Transcriptional Levels of Intercellular Junction Proteins in an Alveolar Epithelial Cell Line Exposed to Irradiation or Bleomycin.

We performed a comparative study of the effects of X-ray irradiation and bleomycin on the mRNA levels of E-cadherin and tight junction proteins (claudin-3, claudin-4, claudin-18, ZO-2, and occludin) in an alveolar epithelial cell line L2. Irradiation decreased claudin-4 levels and increased occludin levels, while the levels of other mRNAs remained unchanged. Bleomycin increased the expression levels of all proteins examined except claudin-3. Irradiation and bleomycin have different effects on the expression level of intercellular junction proteins, indicating different reactions triggered in alveolar epithelial cells and a great prospects of further comparative studies.

Increased risk of acute stroke among patients with severe COVID-19: a multicenter study and meta-analysis.

BACKGROUND AND PURPOSE: Recent observations linked coronavirus disease 2019 (COVID-19) to thromboembolic complications possibly mediated by increased blood coagulability and inflammatory endothelial impairment. We aimed to define the risk of acute stroke in patients with severe and non-severe COVID-19. METHODS: We performed an observational, multicenter cohort study in four participating hospitals in Saxony, Germany to characterize consecutive patients with laboratory-confirmed COVID-19 who experienced acute stroke during hospitalization. Furthermore, we conducted a systematic review using PubMed/MEDLINE, Embase, Cochrane Library and bibliographies of identified papers following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines including data from observational studies of acute stroke in COVID-19 patients. Data were extracted by two independent reviewers and pooled with multicenter data to calculate risk ratios (RRs) and 95% confidence intervals (95% CIs) for acute stroke related to COVID-19 severity using a random-effects model. Between-study heterogeneity was assessed using Cochran's Q and I2 statistics. International Prospective Register of Systematic Reviews registration number: CRD42020187194. RESULTS: Of 165 patients hospitalized for COVID-19 (49.1% males, median age = 67 years [57-79 years], 72.1% severe or critical) included in the multicenter study, overall stroke rate was 4.2% (95% CI: 1.9-8.7). Systematic literature search identified two observational studies involving 576 patients that were eligible for meta-analysis. Amongst 741 pooled COVID-19 patients, overall stroke rate was 2.9% (95% CI: 1.9-4.5). Risk of acute stroke was increased for patients with severe compared to non-severe COVID-19 (RR = 4.18, 95% CI: 1.7-10.25; P = 0.002) with no evidence of heterogeneity (I2  = 0%, P = 0.82). CONCLUSIONS: Synthesized analysis of data from our multicenter study and previously published cohorts indicates that severity of COVID-19 is associated with an increased risk of acute stroke.

Variable versus conventional lung protective mechanical ventilation during open abdominal surgery (PROVAR): a randomised controlled trial.

BACKGROUND: Experimental studies showed that controlled variable ventilation (CVV) yielded better pulmonary function compared to non-variable ventilation (CNV) in injured lungs. We hypothesized that CVV improves intraoperative and postoperative respiratory function in patients undergoing open abdominal surgery. METHODS: Fifty patients planned for open abdominal surgery lasting >3 h were randomly assigned to receive either CVV or CNV. Mean tidal volumes and PEEP were set at 8 ml kg-1 (predicted body weight) and 5 cm H2O, respectively. In CVV, tidal volumes varied randomly, following a normal distribution, on a breath-by-breath basis. The primary endpoint was the forced vital capacity (FVC) on postoperative Day 1. Secondary endpoints were oxygenation, non-aerated lung volume, distribution of ventilation, and pulmonary and extrapulmonary complications until postoperative Day 5. RESULTS: FVC did not differ significantly between CVV and CNV on postoperative Day 1, 61.5 (standard deviation 22.1) % vs 61.9 (23.6) %, respectively; mean [95% confidence interval (CI)] difference, -0.4 (-13.2-14.0), P=0.95. Intraoperatively, CVV did not result in improved respiratory function, haemodynamics, or redistribution of ventilation compared to CNV. Postoperatively, FVC, forced expiratory volume at the first second (FEV1), and FEV1/FVC deteriorated, while atelectasis volume and plasma levels of interleukin-6 and interleukin-8 increased, but values did not differ between groups. The incidence of postoperative pulmonary and extrapulmonary complications was comparable in CVV and CNV. CONCLUSIONS: In patients undergoing open abdominal surgery, CVV did not improve intraoperative and postoperative respiratory function compared with CNV. CLINICAL TRIAL REGISTRATION: NCT 01683578.

[Acute respiratory distress syndrome : Basic principles and treatment]. / Akutes Lungenversagen : Grundlagen und Therapie.

Even after many years of intensive research acute respiratory distress syndrome (ARDS) is still associated with a high mortality. Epidemiologically, ARDS represents a central challenge for modern intensive care treatment. The multifactorial etiology of ARDS complicates the clear identification and evaluation of new therapeutic interventions. Lung protective mechanical ventilation and adjuvant therapies, such as the prone position and targeted extracorporeal lung support are of particular importance in the treatment of ARDS, depending on the severity of the disease. In order to guarantee an individualized and needs-adapted treatment, ARDS patients benefit from treatment in specialized centers.

Open lung approach vs acute respiratory distress syndrome network ventilation in experimental acute lung injury.

BACKGROUND: Setting and strategies of mechanical ventilation with positive end-expiratory pressure (PEEP) in acute lung injury (ALI) remains controversial. This study compares the effects between lung-protective mechanical ventilation according to the Acute Respiratory Distress Syndrome Network recommendations (ARDSnet) and the open lung approach (OLA) on pulmonary function and inflammatory response. METHODS: Eighteen juvenile pigs were anaesthetized, mechanically ventilated, and instrumented. ALI was induced by surfactant washout. Animals were randomly assigned to mechanical ventilation according to the ARDSnet protocol or the OLA (n=9 per group). Gas exchange, haemodynamics, pulmonary blood flow (PBF) distribution, and respiratory mechanics were measured at intervals and the lungs were removed after 6 h of mechanical ventilation for further analysis. RESULTS: PEEP and mean airway pressure were higher in the OLA than in the ARDSnet group [15 cmH(2)O, range 14-18 cmH(2)O, compared with 12 cmH(2)O; 20.5 (sd 2.3) compared with 18 (1.4) cmH(2)O by the end of the experiment, respectively], and OLA was associated with improved oxygenation compared with the ARDSnet group after 6 h. OLA showed more alveolar overdistension, especially in gravitationally non-dependent regions, while the ARDSnet group was associated with more intra-alveolar haemorrhage. Inflammatory mediators and markers of lung parenchymal stress did not differ significantly between groups. The PBF shifted from ventral to dorsal during OLA compared with ARDSnet protocol [-0.02 (-0.09 to -0.01) compared with -0.08 (-0.12 to -0.06), dorsal-ventral gradients after 6 h, respectively]. CONCLUSIONS: According to the OLA, mechanical ventilation improved oxygenation and redistributed pulmonary perfusion when compared with the ARDSnet protocol, without differences in lung inflammatory response.

[Anesthesia in patients with chronic obstructive pulmonary diseases]. / Anästhesie bei Patienten mit chronisch obstruktiven Lungenerkrankungen.

Chronic obstructive pulmonary disease (COPD/pulmonary emphysema) is a common disease with a high incidence and a medico-economical impact which should not be underestimated. Pathophysiologically it is defined as expiratory obstruction due to increased airway resistance. The extensive comorbidity of COPD patients as well as the impairment of the respiratory system make COPD a key challenge for anesthesiologists. Besides basic drug therapy, differentiated ventilation support represents a hallmark of perioperative management. This article includes the current recommendations of the German national care guidelines for COPD as well as the COPD guidelines of the American Thoracic Society.

Gene flow and genetic differentiation.

A brief analysis is presented for the effects of gene flow upon genetic differentiation within and between populations generated by mutation and drift. Previous results obtained with the "island" model are developed into a form that lends itself to biological interpretation. Attention is focused upon the effective local population size and the ratio of the genetic identity of two genes in different populations to that of two genes in the same population. The biological significance of this ratio, which is independent of population size, is discussed. Similarities between the results of this model and those of the "stepping-stone" model are noted.

Population genetics of allozyme variation in Neurospora intermedia.

Electrophoretically detectable variation in the fungus Neurospora intermedia has been surveyed among isolates from natural populations in Malaya, Papua, Australia and Florida. The principal result is a pattern of genetic variation within and between populations that is qualitatively no different than the well documented patterns for Drosophila and humans. In particular, there is a high level of genetic variation, the majority of which occurs at the level of local populations. Evidence is presented which argues that N. intermedia has a population structure analogous to that of an annual vascular plant with a high level of vegetative reproduction. Sexual reproduction appears to be a regular feature in the biology of the species. Substantial heterokaryon function seems unlikely in natural populations of N. intermedia. Theoretical considerations concerning the mechanisms underlying the observed pattern of variation most likely should be consistent with haploid selection theory. The implications of this constraint upon the theory are discussed in detail, leading to the presentation of a model based upon the concept of environmental heterogenicity. The essence of the model, which is equally applicable to haploid and diploid situations, is a shifting distribution of multiple adaptive niches among local populations such that a given population has a small net selective pressure in favor of one allele or another, depending upon its particular distribution of niches. Gene flow among neighboring populations with differing net selective pressures is postulated as the principal factor underlying intrapopulational allozyme variation.

Spore Killer Polymorphism in FUSARIUM MONILIFORME.

A Spore killer trait, which exhibits genetic and cytological properties analogous to those previously found in Neurospora, exists in natural populations of the fungal plant pathogen Fusarium moniliforme. The genogeography of the polymorphism in F. moniliforme differs from the situation in Neurospora intermedia. It is more akin to the situation in N. sitophila, although more extreme with respect to the prevalence of killer alleles: more than 80% of tested isolates of F. moniliforme carry the killer allele. Nevertheless, sensitive alleles are widely distributed and have been found in California, Italy, Greece and Central America.

Mechanotransduction in the lungs.

Mechanical ventilation may induce or aggravate lung injury, a phenomenon known as ventilator induced lung injury (VILI). On a macroscopic level, the effects of mechanical stress and strain on lung tissue are well described. Increased tidal volumes may lead to volutrauma, raised airway pressures may cause barotrauma and cyclic collapse and reopening of alveolar units contributes to atelectrauma. These three harmful mechanisms may lead to local and systemic pulmonary inflammatory response known as biotrauma. The purpose of this review was to elucidate fundamental mechanisms involved in the mechanotransduction of mechanical stimuli on a cellular level. Bronchial epithelial cells in the distal airways as well as alveolar epithelial cells are exposed to a variety of mechanical forces. These cells are involved in sensing and translation of mechanical stimuli into an inflammatory response. This review provides insight into current knowledge of cellular and molecular pathways during the process of pulmonary epithelial mechanosensation and mechanotransduction under different mechanical conditions. Since evidence for specific pathways is generally lacking in some fields of alveolar epithelial mechanotransduction, this article aims at providing reasonable hypothesis for further investigation.

A year in review in Minerva Anestesiologica 2013.

BACKGROUND: We organized a training program for oral fiber optic intubation (FOI) under conscious sedation. The efficacy of the program was evaluated by comparing the performances of experts and novices. METHODS: The training procedure was divided into two sessions: a theoretical session on difficult airways, the fiber optic bronchoscope (FOB), remifentanil, topical anesthesia and patient interactions; and a session involving simulations of the FOI technique on dummies. For in vivo FOI, we enrolled patients requiring orotracheal intubation for elective surgery. Electrocardiograms, mean arterial pressure was railroaded over the fiberscope, and tracheal intubati6 and 7) FOIs, respectively, joined the study. To reach ±23 bpm, P=0.02), and RR was decreased (from 16±3 to 12±4 bpm, P<0.05). No differences were recorded between the experts and less-experienced anesthesiologists. The average duration of FOI was 3.3±2.0 min for experts and 4.2±2.4 min for novices (P=0.03). Procedures were successful in both groups, with patients in each group being equally satisfied with the procedures. CONCLUSION: This study highlights the importance of a structured FOI training program, demonstrating that it is possible to learn to perform FOI proficiently by practicing on dummies.

Comparison of objective methods to classify the pattern of respiratory sinus arrhythmia during mechanical ventilation and paced spontaneous breathing.

Respiratory sinus arrhythmia (RSA) is a fluctuation of heart period that occurs during a respiratory cycle. It has been suggested that inspiratory heart period acceleration and expiratory deceleration during spontaneous ventilation (henceforth named positive RSA) improve the efficiency of gas exchange compared to the absence or the inversion of such a pattern (negative RSA). During mechanical ventilation (MV), for which maximizing the efficiency of gas exchange is of critical importance, the pattern of RSA is still the object of debate. In order to gain a better insight into this matter, we compared five different methods of RSA classification using the data of five mechanically ventilated piglets. The comparison was repeated using the data of 15 volunteers undergoing a protocol of paced spontaneous breathing, which is expected to result in a positive RSA pattern. The results showed that the agreement between the employed methods is limited, suggesting that the lack of a consensus about the RSA pattern during MV is, at least in part, of methodological origin. However, independently of the method used, the pattern of RSA within the respiratory cycle was not consistent among the subjects and conditions of MV considered. Also, the outcomes showed that even during paced spontaneous breathing a negative RSA pattern might be present, when a low respiratory frequency is imposed.