Retention of mouth-to-mouth, mouth-to-mask and mouth-to-face shield ventilation

Background: Retention of mouth-to-mouth, mouth-to-mask and mouth-to-face shield ventilation techniques is poorly understood.Methods: A prospective randomised clinical trial was undertaken in January 2004 in 70 candidates randomly assigned to training in mouth-to-mouth, mouth-to-mask or mouth-to-face shield ventilation. Each candidate was trained for 10 min, after which tidal volume, respiratory rate, minute volume, peak airway pressure and the presence or absence of stomach inflation were measured. 58 subjects were reassessed 1 year later and study parameters were recorded again. Data were analysed with ANOVA, \textgreekq2 and McNemar tests.Results: Tidal volume, minute volume, peak airway pressure, ventilation rate and stomach inflation rate increased significantly at reassessment with all ventilation techniques compared with the initial assessment. However, at reassessment, mean (SD) tidal volume (960 (446) vs 1008 (366) vs 1402 (302) ml; p<0.05), minute volume (12 (5) vs 13 (7) vs 18 (3) l/min; p<0.05), peak airway pressure (14 (8) vs 17 (13) vs 25 (8) cm H2O; p<0.05) and stomach inflation rate (63% vs 58% vs 100%; p<0.05) were significantly lower with mouth-to-mask and mouth-to-face shield ventilation than with mouth-to-mouth ventilation. The ventilation rate at reassessment did not differ significantly between the ventilation techniques.Conclusions: One year after a single episode of ventilation training, lay persons tended to hyperventilate; however, the degree of hyperventilation and resulting stomach inflation were lower when a mouth-to-mask or a face shield device was employed. Regular training is therefore required to retain ventilation skills; retention of skills may be better with ventilation devices

Hypoxia induced downregulation of hepcidin is mediated by platelet derived growth factor BB

OBJECTIVE: Hypoxia affects body iron homeostasis; however, the underlying mechanisms are incompletely understood. DESIGN: Using a standardised hypoxia chamber, 23 healthy volunteers were subjected to hypoxic conditions, equivalent to an altitude of 5600 m, for 6 h. Subsequent experiments were performed in C57BL/6 mice, CREB-H knockout mice, primary hepatocytes and HepG2 cells. RESULTS: Exposure of subjects to hypoxia resulted in a significant decrease of serum levels of the master regulator of iron homeostasis hepcidin and elevated concentrations of platelet derived growth factor (PDGF)-BB. Using correlation analysis, we identified PDGF-BB to be associated with hypoxia mediated hepcidin repression in humans. We then exposed mice to hypoxia using a standardised chamber and observed downregulation of hepatic hepcidin mRNA expression that was paralleled by elevated serum PDGF-BB protein concentrations and higher serum iron levels as compared with mice housed under normoxic conditions. PDGF-BB treatment in vitro and in vivo resulted in suppression of both steady state and BMP6 inducible hepcidin expression. Mechanistically, PDGF-BB inhibits hepcidin transcription by downregulating the protein expression of the transcription factors CREB and CREB-H, and pharmacological blockade or genetic ablation of these pathways abrogated the effects of PDGF-BB toward hepcidin expression. CONCLUSIONS: Hypoxia decreases hepatic hepcidin expression by a novel regulatory pathway exerted via PDGF-BB, leading to increased availability of circulating iron that can be used for erythropoiesis

The role of innate immunity and bioactive lipid mediators in COVID-19 and influenza

In this review, we discuss spatiotemporal kinetics and inflammatory signatures of innate immune cells specifically found in response to SARS-CoV-2 compared to influenza virus infection. Importantly, we cover the current understanding on the mechanisms by which SARS-CoV-2 may fail to engage a coordinated type I response and instead may lead to exaggerated inflammation and death. This knowledge is central for the understanding of available data on specialized pro-resolving lipid mediators in severe SARS-CoV-2 infection pointing toward inhibited E-series resolvin synthesis in severe cases. By investigating a publicly available RNA-seq database of bronchoalveolar lavage cells from patients affected by COVID-19, we moreover offer insights into the regulation of key enzymes involved in lipid mediator synthesis, critically complementing the current knowledge about the mediator lipidome in severely affected patients. This review finally discusses different potential approaches to sustain the synthesis of 3-PUFA-derived pro-resolving lipid mediators, including resolvins and lipoxins, which may critically aid in the prevention of acute lung injury and death from COVID-19.Proteomic

Computational Study of Aero-acoustic Sources in Perforate Silencers

Reynolds Averaged Navier Stokes and Large Eddy Simulations of two perforate plates at a overall pressure ratio of 1.45 have been performed to allow analysis of the sensitivity of acoustic noise sources to porosity. Two geometries are presented: A 23% porosity and a 40% porosity 1mm plate with 2mm diameter holes. Results presented in this paper show the initial jetlet and fully merged jet flow-field to be sensitive to the porosity and the presence of partial holes around the circumference of the plate. The increase in porosity reduces the available entrainment flow, and increases the local jetlet interaction and resultant turbulence levels. This interaction fundamentally changes the flow structure from coherent vortex rings (found at low porosity) to a helical structure. The 2nd and 4th order spatio- temporal correlation Rij and Rij,kl are presented as suggested validation data for acoustic source modeling together with far-field noise spectra obtained via a Ffowcs-Williams & Hawkings surface integral method

The genetic study of three population microisolates in South Tyrol (MICROS): study design and epidemiological perspectives

<p>Abstract</p> <p>Background</p> <p>There is increasing evidence of the important role that small, isolated populations could play in finding genes involved in the etiology of diseases. For historical and political reasons, South Tyrol, the northern most Italian region, includes several villages of small dimensions which remained isolated over the centuries.</p> <p>Methods</p> <p>The MICROS study is a population-based survey on three small, isolated villages, characterized by: old settlement; small number of founders; high endogamy rates; slow/null population expansion. During the stage-1 (2002/03) genealogical data, screening questionnaires, clinical measurements, blood and urine samples, and DNA were collected for 1175 adult volunteers. Stage-2, concerning trait diagnoses, linkage analysis and association studies, is ongoing. The selection of the traits is being driven by expert clinicians. Preliminary, descriptive statistics were obtained. Power simulations for finding linkage on a quantitative trait locus (QTL) were undertaken.</p> <p>Results</p> <p>Starting from participants, genealogies were reconstructed for 50,037 subjects, going back to the early 1600s. Within the last five generations, subjects were clustered in one pedigree of 7049 subjects plus 178 smaller pedigrees (3 to 85 subjects each). A significant probability of familial clustering was assessed for many traits, especially among the cardiovascular, neurological and respiratory traits. Simulations showed that the MICROS pedigree has a substantial power to detect a LOD score ≥ 3 when the QTL specific heritability is ≥ 20%.</p> <p>Conclusion</p> <p>The MICROS study is an extensive, ongoing, two-stage survey aimed at characterizing the genetic epidemiology of Mendelian and complex diseases. Our approach, involving different scientific disciplines, is an advantageous strategy to define and to study population isolates. The isolation of the Alpine populations, together with the extensive data collected so far, make the MICROS study a powerful resource for the study of diseases in many fields of medicine. Recent successes and simulation studies give us confidence that our pedigrees can be valuable both in finding new candidates loci and to confirm existing candidate genes.</p

Stable population structure in Europe since the Iron Age, despite high mobility

Ancient DNA research in the past decade has revealed that European population structure changed dramatically in the prehistoric period (14,000–3000 years before present, YBP), reflecting the widespread introduction of Neolithic farmer and Bronze Age Steppe ancestries. However, little is known about how population structure changed from the historical period onward (3000 YBP - present). To address this, we collected whole genomes from 204 individuals from Europe and the Mediterranean, many of which are the first historical period genomes from their region (e.g. Armenia and France). We found that most regions show remarkable inter-individual heterogeneity. At least 7% of historical individuals carry ancestry uncommon in the region where they were sampled, some indicating cross-Mediterranean contacts. Despite this high level of mobility, overall population structure across western Eurasia is relatively stable through the historical period up to the present, mirroring geography. We show that, under standard population genetics models with local panmixia, the observed level of dispersal would lead to a collapse of population structure. Persistent population structure thus suggests a lower effective migration rate than indicated by the observed dispersal. We hypothesize that this phenomenon can be explained by extensive transient dispersal arising from drastically improved transportation networks and the Roman Empire’s mobilization of people for trade, labor, and military. This work highlights the utility of ancient DNA in elucidating finer scale human population dynamics in recent history

The Effects of Endurance Exercise and Diet on Atherosclerosis in Young and Aged ApoE -/- and Wild-Type Mice

Background: Atherosclerosis is the leading cause of death worldwide. The disease development is by and large driven by old age and lifestyle factors, such as diet, physical activity, and smoking. In the present study, we have investigated the effect of exercise and diet on the development of atherosclerosis in young and aged mice. Objective: This study aimed at comparing multiple age-dependent factors that may influence atherosclerosis in a transgenic mouse model. Methods: Young (14 weeks) and aged (49-52 weeks) C57BL/6 wild-type (WT) and atherosclerosis-prone ApoE -/- mice were subjected to physical endurance exercise on a treadmill, with or without a high-fat diet. Five weeks later, the frequencies of regulatory T cells (T REGs ) in lymph nodes were assessed by flow cytometry, plasmatic cytokines (interleukin [IL]-1\u3b2, IL-6, IL-10, IL-17, interferon-\u3b3, tumor necrosis factor-\u3b1, and transforming growth factor [TGF]-\u3b2 1 ) levels were determined by Luminex assay. Lipids (cholesterol and triglycerides) and anti-heat shock protein 60 (HSP60) autoantibodies were measured by ELISA. Aortic lesion sizes were assessed by en face imaging. Microarray analysis and qPCR of skeletal muscle gene expression were also performed. Results: Exercise leads to a reduction of aortic lesions in young ApoE -/- and aged WT mice independent of diet. In most groups, this reduction was followed by an increased proportion of T REGs and TGF-\u3b2 1 levels. Moreover, gene expression analysis showed that exercise seems to affect the AMPK signaling pathway. In particular, PGC-1\u3b1 1 mRNA was induced in aged WT mice, whereas it was reduced in young ApoE -/- mice. In addition, GSEA analysis showed a marked reduction in the insulin signaling pathway in aged ApoE -/- mice. Conclusion: Practicing endurance exercise seems to be enough for reducing early aortic lesion formation, independent of diet. However, this was only true in mice with smaller aortic lesions, since mice with large, advanced, complicated atherosclerotic plaques did not show any reduction in lesion size with exercise training

Haptoglobin 2-2 genotype is not associated with cardiovascular risk in subjects with elevated glycohemoglobin-results from the Bruneck Study.

BACKGROUND: Haptoglobin (Hp) is an abundant plasma protein with antioxidant properties. The Hp 2-2 genotype has previously been linked to coronary heart disease risk in individuals with elevated glycosylated hemoglobin (HbA1c). We investigated the association of Hp and HbA1c with cardiovascular disease (CVD) in the longitudinal, population-based Bruneck Study. METHODS AND RESULTS: Hp genotype was determined by polymerase chain reaction according to standard procedures and HbA1c concentration by a Diabetes Control and Complications Trial-aligned assay. HbA1c was measured in 1995, 2000, and 2005. Occurrence of the combined CVD endpoint of myocardial infarction or stroke was recorded between 1995 and 2010. Outcome analyses employed the Cox proportional hazards model with HbA1c category as time-varying covariate. At baseline in 1995, 806 subjects (male sex, 49.3%; age, mean \ub1 standard deviation, 62.70 \ub1 11.08 years) were included. During follow-up, 123 subjects experienced at least 1 CVD event (48 suffered myocardial infarction, 68 stroke, and 7 both). Among subjects with HbA1c 65 6.5% ( 65 48 mmol/mol), those with the Hp 2-2 genotype did not show an elevated risk of incident CVD compared with those with other genotypes (age- and sex-adjusted hazard ratio [95% CI], 0.47 [0.19, 1.13], P=0.092) and a null association was also observed in subjects with HbA1c<6.5% (1.10 [0.75, 1.62], P=0.629) (P for interaction=0.082). CONCLUSIONS: Subjects with the Hp 2-2 genotype and elevated HbA1c compared with subjects with other Hp genotypes and elevated HbA1c did not show increased CVD risk