1,294 research outputs found
Piloting a âTimeline of Crisis Toolâ with service users on admission to an acute psychiatric ward
Zika Virus Non-Structural Protein NS5 Inhibits the RIG-I Pathway and Interferon Lambda 1 Promoter Activation by Targeting IKK Epsilon
The Zika virus (ZIKV) is a member of the Flaviviridae family and an important human pathogen. Most pathogenic viruses encode proteins that interfere with the activation of host innate immune responses. Like other flaviviruses, ZIKV interferes with the expression of interferon (IFN) genes and inhibits IFN-induced antiviral responses. ZIKV infects through epithelial barriers where IFN-λ1 is an important antiviral molecule. In this study, we analyzed the effects of ZIKV proteins on the activation of IFN-λ1 promoter. All ZIKV proteins were cloned and transiently expressed. ZIKV NS5, but no other ZIKV protein, was able to interfere with the RIG-I signaling pathway. This inhibition took place upstream of interferon regulatory factor 3 (IRF3) resulting in reduced phosphorylation of IRF3 and reduced activation of IFN-λ1 promoter. Furthermore, we showed that ZIKV NS5 interacts with the protein kinase IKKΔ, which is likely critical to the observed inhibition of phosphorylation of IRF3
Zika Virus Non-Structural Protein NS5 Inhibits the RIG-I Pathway and Interferon Lambda 1 Promoter Activation by Targeting IKK Epsilon
The Zika virus (ZIKV) is a member of the Flaviviridae family and an important human pathogen. Most pathogenic viruses encode proteins that interfere with the activation of host innate immune responses. Like other flaviviruses, ZIKV interferes with the expression of interferon (IFN) genes and inhibits IFN-induced antiviral responses. ZIKV infects through epithelial barriers where IFN-lambda 1 is an important antiviral molecule. In this study, we analyzed the effects of ZIKV proteins on the activation of IFN-lambda 1 promoter. All ZIKV proteins were cloned and transiently expressed. ZIKV NS5, but no other ZIKV protein, was able to interfere with the RIG-I signaling pathway. This inhibition took place upstream of interferon regulatory factor 3 (IRF3) resulting in reduced phosphorylation of IRF3 and reduced activation of IFN-lambda 1 promoter. Furthermore, we showed that ZIKV NS5 interacts with the protein kinase IKK epsilon, which is likely critical to the observed inhibition of phosphorylation of IRF3.Peer reviewe
Direct microscopy versus sputum cytology analysis and bleach sedimentation for diagnosis of tuberculosis: a prospective diagnostic study.
ABSTRACT: BACKGROUND: Diagnostic options for pulmonary tuberculosis in resource-poor settings are commonly limited to smear microscopy. We investigated whether bleach concentration by sedimentation and sputum cytology analysis (SCA) increased the positivity rate of smear microscopy for smear-positive tuberculosis. METHODS: We did a prospective diagnostic study in a Medecins Sans Frontieres-supported hospital in Mindouli, Republic of Congo. Three sputum samples were obtained from 280 consecutive pulmonary tuberculosis suspects, and were processed according to WHO guidelines for direct smear microscopy. The remainder of each sputum sample was homogenised with 2.6% bleach, sedimented overnight, smeared, and examined blinded to the direct smear result for acid-fast bacilli (AFB). All direct smears were assessed for quality by SCA. If a patient produced fewer than three good-quality sputum samples, further samples were requested. Sediment smear examination was performed independently of SCA result on the corresponding direct smear. Positivity rates were compared using McNemar's test. RESULTS: Excluding SCA, 43.2% of all patients were diagnosed as positive on direct microscopy of up to three samples. 47.9% were diagnosed on sediment microscopy, with 48.2% being diagnosed on direct microscopy, sediment microscopy, or both. The positivity rate increased from 43.2% to 47.9% with a case definition of one positive smear ([greater than or equal to]1 AFB/100 high power fields) of three, and from 42.1% to 43.9% with two positive smears. SCA resulted in 87.9% of patients producing at least two good-quality sputum samples, with 75.7% producing three or more. Using a case definition of one positive smear, the incremental yield of bleach sedimentation was 14/121, or 11.6% (95% CI 6.5-18.6, p=0.001) and in combination with SCA was 15/121, or 12.4% (95% CI 7.1-19.6, p=0.002). Incremental yields with two positive smears were 5/118, or 4.2% (95% CI 1.4-9.6, p=0.062) and 7/118, or 5.9% (95% CI 2.4-11.8, p=0.016), respectively. CONCLUSIONS: The combination of bleach sedimentation and SCA resulted in significantly increased microscopy positivity rates with a case definition of either one or two positive smears. Implementation of bleach sedimentation led to a significant increase in the diagnosis of smear-positive patients. Implementation of SCA did not result in significantly increased diagnosis of tuberculosis, but did result in improved sample quality. Requesting extra sputum samples based on SCA results, combined with bleach sedimentation, could significantly increase the detection of smear-positive patients if routinely implemented in resource-limited settings where gold standard techniques are not available. We recommend that a pilot phase is undertaken before routine implementation to determine the impact in a particular context
Recommendations for SARS-CoV- 2/ COVID-19 testing: a scoping review of current guidance
Background Testing used in screening, diagnosis and
follow-up
of COVID-19 has been a subject of debate.
Several organisations have developed formal advice about
testing for COVID-19 to assist in the control of the disease.
We collated, delineated and appraised current worldwide
recommendations about the role and applications of tests
to control SARS-CoV-
2/COVID-19.
Methods We searched for documents providing
recommendations for COVID-19 testing in PubMed,
EMBASE, LILACS, the Coronavirus Open Access Project
living evidence database and relevant websites such as
TRIP database, ECRI Guidelines Trust, the GIN database,
from inception to 21 September 2020. Two reviewers
applied the eligibility criteria to potentially relevant
citations without language or geographical restrictions.
We extracted data in duplicate, including assessment of
methodological quality using the Appraisal of Guidelines
for Research and Evaluation-II
tool.
Results We included 47 relevant documents and 327
recommendations about testing. Regarding the quality of
the documents, we found that the domains with the lowest
scores were âEditorial independenceâ (Median=4%) and
âApplicabilityâ (Median=6%). Only six documents obtained
at least 50% score for the âRigour of developmentâ
domain. An important number of recommendations
focused on the diagnosis of suspected cases (48%)
and deisolation measures (11%). The most frequently
recommended test was the reverse transcription-PCR
(RT-PCR)
assay (87 recommendations) and the chest
CT (38 recommendations). There were 22 areas of
agreement among guidance developers, including the
use of RT-PCR
for SARS-Cov-
2 confirmation, the limited
role of bronchoscopy, the use chest CT and chest X-rays
for grading severity and the co-assessment
for other
respiratory pathogens.
Conclusion This first scoping review of recommendations
for COVID-19 testing showed many limitations in the
methodological quality of included guidance documents
that could affect the confidence of clinicians in their
implementation. Future guidance documents should
incorporate a minimum set of key methodological
characteristics to enhance their applicability for decision
making.Instituto de Salud Carlos III
2017/CD17/00219European Social Fund 2014-2020, 'Investing in your future'Spanish Governmen
Mapping Pediatric Oncology Clinical Trial Collaborative Groups on the Global Stage
The global pediatric oncology clinical research landscape, particularly in Central and South America, Africa, and Asia, which bear the highest burden of global childhood cancer cases, is less characterized in the literature. Review of how existing pediatric cancer clinical trial groups internationally have been formed and how their research goals have been pursued is critical for building global collaborative research and data-sharing efforts, in line with the WHO Global Initiative for Childhood Cancer. METHODS: A narrative literature review of collaborative groups performing pediatric cancer clinical research in each continent was conducted. An inventory of research groups was assembled and reviewed by current pediatric cancer regional and continental leaders. Each group was narratively described with identification of common structural and research themes among consortia. RESULTS: There is wide variability in the structure, history, and goals of pediatric cancer clinical trial collaborative groups internationally. Several continental regions have longstanding endogenously-formed clinical trial groups that have developed and published numerous adapted treatment regimens to improve outcomes, whereas other regions have consortia focused on developing foundational database registry infrastructure supported by large multinational organizations or twinning relationships. CONCLUSION: There cannot be a one-size-fits-all approach to increasing collaboration between international pediatric cancer clinical trial groups, as this requires a nuanced understanding of local stakeholders and resources necessary to form partnerships. Needs assessments, performed either by local consortia or in conjunction with international partners, have generated productive clinical trial infrastructure. To achieve the goals of the Global Initiative for Childhood Cancer, global partnerships must be sufficiently granular to account for the distinct needs of each collaborating group and should incorporate grassroots approaches, robust twinning relationships, and implementation science
Evolution of epidemiologic methods and concepts in selected textbooks of the 20th century
Summary: Textbooks are an expression of the state of development of a discipline at a given moment in time. By reviewing eight epidemiology textbooks published over the course of a century, we have attempted to trace the evolution of five epidemiologic concepts and methods: study design (cohort studies and case-control studies), confounding, bias, interaction and causal inference. Overall, these eight textbooks can be grouped into three generations. Greenwood (1935) and Hill (first edition 1937; version reviewed 1961)'s textbooks belong to the first generation, "early epidemiologyâ, which comprise early definitions of bias and confounding. The second generation, "classic epidemiologyâ, represented by the textbooks of Morris (first edition 1957; version reviewed 1964), MacMahon & Pugh (first edition 1960; version reviewed 1970), Susser (1973), and Lilienfeld & Lilienfeld (first edition 1976; version reviewed 1980), clarifies the properties of cohort and case-control study designs and the theory of disease causation. Miettinen (1985) and Rothman (1986)'s textbooks belong to a third generation, "modern epidemiologyâ, presenting an integrated perspective on study designs and their measures of outcome, as well as distinguishing and formalizing the concepts of confounding and interaction. Our review demonstrates that epidemiology, as a scientific discipline, is in constant evolution and transformation. It is likely that new methodological tools, able to assess the complexity of the causes of human health, will be proposed in future generations of textbook
- âŠ