The mechanisms by which cigarette smoke attenuates airway eosinop

The mechanisms by which cigarette smoke attenuates airway eosinophilia are not currently understood. Trimble et al. (2009) observed robust eosinophilic airway inflammation in mice that

were exposed to smoke over a sensitization period only, while eosinophilic airway inflammation was attenuated by continuous cigarette smoke exposure (Trimble et al., 2009). These findings imply that cigarette smoke has both adjuvant and anti-inflammatory properties in models of allergic airway inflammation. Moerloose et al. (2005) observed an exacerbation of the inflammatory responses in animals exposed to smoke (Moerloose et al., 2005). The reasons for these discordant results are unclear. Differences in the experimental approaches may partially explain these results. 5-Fluoracil Seymour et al. (1997) suggested that exposure to mainstream cigarette smoke or environmental tobacco smoke (ETS) can result in different effects on inflammation and sensitization. In their experiment, they observed that exposure of mice to ETS up-regulated allergic responses to inhaled allergens, while mainstream exposure to cigarette smoke (similar to our experimental model) could act in an opposite way (Seymour et al., 1997). In our experimental model, we observed an increase in the selleck products elastance response to a nebulized

methacholine solution in the OVA group. This increase in pulmonary responsiveness was observed when Htis was measured but not when Raw was studied, suggesting that the site of the response was in the lung parenchyma and/or distal airways and not in the central airways. Peták et al. (1997) studied the effects of methacholine-induced bronchoconstriction in rats in response to intravenous (i.v.) versus aerosol administration and suggested that Mch acts on distinct structures when delivered by inhalation or i.v. Mch produces a muscle contraction by stimulating the muscarinic cholinergic receptors (Peták et al., 1997). Sly et al. (1995) investigated the

role of the muscarinic receptors in puppies and observed that different receptors may be involved in producing airway and parenchymal constriction in response Orotic acid to inhaled Mch. M3 receptors located on the airway smooth muscle are likely to be responsible for airway responses and may be more easily reached by i.v.-delivered Mch, whereas Mch delivered by the aerosol route must diffuse across the respiratory epithelium before reaching the muscle (Barnes, 1993). In contrast, M1 receptors in the alveolar wall, which are reported to be involved in the parenchymal response (Sly et al., 1995), are likely to be reached more easily by aerosol delivery than by the i.v. route.

e the decrease in PO2PO2, as seen in Fig 1 and Fig 2) This ph

e. the decrease in PO2PO2, as seen in Fig. 1 and Fig. 2). This phenomenon was observed at all RR and I:E ratios, including I:E ratios of 1:3 and 1:2 (data not shown, but recorded in our studies). In critical care settings,

the PMMA sensor’s fast response time could offer the possibility LDN-193189 manufacturer to detect the kinetics of lung collapse more accurately, and to monitor the effects of lung recruiting manoeuvres on a breath-by-breath basis. In a wider perspective, it could provide information on the kinetics of alveolar recruitment, the understanding of which might form the basis of attempts to moderate the risks of ventilation-induced lung injury ( Albert, 2012), and to support the development of new mathematical models of the lung ( Hahn and Farmery, 2003, Suki et al., 1994 and Whiteley et al., 2003). A comment can also be made here on the limitations of the technology used by the AL300 sensor. The fluorescence intensity   measurement Screening Library in vivo ( Baumgardner et al., 2002 and Syring et al., 2007) is not only a function of the local PO2PO2, but it also depends on the optical properties of the medium, the ambient light intensity

and potential degradation of the sensor fluorophore itself ( McDonagh et al., 2001). Some fluorescence will be transmitted directly down the fibre to be measured, and a variable amount of light will be scattered by the red blood cells before being transmitted back down the fibre. This scattered light intensity will vary with haematocrit and with the

colour (i.e. saturation) of the blood, meaning that the signal is also influenced by SaO2. Light intensity dependent sensors must be calibrated uniquely for each clinical setting, and their output will be somewhat non-linear. In particular, intensity measurement could become particularly inaccurate when saturation drops below ∼90%, where relatively small changes in PO2PO2 are associated with large changes in saturation. Because of this limitation, it is not possible to compare directly PaO2PaO2 oscillations and varying shunt fraction for oxygen saturation levels below 90%. In order to avoid this technical limitation, previous studies [apart from Bergman, 1961a and Bergman, 1961b] have restricted their ARDS animal models Telomerase to small shunts (where arterial blood saturation was maintained near to 100%) and so changes in saturation did not influence the measurements (Baumgardner et al., 2002 and Syring et al., 2007). This, however, is not entirely reflective of the population of patients in the critical care setting who may have more significant degrees of recruitable and non-recruitable shunt and who may be desaturated throughout the respiratory cycle, or at least at end-expiration. An alternative solution is to measure fluorescence quenching lifetime (McDonagh et al.

, 2011) The preponderance of deposition in small watersheds sugg

, 2011). The preponderance of deposition in small watersheds suggests that LS deposits are most likely to be found in tributary locations if storage sites

are available, OTX015 but that this sediment will be reworked and redistributed downstream through time. A late 20th century trend in some North American catchments has been for SDRs that were much less than one, owing to high soil erosion rates, to increase as soil conservation measures were employed. As upland sediment production decreases, sediment yields remain constant by recruitment of LS from channel banks and floodplains (Robinson, 1977). The dynamics implied by sediment delivery theory have great import to interpretations of LS. Sediment yields in the modern world are not static as was once assumed, but have a dynamic behavior that is largely driven by the legacy of past sedimentation events (Walling, 1996). Temporal variability occurs in the form of regional differences between large basins

and by variability in sediment retention times within a basin. Regional differences reflect the cultural histories of landscapes; i.e., times of settlement and intensities of land use, as well as differences in the physical characteristics. Variations in sediment Dorsomorphin concentration retention time within a catchment is one of the greatest sources of uncertainty LY294002 in computing sediment yields and sediment budgets for watersheds (Wolman, 1977 and Gellis et al., 2009). Temporal connectivity is an important element of LS and sediment delivery theory, because past deposits are reworked and transported downslope for long periods of time after initial

deposition. This is, in fact, why ‘legacy’ is an appropriate way to describe these sediments; they are an inheritance from times past that should be reckoned with. Numerous studies of anthropogeomorphic impacts since the Neolithic have documented sedimentation events in a variety of geomorphic environments. Legacy sediment (LS) is now commonly used in geomorphic, ecological, water quality, and toxicological studies to describe post-settlement alluvium on river floodplains. Most applications of LS imply or explicitly attribute the sediment to human landscape changes, but explicit definitions have been lacking that are sufficiently broad to apply LS to the variety of applications now common. The concept of LS should apply to anthropogenic sediment that was produced episodically over a period of decades or centuries, regardless of position on the landscape, geomorphic process of deposition, or sedimentary characteristics; i.e., it may occur as hillslope colluvium, floodplain alluvium, or lacustrine and estuarine slackwater deposits.

, 2002a, DeLuca et al , 2002b and Zackrisson et al , 2004) Assum

, 2002a, DeLuca et al., 2002b and Zackrisson et al., 2004). Assuming GSK1349572 wildfires

consume approximately 30–60% of the total N in the O horizon ( Neary et al., 2005) (which in this case would be about 200 kg N ha−1), the annual contribution of N by feathermosses could have replenished this N loss in about 200 years (100 years of forest succession followed by 100 years of N2 fixation). Regular burning would have consumed the moss bottom layer ( Payette and Delwaide, 2003) and greatly reduced the presence of juniper ( Diotte and Bergeron, 1989 and Thomas et al., 2007) resulting in an un-surmountable loss of N, the loss of the predominant N source, and ultimately the loss of the capacity to support stand N demands (approximately 30 kg available N ha−1 yr−1) of a mature Scots pine, Norway spruce forest of ( Mälkönen, 1974). Reindeer do LBH589 solubility dmso not eat feathermosses, thus their presence on the forest floor was likely of no value to reindeer herders and may have

been looked upon as a nuisance. Consequently, the use of fire to transform dwarf-shrub/moss dominated forests into lichen dominated heaths to provide reindeers with winter grazing land would rather be essential for, and not be in conflict with, the traditional way of living for reindeer herders. The findings of these studies build upon the thesis put forth by Hörnberg et al. (1999) which suggested that the spruce-Cladina forests were altered by past land management and specifically repeated use of fire. The recurrent fires led to the loss of nutrient capital on these sites and thereby reducing the potential for pines to regenerate and recolonize these otherwise open forest stands.

This is further enough supported by previous findings on the black spruce-Cladina forests within the permafrost zone of North America which suggest that repeated disturbance, predominantly fire, induced a change in structure, composition and function of boreal coniferous stands ( Girard et al., 2009, Payette et al., 2000 and Payette and Delwaide, 2003). Natural fire frequency due to lightning strikes in this region in northern Sweden is relatively low ( Granström, 1993) and historical fire intervals mainly driven by climate were likely 300 or more years ( Carcaillet et al., 2007). Human use of fire as a management tool apparently altered historical vegetative communities, reduced nutrient capital, and ultimately created conditions that have perpetuated the vegetative communities present in this region today. Even in subarctic areas of Fennoscandia, that are often considered to be the last wilderness of northern Europe, impact by low technology societies has consequently lead to profound changes in some ecosystems that were carefully selected due to some specific condition that made them manageable by simple means to serve a specific purpose; e.g. use of fire to provide winter grazing land.

Another study conducted in the Chianti area showed that, followin

Another study conducted in the Chianti area showed that, following the expansion of cultivations Afatinib mw in longitudinal rows, versus continued maintenance of terraces, erosion increased by 900% during the period 1954–1976, and the annual erosion in the longitudinal vineyards was approximately 230 t/ha (Zanchi and Zanchi, 2006). As a typical example, we chose the area of Lamole, situated in the municipality of Greve in Chianti, in the province of Florence. The area is privately

owned. The geological substrate is characterized by quartzose turbidites (42%), feldspathic (27%) sandstones, with calcite (7%), phyllosilicates (24%) and silty schists, while in the south there are friable yellow and grey marls of Oligocene origin (Agnoletti et al., 2011). For this specific area, where the terracing stone

wall practice has been documented since the nineteenth century (see the detail of Fig. 7, where the year “1868” is carved in the stone), some authors have underlined a loss of approximately 40% of the terracing over the last 50 years due to less regular maintenance of the dry-stone walls (Agnoletti et al., 2011). As of today, 10% of the remaining terraces are affected by secondary successions following the abandonment of farming activities. Beginning in 2003, the restoring of the terraces and the planting of new vineyards follows an avant-garde project that aims at reaching an optimal level of mechanization as well as leaving the typical landscape elements undisturbed. However, a few months after the restoration, see more the terraces displayed deformations and slumps that became a critical issue for the Lamole vineyards. Recently, several field surveys have been carried out using a differential GPS (DGPS) with the purpose of mapping all the terrace failure signatures that have occurred since

terraces restoration in 2003, and to better analyze the triggering mechanisms and failures through hydrologic and geotechnical instrumentation analysis. Fig. 8a very shows an example of terrace failure surveyed in the Lamole area during the spring 2013. In addition to these evident wall slumps, several minor but significant signatures of likely instabilities and before failure wall deformations have been observed (Fig. 8b and c). The Fig. 8b shows a crack failure signature behind the stone wall, while Fig. 8c shows an evident terrace wall deformation. The research is ongoing, anyway it seems that the main problem is related both to a lack of a suitable drainage system within terraces and to the 2003 incorrect restoration of the walls that reduced the drainage capability of the traditional building technique (a more detailed description and illustrations about this problem are given in Section 3.2).

3 m diameter) Vegetation analyses were performed during the summ

3 m diameter). Vegetation analyses were performed during the summer of 2011. Soil samples find more were collected in the summer of 2008. Linear transects were established in the spruce-Cladina forest and in the reference forest. Subplots were established at 12 stops spaced approximately 20 m apart along each transect. The

depth of the soil humus layer was measured in each subplot and soil humus samples were collected using a 5 cm diameter soil core with the whole humus layer being collected in each sample. Humus bulk density was determined on each of these samples by drying the humus samples at 70 °C, weighing the mass of the sample and dividing that value by the volume of the soil core collected. Humus samples were also measured for total C and N by using a dry combustion analyzer (Leco True Spec, St Joe Michigan). Mineral soil samples were

collected to a depth of 10 cm using a 1 cm diameter soil probe. Each sample was created as a composite of three subsamples with a total of eight samples per stand and 24 for each stand type. Samples were dried at 70 °C, sieved through a 2 mm sieve and analyzed for pH, total C, N, phosphorus (P), potassium (K) and zinc (Zn). Samples were analyzed for available magnesium (Mg) and calcium (Ca) by shaking 10 g sample in 50 ml of 1 M NH4AOc and analyzed on an atomic absorption spectrophotometer. To evaluate concentrations of plant available N and P, ionic resin capsules (Unibest, Bozeman, MT) were buried at the interface of the humus layer and mineral soil in June 2008 and allowed to remain in place until June 2009. Resins were collected from the field and placed in mTOR inhibitor a −20 °C constant temperature cabinet until Clomifene analysis. Resins were extracted by placing the capsules into 10 ml of 1.0 M KCl, shaking for 30 min, decanting, and repeating this process two more times to create a total volume of 30 ml of extractant. Resin extracts were then measured for NH4+-N by using the Bertholet reaction ( Mulvaney, 1996), NO3−-N by a hydrazine method ( Downes, 1978), and phosphate by

molybdate method ( Kuo, 1996) using a 96 well plate counter. Three replicate soil samples (0–5 cm of mineral soil) were collected for charcoal analyses by using a 1 cm diameter soil core with each sample created as a composite of five subsamples. Samples were measured for total charcoal content using a 16 h peroxide, dilute nitric acid digestion in digestion tubes fitted with glass reflux caps ( Kurth et al., 2006). Total C remaining in the digests was determined by dry combustion. Peat samples were collected in the summer of 2011 in an ombrothrophic mire located immediately adjacent to the spruce-Cladina forest at Kartajauratj and east of Lake Kartajauratj, 66°57′48″ N; 19°26′12″ E, by the use of a Russian peat sampler ( Jowsey, 1966). The total peat depth was 125 cm from which the uppermost 40 cm were used for pollen analysis. Samples of 1.

In the 13th century the city of Venice had around 100,000 inhabit

In the 13th century the city of Venice had around 100,000 inhabitants. The data set consists of more than 850 acoustic survey lines for a total of about 1100 km (Fig. 1b). The acoustic survey was carried out with a 30 kHz Elac LAZ 72 single-beam echosounder with a DGPS positioning system mounted on a small boat with an average survey speed of 3–4 knots. The survey grid is composed of parallel lines mainly in the north-south direction with a spacing of 50 m and some profiles in the east–west direction. The sampling frequency was 50 Hz, with 500 samples (10 ms) recorded for each echo signal envelope and the pulse length of the SBE was 0.15 ms. The pulse

repetition rate was 1.5 pulses s−1. Data Alisertib nmr were collected between 2003 and 2009. During the acquisition, we changed the settings to obtain the best information over the buried structures visible in the acoustic profiles. We used the highest transmitting power together with suitable amplification of the signal in order to achieve the maximum penetration of the 30 kHz waves (5 cm wave length in the water) in the lagoon sediments. The gain value was set between 4 and 5 (scale from 1 to 10). These settings

provided a 6–7 m visibility of the sub-bottom layers. A more detailed description of the method used to acquire the profiles can be found in Madricardo Baf-A1 cost et al., Farnesyltransferase 2007 and Madricardo et al., 2012. Numerous sediment cores were extracted in the central lagoon

(Fig. 1b) with an average recovery of about 8.5 m, permitting the definition of all the features identified in the acoustic profiles. Most of the cores crossed acoustic reflectors interpreted as palaeochannels and palaeosurfaces. Five cores were used in this study: SG24, SG25, SG26, SG27, SG28. The cores (core diameter 101 mm) were acquired using a rotation method with water circulation. Each core was split, photographed, and described for lithology, grain size (and degree of sorting), sedimentary structures, physical properties, Munsell color, presence of plant remains and palaeontological content. Moreover, we sampled the sediment cores for micropalaeontological and radiometric analyses. The quantitative study of foraminifera distribution patterns is very important for palaeoenvironmental reconstruction. The organic content was composed of crushed mollusc shells mixed with abundant tests of benthic foraminifera. We classified at least 150 foraminiferal specimens from each sample according to the taxonomic results of Loeblich and Tappan (1987), in order to identify the biofacies corresponding to different environmental conditions. Percent abundance was used for statistical data processing. Through analyses of the sediment cores, we identified the diagnostic sedimentary facies that are described in detail in Madricardo et al. (2012).

CD usually presents in younger patients with oedema and ulceratio

CD usually presents in younger patients with oedema and ulcerations in the small and large intestines, and intestinal strictures and fistulas often develop. CD most commonly affects the terminal ileum, but any site in the gastrointestinal tract may be involved [5]. Extra-intestinal complications of CD include joint complications (ankylosing spondylitis, sacroiliitis, peripheral arthritis), skin complications (erythema nodosum, pyoderma gangrenosum), ocular complications (episcleritis, scleritis, uveitis), hepatobiliary complications (primary sclerosing cholangitis), and pulmonary complications (organizing pneumonia) [6]. Alpelisib clinical trial When granulomatous lesions develop in CD

patients, granulomatous infections such as mycobacterial or fungal ISRIB purchase infections, drug-induced pneumonia, and sarcoidosis must be included in the differential diagnosis. Granulomas in CD are sarcoid-like granulomas, and the differential diagnosis between these two diseases is particularly important. A diagnosis of sarcoidosis requires 2 or more of the following 6 findings indicating a systemic reaction: bilateral pulmonary hilar lymphadenopathy, elevated serum ACE levels, a negative tuberculin reaction, marked uptake on gallium67 citrate scintigraphy,

lymphocytosis or an increased CD4/CD8 ratio in BAL fluid, and serum hypercalcaemia. Evaluation of these 6 items is important to exclude a diagnosis of sarcoidosis [7] and [8]. In patient 1 at the time of hospital admission, a QuantiFERON-TB blood assay was negative, acid-fast smear cultures of the bronchial lavage fluid were negative, and acid-fast staining of 4��8C TBLB specimens was negative. Thus, tuberculosis was unlikely. Grocott staining, β-D glucan, and cryptococcal antigen testing of the TBLB specimens were negative, so a fungal infection was also unlikely. The only item meeting the diagnostic criteria for sarcoidosis was a negative tuberculin reaction, but because the QuantiFERON-TB test was also negative, this was thought to be of weak diagnostic significance, and sarcoidosis was

ruled out. In addition, drug treatment had not been switched during follow-up, so drug-induced pneumonia was also unlikely. Based on a diagnosis of exclusion and the histopathology, the findings were consistent with CD-related pulmonary lesions. In patient 2, the histopathologic examination revealed an epithelioid cell granuloma, multi-nucleated giant cells, and lymphocytic infiltration (Fig. 5). Acid-fast cultures of the bronchial lavage fluid and lung biopsy tissue were negative, so mycobacterial infection was unlikely. Sarcoidosis was also ruled out based on lack of elevation of serum ACE (15.5 IU/L) and a positive tuberculin reaction. Drug-induced lung disorder was also unlikely because the drug regimen had not been changed during outpatient treatment.

La confirmation se fait grâce à un examen ophtalmologique complet

La confirmation se fait grâce à un examen ophtalmologique complet et au test de Schirmer [7]. L’achalasie est le deuxième signe majeur du triple A

syndrome. C’est le motif de consultation le plus fréquent. Il se voit dans75% des cas [5]. L’âge d’apparition variant entre 6 mois et 16 ans. Elle est révélée par des vomissements à répétitions, une dysphagie, buy PD-0332991 des complications broncho-pulmonaires consécutive à des fausses routes. Chez nos patientes, l’achalasie est diagnostiquée à 4 et 5 ans respectivement suite à des fausses routes et des troubles de déglutitions. La confirmation diagnostique fait appel à la manométrie œsophagienne [9]. La TOGD a aussi un grand apport dans le diagnostic positif [10]. L’insuffisance surrénalienne est l’autre signe de la triade clinique du syndrome 3A, son âge de découverte

est variable, rare au cours de la première année de vie souvent il reste asymptomatique jusqu’à l’âge adulte. Les signes fonctionnels qui orientent vers le diagnostic sont des épisodes fréquents d’hypoglycémies, une fatigue intense, une perte de poids et surtout une hyperpigmentation [11]. L’atteinte surrénalienne au cours de ce syndrome prédomine sur le composant glucocorticoïde par résistance à l’ACTH. Cependant, une association à une atteinte minéralocorticoide peut se voir dans 15% des cas [5]. C’est le cas de notre première observation qui avait une atteinte en glucocorticoïde latente avec une hypokaliémie et une ARP pathologique. En plus de la triade classique, à ce syndrome peut s’associer une atteinte neurologique. En LY294002 datasheet 1987, Ehrich

et al. ont rapporté pour la première fois des manifestations neurologiques à type d’ataxie cérébelleuse, for atrophie optique et microcéphalie chez deux frères suivis pour le triple A syndrome [12]. C’est ne qu’en 1995, que Gazarini et al. ont noté l’association du syndrome 3A à des manifestations neurologiques et dysautonomiques, proposant ainsi le terme syndrome en 4A syndrome [12]. Les manifestations neurologiques sont présentes dans un tiers des cas, rare d’emblée [13] révélés souvent au cours de l’évolution. Elles sont hétérogènes et peuvent intéresser le système nerveux central, périphérique et autonome [13]. Les manifestations dysautonomiques sont rapportées dans 30% des cas [2]. Il peut s’agir d’une hypotension orthostatique, d’une impuissance sexuelle ou d’une atteinte des réflexes cardiovasculaire pouvant mettre le pronostic vital par arythmie sévère [5]. Concernant le système nerveux central l’atteinte peut comporter une épilepsie, un parkinsonisme, une ataxie cérébelleuse, une paraplégie spastique [7], un syndrome démentiel et un retard mental d’aggravation progressive [5]. Les manifestations périphériques, sont les moins documentées dans la littérature [14]. Vallet et al. [15] ont rapporté 4 patients avec une symptomatologie très évocatrice d’une polyneuropathie héréditaire ou une amyotrophie spinale distale.

Shortly thereafter, we discovered 4 more patients infected with H

Shortly thereafter, we discovered 4 more patients infected with H7N9. Finally, 4 of the 6 patients died, while 2 patients recovered. To the best of our knowledge, this is the first report of a patient who recovered from pneumonia induced by H7N9 infection. A 40-year-old man who complained of ‘fever, cough, and blood in sputum persisting for 3 days’ was admitted to the Fifth People’s Hospital of Shanghai, Fudan University, on 6 March 2013. He had a smoking history for 20 years (approximately 800 cigarettes/year)

with an unremarkable medical history. On admission (6 March), physical examination showed a stable respiratory rate (20/min), normal blood pressure (130/80 mmHg), tachycardia (heart rate, 120 bpm), and fever (body temperature, 39 °C). Moist rales were heard in the lower lobe of MG-132 in vivo the left lung. Arterial blood gas analysis revealed hypoxaemia (arterial oxygen, 64 mmHg). Blood test showed normal white blood cell (WBC) count (4.99 × 109/L), while the percentage of neutrophils (78.4%) was higher than the normal range. Chest-CT showed multiple

areas of segmental ground-glass opacity in the middle and lower lobe of the right lung with clear signs of air bronchogram; the left lung showed no pathological abnormality, and there were no signs of enlarged mediastinal lymph nodes (Fig. 1a). The patient was initially treated by moxifloxacin and oxygen treatment Selleck Pifithrin �� (nasal catheter oxygen inhalation with an oxygen flow rate of 4 L/min). On the day after admission (7 March), laboratory tests

showed elevated enzyme levels: creatine kinase (CK), 984 Methisazone U/L, creatine kinase isoenzymes (CK-MB), 20 U/L, lactate dehydrogenase (LDH), 498 U/L, alanine aminotransferase (ALT), 46 U/L, and aspartate aminotransferase (AST), 51 U/L. The patient’s body temperature did not return to normal. We continued to obverse him while providing physical cooling. On day 2 after admission (8 March), the patient’s clinical symptoms were not resolved, and his body temperature increased to 39.7 °C. Hypoxaemia persisted after inhaling oxygen (arterial blood gas analysis: pH 7.5; arterial partial pressure of carbon dioxide, 30 mmHg; arterial partial pressure of oxygen, 64 mmHg) (Table 1). We replaced moxifloxacin with meropenem as antibacterial therapy. After 4 days of treatment (10 March), the patient’s clinical symptoms were not resolved. A blood test revealed a decreased WBC count of 3.38 × 109/L, and increased levels of ALT of 217 U/L and AST of 160 U/L (Table 1). Chest-computed tomography (CT) showed that the opacities had become more confluent and dense, with a new large field of opacities in the right lung and patchy opacities in the lower lobe of the left lung. Inflammation had also clearly progressed (Fig. 1b). On the same day, a 27-year-old male patient died of progressive pneumonia and acute respiratory distress syndrome.