Determination of respiratory gas flow by electrical impedance tomography in an animal model of mechanical ventilation

Background A recent method determines regional gas flow of the lung by electrical impedance tomography (EIT). The aim of this study is to show the applicability of this method in a porcine model of mechanical ventilation in healthy and diseased lungs. Our primary hypothesis is that global gas flow measured by EIT can be correlated with spirometry. Our secondary hypothesis is that regional analysis of respiratory gas flow delivers physiologically meaningful results. Methods In two sets of experiments n = 7 healthy pigs and n = 6 pigs before and after induction of lavage lung injury were investigated. EIT of the lung and spirometry were registered synchronously during ongoing mechanical ventilation. In-vivo aeration of the lung was analysed in four regions-of-interest (ROI) by EIT: 1) global, 2) ventral (non-dependent), 3) middle and 4) dorsal (dependent) ROI. Respiratory gas flow was calculated by the first derivative of the regional aeration curve. Four phases of the respiratory cycle were discriminated. They delivered peak and late inspiratory and expiratory gas flow (PIF, LIF, PEF, LEF) characterizing early or late inspiration or expiration. Results Linear regression analysis of EIT and spirometry in healthy pigs revealed a very good correlation measuring peak flow and a good correlation detecting late flow. PIFEIT = 0.702 · PIFspiro + 117.4, r2 = 0.809; PEFEIT = 0.690 · PEFspiro-124.2, r2 = 0.760; LIFEIT = 0.909 · LIFspiro + 27.32, r2 = 0.572 and LEFEIT = 0.858 · LEFspiro-10.94, r2 = 0.647. EIT derived absolute gas flow was generally smaller than data from spirometry. Regional gas flow was distributed heterogeneously during different phases of the respiratory cycle. But, the regional distribution of gas flow stayed stable during different ventilator settings. Moderate lung injury changed the regional pattern of gas flow. Conclusions We conclude that the presented method is able to determine global respiratory gas flow of the lung in different phases of the respiratory cycle. Additionally, it delivers meaningful insight into regional pulmonary characteristics, i.e. the regional ability of the lung to take up and to release air.

Autonomy as a protective factor against the detrimental effects of ego depletion on tennis serve accuracy under pressure

It has been repeatedly demonstrated that athletes in a state of ego depletion do not perform up to their capabilities. We assume that autonomous self-control exertion, in contrast to forced self-control exertion, can serve as a buffer against ego depletion effects and can help individuals to show superior performance. In the present study, we applied a between-subjects design to test the assumption that autonomously exerted self-control is less detrimental for subsequent self-control performance in sports than is forced self-control exertion. In a primary self-control task, the level of autonomy was manipulated through specific instructions, resulting in three experimental conditions (autonomy-supportive: n = 19; neutral: n = 19; controlling: n = 19). As a secondary self-control task, participants executed a series of tennis serves under high-pressure conditions, and performance accuracy served as our dependent variable. As expected, a one-way between-groups ANOVA revealed that participants from the autonomy-supportive condition performed significantly better under pressure than did participants from the controlling condition. These results further highlight the importance of autonomy-supportive instructions in order to enable athletes to show superior achievements in high-pressure situations. Practical implications for the coach–athlete relationship are discussed.

Protective role of autophagy and autophagy-related protein 5 in early tumorigenesis.

Autophagy, a fundamental cellular catabolic process, is involved in the development of numerous diseases including cancer. Autophagy seems to have an ambivalent impact on tumor development. While increasing evidence indicates a cytoprotective role for autophagy that can contribute to resistance against chemotherapy and even against the adverse, hypoxic environment of established tumors, relatively few publications focus on the role of autophagy in early tumorigenesis. However, the consensus is that autophagy is inhibitory for the genesis of tumors. To understand this apparent contradiction, more detailed information about the roles of the individual participants in autophagy is needed. This review will address this topic with respect to autophagy-related protein 5 (ATG5), which in several lines of investigation has been ascribed special significance in the autophagic pathway. Furthermore, it was recently shown that an ATG5 deficiency in melanocytes interferes with oncogene-induced senescence, thus promoting melanoma tumorigenesis. Similarly, an ATG5 deficiency resulted in tumors of the lung and liver in experimental mouse models. Taken together, these findings indicate that ATG5 and the autophagy to which it contributes are essential gatekeepers restricting early tumorigenesis in multiple tissues.

The future of fluorides and other protective agents in erosion prevention

The effectiveness of fluoride in caries prevention has been convincingly proven. In recent years, researchers have investigated the preventive effects of different fluoride formulations on erosive tooth wear with positive results, but their action on caries and erosion prevention must be based on different requirements, because there is no sheltered area in the erosive process as there is in the subsurface carious lesions. Thus, any protective mechanism from fluoride concerning erosion is limited to the surface or the near surface layer of enamel. However, reports on other protective agents show superior preventive results. The mechanism of action of tin-containing products is related to tin deposition onto the tooth surface, as well as the incorporation of tin into the near-surface layer of enamel. These tin-rich deposits are less susceptible to dissolution and may result in enhanced protection of the underlying tooth. Titanium tetrafluoride forms a protective layer on the tooth surface. It is believed that this layer is made up of hydrated hydrogen titanium phosphate. Products containing phosphates and/or proteins may adsorb either to the pellicle, rendering it more protective against demineralization, or directly to the dental hard tissue, probably competing with H(+) at specific sites on the tooth surface. Other substances may further enhance precipitation of calcium phosphates on the enamel surface, protecting it from additional acid impacts. Hence, the future of fluoride alone in erosion prevention looks grim, but the combination of fluoride with protective agents, such as polyvalent metal ions and some polymers, has much brighter prospects.

Effectiveness of Personal Protective Equipment for Healthcare Workers Caring for Patients with Filovirus Disease: A Rapid Review.

BACKGROUND A rapid review, guided by a protocol, was conducted to inform development of the World Health Organization's guideline on personal protective equipment in the context of the ongoing (2013-present) Western African filovirus disease outbreak, with a focus on health care workers directly caring for patients with Ebola or Marburg virus diseases. METHODS Electronic databases and grey literature sources were searched. Eligibility criteria initially included comparative studies on Ebola and Marburg virus diseases reported in English or French, but criteria were expanded to studies on other viral hemorrhagic fevers and non-comparative designs due to the paucity of studies. After title and abstract screening (two people to exclude), full-text reports of potentially relevant articles were assessed in duplicate. Fifty-seven percent of extraction information was verified. The Grading of Recommendations Assessment, Development and Evaluation framework was used to inform the quality of evidence assessments. RESULTS Thirty non-comparative studies (8 related to Ebola virus disease) were located, and 27 provided data on viral transmission. Reporting of personal protective equipment components and infection prevention and control protocols was generally poor. CONCLUSIONS Insufficient evidence exists to draw conclusions regarding the comparative effectiveness of various types of personal protective equipment. Additional research is urgently needed to determine optimal PPE for health care workers caring for patients with filovirus.

Biological and protective properties of immune sera directed to the influenza virus neuraminidase

The envelope of influenza A viruses contains two large antigens, hemagglutinin (HA) and neuraminidase (NA). Conventional influenza virus vaccines induce neutralizing antibodies that are predominantly directed to the HA globular head, a domain that is subject to extensive antigenic drift. Antibodies directed to NA are induced at much lower levels, probably as a consequence of the immunodominance of the HA antigen. Although antibodies to NA may affect virus release by inhibiting the sialidase function of the glycoprotein, the antigen has been largely neglected in past vaccine design. In this study, we characterized the protective properties of monospecific immune sera that were generated by vaccination with recombinant RNA replicon particles encoding NA. These immune sera inhibited hemagglutination in an NA subtype-specific and HA subtype-independent manner and interfered with infection of MDCK cells. In addition, they inhibited the sialidase activities of various influenza viruses of the same and even different NA subtypes. With this, the anti-NA immune sera inhibited the spread of H5N1 highly pathogenic avian influenza virus and HA/NA-pseudotyped viruses in MDCK cells in a concentration-dependent manner. When chickens were immunized with NA recombinant replicon particles and subsequently infected with low-pathogenic avian influenza virus, inflammatory serum markers were significantly reduced and virus shedding was limited or eliminated. These findings suggest that NA antibodies can inhibit virus dissemination by interfering with both virus attachment and egress. Our results underline the potential of high-quality NA antibodies for controlling influenza virus replication and place emphasis on NA as a vaccine antigen. IMPORTANCE The neuraminidase of influenza A viruses is a sialidase that acts as a receptor-destroying enzyme facilitating the release of progeny virus from infected cells. Here, we demonstrate that monospecific anti-NA immune sera inhibited not only sialidase activity, but also influenza virus hemagglutination and infection of MDCK cells, suggesting that NA antibodies can interfere with virus attachment. Inhibition of both processes, virus release and virus binding, may explain why NA antibodies efficiently blocked virus dissemination in vitro and in vivo. Anti-NA immune sera showed broader reactivity than anti-HA sera in hemagglutination inhibition tests and demonstrated cross-subtype activity in sialidase inhibition tests. These remarkable features of NA antibodies highlight the importance of the NA antigen for the development of next-generation influenza virus vaccines.

Impact of Sn/F Pre-Treatments on the Durability of Protective Coatings against Dentine Erosion/Abrasion.

For preventing erosive wear in dentine, coating with adhesives has been suggested as an alternative to fluoridation. However, clinical studies have revealed limited efficacy. As there is first evidence that Sn(2+) increases bond strength of the adhesive Clearfil SE (Kuraray), the aim of the present study was to investigate whether pre-treatment with different Sn(2+)/F(-) solutions improves the durability of Clearfil SE coatings. Dentine samples (eight groups, n=16/group) were freed of smear layer (0.5% citric acid, 10 s), treated (15 s) either with no solution (control), aminefluoride (AmF, 500 ppm F(-), pH 4.5), SnCl2 (800/1600 ppm Sn(2+); pH 1.5), SnCl2/AmF (500 ppm F(-), 800 ppm Sn(2+), pH 1.5/3.0/4.5), or Elmex Erosion Protection Rinse (EP, 500 ppm F-, 800 ppm Sn(2+), pH 4.5; GABA International), then rinsed with water (15 s) and individually covered with Clearfil SE. Subsequently the specimens were subjected to an erosion/abrasion protocol consisting of 1320 cycles of immersion in 0.5% citric acid (5 °C/55 °C; 2 min) and automated brushing (15 s, 200 g, NaF-toothpaste, RDA 80). As the coatings proved stable up to 1320 cycles, 60 modified cycles (brushing time 30 min/cycle) were added. Wear was measured profilometrically. After SnCl2/AmF, pH 4.5 or EP pre-treatment all except one coating survived. In the other groups, almost all coatings were lost and there was no significant difference to the control group. Pre-treatment with a Sn(2+)/F(-) solution at pH 4.5 seems able to improve the durability of adhesive coatings, rendering these an attractive option in preventing erosive wear in dentine.

Ventilation/perfusion SPECT/CT in patients with pulmonary emphysema. Evaluation of software-based analysing

UNLABELLED The purpose of this study was to evaluate the reproducibility of a new software based analysing system for ventilation/perfusion single-photon emission computed tomography/computed tomography (V/P SPECT/CT) in patients with pulmonary emphysema and to compare it to the visual interpretation. PATIENTS, MATERIAL AND METHODS 19 patients (mean age: 68.1 years) with pulmonary emphysema who underwent V/P SPECT/CT were included. Data were analysed by two independent observers in visual interpretation (VI) and by software based analysis system (SBAS). SBAS PMOD version 3.4 (Technologies Ltd, Zurich, Switzerland) was used to assess counts and volume per lung lobe/per lung and to calculate the count density per lung, lobe ratio of counts and ratio of count density. VI was performed using a visual scale to assess the mean counts per lung lobe. Interobserver variability and association for SBAS and VI were analysed using Spearman's rho correlation coefficient. RESULTS Interobserver agreement correlated highly in perfusion (rho: 0.982, 0.957, 0.90, 0.979) and ventilation (rho: 0.972, 0.924, 0.941, 0.936) for count/count density per lobe and ratio of counts/count density in SBAS. Interobserver agreement correlated clearly for perfusion (rho: 0.655) and weakly for ventilation (rho: 0.458) in VI. CONCLUSIONS SBAS provides more reproducible measures than VI for the relative tracer uptake in V/P SPECT/CTs in patients with pulmonary emphysema. However, SBAS has to be improved for routine clinical use.

Ventilation/perfusion SPECT or SPECT/CT for lung function imaging in patients with pulmonary emphysema?

PURPOSE To evaluate the utility of attenuation correction (AC) of V/P SPECT images for patients with pulmonary emphysema. MATERIALS AND METHODS Twenty-one patients (mean age 67.6 years) with pulmonary emphysema who underwent V/P SPECT/CT were included. AC/non-AC V/P SPECT images were compared visually and semiquantitatively. Visual comparison of AC/non-AC images was based on a 5-point likert scale. Semiquantitative comparison assessed absolute counts per lung (aCpLu) and lung lobe (aCpLo) for AC/non-AC images using software-based analysis; percentage counts (PC = (aCpLo/aCpLu) × 100) were calculated. Correlation between AC/non-AC V/P SPECT images was analyzed using Spearman's rho correlation coefficient; differences were tested for significance with the Wilcoxon rank sum test. RESULTS Visual analysis revealed high conformity for AC and non-AC V/P SPECT images. Semiquantitative analysis of PC in AC/non-AC images had an excellent correlation and showed no significant differences in perfusion (ρ = 0.986) or ventilation (ρ = 0.979, p = 0.809) SPECT/CT images. CONCLUSION AC of V/P SPECT images for lung lobe-based function imaging in patients with pulmonary emphysema do not improve visual or semiquantitative image analysis.

Less invasive ventilation in extremely low birth weight infants from 1997 to 2011: survey versus evidence.

UNLABELLED Evidence for target values of arterial oxygen saturation (SaO2), CO2, and pH has changed substantially over the last 20 years. A representative survey concerning treatment strategies in extremely low-birth-weight infants (ELBW) was sent to all German neonatal intensive care units (NICUs) treating ELBW infants in 1997. A follow-up survey was conducted in 2011 and sent to all NICUs in Germany, Austria, and Switzerland. During the observation period, NICUs targeting SaO2 of 80, 85, and 90 % have increased, while units aiming for 94 and 96 % decreased (all p < 0.001). Similarly, NICUs aiming for pH 7.25 or lower increased, while 7.35 or higher decreased (both p < 0.001). Furthermore, more units targeted a CO2 of 50 mmHg (7.3 kPa) or higher (p < 0.001), while fewer targeted 40 or 35 mmHg (p < 0.001). Non-invasive ventilation (NIV) was used in 80.2 % of NICUs in 2011. The most frequently used ventilation modes were synchronized intermittent mandatory ventilation (SIMV) (67.5 %) and intermittent positive pressure ventilation (IPPV) (59.7 %) in 1997 and SIMV (77.2 %) and synchronized intermittent positive pressure ventilation (SIPPV) (26.8 %) in 2011. NICUs reporting frequent or always use of IPPV decreased to 11.0 % (p < 0.001). SIMV (77.2 %) and SIPPV (26.8 %) did not change from 1997 to 2011, while high-frequency oscillation (HFO) increased from 9.1 to 19.7 % (p = 0.018). Differences between countries, level of care, and size of the NICU were minimal. CONCLUSIONS Target values for SaO2 decreased, while CO2 and pH increased significantly during the observation period. Current values largely reflect available evidence at time of the surveys. WHAT IS KNOWN • Evidence concerning target values of oxygen saturation, CO 2 , and pH in extremely low-birth-weight infants has grown substantially. • It is not known to which extent this knowledge is transferred into clinical practice and if treatment strategies have changed. WHAT IS NEW • Target values for oxygen saturation in ELBW infants decreased between 1997 and 2011 while target values for CO 2 and pH increased. • Similar treatment strategies existed in different countries, hospitals of different size, or university versus nonuniversity hospitals in 2011.

Protective effect of a germline, IL-17-neutralizing antibody in murine models of autoimmune inflammatory disease.

Monoclonal antibodies (mAbs) inhibiting cytokines have recently emerged as new drug modalities for the treatment of chronic inflammatory diseases. Interleukin-17 (IL-17) is a T-cell-derived central mediator of autoimmunity. Immunization with Qβ-IL-17, a virus-like particle based vaccine, has been shown to produce autoantibodies in mice and was effective in ameliorating disease symptoms in animal models of autoimmunity. To characterize autoantibodies induced by vaccination at the molecular level, we generated mouse mAbs specific for IL-17 and compared them to germline Ig sequences. The variable regions of a selected hypermutated high-affinity anti-IL-17 antibody differed in only three amino acid residues compared to the likely germline progenitor. An antibody, which was backmutated to germline, maintained a surprisingly high affinity (0.5 nM). The ability of the parental hypermutated antibody and the derived germline antibody to block inflammation was subsequently tested in murine models of multiple sclerosis (experimental autoimmune encephalomyelitis), arthritis (collagen-induced arthritis), and psoriasis (imiquimod-induced skin inflammation). Both antibodies were able to delay disease onset and significantly reduced disease severity. Thus, the mouse genome unexpectedly encodes for antibodies with the ability to functionally neutralize IL-17 in vivo.

Transmission of Mycobacterium chimaera from Heater-Cooler Units during Cardiac Surgery despite an Ultraclean Air Ventilation System.

Heater-cooler units (HCUs) were recently identified as a source of Mycobacterium chimaera causing surgical site infections. We investigated transmission of this bacterium from HCUs to the surgical field by using a thermic anemometer and particle counter, videotape of an operating room equipped with an ultraclean laminar airflow ventilation system, and bacterial culture sedimentation plates in a nonventilated room. Smoke from the HCU reached the surgical field in 23 s by merging with ultraclean air. The HCU produced on average 5.2, 139, and 14.8 particles/min in the surgical field at positions Off, On/oriented toward, and On/oriented away, respectively. Culture plates were positive for M. chimaera <5 m from the HCU in the test room. These experiments confirm airborne transmission of M. chimaera aerosols from a contaminated HCU to an open surgical field despite ultraclean air ventilation. Efforts to mitigate infectious risks during surgery should consider contamination from water sources and airflow-generating devices.