StemMapper: a curated gene expression database for stem cell lineage analysis.

Transcriptomic data have become a fundamental resource for stem cell (SC) biologists as well as for a wider research audience studying SC-related processes such as aging, embryonic development and prevalent diseases including cancer, diabetes and neurodegenerative diseases. Access and analysis of the growing amount of freely available transcriptomics datasets for SCs, however, are not trivial tasks. Here, we present StemMapper, a manually curated gene expression database and comprehensive resource for SC research, built on integrated data for different lineages of human and mouse SCs. It is based on careful selection, standardized processing and stringent quality control of relevant transcriptomics datasets to minimize artefacts, and includes currently over 960 transcriptomes covering a broad range of SC types. Each of the integrated datasets was individually inspected and manually curated. StemMapper's user-friendly interface enables fast querying, comparison, and interactive visualization of quality-controlled SC gene expression data in a comprehensive manner. A proof-of-principle analysis discovering novel putative astrocyte/neural SC lineage markers exemplifies the utility of the integrated data resource. We believe that StemMapper can open the way for new insights and advances in SC research by greatly simplifying the access and analysis of SC transcriptomic data. StemMapper is freely accessible at http://stemmapper.sysbiolab.eu

Rituximab in refractory Vogt–Koyanagi–Harada disease

IntroductionVogt–Koyanagi–Harada (VKH) prognosis depends on early recognition and treatment; chronic disease may be developed when either delayed or inadequate treatment is performed, whereas other cases despite correct treatment are refractory to different drugs and also become chronic. We report a case of refractory VKH controlled with rituximab treatment.Case reportA 41-year-old female with painful visual loss and headache was examined. (VA 0.4 in RE and hand movements (HM) in LE). Retinal examination demonstrated multiple serous retinal detachments in both eyes. High-dose oral steroids were started, followed by progressive tapering of prednisone. New acute anterior and posterior relapses were achieved, and other immunommodulators were progressively added—new high-dose steroid treatment, adalimumab, cyclosporine, and methotrexate—but patient had new anterior and posterior recurrences associated with tinnitus and headache. Thus, an infusion of 1 g of rituximab was administered after 15 months follow-up; the VA was 0.2 in RE and counting fingers in LE. Three additional doses of 1 g each were administered 1, 6, and 16 months later. We have achieved a final VA after 34 months follow-up of 0.2 in RE and HM in LE, with definitive control of inflammation, without acute relapses since rituximab was administered.ConclusionAfter searching PubMed/Medline, this is the first report of VKH disease treated with rituximab. Additional studies are warranted to confirm the efficacy of this new approach for inflammatory control in refractory cases of VKH disease

Contribution of microscopy for understanding the mechanism of action against trypanosomatids

Transmission electron microscopy (TEM) has proved to be a useful tool to study the ultrastructural alterations and the target organelles of new antitrypanosomatid drugs. Thus, it has been observed that sesquiterpene lactones induce diverse ultrastructural alterations in both T. cruzi and Leishmania spp., such as cytoplasmic vacuolization, appearance of multilamellar structures, condensation of nuclear DNA, and, in some cases, an important accumulation of lipid vacuoles. This accumulation could be related to apoptotic events. Some of the sesquiterpene lactones (e.g., psilostachyin) have also been demonstrated to cause an intense mitochondrial swelling accompanied by a visible kinetoplast deformation as well as the appearance of multivesicular bodies. This mitochondrial swelling could be related to the generation of oxidative stress and associated to alterations in the ergosterol metabolism. The appearance of multilamellar structures and multiple kinetoplasts and flagella induced by the sesquiterpene lactone psilostachyin C indicates that this compound would act at the parasite cell cycle level, in an intermediate stage between kinetoplast segregation and nuclear division. In turn, the diterpene lactone icetexane has proved to induce the external membrane budding on T. cruzi together with an apparent disorganization of the pericellar cytoskeleton. Thus, ultrastructural TEM studies allow elucidating the possible mechanisms and the subsequent identification of molecular targets for the action of natural compounds on trypanosomatids.Fil: Lozano, Esteban Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Spina Zapata, Renata María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Barrera, Patricia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Tonn, Carlos Eugenio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Investigaciones en Tecnología Química. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Investigaciones en Tecnología Química; ArgentinaFil: Sosa Escudero, Miguel Angel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentin

Gravitational Radiation from Post-Newtonian Sources and Inspiralling Compact Binaries

The article reviews the current status of a theoretical approach to the problem of the emission of gravitational waves by isolated systems in the context of general relativity. Part A of the article deals with general post-Newtonian sources. The exterior field of the source is investigated by means of a combination of analytic post-Minkowskian and multipolar approximations. The physical observables in the far-zone of the source are described by a specific set of radiative multipole moments. By matching the exterior solution to the metric of the post-Newtonian source in the near-zone we obtain the explicit expressions of the source multipole moments. The relationships between the radiative and source moments involve many non-linear multipole interactions, among them those associated with the tails (and tails-of-tails) of gravitational waves. Part B of the article is devoted to the application to compact binary systems. We present the equations of binary motion, and the associated Lagrangian and Hamiltonian, at the third post-Newtonian (3PN) order beyond the Newtonian acceleration. The gravitational-wave energy flux, taking consistently into account the relativistic corrections in the binary moments as well as the various tail effects, is derived through 3.5PN order with respect to the quadrupole formalism. The binary's orbital phase, whose prior knowledge is crucial for searching and analyzing the signals from inspiralling compact binaries, is deduced from an energy balance argument.Comment: 109 pages, 1 figure; this version is an update of the Living Review article originally published in 2002; available on-line at http://www.livingreviews.org

Adherence to antidepressant therapy for major depressive patients in a psychiatric hospital in Thailand

Poor adherence to antidepressant therapy is an important barrier to the effective management of major depressive disorder. This study aims to quantify the adherence rate to antidepressant treatment and to determine the pattern of prescriptions of depressed patients in a psychiatric institute in Thailand.This retrospective study used electronic pharmacy data of outpatients aged 15 or older, with a new diagnosis of major depression who received at least one prescription of antidepressants between August 2005 and September 2008. The medication possession ratio (MPR) was used to measure adherence over a 6 month period.1,058 were eligible for study inclusion. The overall adherence (MPR > 80%) in those attending this facility at least twice was 41% but if we assume that all patients who attended only once were non-adherent, adherence may be as low as 23%. Fluoxetine was the most commonly prescribed drug followed by TCAs. A large proportion of cases received more than one drug during one visit or was switched from one drug to another (39%).Adherence to antidepressant therapy for treatment of major depression in Thailand is rather low compared to results of adherence from elsewhere

Budget impact analysis of medicines : updated systematic review and implications

This evaluation determines whether published studies to date meet the key characteristics identified for budget impact analyses (BIA) for medicines, accomplished through a systematic review and assessment against identified key characteristics. Studies from 2001 to 2015 on "budget impact analysis" with "drug" interventions were assessed, selected based on their titles/abstracts and full texts, with their characteristics checked according to key criteria. Out of 1984 studies, 92 were identified. Of these, 95% were published in Europe and the USA. 2012 saw the largest number of publications (16%) with a decline thereafter. 48% met up to 6 or 7 out of the 9 key characteristics. Only 22% stated no conflict of interest. The results indicate low adherence to the key characteristics that should be considered for BIAs and strong conflict of interest. This is an issue since BIAs can be of fundamental importance in managing the entry of new medicines including reimbursement decisions

Intra-abdominal pressure in patients with abdominal trauma

Objetivos: Pacientes com trauma abdominal tratados cirurgicamente são muito suscetíveis ao desenvolvimento de hipertensão intra-abdominal e síndrome do compartimento abdominal, cujo diagnóstico é baseado na medição da pressão intraabdominal associada a parâmetros clínicos. Este estudo teve por objetivos avaliar prospectivamente o comportamento da pressão intra-abdominal de pacientes com trauma abdominal cirurgicamente tratados e identificar se há relação entre tal comportamento e parâmetros clínicos destes pacientes. Método: A técnica de Kron foi utilizada para medir a pressão intra-abdominal. A casuística foi composta por 17 homens e três mulheres com média de idade de 36,9 anos (D.P. 12,943). O mecanismo de trauma mais freqüente foi contusão abdominal 12 (60%) contra oito (40%) pacientes com ferimentos penetrantes. Os dados foram coletados em 6 e 18 horas de pós-operatório. Resultados: As médias de pressão intra-abdominal foram 10,4 cmH2O (D.P. 3,939) em 6 horas e 10,263 cmH2O (D.P. 3,445) em 18 horas de pós operatório. A análise dos resultados mostrou correlação estatisticamente significante entre o volume de colóides infundidos e a pressão intra-abdominal em 6 e 18 horas pós-operatórias (p = 0,0380 e p = 0,0033 respectivamente). É provável que tal correlação se deva ao edema visceral causado pelo extravasamento capilar de soluções, aumentando a pressão intra-abdominal. Conclusões: Os achados deste estudo ratificam a idéia de relação entre grandes volumes de infusão venosa, sobretudo colóides, e o aumento da pressão intra-abdominal e destacam a importância da avaliação da pressão intra-abdominal em pacientes com trauma abdominal submetidos a grandes reposições volêmicas, sobretudo as soluções coloidais. _________________________________________________________________________________________ ABSTRACT: Bacjground: Patients with significant abdominal traumatism submitted to surgical treatment are susceptible to develop intra-abdominal hypertension and abdominal compartment syndrome. Those diagnosis are based on intra-abdominal pressure measurement associated with clinical parameters. The aims of this study were: to study prospectively the behavior of intra-abdominal pressure in patients with abdominal trauma submitted to surgical treatment; to identify if there is association between that behavior and clinical parameters. Methods: There were 17 males and three females with an average age of 36.9 years (S.D. 12.9). The data was collected in two times, six and 18 hours in the immediate postoperative period. The averages of intra-abdominal pressures found were 10.4 cmH2O (S.D. 3.9) in the first six hours and 10.3 cmH2O (S.D. 3.5) in 18 hours of postoperative period. Results: There was significant statistical correlation between the volume of infused colloids and intra-abdominal pressure at six and 18 hours of postoperative period (p = 0.0380 and p = 0.0033, respectively). These correlations are probably explained by visceral edema caused by the capillary leak of solutions, increasing intra-abdominal pressure. Conclusions: Our findings confirm the relationship between large volumes of fluid infusion, mainly colloid solutions, and the increase of intra-abdominal pressure and detach the importance of intraabdominal pressure monitorization in patients with abdominal trauma submitted to massive replacement of liquids, mainly when this replacement was done with colloids solutions