrent ischemic stroke should be avoided

From PALSA PLUS to PALM PLUS: adapting and developing a South African guideline and training intervention to better integrate HIV/AIDS care with primary care in rural health centers in Malawi

<p>Abstract</p> <p>Background</p> <p>Only about one-third of eligible HIV/AIDS patients receive anti-retroviral treatment (ART). Decentralizing treatment is crucial to wider and more equitable access, but key obstacles are a shortage of trained healthcare workers (HCW) and challenges integrating HIV/AIDS care with other primary care. This report describes the development of a guideline and training program (PALM PLUS) designed to integrate HIV/AIDS care with other primary care in Malawi. PALM PLUS was adapted from PALSA PLUS, developed in South Africa, and targets middle-cadre HCWs (clinical officers, nurses, and medical assistants). We adapted it to align with Malawi's national treatment protocols, more varied healthcare workforce, and weaker health system infrastructure.</p> <p>Methods/Design</p> <p>The international research team included the developers of the PALSA PLUS program, key Malawi-based team members and personnel from national and district level Ministry of Health (MoH), professional associations, and an international non-governmental organization. The PALSA PLUS guideline was extensively revised based on Malawi national disease-specific guidelines. Advice and input was sought from local clinical experts, including middle-cadre personnel, as well as Malawi MoH personnel and representatives of Malawian professional associations.</p> <p>Results</p> <p>An integrated guideline adapted to Malawian protocols for adults with respiratory conditions, HIV/AIDS, tuberculosis, and other primary care conditions was developed. The training program was adapted to Malawi's health system and district-level supervision structure. PALM PLUS is currently being piloted in a cluster-randomized trial in health centers in Malawi (ISRCTN47805230).</p> <p>Discussion</p> <p>The PALM PLUS guideline and training intervention targets primary care middle-cadre HCWs with the objective of improving HCW satisfaction and retention, and the quality of patient care. Successful adaptations are feasible, even across health systems as different as those of South Africa and Malawi.</p

The centrosome and spindle as a ribonucleoprotein complex

Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Chromosome Research 19 (2011): 367-376, doi:10.1007/s10577-011-9186-7.The presence of nucleic acids in centrosomes and the spindle have been proposed, observed, and reported since the 1950s. Why did the subject remain, perhaps even until today, such a controversial issue? The explanation is manifold, and includes legitimate concern over contamination from other cellular compartments in biochemical preparations. With a typically high background of cytoplasmic ribosomes, even microscopic images of stained intact cells could be difficult to interpret. Also, evidence for RNA and DNA in centrosomes accumulated for approximately 40 years but was interspersed with contradictory studies, primarily regarding the presence of DNA (reviewed in Johnson and Rosenbaum, 1991; Marshall and Rosenbaum, 2000). Perhaps less tangible but still a likely cause for lingering controversy is that the presence of nucleic acids in the spindle or centrosomes will require us to look differently at these structures from a functional, and more to the point, evolutionary standpoint.This work was supported by grants from the NIH (GM088503) and NSF (MCB0843092) to MCA

Centrosome amplification induced by survivin suppression enhances both chromosome instability and radiosensitivity in glioma cells

Glioblastoma is characterised by invasive growth and a high degree of radioresistance. Survivin, a regulator of chromosome segregation, is highly expressed and known to induce radioresistance in human gliomas. In this study, we examined the effect of survivin suppression on radiosensitivity in malignant glioma cells, while focusing on centrosome aberration and chromosome instability (CIN). We suppressed survivin by small interfering RNA transfection, and examined the radiosensitivity using a clonogenic assay and a trypan blue exclusion assay in U251MG (p53 mutant) and D54MG (p53 wild type) cells. To assess the CIN status, we determined the number of centrosomes using an immunofluorescence analysis, and the centromeric copy number by fluorescence in situ hybridisation. As a result, the radiosensitisation differed regarding the p53 status as U251MG cells quickly developed extreme centrosome amplification (=CIN) and enhanced the radiosensitivity, while centrosome amplification and radiosensitivity increased more gradually in D54MG cells. TUNEL assay showed that survivin inhibition did not lead to apoptosis after irradiation. This cell death was accompanied by an increased degree of aneuploidy, suggesting mitotic cell death. Therefore, survivin inhibition may be an attractive therapeutic target to overcome the radioresistance while, in addition, proper attention to CIN (centrosome number) is considered important for improving radiosensitivity in human glioma

The Uptake of Integrated Perinatal Prevention of Mother-to-Child HIV Transmission Programs in Low- and Middle-Income Countries: A Systematic Review

BACKGROUND: The objective of this review was to assess the uptake of WHO recommended integrated perinatal prevention of mother-to-child transmission (PMTCT) of HIV interventions in low- and middle-income countries. METHODS AND FINDINGS: We searched 21 databases for observational studies presenting uptake of integrated PMTCT programs in low- and middle-income countries. Forty-one studies on programs implemented between 1997 and 2006, met inclusion criteria. The proportion of women attending antenatal care who were counseled and who were tested was high; 96% (range 30-100%) and 81% (range 26-100%), respectively. However, the overall median proportion of HIV positive women provided with antiretroviral prophylaxis in antenatal care and attending labor ward was 55% (range 22-99%) and 60% (range 19-100%), respectively. The proportion of women with unknown HIV status, tested for HIV at labor ward was 70%. Overall, 79% (range 44-100%) of infants were tested for HIV and 11% (range 3-18%) of them were HIV positive. We designed two PMTCT cascades using studies with outcomes for all perinatal PMTCT interventions which showed that an estimated 22% of all HIV positive women attending antenatal care and 11% of all HIV positive women delivering at labor ward were not notified about their HIV status and did not participate in PMTCT program. Only 17% of HIV positive antenatal care attendees and their infants are known to have taken antiretroviral prophylaxis. CONCLUSION: The existing evidence provides information only about the initial PMTCT programs which were based on the old WHO PMTCT guidelines. The uptake of counseling and HIV testing among pregnant women attending antenatal care was high, but their retention in PMTCT programs was low. The majority of women in the included studies did not receive ARV prophylaxis in antenatal care; nor did they attend labor ward. More studies evaluating the uptake in current PMTCT programs are urgently needed

Integrating Prevention of Mother-to-Child HIV Transmission Programs to Improve Uptake: A Systematic Review

BACKGROUND: We performed a systematic review to assess the effect of integrated perinatal prevention of mother-to-child transmission of HIV interventions compared to non- or partially integrated services on the uptake in low- and middle-income countries. METHODS: We searched for experimental, quasi-experimental and controlled observational studies in any language from 21 databases and grey literature sources. RESULTS: Out of 28 654 citations retrieved, five studies met our inclusion criteria. A cluster randomized controlled trial reported higher probability of nevirapine uptake at the labor wards implementing HIV testing and structured nevirapine adherence assessment (RRR 1.37, bootstrapped 95% CI, 1.04-1.77). A stepped wedge design study showed marked improvement in antiretroviral therapy (ART) enrolment (44.4% versus 25.3%, p<0.001) and initiation (32.9% versus 14.4%, p<0.001) in integrated care, but the median gestational age of ART initiation (27.1 versus 27.7 weeks, p = 0.4), ART duration (10.8 versus 10.0 weeks, p = 0.3) or 90 days ART retention (87.8% versus 91.3%, p = 0.3) did not differ significantly. A cohort study reported no significant difference either in the ART coverage (55% versus 48% versus 47%, p = 0.29) or eight weeks of ART duration before the delivery (50% versus 42% versus 52%; p = 0.96) between integrated, proximal and distal partially integrated care. Two before and after studies assessed the impact of integration on HIV testing uptake in antenatal care. The first study reported that significantly more women received information on PMTCT (92% versus 77%, p<0.001), were tested (76% versus 62%, p<0.001) and learned their HIV status (66% versus 55%, p<0.001) after integration. The second study also reported significant increase in HIV testing uptake after integration (98.8% versus 52.6%, p<0.001). CONCLUSION: Limited, non-generalizable evidence supports the effectiveness of integrated PMTCT programs. More research measuring coverage and other relevant outcomes is urgently needed to inform the design of services delivering PMTCT programs

Patterns of ash (Fraxinus excelsior L.) colonization in mountain grasslands: the importance of management practices

International audienceWoody colonization of grasslands is often associated with changes in abiotic or biotic conditions or a combination of both. Widely used as fodder and litter in the past traditional agro-pastoral system, ash (Fraxinus excelsior L.) has now become a colonizing species of mountain grasslands in the French Pyrenees. Its present distribution is dependent on past human activities and it is locally controlled by propagule pressure and abiotic conditions. However, even when all favourable conditions are met, all the potentially colonizable grasslands are not invaded. We hypothesize that management practices should play a crucial role in the control of ash colonization. From empirical field surveys we have compared the botanical composition of a set of grasslands (present and former) differing in management practices and level of ash colonization. We have displayed a kind of successional gradient positively linked to both ash cover and height but not to the age of trees. We have tested the relationships between ash presence in grassland and management types i.e. cutting and/or grazing, management intensity and some grassland communities' features i.e. total and local specific richness and species heterogeneity. Mixed use (cutting and grazing) is negatively linked to ash presence in grassland whereas grazing alone positively. Mixed use and high grazing intensity are directly preventing ash seedlings establishment, when low grazing intensity is allowing ash seedlings establishment indirectly through herbaceous vegetation neglected by livestock. Our results show the existence of a limit between grasslands with and without established ashes corresponding to a threshold in the intensity of use. Under this threshold, when ash is established, the colonization process seems to become irreversible. Ash possesses the ability of compensatory growth and therefore under a high grazing intensity develops a subterranean vegetative reproduction. However the question remains at which stage of seedling development and grazing intensity these strategies could occur