Procedural and physical interventions for vaccine injections systematic review of randomized controlled trials and quasi-randomized controlled trials

Background: This systematic review evaluated the effectiveness of physical and procedural interventions for reducing pain and related outcomes during vaccination. Design/Methods: Databases were searched using a broad search strategy to identify relevant randomized and quasi-randomized controlled trials. Data were extracted according to procedure phase (preprocedure, acute, recovery, and combinations of these) and pooled using established methods. Results: A total of 31 studies were included. Acute infant distress was diminished during intramuscular injection without aspiration (n=313): standardized mean difference (SMD) -0.82 (95% confidence interval [CI]: -1.18, -0.46). Injecting the most painful vaccine last during vaccinations reduced acute infant distress (n=196): SMD -0.69 (95%CI: -0.98, -0.4). Simultaneous injections reduced acute infant distress compared with sequential injections (n=172): SMD -0.56 (95%CI: -0.87, -0.25). There was no benefit of simultaneous injections in children. Less infant distress during the acute and recovery phases combined occurred with vastus lateralis (vs. deltoid) injections (n=185): SMD -0.70 (95%CI: -1.00, -0.41). Skin-to-skin contact in neonates (n=736) reduced acute distress: SMD -0.65 (95% CI: -1.05, -0.25). Holding infants reduced acute distress after removal of the data from 1 methodologically diverse study (n=107): SMD -1.25 (95% CI: -2.05, -0.46). Holding after vaccination (n=417) reduced infant distress during the acute and recovery phases combined: SMD -0.65 (95% CI: -1.08, -0.22). Self-reported fear was reduced for children positioned upright (n=107): SMD -0.39 (95% CI: -0.77, -0.01). Non-nutritive sucking (n=186) reduced acute distress in infants: SMD -1.88 (95% CI: -2.57, -1.18). Manual tactile stimulation did not reduce pain across the lifespan. An external vibrating device and cold reduced pain in children (n=145): SMD -1.23 (95% CI: -1.58, -0.87). There was no benefit of warming the vaccine in adults. Muscle tension was beneficial in selected indices of fainting in adolescents and adults. Conclusions: Interventions with evidence of benefit in select populations include: no aspiration, injecting most painful vaccine last, simultaneous injections, vastus lateralis injection, positioning interventions, non-nutritive sucking, external vibrating device with cold, and muscle tension

Phylogenetic analysis of Croatian orf viruses isolated from sheep and goats

<p>Abstract</p> <p>Background</p> <p>The <it>Orf virus </it>(ORFV) is the prototype of the parapoxvirus genus and it primarily causes contagious ecthyma in goats, sheep, and other ruminants worldwide. In this paper, we described the sequence and phylogenetic analysis of the B2L gene of ORFV from two natural outbreaks: i) in autochthonous Croatian Cres-breed sheep and ii) on small family goat farm.</p> <p>Results</p> <p>Sequence and phylogenetic analyses of the ORFV B2L gene showed that the Cro-Cres-12446/09 and Cro-Goat-11727/10 were not clustered together. Cro-Cres-12446/09 shared the highest similarity with ORFV NZ2 from New Zealand, and Ena from Japan; Cro-Goat-11727/10 was closest to the HuB from China and Taiping and Hoping from Taiwan.</p> <p>Conclusion</p> <p>Distinct ORFV strains are circulating in Croatia. Although ORFV infections are found ubiquitously wherever sheep and goats are farmed in Croatia, this is the first information on genetic relatedness of any Croatian ORFV with other isolates around the world.</p

Microbiomes of Velloziaceae from phosphorus-impoverished soils of the campos rupestres, a biodiversity hotspot

The rocky, seasonally-dry and nutrient-impoverished soils of the Brazilian campos rupestres impose severe growth-limiting conditions on plants. Species of a dominant plant family, Velloziaceae, are highly specialized to low-nutrient conditions and seasonal water availability of this environment, where phosphorus (P) is the key limiting nutrient. Despite plant-microbe associations playing critical roles in stressful ecosystems, the contribution of these interactions in the campos rupestres remains poorly studied. Here we present the first microbiome data of Velloziaceae spp. thriving in contrasting substrates of campos rupestres. We assessed the microbiomes of Vellozia epidendroides, which occupies shallow patches of soil, and Barbacenia macrantha, growing on exposed rocks. The prokaryotic and fungal profiles were assessed by rRNA barcode sequencing of epiphytic and endophytic compartments of roots, stems, leaves and surrounding soil/rocks. We also generated root and substrate (rock/soil)-associated metagenomes of each plant species. We foresee that these data will contribute to decipher how the microbiome contributes to plant functioning in the campos rupestres, and to unravel new strategies for improved crop productivity in stressful environments6COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP88881.068071/2014-012016/23218-0Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2016/23218-0]; U.S. Department of Energy Joint Genome Institute (DOE-JGI)United States Department of Energy (DOE) [CSP 503222]; Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)CAPES [88881.068071/2014-01]; FAPESPFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2018/04240-0]; CAPESCAPES; Office of Science of the U.S. Department of EnergyUnited States Department of Energy (DOE) [DE-AC02-05CH11231

Novel event classification based on spectral analysis of scintillation waveforms in Double Chooz

Liquid scintillators are a common choice for neutrino physics experiments, but their capabilities to perform background rejection by scintillation pulse shape discrimination is generally limited in large detectors. This paper describes a novel approach for a pulse shape based event classification developed in the context of the Double Chooz reactor antineutrino experiment. Unlike previous implementations, this method uses the Fourier power spectra of the scintillation pulse shapes to obtain event-wise information. A classification variable built from spectral information was able to achieve an unprecedented performance, despite the lack of optimization at the detector design level. Several examples of event classification are provided, ranging from differentiation between the detector volumes and an efficient rejection of instrumental light noise, to some sensitivity to the particle type, such as stopping muons, ortho-positronium formation, alpha particles as well as electrons and positrons. In combination with other techniques the method is expected to allow for a versatile and more efficient background rejection in the future, especially if detector optimization is taken into account at the design level

Correlation of gene expression and protein production rate - a system wide study

<p>Abstract</p> <p>Background</p> <p>Growth rate is a major determinant of intracellular function. However its effects can only be properly dissected with technically demanding chemostat cultivations in which it can be controlled. Recent work on <it>Saccharomyces cerevisiae </it>chemostat cultivations provided the first analysis on genome wide effects of growth rate. In this work we study the filamentous fungus <it>Trichoderma reesei </it>(<it>Hypocrea jecorina</it>) that is an industrial protein production host known for its exceptional protein secretion capability. Interestingly, it exhibits a low growth rate protein production phenotype.</p> <p>Results</p> <p>We have used transcriptomics and proteomics to study the effect of growth rate and cell density on protein production in chemostat cultivations of <it>T. reesei</it>. Use of chemostat allowed control of growth rate and exact estimation of the extracellular specific protein production rate (SPPR). We find that major biosynthetic activities are all negatively correlated with SPPR. We also find that expression of many genes of secreted proteins and secondary metabolism, as well as various lineage specific, mostly unknown genes are positively correlated with SPPR. Finally, we enumerate possible regulators and regulatory mechanisms, arising from the data, for this response.</p> <p>Conclusions</p> <p>Based on these results it appears that in low growth rate protein production energy is very efficiently used primarly for protein production. Also, we propose that flux through early glycolysis or the TCA cycle is a more fundamental determining factor than growth rate for low growth rate protein production and we propose a novel eukaryotic response to this i.e. the lineage specific response (LSR).</p

Implementation of the COVID-19 vulnerability index across an international network of health care data sets: collaborative external validation study

Background: SARS-CoV-2 is straining health care systems globally. The burden on hospitals during the pandemic could be reduced by implementing prediction models that can discriminate patients who require hospitalization from those who do not. The COVID-19 vulnerability (C-19) index, a model that predicts which patients will be admitted to hospital for treatment of pneumonia or pneumonia proxies, has been developed and proposed as a valuable tool for decision-making during the pandemic. However, the model is at high risk of bias according to the "prediction model risk of bias assessment" criteria, and it has not been externally validated.Objective: The aim of this study was to externally validate the C-19 index across a range of health care settings to determine how well it broadly predicts hospitalization due to pneumonia in COVID-19 cases.Methods: We followed the Observational Health Data Sciences and Informatics (OHDSI) framework for external validation to assess the reliability of the C-19 index. We evaluated the model on two different target populations, 41,381 patients who presented with SARS-CoV-2 at an outpatient or emergency department visit and 9,429,285 patients who presented with influenza or related symptoms during an outpatient or emergency department visit, to predict their risk of hospitalization with pneumonia during the following 0-30 days. In total, we validated the model across a network of 14 databases spanning the United States, Europe, Australia, and Asia.Results: The internal validation performance of the C-19 index had a C statistic of 0.73, and the calibration was not reported by the authors. When we externally validated it by transporting it to SARS-CoV-2 data, the model obtained C statistics of 0.36, 0.53 (0.473-0.584) and 0.56 (0.488-0.636) on Spanish, US, and South Korean data sets, respectively. The calibration was poor, with the model underestimating risk. When validated on 12 data sets containing influenza patients across the OHDSI network, the C statistics ranged between 0.40 and 0.68.Conclusions: Our results show that the discriminative performance of the C-19 index model is low for influenza cohorts and even worse among patients with COVID-19 in the United States, Spain, and South Korea. These results suggest that C-19 should not be used to aid decision-making during the COVID-19 pandemic. Our findings highlight the importance of performing external validation across a range of settings, especially when a prediction model is being extrapolated to a different population. In the field of prediction, extensive validation is required to create appropriate trust in a model.Development and application of statistical models for medical scientific researc

Intersection of phosphate transport, oxidative stress and TOR signalling in Candida albicans virulence

Phosphate is an essential macronutrient required for cell growth and division. Pho84 is the major high-affinity cell-surface phosphate importer of Saccharomyces cerevisiae and a crucial element in the phosphate homeostatic system of this model yeast. We found that loss of Candida albicans Pho84 attenuated virulence in Drosophila and murine oropharyngeal and disseminated models of invasive infection, and conferred hypersensitivity to neutrophil killing. Susceptibility of cells lacking Pho84 to neutrophil attack depended on reactive oxygen species (ROS): pho84-/- cells were no more susceptible than wild type C. albicans to neutrophils from a patient with chronic granulomatous disease, or to those whose oxidative burst was pharmacologically inhibited or neutralized. pho84-/- mutants hyperactivated oxidative stress signalling. They accumulated intracellular ROS in the absence of extrinsic oxidative stress, in high as well as low ambient phosphate conditions. ROS accumulation correlated with diminished levels of the unique superoxide dismutase Sod3 in pho84-/- cells, while SOD3 overexpression from a conditional promoter substantially restored these cells’ oxidative stress resistance in vitro. Repression of SOD3 expression sharply increased their oxidative stress hypersensitivity. Neither of these oxidative stress management effects of manipulating SOD3 transcription was observed in PHO84 wild type cells. Sod3 levels were not the only factor driving oxidative stress effects on pho84-/- cells, though, because overexpressing SOD3 did not ameliorate these cells’ hypersensitivity to neutrophil killing ex vivo, indicating Pho84 has further roles in oxidative stress resistance and virulence. Measurement of cellular metal concentrations demonstrated that diminished Sod3 expression was not due to decreased import of its metal cofactor manganese, as predicted from the function of S. cerevisiae Pho84 as a low-affinity manganese transporter. Instead of a role of Pho84 in metal transport, we found its role in TORC1 activation to impact oxidative stress management: overexpression of the TORC1-activating GTPase Gtr1 relieved the Sod3 deficit and ROS excess in pho84-/- null mutant cells, though it did not suppress their hypersensitivity to neutrophil killing or hyphal growth defect. Pharmacologic inhibition of Pho84 by small molecules including the FDA-approved drug foscarnet also induced ROS accumulation. Inhibiting Pho84 could hence support host defenses by sensitizing C. albicans to oxidative stress