12 research outputs found
O processo de morte e morrer
A equipe de enfermagem é educada visando a promoção, prevenção e tratamento dos pacientes. Diariamente permanecem em conflito lutando a favor da vida e contra a morte. Mesmo que os avanços científicos e tecnológicos proporcionem a elevação da expectativa de vida dos assistidos, a formação e o amadurecimento destes trabalhadores para lidarem com a possível prorrogação, porém inevitável finitude parece não acompanhar esse cenário. O ensaio teórico apresentado busca demonstrar que a necessidade de implementação de disciplinas que contemplem o processo de morte e morrer nos currículos escolares, bem como a educação em serviço para enfermeiros e técnicos em enfermagem se faz urgente. Conclui-se que a abertura do espaço para discussão que enfoque a temática poderá instrumentalizar os trabalhadores de saúde para o enfrentamento de um processo que é natural, mas que envolve muitas variáveis, especialmente no que tange a própria saúde emocional da equipe e as relações interpessoais
The Science Performance of JWST as Characterized in Commissioning
This paper characterizes the actual science performance of the James Webb
Space Telescope (JWST), as determined from the six month commissioning period.
We summarize the performance of the spacecraft, telescope, science instruments,
and ground system, with an emphasis on differences from pre-launch
expectations. Commissioning has made clear that JWST is fully capable of
achieving the discoveries for which it was built. Moreover, almost across the
board, the science performance of JWST is better than expected; in most cases,
JWST will go deeper faster than expected. The telescope and instrument suite
have demonstrated the sensitivity, stability, image quality, and spectral range
that are necessary to transform our understanding of the cosmos through
observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures;
https://iopscience.iop.org/article/10.1088/1538-3873/acb29
Pf7: an open dataset of Plasmodium falciparum genome variation in 20,000 worldwide samples
We describe the MalariaGEN Pf7 data resource, the seventh release of Plasmodium falciparum genome variation data from the MalariaGEN network. It comprises over 20,000 samples from 82 partner studies in 33 countries, including several malaria endemic regions that were previously underrepresented. For the first time we include dried blood spot samples that were sequenced after selective whole genome amplification, necessitating new methods to genotype copy number variations. We identify a large number of newly emerging crt mutations in parts of Southeast Asia, and show examples of heterogeneities in patterns of drug resistance within Africa and within the Indian subcontinent. We describe the profile of variations in the C-terminal of the csp gene and relate this to the sequence used in the RTS,S and R21 malaria vaccines. Pf7 provides high-quality data on genotype calls for 6 million SNPs and short indels, analysis of large deletions that cause failure of rapid diagnostic tests, and systematic characterisation of six major drug resistance loci, all of which can be freely downloaded from the MalariaGEN website
Altered Intraerythrocytic Development Phenotypes of Artemisinin-Resistant \u3ci\u3ePlasmodium falciparum\u3c/i\u3e Confer a Fitness Advantage
Resistance to artemisinin combination therapies (ACTs) has emerged in southeast Asia threatening the most widely used treatment against antimalarial-resistant Plasmodium falciparum worldwide. Artemisinin resistance has been associated with a reduced rate of parasite clearance following treatment with an ACT and is attributed to increased survival of ring-stage parasites. Single nucleotide polymorphisms (SNPs) in kelch gene (K13) has been associated with delayed in vivo clearance half-life of artemisinin-resistant P. falciparum and is the only known molecular marker of resistance. The absence of reliable in vitro phenotypes for artemisinin resistance has limited our understanding of the resistance mechanism(s) and fitness costs, therefore we have culture adapted and cloned patient isolates from Thailand and Cambodia that had clinical resistant phenotypes. Stable reduced susceptibility to artemisinin derivatives and mefloquine was observed using a modified [3H]hypoxanthine drug susceptibility assay. In addition we devised an in vitro phenotype assay of artemisinin resistance, known as the delayed clearance assay (DCA), that was positively correlated with the in vivo delayed clearance and presence of K13 SNPs of artemisinin resistance. Remarkably we discovered for the first time altered patterns of intraerythrocytic development in artemisinin-resistant P. falciparum. In the absence of drug pressure most artemisinin-resistant clones have a prolonged ring phenotype with temporally compressed trophozoite stage, yet with the normal overall asexual life cycle period. Parasites remain in ring-stage up to 14 hours longer than wild-type, whereas time spent in trophozoite-stage is dramatically reduced. One parasite, PL08-09 (5C), exhibited an accelerated 36-hour life cycle in the absence of drug pressure and progressed through asexual development in equal time spent at each intraerythrocytic stage. These data support our hypothesis that parasite resistance to artemisinin results from reduced exposure to drug at the most susceptible stage of development (trophozoite). Interestingly, the most prevalent K13 mutation C580Y is associated with both cell cycle phenotypes. Another cell cycle phenotype, ring-stage dormancy, has been associated with artemisinin resistance in vitro reducing the dormant period of artemisinin-resistant parasites following dihydroartemisinin exposure allowing resistant parasite cultures recrudesce before wild-type. However, sensitive parasites have the ability to enter ring-stage dormancy causing recrudescence in vitro. It is possible that multiple cell cycle phenotypes enhance the survival and fitness of the resistant parasite population as a whole in the face of antimalarial exposure. We have demonstrated that there is a fitness cost associated with artemisinin resistance and remains an important component in the spread of genetic mutations associated with artemisinin resistance. Resistant parasites outcompeted sensitive in vitro only when exposed to dihydroartemisinin. Two mutations associated with artemisinin resistance, including a mutation in K13, were lost in artemisinin resistant parasite by the end of the study. Conversely, parasite cultures maintained artemisinin resistance phenotypes in vitro only if exposed to artemisinin drug pressure every 21-42 days. The mechanism of artemisinin resistance remains elusive and how the parasites alter their intraerythrocytic development is unknown. Therefore. we transfected green fluorescent protein (GFP) or luciferase into artemisinin-resistant P. falciparum clones from Thailand and Cambodia to aid the study the cell cycle phenotypes associated with artemisinin resistance. Artemisinin resistance phenotypes were maintained in stably transfected clones. Increased growth of artemisinin-resistant clones was observed following exposure to ACT partner drug. Low concentrations of antimalarials synchronized the luciferase expression of artemisinin-resistant parasites having different cell cycle phenotypes in the absence of drug pressure. Ring-stage dormancy was observed with many antimalarial drugs and contributes to recrudescence observed by antimalarials other than artemisinin. Our results show evidence that current ACT treatments are selecting multidrug resistant parasites in the field that are better able to tolerate all antimalarials through regulatory cell cycle mechanisms. These cell cycle phenotypes associated with artemisinin resistance contribute to reducing the fitness cost associated with genetic mutations causing artemisinin resistance. This leads to the survival of the most fit population of parasites that survive combination drug treatments, thus demonstrating the importance of discovering novel drugs to target ACT-resistant P. falciparum
Novel phenotypic resistance to artemisinin results in reduced exposure to drug at the most sensitive stage of intraerythrocytic development in Plasmodium falciparum
Artemisinin-Resistant Plasmodium falciparum Parasites Exhibit Altered Patterns of Development in Infected Erythrocytes
Pf7: an open dataset of Plasmodium falciparum genome variation in 20,000 worldwide samples.
We describe the MalariaGEN Pf7 data resource, the seventh release of Plasmodium falciparum genome variation data from the MalariaGEN network. It comprises over 20,000 samples from 82 partner studies in 33 countries, including several malaria endemic regions that were previously underrepresented. For the first time we include dried blood spot samples that were sequenced after selective whole genome amplification, necessitating new methods to genotype copy number variations. We identify a large number of newly emerging crt mutations in parts of Southeast Asia, and show examples of heterogeneities in patterns of drug resistance within Africa and within the Indian subcontinent. We describe the profile of variations in the C-terminal of the csp gene and relate this to the sequence used in the RTS,S and R21 malaria vaccines. Pf7 provides high-quality data on genotype calls for 6 million SNPs and short indels, analysis of large deletions that cause failure of rapid diagnostic tests, and systematic characterisation of six major drug resistance loci, all of which can be freely downloaded from the MalariaGEN website
The Science Performance of JWST as Characterized in Commissioning
This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies