title: Biochemical analysis of the mouse mammary tumor virus long terminal repeat product. Evidence for the molecular structure of an endogenous superantigen

text: Recent reports have shown that both exogenous and endogenous mouse mammary tumor viruses (MMTV) can encode superantigens. Transfection and transgenic studies have identified the open reading frame (ORF) present in the 3′ long terminal repeat (LTR) as encoding superantigen function. In this study, we have used an in vitro translation system in an attempt to characterize the molecular nature of the protein encoded by the 3′ ORF of Mtv‐8. Using various constructs encoding full‐length and truncated versions of the ORF product, we report that the hydrophobic region close to the amino terminus of the 36‐kDa protein can function as a transmembrane domain. Protease digestion experiments also demonstrate that the protein has a type‐II transmembrane conformation with an extra‐cytoplasmic carboxy terminus. Since this hydrophobic region is conserved between all known MMTV, we speculate that LTR ORF, including those proposed to encode the minor lymphocyte stimulatory antigens, are also capable of encoding type‐II transmembrane glycoproteins. The polymorphism between MMTV LTR ORF products, which correlates with deletion phenotypes, is predominantly in the carboxy‐terminal extracellular region, consistent with a major role in interaction with the T cell receptor.


title: Ecohydrogeochemical functioning of coastal freshwater herbaceous wetlands in the Protected Natural Area, Ciénaga del Fuerte (American tropics): Spatiotemporal behaviour

text: Coastal zones are characterized by the interactions between continents and oceans and, therefore, between fresh and salt surface and groundwater. The wetlands of coastal zones represent transitional ecosystems that are affected by these conditions, although little is known about the hydrogeochemistry of wetlands, especially coastal wetlands. In the present study, the hydrogeochemical characterization of coastal freshwater herbaceous wetlands in the Ciénaga del Fuerte Protected Natural Area in Veracruz, Mexico, in the American tropics was carried out per plant community. Four herbaceous wetlands (alligator flag, saw grass, cattail, and floodplain pasture) were monitored to understand the origin of the water feeding these ecosystems, the hydrogeochemical composition of groundwater, and the relationship between the groundwater and ecology of these ecosystems during dry and rainy seasons. The results indicate that Ciénaga del Fuerte is located in a regional discharge area and receives local recharge, so it is fed by both regional and local flows. The chemical composition varied temporally and spatially, creating unique conditions that determined the habitat occupied by the hydrophytic vegetation. The spatiotemporal behaviour of groundwater is one factor that, along with the hydroperiod, determines wetland dynamics and affects wetland biota (ecohydrogeochemistry). Generalist plant communities established in zones of local recharge, whereas other more specialized and/or plastic communities inhabited zones receiving regional flows with greater ion concentrations. This information forms the basis for establishing an appropriate scale (municipal, state, or larger regions) for the sustainable management of goods and services provided by the wetlands.


title: Meta‐analysis of avian and small‐mammal response to fire severity and fire surrogate treatments in U.S. fire‐prone forests

text: Management in fire‐prone ecosystems relies widely upon application of prescribed fire and/or fire surrogate (e.g., forest thinning) treatments to maintain biodiversity and ecosystem function. Recently, published literature examining wildlife response to fire and fire management has increased rapidly. However, none of this literature has been synthesized quantitatively, precluding assessment of consistent patterns of wildlife response among treatment types. Using meta‐analysis, we examined the scientific literature on vertebrate demographic responses to burn severity (low/moderate, high), fire surrogates (forest thinning), and fire and fire surrogate combined treatments in the most extensively studied fire‐prone, forested biome (forests of the United States). Effect sizes (magnitude of response) and their 95% confidence limits (response consistency) were estimated for each species‐by‐treatment combination with two or more observations. We found 41 studies of 119 bird and 17 small‐mammal species that examined short‐term responses (≤4 years) to thinning, low/moderate‐ and high‐severity fire, and thinning plus prescribed fire; data on other taxa and at longer time scales were too sparse to permit quantitative assessment. At the stand scale (<50 ha), thinning and low/moderate‐severity fire demonstrated similar response patterns in these forests. Combined thinning plus prescribed fire produced a higher percentage of positive responses. High‐severity fire provoked stronger responses, with a majority of species possessing higher or lower effect sizes relative to fires of lower severity. In the short term and at fine spatial scales, fire surrogate forest‐thinning treatments appear to effectively mimic low/moderate‐severity fire, whereas low/moderate‐severity fire is not a substitute for high‐severity fire. The varied response of taxa to each of the four conditions considered makes it clear that the full range of fire‐based disturbances (or their surrogates) is necessary to maintain a full complement of vertebrate species, including fire‐sensitive taxa. This is especially true for high‐severity fire, where positive responses from many avian taxa suggest that this disturbance (either as wildfire or prescribed fire) should be included in management plans where it is consistent with historic fire regimes and where maintenance of regional vertebrate biodiversity is a goal.


17th International Congress of Immunology, 19–23 October 2019, Beijing, China


title: CHROMOSOME 15 IN PRADER‐WILLI SYNDROME

text: SUMMARY: Nineteen children with the clinical features of Prader‐Willi syndrome were karyotyped, using both routine Giemsa banding and high‐resolution techniques. Chromosome abnormalities involving chromosome 15 were found in 10, entirely normal chromosomes in five and for the remaining four the findings were either equivocal or difficult to interpret. There was no clinical distinction between cases with and without the chromosome anomaly. Examination of three parents and a group of controls showed that the proximal end of the long arm of chromosome 15 may have a considerable degree of normal variation, which can make interpretation difficult. RÉSUMÉ: Chromosome 15 et syndrome de Prader‐ Willi Un caryotype, utilisant les techniques de routine de bandes de Giemsa et de haute résolution, a été pratique chez 19 enfants présentant les caractéristiques cliniques du syndrome de Prader‐Willi. Des anomalies chromosomiques impliquant le chromosome 15 ont été trouvées dans 10 cas, les chromosomes étaient entièrement normaux dans cinq cas, les données étaient équivoques ou difficiles à interpréter dans les quatre cas restants. II n'y avait pas de distinction clinique entre les cas avec ou sans les anomalies chromosomiques. L'examen de la parenté et des contrôles a montré que l'extrémité proximale du bras long du chromosome 15 peut présenter un degré considérable de variation normale, ce qui peut rendre l'interprétation difficile. ZUSAMMENFASSUNG: Chromosom IS beim Prader‐ Willi Syndrom Von 19 Kindern mit den klinischen Merkmalen des Prader‐Willi syndroms wurde durch die Giemsa Bandentechnik und durch hone Auflösungstechniken der Karyotyp bestimmt. Bei 10 Kindern wurden Veränderungen des Chromosoms 15 gefunden, fünf hatten ganz normale Chromosomen und bei den restlichen vier waren die Befunde unklar oder schwer zu interpretieren. Klinisch fand sich kein Unterschied zwischen den Fällen mit und ohne Chromosomenveränderung. Untersuchungen von Eltern und Kontrollen ha ben gezeigt, daß das proximale Ende des langen Armes beim Chromosom 15 viele Normvarianten hat, wodurch die Interpretation erschwert werden kann. RESUMEN: El cromosoma 15 en el sindrome de Prader‐ Willi Se determinó el cariotipo de diecinueve niños con las caracteristicas clínicas del sindrome de Prader‐Willi, utilizando las técnicas de las bandas de Giemsa y de alta resolución. En 10 casos se hallaron anomalías en el cromosoma 15 y cromosomas normales en cinco, mientras que los otros cuatro casos era de interpretación equívoca o dificil. No había ninguna diferencia clínica entre los casos con o sin la anomalia cromosómica. El examen de los padres y de los controles mostró que el extremo proximal del brazo largo del cromosoma 15 muestra un grado considerable de variación normal, lo cual puede dificultar la interpretación.


title: Comparing agglomerative clustering and three weed classification frameworks to assess the invasiveness of alien species across spatial scales

text: To prioritize weed management at the catchment scale, information is required on the species present, their relatively frequency, abundance, and likely spread and impact. The objective of this study was to classify the invasiveness of alien species that have invaded the Upper Burdekin Catchment in Queensland, Australia, at three spatial scales. A combination of three published weed classification frameworks and multivariate techniques were employed to classify species based on their frequency and cover at a range of spatial scales. We surveyed the Upper Burdekin Catchment for alien species, and for each species determined the following distribution indices — site frequency, total cover, transect frequency per site frequency and quadrat frequency per site frequency, cover per quadrat when present, cover per transect when present, and cover per site when present. These indices capture the effect of species abundance and frequency between sites (site frequency and total cover), within sites (transect frequency per site and cover per transect when present), and within transects (quadrat frequency per site frequency and cover per site). They were used to classify the species into seven groups using a hierarchical cluster analysis. The relationship between the indices was explored to determine how effective the small scale, site‐specific indices were at predicting the broader, landscape‐scale patterns. Strong correlations were observed between transect frequency per site and frequency (r (2) = 0.89) and cover per transect when present and total cover (r (2) = 0.62). This suggests that if a weed is abundant at the site level, it has the potential to occupy large areas of the catchment. The species groupings derived from the application of the three published weed classification frameworks were compared graphically to the groupings derived from the cluster analysis. One of the frameworks classified species into three groups. The other two frameworks classified species into four groups. There was a high degree of subjectivity in applying the frameworks to the survey data. Some of the data were of no relevance to the classification frameworks and were therefore ignored. We suggest that the weed classification frameworks should be used in conjunction with existing multivariate techniques to ensure that classifications capture important natural variations in observed data that may reflect invasion processes. The combined use of the frameworks and multivariate techniques enabled us to aggregate species into categories appropriate for management.


title: Nodulation of Sesbania species by Rhizobium (Agrobacterium) strain IRBG74 and other rhizobia

text: Concatenated sequence analysis with 16S rRNA, rpoB and fusA genes identified a bacterial strain (IRBG74) isolated from root nodules of the aquatic legume Sesbania cannabina as a close relative of the plant pathogen Rhizobium radiobacter (syn. Agrobacterium tumefaciens). However, DNA:DNA hybridization with R. radiobacter, R. rubi, R. vitis and R. huautlense gave only 44%, 5%, 8% and 8% similarity respectively, suggesting that IRBG74 is potentially a new species. Additionally, it contained no vir genes and lacked tumour‐forming ability, but harboured a sym‐plasmid containing nifH and nodA genes similar to those in other Sesbania symbionts. Indeed, IRBG74 effectively nodulated S. cannabina and seven other Sesbania spp. that nodulate with Ensifer (Sinorhizobium)/Rhizobium strains with similar nodA genes to IRBG74, but not species that nodulate with Azorhizobium or Mesorhizobium. Light and electron microscopy revealed that IRBG74 infected Sesbania spp. via lateral root junctions under flooded conditions, but via root hairs under non‐flooded conditions. Thus, IRBG74 is the first confirmed legume‐nodulating symbiont from the Rhizobium (Agrobacterium) clade. Cross‐inoculation studies with various Sesbania symbionts showed that S. cannabina could form fully effective symbioses with strains in the genera Rhizobium and Ensifer, only ineffective ones with Azorhizobium strains, and either partially effective (Mesorhizobium huakii) or ineffective (Mesorhizobium plurifarium) symbioses with Mesorhizobium. These data are discussed in terms of the molecular phylogeny of Sesbania and its symbionts.


Sixth International Conference on Equine Infectious Diseases: Robinson College, Cambridge 7th–11th July 1991


title: NESTEDNESS OF REMNANT SONORAN DESERT PLANT COMMUNITIES IN METROPOLITAN PHOENIX, ARIZONA

text: Urbanization can have profound effects on the plant communities persisting in remnant habitats. That process can be explored by examining patterns of nestedness. Species composition for a set of communities exhibits a nested pattern if species present in progressively richer assemblages form a series of subsets. Nestedness can form as a result of the dynamic processes of extinction or colonization. It can also reflect a nested distribution of habitats among the sites or the differential abundance properties of species through passive sampling. This study investigated whether Sonoran Desert woody vegetation in remnant islands within metropolitan Phoenix is nested and explored which mechanisms are responsible for the pattern. It also examined whether vegetation is nested in similar habitat types across islands, and how species abundance relates to the nested pattern and hypothesized mechanisms. All data sets were significantly nested, indicating a nested pattern at the island and habitat levels. Community‐level analyses did not indicate a primary mechanism leading to the nested pattern. Among species with abundances correlated with the nested rank‐order of sites, abundance properties were significantly related to different variables. This suggests that individual taxa respond to divergent ecological mechanisms, leading to nestedness. Thus, nestedness in plant communities can result from a complex set of contributors and may not be attributable to a single factor.


CLINICAL QUIZ


title: Landscape structure influences modularity patterns in farm food webs: consequences for pest control

text: Landscape management affects species interactions within a community, leading to alterations in the structure of networks. Modules are link‐dense regions of the network where species interact more closely within the module than between modules of the network. Insufficient network resolution has meant that modules have proved difficult to identify, even though they appear important in the propagation of disturbance impacts. We applied a standardized approach across 20 farms to obtain well‐resolved food webs to characterize network structure and explore how modularity changes in response to management (organic and conventional). All networks showed significantly higher modularity than random networks. Farm management had no effect on the number of modules per farm or module richness, but there was a significant loss of links between modules on conventional farms, which may affect the long‐term stability of these networks. We found a significant association between modules and major habitat groups. If modules form as a result of interactions between species that utilize similar habitats, then ecosystem services to the crop components of the landscape, such as pest control by parasitoids originating in the non‐crop vegetation, are less likely to occur on these farms.


title: Multidimensional tree niches in a tropical dry forest

text: The extent to which interspecific niche differences structure plant communities is highly debated, with extreme viewpoints ranging from fine‐scaled niche partitioning, where every species in the community is specialized to a distinct niche, to neutrality, where species have no niche or fitness differences. However, there exists a default position wherein niches of species in a community are determined by their evolutionary and biogeographic histories, irrespective of other species within the community. According to this viewpoint, a broad range of pair‐wise niche overlaps—from completely overlapping to completely distinct—are expected in any community without the need to invoke interspecific interactions. We develop a method that can test for both habitat associations and niche differences along an arbitrary number of spatial and temporal niche dimensions and apply it to a 24‐yr data set of the eight dominant woody‐plant species (representing 84% and 76% of total community abundance and basal area, respectively) from a 50‐ha permanent plot in a southern Indian tropical dry forest, using edaphic, topographic, and precipitation variables as niche axes. Species separated into two broad groups in niche space—one consisting of three canopy species and the other of a canopy species and four understory species—along axes that corresponded mainly to variation in soil P, Al and a topographic index of wetness. Species within groups tended to have significantly greater niche overlap than expected by chance. Community‐wide niche overlap in spatial and temporal niche axes was never smaller than expected by chance. Species‐habitat associations were neither necessary nor sufficient preconditions for niche differences to be present. Our results suggest that this tropical dry‐forest community consists of several tree species with broadly overlapping niches, and where significant niche differences do exist, they are not readily interpretable as evidence for niche differentiation. We argue, based on a survey of the literature, that many of the observed niche differences in tropical forests are more parsimoniously viewed as autecological differences between species that exist independently of interspecific interactions.


title: MULTIPLE ORIGINS OF SEX CHROMOSOME FUSIONS CORRELATED WITH CHIASMA LOCALIZATION IN HABRONATTUS JUMPING SPIDERS (ARANEAE: SALTICIDAE)

text: Entelegyne spiders rarely show fusions yielding neo‐Y chromosomes, which M. J. D. White attributed to a constraint in spiders, namely their proximal chiasma localization acting to upset meiotic segregation in males with fusions. Of the 75 taxa of Habronattus and outgroups studied, 47 have X(1)X(2)0 sex chromosomes in males, 10 have X(1)X(2)Y, 15 have X(1)X(2)X(3)Y, 2 have X0, and one has both X(1)X(2)0 and X(1)X(2)X(3)Y. Chromosome numbers and behavior suggest neo‐Ys formed by an autosome‐X fusion to make X(1)X(2)Y, with a second fusion to an autosome to make X(1)X(2)X(3)Y. Phylogeny shows at least 8–15 gains (or possibly some losses) of neo‐Y (i.e., X‐autosome fusions), a remarkable number for such a small clade. In contrast to the many X‐autosome fusions, at most one autosome–autosome fusion is indicated. Origins of neo‐Y are correlated significantly with distal localization of chiasmata, supporting White's hypothesis that evolution of neo‐Y systems is facilitated by looser pairing (distal chiasmata) at meiosis. However, an alternative (or contributing) explanation for the correlation is that X‐autosome fusions were selected to permit isolation of male‐favored alleles to the neo‐Y chromosome, aided by distal chiasmata limiting recombination. This intralocus sexual conflict hypothesis could explain both the many X‐autosome fusions, and the stunning complexity of male Habronattus courtship displays.


Science‐in‐brief: Report on the Havemeyer Foundation workshop on acute colitis of the adult horse


title: Serum amyloid A in equine health and disease

text: Serum amyloid A (SAA) is the major acute phase protein in horses. It is produced during the acute phase response (APR), a nonspecific systemic reaction to any type of tissue injury. In the blood of healthy horses, SAA concentration is very low, but it increases dramatically with inflammation. Due to the short half‐life of SAA, changes in its concentration in blood closely reflect the onset of inflammation and, therefore, measurement of SAA useful in the diagnosis and monitoring of disease and response to treatment. Increases in SAA concentration have been described in equine digestive, reproductive and respiratory diseases and following surgical procedures. Moreover, SAA has proven useful for detection of some subclinical pathologies that can disturb training and competing in equine athletes. Increasing availability of diagnostic tests for both laboratory and field use adds to SAA's applicability as a reliable indicator of horses’ health status. This review article presents the current information on changes in SAA concentrations in the blood of healthy and diseased horses, focussing on clinical application of this biomarker.


Opinion of the Scientific Panel Animal Health and Welfare (AHAW) related with the Migratory Birds and their Possible Role in the Spread of Highly Pathogenic Avian Influenza


title: Processing of a viral glycoprotein in the endoplasmic reticulum for class II presentation

text: Endogenous processing of viral glycoproteins for presentation to CD4(+) T cells is a poorly investigated aspect of antigen processing and presentation. This pathway may involve not only pathogens, but also self proteins, and may thus be involved in self‐tolerance. We have characterized the processing of the endoplasmic reticulum‐restricted glycoprotein (G) of vesicular stomatitis virus, termed poison tail (Gpt), biochemically and enzymatically, and by T cell recognition assays. Expressed with a vaccinia vector, Gpt remains endoglycosidase H‐sensitive and does not mature to endoglycosidase D sensitivity. The protein is degraded in the ER with a T1/2 of 4 h. Gpt peptides are not secreted since Gpt‐infected cells are unable to sensitize uninfected antigen‐presenting cells in an innocent bystander assay. Using flow cytometry, Gpt is undetectable on the plasma membrane; in contrast, wild‐type G is readily found on the surface or secreted into the milieu as soluble G following infection of A20 cells with a vaccinia recombinant expressing G. The degradation of Gpt is sensitive to the thiol reagent diamide and occurs optimally at physiological pH. A series of proteolytic inhibitors were tested: 3,4‐dichloroisocoumarin and 1‐chloro‐3‐tosylamido‐7‐amino‐2‐heptanone inhibited degradation, which suggests the involvement of a serine protease. The degradation does not require transport to the Golgi complex, and is not sensitive to a variety of lysosomotropic agents. We show that the degradation products include the immunogenic epitopes recognized by a panel of T cell clones and hybridomas.


title: Development and implementation of a system for the early identification of emerging risks in food and feed

text: According to EFSA's Founding Regulation, the Authority is required to “undertake action to identify and characterise emerging risks” in the field of food and feed safety. EFSA provides scientific advice to the risk manager, at both European and Member State level, for the identification of risks present in the food chain. In the area of currently unrecognised but potentially significant risks for public health, EFSA has set up a dedicated unit on emerging risks (EMRISK). Through the identification of drivers of emerging risks, EFSA also intends to anticipate future risks derived from changes in current food/feed production practices or factors impinging on food/feed production or changes in human exposure through food consumption. EFSA aims to establish a data monitoring capacity, data filtering methodology and networking structures to identify emerging risks and drivers of emerging risks in a timely fashion and to communicate these to the risk manager. To date, the first step of this process (data monitoring) is in place. The following steps, that is, filtering and communication, are being rapidly established. Whilst the current data sources monitored are limited, they have been sufficient to enable the elaboration of the procedures for the next steps in the emerging risks identification process. As more data sources become accessible, the process will become more effective. All processes should be in place by mid −2010 and reported on in EFSA's first annual report on emerging risks in 2011. By the end of the second year of operation (2012), the soundness and utility of this approach will be given an initial review.


title: Scientific Opinion on the public health hazards to be covered by inspection of meat from sheep and goats

text: A risk ranking process identified Toxoplasma gondii and pathogenic verocytotoxin‐producing Escherichia coli (VTEC) as the most relevant biological hazards for meat inspection of sheep and goats. As these are not detected by traditional meat inspection, a meat safety assurance system using risk‐based interventions was proposed. Further studies are required on T. gondii and pathogenic VTEC. If new information confirms these hazards as a high risk to public health from meat from sheep or goats, setting targets at carcass level should be considered. Other elements of the system are risk‐categorisation of flocks/herds based on improved Food Chain Information (FCI), classification of abattoirs according to their capability to reduce faecal contamination, and use of improved process hygiene criteria. It is proposed to omit palpation and incision from post‐mortem inspection in animals subjected to routine slaughter. For chemical hazards, dioxins and dioxin‐like polychlorinated biphenyls were ranked as being of high potential concern. Monitoring programmes for chemical hazards should be more flexible and based on the risk of occurrence, taking into account FCI, which should be expanded to reflect the extensive production systems used, and the ranking of chemical substances, which should be regularly updated and include new hazards. Control programmes across the food chain, national residue control plans, feed control and monitoring of environmental contaminants should be better integrated. Meat inspection is a valuable tool for surveillance and monitoring of animal health and welfare conditions. Omission of palpation and incision would reduce detection effectiveness for tuberculosis and fasciolosis at animal level. Surveillance of tuberculosis at the slaughterhouse in small ruminants should be improved and encouraged, as this is in practice the only surveillance system available. Extended use of FCI could compensate for some, but not all, the information on animal health and welfare lost if only visual post‐mortem inspection is applied.


title: The distribution, abundance and host plant relationships of Salix‐ feeding psyllids (Homoptera: Psylloidea) in arctic Alaska

text: Abstract. 1. Five species of psyllid occurred on seven species of Salix at Meade River, Alaska. Studies were made on the two common species Psylla pclmeni Löw and P.phlebophyllae Hodkinson. The former feeds on the phanerophy tes Salix pulchra, S.lanata, S.alaxensis and S.glauca, the latter on the chamaephytes S.phlebophylla and S.reticulata. 2. Both P.palmeni and P.phlebophyllae had a 1‐year life cycle and nymphal development took place on the female Salix catkin. The life cycle was generally closely synchronized with the period of catkin development. However, only a few eggs were laid on S.glauca 3. Seasonal perturbation of the host plant by flooding, ice movement and blown sand prevented psyllids breeding in certain areas colonized by the host plant. 4. In P.palmenidensities and ‘feeding pressure’, measured as biomass of psyllids per gram of catkin, on the different host plants followed the sequence S.pulchra>S.lanata> S.alaxensis > S.glauca. In P.phlebophyllae densities and feeding intensities were similar onS.phlebophyllaandS.reticulataand grazing intensity was comparable withP.palmenion S.pulchra. 5. A highly significant negative correlation was found between psyllid density and catkin dry weight in S.pulchra, S.phlebophylla and S.reticulata, suggesting that psyllid feeding is affecting catkin growth. 6. Predation of psyllid nymphs by syrphid larvae was heavy but there was no evidence of parasitism. 7. The life history strategies of the five psyllid species are discussed within the context of the constraints imposed by the arctic environment.


Second Congress of Equine Surgery, Geneva, Switzerland — 11th to 13th December, 1991


title: Species prioritization for monitoring and management in regional multiple species conservation plans

text: Successful conservation plans are not solely achieved by acquiring optimally designed reserves. Ongoing monitoring and management of the biodiversity in those reserves is an equally important, but often neglected or poorly executed, part of the conservation process. In this paper we address one of the first and most important steps in designing a monitoring program – deciding what to monitor. We present a strategy for prioritizing species for monitoring and management in multispecies conservation plans. We use existing assessments of threatened status, and the degree and spatial and temporal extent of known threats to link the prioritization of species to the overarching goals and objectives of the conservation plan. We consider both broad and localized spatial scales to capture the regional conservation context and the practicalities of local management and monitoring constraints. Spatial scales that are commensurate with available data are selected. We demonstrate the utility of this strategy through application to a set of 85 plants and animals in an established multispecies conservation plan in San Diego County, California, USA. We use the prioritization to identify the most prominent risk factors and the habitats associated with the most threats to species. The protocol highlighted priorities that had not previously been identified and were not necessarily intuitive without systematic application of the criteria; many high‐priority species have received no monitoring attention to date, and lower‐priority species have. We recommend that in the absence of clear focal species, monitoring threats in highly impacted habitats may be a way to circumvent the need to monitor all the targeted species.


title: Politics of monitoring and evaluation: Lessons from the AIDS epidemic

text: Monitoring and evaluation programs must strike a balance between generating meaningful tactical information for program managers while taking steps to ensure that public data use does not worsen discrimination and stigma toward people who are positive for the human immunodeficiency virus.


title: Host–parasite interaction: multiple sites in the Plasmodium vivax tryptophan‐rich antigen PvTRAg38 interact with the erythrocyte receptor band 3

text: Tryptophan‐rich antigens of malarial parasites interact with host molecules and play an important role in parasite survival. Merozoite expressed Plasmodium vivax tryptophan‐rich antigen PvTRAg38 binds to human erythrocytes and facilitates parasite growth in a heterlologous Plasmodium falciparum culture system. Recently, we identified band 3 in human erythrocytes as one of its receptors, although the receptor‐ligand binding mechanisms remain unknown. In the present study, using synthetic mutated peptides of PvTRAg38, we show that multiple amino acid residues of its 12 amino acid domain (KWVQWKNDKIRS) at position 197–208 interact with three different ectodomains of band 3 receptor on human erythrocytes. Our findings may help in the design of new therapeutic approaches for malaria.


title: Components and regulation of nuclear transport processes

text: The spatial separation of DNA replication and gene transcription in the nucleus and protein translation in the cytoplasm is a uniform principle of eukaryotic cells. This compartmentalization imposes a requirement for a transport network of macromolecules to shuttle these components in and out of the nucleus. This nucleo‐cytoplasmic transport of macromolecules is critical for both cell physiology and pathology. Consequently, investigating its regulation and disease‐associated alterations can reveal novel therapeutic approaches to fight human diseases, such as cancer or viral infection. The characterization of the nuclear pore complex, the identification of transport signals and transport receptors, as well as the characterization of the Ran system (providing the energy source for efficient cargo transport) has greatly facilitated our understanding of the components, mechanisms and regulation of the nucleo‐cytoplasmic transport of proteins in our cells. Here we review this knowledge with a specific emphasis on the selection of disease‐relevant molecular targets for potential therapeutic intervention.


title: Seasonal changes in distribution and abundance of euphausiids in the coastal area of north‐eastern Japan

text: ABSTRACT: Seasonal changes in distribution and abundance of euphausiids off south‐eastern Hokkaido (41°−43°N), Sanriku (38°−41°N), and Joban (36°−38°N) were investigated using cylindrical‐conical nets every two months from March 1997 to February 1998. Twenty‐six species of seven genera of euphausiids occurred during the survey. Among them, subarctic‐transitional Euphausia pacifica was the most abundant throughout the year in coastal waters, as their relative contribution to the total abundance of euphausiids was 89–92%. This species occurred in each coastal water throughout the survey and was abundant from winter to early summer (February–June) off Sanriku and Joban and in autumn in south‐eastern Hokkaido. Thysanoessa inspinata occurred off south‐eastern Hokkaido and Sanriku throughout the survey, mainly in spring (April) but rarely occurred off Joban. Three other subarctic Thysanoessa species occurred mainly off south‐eastern Hokkaido from winter to spring. Conversely, warm‐ and transitional‐water epipelagic species occurred exclusively off Sanriku and Joban in autumn. The characteristics of seasonal distributional patterns of euphausiids are discussed in relation to the spatial and temporal changes of oceanographic conditions and several predators off north‐eastern Japan.


Endoplasmic reticulum (ER) stress triggers the integrated ER‐stress response (IERSR) that ensures cellular survival of ER stress and represents a primordial form of innate immunity. We investigated the role of IERSR during Leishmania amazonensis infection. Treatment of RAW 264.7 infected macrophages with the ER stress‐inducing agent thapsigargin (TG; 1 μM) increased L. amazonensis infectivity in an IFN1‐α receptor (IFNAR)‐dependent manner. In Western blot assays, we showed that L. amazonensis activates the inositol‐requiring enzyme (IRE1)/ X‐box binding protein (XBP)‐1‐splicing arms of the IERSR in host cells. In chromatin immunoprecipitation (ChIP) assays, we showed an increased occupancy of enhancer and promoter sequences for the Ifnb gene by XBP1 in infected RAW 264.7 cells. Knocking down XBP1 expression by transducing RAW 264.7 cells with the short hairpin XBP1 lentiviral vector significantly reduced the parasite proliferation associated with impaired translocation of phosphorylated IFN regulatory transcription factor (IRF)‐3 to the nucleus and a decrease in IFN1‐β expression. Knocking down XBP1 expression also increased NO concentration, as determined by Griess reaction and reduced the expression of antioxidant genes, such as heme oxygenase (HO)‐1, that protect parasites from oxidative stress. We conclude that L. amazonensis activation of XBP1 plays a critical role in infection by protecting the parasites from oxidative stress and increasing IFN1‐β expression.—Dias‐Teixeira, K. L., Calegari‐Silva, T. C., Dos Santos, G. R. R. M., Vitorino dos Santos, J., Lima, C., Medina, J. M., Aktas, B. H., Lopes, U. G. The integrated endoplasmic reticulum stress response in Leishmania amazonensis macrophage infection: the role of X‐box binding protein 1 transcription factor. FASEB J. 30, 1557–1565 (2016). http://www.fasebj.org


title: Arabidopsis HY5 protein functions as a DNA‐binding tag for purification and functional immobilization of proteins on agarose/DNA microplate

text: Protein microarray is considered to be one of the key analytical tools for high‐throughput protein function analysis. Here, we report that the Arabidopsis HY5 functions as a novel DNA‐binding tag (DBtag) for proteins. We also demonstrate that the DBtagged proteins could be immobilized and purified on a newly designed agarose/DNA microplate. Furthermore, we show three applications using the microarray: (1) detection of autophosphorylation activity of DBtagged human protein kinases and inhibition of their activity by staurosporine, (2) specific cleavage of DBtagged proteins by a virus protease and caspase 3, and (3) detection of a protein–protein interaction between the DBtagged UBE2N and UBE2v1. Thus, this method may facilitate rapid functional analysis of a wide range of proteins.


title: Aquatic bryophytes in Himalayan streams: testing a distribution model in a highly heterogeneous environment

text: 1. Aquatic bryophytes were sampled from 108 streams spanning over 3000 m of altitude in four regions of Nepal. Richness, cover and community composition were related to physicochemistry using multiple regression, DECORANA ordination and TWINSPAN. The performance of a hierarchically scaled descriptive model, developed in New Zealand for predicting bryophyte distribution, was examined in this highly heterogeneous Himalayan region. 2. Community composition and cover varied highly significantly with altitude, streambed stability and alkalinity, with evidence of effects of riparian land use on bryophyte cover. Cover was greatest in streams at low to middle altitudes with steep slopes (> 15°), high stability and low conductivity (< 60 μS cm(–1)), where communities were dominated by two Isopterygium spp., two Philonotis spp., Mnium punctatum and Lejeuneaceae. 3. Richness, by contrast, increased significantly but weakly at high altitude and moderate stability, where streams were dominated by Eurynchium praelongum, Rhynchostegium spp., Fissidens grandifrons and Hygroamblystegium spp. Richness and cover were lowest in unstable streams at the lowest altitude, where no single taxon was consistently most abundant. 4. Although these results were similar to those in the descriptive model developed for bryophytes in New Zealand, subtle differences were apparent. Substrate size, although influencing the presence of bryophytes in New Zealand streams, appeared to be unimportant in Nepal. By contrast, streambed stability was more important in Nepal than New Zealand, perhaps reflecting pronounced monsoonal floods, and subsequent increased frequency of bed movement in the former. A suggested habitat template indicates that large plant size and vegetative reproduction may be responsible for the widespread distribution of some species, even into unstable Himalayan streams.


On the reduction of chlorophyll‐A (I) in the presence of the plastoquinone antagonist dibromothymoquinone


title: Template‐assisted rational design of peptide inhibitors of furin using the lysine fragment of the mung bean trypsin inhibitor

text: Highly active, small‐molecule furin inhibitors are attractive drug candidates to fend off bacterial exotoxins and viral infection. Based on the 22‐residue, active Lys fragment of the mung bean trypsin inhibitor, a series of furin inhibitors were designed and synthesized, and their inhibitory activity towards furin and kexin was evaluated using enzyme kinetic analysis. The most potent inhibitor, containing 16 amino acid residues with a K (i) value of 2.45 × 10(−9) m for furin and of 5.60 × 10(−7) m for kexin, was designed with three incremental approaches. First, two nonessential Cys residues in the Lys fragment were deleted via a Cys‐to‐Ser mutation to minimize peptide misfolding. Second, residues in the reactive site of the inhibitor were replaced by the consensus substrate recognition sequence of furin, namely, Arg at P(1), Lys at P(2), Arg at P(4) and Arg at P(6). In addition, the P(7) residue Asp was substituted with Ala to avoid possible electrostatic interference with furin inhibition. Finally, the extra N‐terminal and C‐terminal residues beyond the doubly conjugated disulfide loops were further truncated. However, all resultant synthetic peptides were found to be temporary inhibitors of furin and kexin during a prolonged incubation, with the scissile peptide bond between P(1) and P(1)′ being cleaved to different extents by the enzymes. To enhance proteolytic resistance, the P(1)′ residue Ser was mutated to d‐Ser or N‐methyl‐Ser. The N‐methyl‐Ser mutant gave rise to a K (i) value of 4.70 × 10(−8) m for furin, and retained over 80% inhibitory activity even after a 3 h incubation with the enzyme. By contrast, the d‐Ser mutant was resistant to cleavage, although its inhibitory activity against furin drastically decreased. Our findings identify a useful template for the design of potent, specific and stable peptide inhibitors of furin, shedding light on the molecular determinants that dictate the inhibition of furin and kexin.


title: The role of ecological theory and practice in poverty alleviation and environmental conservation

text: The fight against global poverty has gained momentum following the creation of the Millennium Development Goals, which aim to halve extreme poverty by 2015. Traditionally, ecologists have not played leading roles in poverty alleviation. Yet, knowledge of ecosystem functions and processes can be applied to improve the lives of millions of people, suffering from hunger, lacking clean drinking water and reliable, efficient energy sources, dying from preventable diseases, and suffering disproportionately from natural disasters. Here, we describe ways in which ecologists can apply ecological theory and tools to help improve the efficacy of poverty alleviation programs.


title: Thylakoid protein phosphorylation in evolutionally divergent species with oxygenic photosynthesis

text: Phosphothreonine antibody was used to explore reversible thylakoid protein phosphorylation in vivo in evolutionally divergent organisms with oxygenic photosynthesis. Three distinct groups of organisms were found. Cyanobacteria and red algae, both with phycobilisome antenna system, did not show phosphorylation of any of the photosystem II (PSII) proteins and belong to group 1. Group 2 species, consisting of a moss, a liverwort and a fern, phosphorylated both the light‐harvesting chlorophyll a/b proteins (LHCII) and the PSII core proteins D2 and CP43, but not the D1 protein. Reversible phosphorylation of the D1 protein seems to be the latest event in the evolution of PSII protein phosphorylation and was found only in seed plants, in group 3 species. Light‐intensity‐dependent regulation of LHCII protein phosphorylation was similar in group 2 and 3 species, with maximal phosphorylation of LHCII at low light and nearly complete dephosphorylation at high light.


title: Characterization of inhibitory mechanism and antifungal activity between group‐1 and group‐2 phytocystatins from taro (Colocasia esculenta)

text: Tarocystatin from Colocasia esculenta, a group‐2 phytocystatin, is a defense protein against phytopathogenic nematodes and fungi. It is composed of a highly conserved N‐terminal region, which is homological to group‐1 cystatin, and a repetitive peptide at the C‐terminus. The purified recombinant proteins of tarocystatin, such as full‐length (FL), N‐terminus (Nt) and C‐terminus (Ct) peptides, were produced and their inhibitory activities against papain as well as their antifungal effects were investigated. Kinetic analysis revealed that FL peptide exhibited mixed type inhibition (K (ia) = 0.098 μm and K (ib) = 0.252 μm) and Nt peptide showed competitive inhibition (K (i) = 0.057 μm), whereas Ct peptide possessed weak papain activation properties. A shift in the inhibitory pattern from competitive inhibition of Nt peptide alone to mixed type inhibition of FL peptide implied that the Ct peptide has an regulatory effect on the function of FL peptide. Based on the inhibitory kinetics of FL (group‐2) and Nt (group‐1) peptides on papain activity, an inhibitory mechanism of group‐2 phytocystatins and a regulatory mechanism of extended Ct peptide have each been proposed. By contrast, the antifungal activity of Nt peptide appeared to be greater than that of FL peptide, and the Ct peptide showed no effect on antifungal activity, indicating that the antifungal effect is not related to proteinase inhibitory activity. The results are valid for most phytocystatins with respect to the inhibitory mechanism against cysteine proteinase.


title: An insect picornavirus may have genome organization similar to that of caliciviruses

text: Computer‐assisted analysis of the amino acid sequence of the product encoded by the sequenced 3′ portion of the cricket paralysis virus (CrPV), an insect picornavirus, genome showed that this protein is homologous not to the RNA‐directed RNA polymerases, as originally suggested, but to the capsid proteins of mammalian picornaviruses. Alignment of the CrPV protein sequence with those of picornavirus and calicivirus capsid proteins demonstrated that the sequenced portion of the insect picornavirus genome encodes the C‐terminal part of VP3 and the entire VP1. Thus CrPV seems to have a genome organization distinct from that of other picornaviruses but closely resembling that of caliciviruses, with the capsid proteins encoded in the 3′ part of the genome. On the other hand, the tentative phylogenetic trees generated from the VP3 alignment revealed grouping of CrPV with hepatitis A virus, a true picornavirus, not with caliciviruses. Thus CrPV may be a picornavirus with a calicivirus‐like genome organization. Different options for CrPV genome expression are discussed.


title: Prokaryotic and eukaryotic DNA helicases: Essential molecular motor proteins for cellular machinery

text: DNA helicases are ubiquitous molecular motor proteins which harness the chemical free energy of ATP hydrolysis to catalyze the unwinding of energetically stable duplex DNA, and thus play important roles in nearly all aspects of nucleic acid metabolism, including replication, repair, recombination, and transcription. They break the hydrogen bonds between the duplex helix and move unidirectionally along the bound strand. All helicases are also translocases and DNA‐dependent ATPases. Most contain conserved helicase motifs that act as an engine to power DNA unwinding. All DNA helicases share some common properties, including nucleic acid binding, NTP binding and hydrolysis, and unwinding of duplex DNA in the 3′ to 5′ or 5′ to 3′ direction. The minichromosome maintenance (Mcm) protein complex (Mcm4/6/7) provides a DNA‐unwinding function at the origin of replication in all eukaryotes and may act as a licensing factor for DNA replication. The RecQ family of helicases is highly conserved from bacteria to humans and is required for the maintenance of genome integrity. They have also been implicated in a variety of human genetic disorders. Since the discovery of the first DNA helicase in Escherichia coli in 1976, and the first eukaryotic one in the lily in 1978, a large number of these enzymes have been isolated from both prokaryotic and eukaryotic systems, and the number is still growing. In this review we cover the historical background of DNA helicases, helicase assays, biochemical properties, prokaryotic and eukaryotic DNA helicases including Mcm proteins and the RecQ family of helicases. The properties of most of the known DNA helicases from prokaryotic and eukaryotic systems, including viruses and bacteriophages, are summarized in tables.


AB 2.1.1.1 (or EC 2.1.1.?)


title: Unfolding of in planta activity of anti‐rep ribozyme in presence of a RNA silencing suppressor

text: Antisense RNA ribozymes have intrinsic endonucleolytic activity to effect cleavage of the target RNA. However, this activity in vivo is often controlled by the dominance of antisense or other double‐stranded RNA mechanism. In this work, we demonstrate the in planta activity of a hammerhead ribozyme designed to target rep‐mRNA of a phytopathogen Mungbean Yellow Mosaic India virus (MYMIV) as an antiviral agent. We also found RNA‐silencing is induced on introduction of catalytically active as well as inactive ribozymes. Using RNA‐silencing suppressors (RSS), we demonstrate that the endonucleolytic activity of ribozymes is a true phenomenon, even while a mutated version may demonstrate a similar down‐regulation of the target RNA. This helps to ease the confusion over the action mechanism of ribozymes in vivo.


title: Spatial modelling of the infestation indices of Aedes aegypti: an innovative strategy for vector control actions in developing countries

text: BACKGROUND: Larval indices such as the house index (HI), Breteau index (BI) and container index (CI) are widely used to interpret arbovirus vector density in surveillance programmes. However, the use of such data as an alarm signal is rarely considered consciously when planning programmes. The present study aims to investigate the spatial distribution pattern of the infestation of Aedes aegypti, considering the data available in the Ae. aegypti Infestation Index Rapid Survey (LIRAa) for the city of Campina Grande, Paraíba State in Brazil. METHODS: The global and local Moranʼs indices were used in spatial analysis to measure the effects of spatial dependencies between neighbourhoods, using secondary data related to HI and BI gathered from surveillance service. RESULTS: Our analysis shows that there is a predominance of high rates of mosquito infestation, placing Campina Grande at a near-constant risk of arbovirus outbreaks and epidemics. A highly significant Moranʼs index value (P < 0.001) was observed, indicating a positive spatial dependency between the neighbourhoods in Campina Grande. Using the Moran mapping and LISA mapping, the autocorrelation patterns of Ae. aegypti infestation rates among neighbourhoods have revealed hotpots that should be considered a priority to preventive actions of the entomological surveillance services. Predominance of high infestation rates and clearer relationships of these between neighbourhoods were observed between the months of May and July, the period with the highest rainfall in the city. CONCLUSIONS: This analysis is an innovative strategy capable of providing detailed information on infestation locations to the relevant public health authorities, which will enable a more efficient allocation of resources, particularly for arbovirus prevention. [Image: see text]


Letter to the editor by Dobran Mauro, Paracino Riccardo, and Iacoangeli Maurizio regarding “Neurosurgery during the COVID-19 pandemic: update from Lombardy, northern Italy.” Zoia C, Bongetta D, Veiceschi P, Cenzato M, Di Meco F, Locatelli D, Boeris D, Fontanella MM. Acta Neurochir (Wien). 2020 Mar 28. doi: 10.1007/s00701-020-04305-w


title: Use of antimalarials in dermatology

text: The antimalarials chloroquine and hydroxychloroquine have been used for the treatment of inflammatory diseases for more than 60 years. Even today new indications evolve due to the complex mode of action of these compounds. Due to the fear of side effects, especially irreversible retinopathy, their use is often limited. These side‐effects, however, are a consequence of excessive daily dosages. An effective, safe therapy needs correct dosing, i. e. adherence to maximal daily dosages of 3.5(–4) mg chloroquine or 6(–6.5) mg hydroxychloroquine per kilogram ideal body weight. If the actual body weight is lower than the ideal body weight, this actual weight is used for the calculation of the dosage. Observing these limits allows a rather safe therapy of the diseases like lupus erythematosus, REM syndrome, porphyria cutanea tarda (2 × 125 mg chloroquine/week), cutaneous sarcoidosis and dermatomyositis. If standard therapies fail, then antimalarials can be tried to treat Sjögren syndrome, granu‐loma annulare or erosive lichen planus. If therapy fails, either can be combined with quinacrine to increase their effectiveness. Chloroquine and hydroxychloroquine are indispensable and well‐tolerated essential drugs in dermatology and especially suited as part of a combination scheme, for example with corticosteroids, as they act synergistically and reduce side‐effects.


Peritoneal Membrane Oxygenation Therapy for Rats With Acute Respiratory Distress Syndrome


title: Mechanopharmacology and Synergistic Relaxation of Airway Smooth Muscle

text: Asthmatic airways are stiffer than normal. We have shown that the cytoskeletal passive stiffness of airway smooth muscle (ASM) can be regulated by intracellular signaling pathways, especially those associated with Rho kinase (ROCK). We have also shown that an oscillatory strain reduces the passive stiffness of ASM and its ability to generate force. Here, we investigated the combined effect of inhibiting the ASM contraction with β(2) agonist and decreasing the ASM cytoskeletal stiffness with ROCK inhibitor and/or force oscillation (FO) on the relaxation of contracted ASM. We hypothesize that the ASM relaxation can be synergistically enhanced by the combination of these interventions, because drug-induced softening of the cytoskeleton enhances the FO-induced relaxation and vice versa. Sheep tracheal strips were isotonically contracted to acetylcholine (3 × 10(−5) M). At the plateau of shortening, β(2) agonist salbutamol (10(−7) M), ROCK inhibitor H1152 (10(−7) M), and FO (square wave, 1 Hz, amplitude 6% maximal active force) were applied either alone or in combination. After adjusting for nonspecific time-dependent variation, relengthening by individual interventions with low-dose salbutamol or H1152, or small amplitude FO was not significantly different from zero. However, significant relengthening was observed in all combination treatments. The relengthening was greater than the mathematical sum of relengthening caused by individual treatments thereby demonstrating synergistic relaxation. The ASM stiffness did not change with salbutamol or H1152 treatments, but was lower with FO in combination with H1152. The results suggest that the mechanopharmacological treatment can be an effective therapy for asthma.


The Treatment of Acute Respiratory Distress Syndrome in Rats With a Peritoneal Dosing System


title: Preliminary Development and Engineering Evaluation of a Novel Cricothyrotomy Device

text: Cricothyrotomy is one of the procedures used to ventilate patients with upper airway blockage. This paper examines the most regularly used and preferred cricothyrotomy devices on the market, suggests critical design specifications for improving cricothyrotomy devices, introduces a new cricothyrotomy device, and performs an engineering evaluation of the device’s critical components. Through a review of literature, manufacturer products, and patents, four principal cricothyrotomy devices currently in clinical use were identified. From the review, the Cook™ Melker device is the preferred method of clinicians but the device has acknowledged problems. A new emergency needle cricothyrotomy device (ENCD) was developed to address all design specifications identified in literature. Engineering, theoretical, and experimental assessments were performed. In situ evaluations of a prototype of the new device using porcine specimens to assess insertion, extraction, and cyclic force capabilities were performed. The device was very successful in its evaluation. Further discussion focuses on these aspects and a comparison of the new device with established devices. The proposed emergency needle cricothyrotomy device performed very well. Further work will be pursued in the future with in-vitro and in-vivo with canine models demonstrates the capabilities of the ENCD.


title: The Effect of Chemical Cleaning on Mechanical Properties of Three-Dimensional Printed Polylactic Acid

text: Three-dimensional (3D) printing may be a solution to shortages of equipment and spare parts in the healthcare sector of low- and middle-income countries (LMICs). Polylactic acid (PLA) for 3D printing is widely available and biocompatible, but there is a gap in knowledge concerning its compatibility with chemical disinfectants. In this study, 3D-printed PLA tensile samples were created with six different printer settings. Each of these six batches consisted of five sets with five or six samples. The first set remained untreated, the others were soaked in Cidex OPA or in a chlorine solution. These were applied for seven consecutive days or in 25 short cycles. All samples were weighed before and after treatment and subjected to a tensile test. Results showed that a third of the treatments led to an increase of the median weight with a maximum of 8.3%, however, the samples with the best surface quality did not change. The median strength increase was 12.5% and the largest decrease was 8.8%. The median stiffness decreased 3.6% in one set and increased in three others up to 13.6%. When 3D printing PLA medical tools, surface porosity must be minimized to prevent transfer of disinfectants to people. The wide variability of mechanical properties due to 3D printing itself and as a consequence of disinfection must be considered when designing medical tools by selecting appropriate printer settings. If these conditions are met, reusing 3D-printed PLA medical tools seems safe from a mechanical point of view.


title: Design and Prototyping of a Low-Cost Portable Mechanical Ventilator

text: This paper describes the design and prototyping of a low-cost portable mechanical ventilator for use in mass casualty cases and resource-poor environments. The ventilator delivers breaths by compressing a conventional bag-valve mask (BVM) with a pivoting cam arm, eliminating the need for a human operator for the BVM. An initial prototype was built out of acrylic, measuring [Formula: see text] and weighing 9 lbs. It is driven by an electric motor powered by a 14.8 VDC battery and features an adjustable tidal volume up to a maximum of 750 ml. Tidal volume and number of breaths per minute are set via user-friendly input knobs. The prototype also features an assist-control mode and an alarm to indicate overpressurization of the system. Future iterations of the device will include a controllable inspiration to expiration time ratio, a pressure relief valve, PEEP capabilities, and an LCD screen. With a prototyping cost of only $420, the bulk-manufacturing price for the ventilator is estimated to be less than $200. Through this prototype, the strategy of cam-actuated BVM compression is proven to be a viable option to achieve low-cost, low-power portable ventilator technology that provides essential ventilator features at a fraction of the cost of existing technology.


title: Custom-Fit Three-Dimensional-Printed BiPAP Mask to Improve Compliance in Patients Requiring Long-Term Noninvasive Ventilatory Support

text: Noninvasive ventilator support using bi-level positive airway pressure/continuous positive airway pressure (BiPAP/CPAP) is commonly utilized for chronic medical conditions like sleep apnea and neuromuscular disorders like amyotrophic lateral sclerosis (ALS) that lead to weakness of respiratory muscles. Generic masks come in standard sizes and are often perceived by patients as being uncomfortable, ill-fitting, and leaky. A significant number of patients are unable to tolerate the masks and eventually stop using their devices. The goal of this project is to develop custom-fit masks to increase comfort, decrease air leakage, and thereby improve patient compliance. A single-patient case study of a patient with variant ALS was performed to evaluate the custom-fit masks. His high nose bridge and overbite of lower jaw caused poor fit with generic masks, and he was noncompliant with his machine. Using desktop Stereolithography three-dimensional (3D) printing and magnetic resonance imaging (MRI) data, a generic mask was extended with a rigid interface such that it was complementary to the patient's unique facial contours. Patient or clinicians interactively select a desired mask shape using a newly developed computer program. Subsequently, a compliant silicone layer was applied to the rigid interface. Ten different custom-fit mask designs were made using computer-aided design software. Patient evaluated the comfort, extent of leakage, and satisfaction of each mask via a questionnaire. All custom-fit masks were rated higher than the standard mask except for two. Our results suggest that modifying generic masks with a 3D-printed custom-fit interface is a promising strategy to improve compliance with BiPAP/CPAP machines.


title: Saponins of Dioscorea Nipponicae Inhibits IL-17A-Induced Changes in Biomechanical Behaviors of In Vitro Cultured Human Airway Smooth Muscle Cells

text: Airway hyperresponsiveness (AHR) is one of the main pathologic features of bronchial asthma, which is largely attributable to enhanced contractile response of asthmatic airway smooth muscle. Although β2 adrenergic receptor agonists are commonly used to relax airway smooth muscle for treating AHR, there are side effects such as desensitization of long-term use. Therefore, it is desirable to develop alternative relaxant for airway smooth muscle, preferably based on natural products. One potential candidate is the inexpensive and widely available natural herb saponins of Dioscorea nipponicae (SDN), which has recently been reported to suppress the level of inflammatory factor IL-17A in ovalbumin-induced mice, thereby alleviating the inflammation symptoms of asthma. Here, we evaluated the biomechanical effect of SDN on IL-17A-mediated changes of cultured human airway smooth muscle cells (HASMCs) in vitro. The stiffness and traction force of the cells were measured by optical magnetic twisting cytometry (OMTC), and Fourier transform traction microscopy (FTTM), respectively. The cell proliferation was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetry, the cell migration was measured by cell scratch test, and the changes of cell cytoskeleton were assessed by laser confocal microscopy. We found that the stiffness and traction force of HASMCs were enhanced along with the increases of IL-17A concentration and exposure time, and SDN treatment dose-dependently reduced these IL-17A-induced changes in cell mechanical properties. Furthermore, SDN alleviated IL-17A-mediated effects on HASMCs proliferation, migration, and cytoskeleton remodeling. These results demonstrate that SDN could potentially be a novel drug candidate as bronchodilator for treating asthma-associated AHR.


title: Airway Transmural Pressures in an Airway Tree During Bronchoconstriction in Asthma

text: Airway transmural pressure in healthy homogeneous lungs with dilated airways is approximately equal to the difference between intraluminal and pleural pressure. However, bronchoconstriction causes airway narrowing, parenchymal distortion, dynamic hyperinflation, and the emergence of ventilation defects (VDefs) affecting transmural pressure. This study aimed to investigate the changes in transmural pressure caused by bronchoconstriction in a bronchial tree. Transmural pressures before and during bronchoconstriction were estimated using an integrative computational model of bronchoconstriction. Briefly, this model incorporates a 12-generation symmetric bronchial tree, and the Anafi and Wilson model for the individual airways of the tree. Bronchoconstriction lead to the emergence of VDefs and a relative increase in peak transmural pressures of up to 84% compared to baseline. The highest increase in peak transmural pressure occurred in a central airway outside of VDefs, and the lowest increase was 27% in an airway within VDefs illustrating the heterogeneity in peak transmural pressures within a bronchial tree. Mechanisms contributing to the increase in peak transmural pressures include increased regional ventilation and dynamic hyperinflation both leading to increased alveolar pressures compared to baseline. Pressure differences between intraluminal and alveolar pressure increased driven by the increased airway resistance and its contribution to total transmural pressure reached up to 24%. In conclusion, peak transmural pressure in lungs with VDefs during bronchoconstriction can be substantially increased compared to dilated airways in healthy homogeneous lungs and is highly heterogeneous. Further insights will depend on the experimental studies taking these conditions into account.


title: The Aftermath of Bronchoconstriction

text: Asthma is characterized by chronic airway inflammation, airway remodeling, and excessive constriction of the airway. Detailed investigation exploring inflammation and the role of immune cells has revealed a variety of possible mechanisms by which chronic inflammation drives asthma development. However, the underlying mechanisms of asthma pathogenesis still remain poorly understood. New evidence now suggests that mechanical stimuli that arise during bronchoconstriction may play a critical role in asthma development. In this article, we review the mechanical effect of bronchoconstriction and how these mechanical stresses contribute to airway remodeling independent of inflammation.


title: Myosin Crossbridge, Contractile Unit, and the Mechanism of Contraction in Airway Smooth Muscle: A Mechanical Engineer's Perspective

text: Muscle contraction is caused by the action of myosin motors within the structural confines of contractile unit arrays. When the force generated by cyclic interactions between myosin crossbridges and actin filaments is greater than the average load shared by the crossbridges, sliding of the actin filaments occurs and the muscle shortens. The shortening velocity as a function of muscle load can be described mathematically by a hyperbola; this characteristic force–velocity relationship stems from stochastic interactions between the crossbridges and the actin filaments. Beyond the actomyosin interaction, there is not yet a unified theory explaining smooth muscle contraction, mainly because the structure of the contractile unit in smooth muscle (akin to the sarcomere in striated muscle) is still undefined. In this review, functional and structural data from airway smooth muscle are analyzed in an engineering approach of quantification and correlation to support a model of the contractile unit with characteristics revealed by mathematical analyses and behavior matched by experimental observation.


title: The Role of Airway Shunt Elastance on the Compartmentalization of Respiratory System Impedance

text: An inverse model consisting of two elastic compartments connected in series and served by two airway conduits has recently been fit to measurements of respiratory impedance in obese subjects. Increases in the resistance of the distal conduit of the model with increasing body mass index have been linked to peripheral airway compression by mass loading of the chest wall. Nevertheless, how the two compartments and conduits of this simple model map onto the vastly more complicated structure of an actual lung remain unclear. To investigate this issue, we developed a multiscale branching airway tree model of the respiratory system that predicts realistic input impedance spectra between 5 and 20 Hz with only four free parameters. We use this model to study how the finite elastances of the conducting airway tree and the proximal upper airways affect impedance between 5 and 20 Hz. We show that progressive constriction of the peripheral airways causes impedance to appear to arise from two compartments connected in series, with the proximal compartment being a reflection of the elastance of upper airway structures proximal to the tracheal entrance and the lower compartment reflecting the pulmonary airways and tissues. We thus conclude that while this simple inverse model allows evaluation of overall respiratory system impedance between 5 and 20 Hz in the presence of upper airway shunting, it does not allow the separate contributions of central versus peripheral pulmonary airways to be resolved.


title: Internet-of-Things-Enabled Dual-Channel Iontophoretic Drug Delivery System for Elderly Patient Medication Management

text: Wireless controllers have found its application in the supervision of the patients in the hospitals. It is not only a valid issue for the developing countries but also for the developed countries. For this reason, scientists are working on the advancement of medical devices that are capable of decreasing the workload of health caregivers. In this study, the development of an iontophoretic drug delivery device that could be controlled using a mobile is described. For the purpose, hardware and a software module were developed. The hardware module consisted of a two-channel voltage-controlled constant current sources that were used for driving the iontophoretic device. A mobile app was developed to control the two-channel iontophoretic device and to monitor the loose lead of the active and the passive patches. In the case of detection of the loose lead, the specific iontophoretic channel was stopped. Further, the audio-visual indicator was developed for the detection of the detachment of the patches (loose lead). The device was tested in vitro by performing the drug release study using drug-loaded emulsion gels that were formulated.


title: The Strain on Airway Smooth Muscle During a Deep Inspiration to Total Lung Capacity

text: The deep inspiration (DI) maneuver entices a great deal of interest because of its ability to temporarily ease the flow of air into the lungs. This salutary effect of a DI is proposed to be mediated, at least partially, by momentarily increasing the operating length of airway smooth muscle (ASM). Concerningly, this premise is largely derived from a growing body of in vitro studies investigating the effect of stretching ASM by different magnitudes on its contractility. The relevance of these in vitro findings remains uncertain, as the real range of strains ASM undergoes in vivo during a DI is somewhat elusive. In order to understand the regulation of ASM contractility by a DI and to infer on its putative contribution to the bronchodilator effect of a DI, it is imperative that in vitro studies incorporate levels of strains that are physiologically relevant. This review summarizes the methods that may be used in vivo in humans to estimate the strain experienced by ASM during a DI from functional residual capacity (FRC) to total lung capacity (TLC). The strengths and limitations of each method, as well as the potential confounders, are also discussed. A rough estimated range of ASM strains is provided for the purpose of guiding future in vitro studies that aim at quantifying the regulatory effect of DI on ASM contractility. However, it is emphasized that, owing to the many limitations and confounders, more studies will be needed to reach conclusive statements.


title: Medical Devices for Low- and Middle-Income Countries: A Review and Directions for Development

text: The development of diagnostics and medical devices has historically been concentrated in high-income countries, despite a significant need to expand healthcare services to low- and middle-income countries (LMIC). Poor quality healthcare extends beyond LMIC to underserved communities in developed countries. This paper reviews diseases and conditions that have not received much attention in the past despite imposing a significant burden on healthcare systems in these circumstances. We review the underlying mechanism of action of these conditions and current technology in use for diagnosis or surgical intervention. We aim to identify areas for technological development and review policy considerations that will enable real-world adoption. Specifically, this review focuses on diseases prevalent in sub-Saharan Africa and south Asia: melioidosis, infant and maternal mortality, schistosomiasis, and heavy metal and pesticide poisoning. Our aim with this review is to identify problems facing the world that require the attention of the medical device community and provide recommendations for research directions for groups interested in this field.


title: Structured Tree Impedance Outflow Boundary Conditions for 3D Lung Simulations

text: In this paper, we develop structured tree outflow boundary conditions for modeling the airflow in patient specific human lungs. The utilized structured tree is used to represent the nonimageable vessels beyond the 3D domain. The coupling of the two different scales (1D and 3D) employs a Dirichlet–Neumann approach. The simulations are performed under a variety of conditions such as light breathing and constant flow ventilation (which is characterized by very rapid acceleration and deceleration). All results show that the peripheral vessels significantly impact the pressure, however, the flow is relatively unaffected, reinforcing the fact that the majority of the lung impedance is due to the lower generations rather than the peripheral vessels. Furthermore, simulations of a hypothetical diseased lung (restricted flow in the superior left lobe) under mechanical ventilation show that the mean pressure at the outlets of the 3D domain is about 28% higher. This hypothetical model illustrates potential causes of volutrauma in the human lung and furthermore demonstrates how different clinical scenarios can be studied without the need to assume the unknown flow distribution into the downstream region.


title: Reorganization of the Vimentin Network in Smooth Muscle

text: Vimentin intermediate filaments (IFs) link to desmosomes (intercellular junctions) on the membrane and dense bodies in the cytoplasm, which provides a structural base for intercellular and intracellular force transmission in smooth muscle. There is evidence to suggest that the vimentin framework plays an important role in mediating smooth muscle mechanical properties such as tension and contractile responses. Contractile activation induces vimentin phosphorylation at Ser-56 and vimentin network reorientation, facilitating contractile force transmission among and within smooth muscle cells. p21-activated kinase 1 and polo-like kinase 1 catalyze vimentin phosphorylation at Ser-56, whereas type 1 protein phosphatase dephosphorylates vimentin at this residue. Vimentin filaments are also involved in other cell functions including migration and nuclear positioning. This review recapitulates our current knowledge how the vimentin network modulates mechanical and biological properties of smooth muscle.


title: Diagnostics as the Key to Advances in Global Health: Proposed Methods for Making Reliable Diagnostics Widely Available

text: This paper proposes a structure and method for the development of an AI diagnostic system as a highly leveraged step toward improvements in delivery of healthcare in underserved regions. First, the paper provides a high-level, general review of the current efforts to provide healthcare services in underserved areas and the many efforts being made to impact health outcomes by various international, governmental, and NGO entities. We also very briefly review university programs and research institutions that have specific technical and institutional assets with significant potential to carry out research or to partially implement such a plan. Our review uses weighted values in a decision-system that takes in a variety of assets we consider fundamental to successful engagement in delivery of new, innovative, technology-enabled healthcare systems for under-resourced settings. We then review nine factors that hinder the advancement in healthcare in under-resourced settings, some of which are well described in current literature and some that may bring new perspectives. The paper then attempts to review how a proposed system can manage to operate successfully within the context of the nine named hindrance factors. The primary focus of the paper is in the description of a system which can increase the availability of diagnostics through technology-enabled systems. Such a system would impact the outcomes of persons in underserved regions. The paper then describes why making diagnostics available is a critical priority among efforts for improvements in global health.


title: Flow and Particle Dispersion in Lung Acini: Effect of Geometric and Dynamic Parameters During Synchronous Ventilation

text: The human lung comprises about 300 million alveoli which are located on bronchioles between the 17th to 24th generations of the acinar tree, with a progressively higher population density in the deeper branches (lower acini). The alveolar size and aspect ratio change with generation number. Due to successive bifurcation, the flow velocity magnitude also decreases as the bronchiole diameter decreases from the upper to lower acini. As a result, fluid dynamic parameters such as Reynolds (Re) and Womersley (α) numbers progressively decrease with increasing generation number. In order to characterize alveolar flow patterns and inhaled particle transport during synchronous ventilation, we have conducted measurements for a range of dimensionless parameters physiologically relevant to the upper acini. Acinar airflow patterns were measured using a simplified in vitro alveolar model consisting of a single transparent elastic truncated sphere (representing the alveolus) mounted over a circular hole on the side of a rigid circular tube (representing the bronchiole). The model alveolus was capable of expanding and contracting in-phase with the oscillatory flow through the bronchiole thereby simulating synchronous ventilation. Realistic breathing conditions were achieved by exercising the model over a range of progressively varying geometric and dynamic parameters to simulate the environment within several generations of the acinar tree. Particle image velocimetry was used to measure the resulting flow patterns. Next, we used the measured flow fields to calculate particle trajectories to obtain particle transport and deposition statistics for massless and finite-size particles under the influence of flow advection and gravity. Our study shows that the geometric parameters (β and ΔV/V) primarily affect the velocity magnitudes, whereas the dynamic parameters (Re and α) distort the flow symmetry while also altering the velocity magnitudes. Consequently, the dynamic parameters have a greater influence on the particle trajectories and deposition statistics compared to the geometric parameters. The results from this study can benefit pulmonary research into the risk assessment of toxicological inhaled aerosols, and the pharmaceutical industry by providing better insight into the flow patterns and particle transport of inhalable therapeutics in the acini.


title: The effect of inhaled and intranasal sodium cromoglyeate on symptoms of upper respiratory tract infections

text: Background A well established drug for the treatment of asthma and allergy, sodium cromoglycale, was found in open trials to be useful as a symptomalic treatment for upper respiratory tract infections. Objective To compare the efficacy of inhaled and intranasal sodium cromoglyeate and matching placebos on the symptoms of upper respiratory tract infections. Methods Adult subjects with symptoms of runny nose, throat pain, or cough for less than 24 h were recruited. They were treated for 7 days using a randomized, double‐blind, placebo‐controlled, group comparative design. The medication given was: sodium cromoglyeate dry powder 20mg per inhalation in spincaps; sodium cromoglycate aqueous nasal spray delivering 5.2mg per dose; or matching placebo as dry powder and nasal spray. One spincap and one spray per nostril were taken every 2h during waking hours on days 1 and 2 and then four times daily on days 3–7. Severity of nine symptoms (general malaise, body aches and pains, chills and shivering, snzeening, nasal running, nasal blocking, sore throat, cough and voice disturbance) was recorded twice daily by subjects on diary cards, using a scale of 0 (absent) to 3 (severe). Results The sludy was conducted between February and April 1993. One hundred and eighteen patients aged 21–63 years (mean 41 years) were included. Symptoms resolved faster (P < 0.001) and the severity in the last three days of treatment was significantly less in patients treated with sodium cromoglycate than with placebo (P < 0.05‐day 5; P < 0.01‐day 6; P < 0.001‐day 7). Side‐effects were local and mild and did not differ between the treatment groups. Conclusion Sodium cromoglyeate administered both by inhalation and intranasally is an effective treatment for the symptoms of upper respiratory tract infection. Its combined safety and efficacy would make it an acceptable form of treatment for these conditions.


title: Amplified rhinovirus colds in atopic subjects

text: Abstract. Evidence suggests that atopic individuals may be predisposed to more severe rhinoviral colds coupled to a worsening of existing airway disease than those with asthma. The role of atopy and IgE levels, as well as their relationship to clinical disease expression have not been defined. We hypothesized that an allergic diathesis modulates rhinoviral colds and have initiated studies of normal, atopic and asthmatic subjects employing experimental rhinoviral infection, with measurements of symptom scores, viral shedding and cultures, albumin in nasal washes and serological responses. Twenty‐two subjects (11 normal, 5 atopic, 6 atopic and asthmatic) participated and were inoculated with human rhinovirus serotype 16 (HRV 16). Measurements of neutralizing antibody and viral culture were performed at screening, pre‐inoculation, during the cold and at 8–10 weeks convalescence. Daily symptoms were noted, nasal washes done, IgE measured and atopy was diagnosed by skin tests. Seventeen volunteers developed clinical colds as assessed by symptom scores, virus shedding was demonstrated (with positive culture) in all subjects and a fourfold or higher seroconversion occurred in 11/22. Neutralizing HRV antibody developed unexpectedly in 10 subjects between screening and inoculation and the presence or absence of this pre‐inoculation antibody determined subsequent severity of colds in normal but not in atopic subjects. Atopic antibody positive individuals developed severe clinical colds that were independent of preinoculation antibody in contrast to normal subjects who developed mild colds in the presence of a neutralizing antibody (.P= 0.01). Both atopic and normal antibody negative subjects developed severe colds. This differential response was matched by nasal wash albumin levels which were significantly increased (P= 0–01) during the cold in atopic (but not in normal) volunteers with pre‐inoculation antibody. Levels of IgE were not correlated with severity of clinical disease or viral shedding. Our studies of HRV disease in atopic subjects suggest heightened susceptibility to the detrimental effects of colds; additional studies are needed to clarify the relevant mechanisms.


title: Effect of experimental rhinovirus 16 colds on airway hyperresponsiveness to histamine and interleukin‐8 in nasal lavage in asthmatic subjects in vivo

text: Background Asthma exacerbations are closely associated with respiratory virus infections. However, the pathophysiological consequences of such infections in asthma are largely unclear. Objective To examine the effect of rhinovirus 16 (RV16) infection on airway hypersensitivity to histamine. and on interleukin‐8 (IL‐8) in nasal lavage. Objective Twenty‐seven non‐smoking atopic, mildly asthmatic subjects participated in a placebo‐controlled, parallel study. A dose of 0.5–2.9 ± 10(4) TCID50 RV16 or placebo was nasally administered. Cold symptoms were recorded by questionnaire throughout the study. Histamine challenges were performed at entry, and on days 4 and 11 after inoculation. Nasal lavages were obtained at entry, and on days 2 and 9. The response to histamine was measured by PC(20) (changes expressed as doubling doses: DD). IL‐8 levels were obtained by ELISA, and were expressed in ng/ml. Results RV infection was confirmed by culture of nasal lavage and/or by antibody titre rise in each of the RV16‐treated subjects. Among the 19 RV16‐treated subjects, eight developed severe cold symptoms. Baseline FEV(1) did not change significantly during the study in either treatment group (P= 0.99). However, in the RV16‐treated subjects there was a decrease in PC(20) at day 4, which was most pronounced in those with a severe cold (mean change ± SEM: –1.14 ± 0.28 DD, P= 0.01). In addition. IL‐8 levels increased in tbe RV16 group at days 2 and 9 (P < 0.001). The increase in nasal IL‐8 at day 2 correlated significantly with the change in PC(20) at day 4 (r=–0.48, P= 0.04). Conclusion We conclude that the severity of cold, as induced by experimental RV16 infection, is a determinant of the increase in airway hypersensitivity to histamine in patients with asthma. Our results suggest that this may be mediated by an infiammatory mechanism, involving the release of chemokines such as IL‐8.


title: A Single Ventilator for Multiple Simulated Patients to Meet Disaster Surge

text: Objectives To determine if a ventilator available in an emergency department could quickly be modified to provide ventilation for four adults simultaneously. Methods Using lung simulators, readily available plastic tubing, and ventilators (840 Series Ventilator; Puritan‐Bennett), human lung simulators were added in parallel until the ventilator was ventilating the equivalent of four adults. Data collected included peak pressure, positive end‐expiratory pressure, total tidal volume, and total minute ventilation. Any obvious asymmetry in the delivery of gas to the lung simulators was also documented. The ventilator was run for almost 12 consecutive hours (5.5 hours of pressure control and more than six hours of volume control). Results Using readily available plastic tubing set up to minimize dead space volume, the four lung simulators were easily ventilated for 12 hours using one ventilator. In pressure control (set at 25 mm H(2)O), the mean tidal volume was 1,884 mL (approximately 471 mL/lung simulator) with an average minute ventilation of 30.2 L/min (or 7.5 L/min/lung simulator). In volume control (set at 2 L), the mean peak pressure was 28 cm H(2)O and the minute ventilation was 32.5 L/min total (8.1 L/min/lung simulator). Conclusions A single ventilator may be quickly modified to ventilate four simulated adults for a limited time. The volumes delivered in this simulation should be able to sustain four 70‐kg individuals. While further study is necessary, this pilot study suggests significant potential for the expanded use of a single ventilator during cases of disaster surge involving multiple casualties with respiratory failure.


title: Isozymes, and the status of Taraxacum (Asteraceae) agamospecies

text: HUGHES, L. & RICHARDS, A. J., 1989. Isozymes and the status of Taraxacum (Asteraceae) agamospecies. Genetic identities I and Similarity Indices SI are calculated between 12 samples of Taraxacum, on the basis of 40 isozymes at 15 loci for 10 enzyme systems. Samples included three polyploid agamospermous populations from northern England (group 1), three sexual diploid populations from south‐central France (group 2), and six accessions of ‘primitive’ diploid self‐compatible sexual taxa from southern Europe and Australia. Samples could be assigned to eight species, classified in seven sections of the genus. Two clusters of high relationship were evident. All the group 1 and group 2 species were very closely related, with pairwise comparisons for I in excess of 0.93. The three group 3 accessions identified as T. bessarabicum showed pairwise comparisons for SI in excess of 0.71. Comparisons for SI between the other group 3 species, and between all the group 3 species and the group 1 and 2 species were all very low, not exceeding 0.45. It is concluded that dissimilarity between samples as assessed by isozymes is probably related to the time of evolutionary divergence of those samples. Although allopolyploid, and morphologically very diverse, the group 1 agamospecies may have very recently diverged asexually from a common stock. The group 2 diploids may have resulted from rediploidization and regained sexuality from the same originally agamospermous stock. In areas of Europe in which such ‘modern’ sexuality is common, it is probable that all ‘modern’ Taraxaca, including at least five sections of the genus, should be included within a single taxon. In contrast, ‘primitive’ self‐compatible sexual species in group 3 appear to have diverged from each other several million years ago, and with the exception of the disjunct accessions of T. bessarabicum, are genetically highly distinct. Such species should be maintained in the taxonomies of all areas. It is probable that an agamospecies classification of ‘modern’Taraxacum will continue to convey much useful information in areas, such as northern Europe, in which sexuality is absent.


COVID-19: endgames


Correction to Lancet Child Adolesc Health 2020; published online April 14. https://doi.org/10.1016/S2352-4642(20)30109-7


Editorial: Introducing the IJDP special collection “The use of mathematical modeling to inform drug policy making”


CORONA-steps for tracheotomy in COVID-19 patients: a staff-safe method for airway management


Commentary: “To list, or not to list? That is the question”


Nurturing the forest of oral and maxillofacial surgery training: Author:


Stress, Inflammation and Autoimmunity: The Three Modern Erinyes


title: VENTILatOry strategies in patients with severe traumatic brain injury: the VENTILO Survey of the European Society of Intensive Care Medicine (ESICM)

text: BACKGROUND: Severe traumatic brain injury (TBI) patients often develop acute respiratory failure. Optimal ventilator strategies in this setting are not well established. We performed an international survey to investigate the practice in the ventilatory management of TBI patients with and without respiratory failure. METHODS: An electronic questionnaire, including 38 items and 3 different clinical scenarios [arterial partial pressure of oxygen (PaO(2))/inspired fraction of oxygen (FiO(2)) > 300 (scenario 1), 150–300 (scenario 2), < 150 (scenario 3)], was available on the European Society of Intensive Care Medicine (ESICM) website between November 2018 and March 2019. The survey was endorsed by ESICM. RESULTS: There were 687 respondents [472 (69%) from Europe], mainly intensivists [328 (48%)] and anesthesiologists [206 (30%)]. A standard protocol for mechanical ventilation in TBI patients was utilized by 277 (40%) respondents and a specific weaning protocol by 198 (30%). The most common tidal volume (TV) applied was 6–8 ml/kg of predicted body weight (PBW) in scenarios 1–2 (72% PaO(2)/FIO(2) > 300 and 61% PaO(2)/FiO(2) 150–300) and 4–6 ml/kg/PBW in scenario 3 (53% PaO(2)/FiO(2) < 150). The most common level of highest positive end-expiratory pressure (PEEP) used was 15 cmH(2)O in patients with a PaO(2)/FiO(2) ≤ 300 without intracranial hypertension (41% if PaO(2)/FiO(2) 150–300 and 50% if PaO(2)/FiO(2) < 150) and 10 cmH(2)O in patients with intracranial hypertension (32% if PaO(2)/FiO(2) 150–300 and 33% if PaO(2)/FiO(2) < 150). Regardless of the presence of intracranial hypertension, the most common carbon dioxide target remained 36–40 mmHg whereas the most common PaO(2) target was 81–100 mmHg in all the 3 scenarios. The most frequent rescue strategies utilized in case of refractory respiratory failure despite conventional ventilator settings were neuromuscular blocking agents [406 (88%)], recruitment manoeuvres [319 (69%)] and prone position [292 (63%)]. CONCLUSIONS: Ventilatory management, targets and practice of adult severe TBI patients with and without respiratory failure are widely different among centres. These findings may be helpful to define future investigations in this topic.


title: Comparison of ELISA with electro-chemiluminescence technology for the qualitative and quantitative assessment of serological responses to vaccination

text: BACKGROUND: Profiling immune responses induced by either infection or vaccination can provide insight into identification of correlates of protection. Furthermore, profiling of serological responses can be used to identify biomarkers indicative of exposure to pathogens. Conducting such immune surveillance requires readout methods that are high-throughput, robust, and require small sample volumes. While the enzyme-linked immunosorbent assay (ELISA) is the classical readout method for assessing serological responses, the advent of multiplex assays has significantly increased the throughput and capacity for immunoprofiling. This report describes the development and assay performance (sensitivity, linearity of detection, requirement for multiple dilutions for each sample, intra- and inter-assay variability) of an electro-chemiluminescence (ECLIA)-based multiplex assay. METHODS: The current study describes the development of a multiplex ECLIA-based assay and characterizes the sensitivity, linear range, and inter- and intra-assay variability of the ECLIA platform and its agreement with the traditional ELISA. Special emphasis was placed on potential antigenic competition when testing closely related antigens in the multiplex format. RESULTS: Multiplexing of antigens in ECLIA provides significant practical benefits in terms of reducing sample volume requirements and experimental time. Beyond the practical advantages of multiplexing, the ECLIA provides superior assay performance when compared to the ELISA. Not only does ECLIA show good agreement with the ELISA assay, but the linear range of ECLIA is also sufficiently wide to permit single-dilution measurements of concentration without the need to do serial dilutions. The lack of antigenic competition allows the simultaneous testing of closely related antigens, such as plate antigens representing different alleles of the same protein, which can inform about cross-reactivities—or lack thereof—of serological responses. CONCLUSION: The advantages of the newly developed tool for assessing the antigen profiles of serological responses may ultimately lead to the identification of biomarkers associated with various disease stages and or protection against disease.


title: Transmembrane serine protease TMPRSS2 activates hepatitis C virus infection

text: The human liver reacts to hepatitis C virus (HCV) with a balanced response consisting of host anti‐ and proviral activities. To explore these subtle host responses, we used oligonucleotide microarrays to investigate the differential gene expression between two groups of liver samples with high and low HCV loads (>100‐fold difference). We identified and validated 26 genes that were up‐regulated in livers with high HCV loads, including transmembrane protease serine 2 (TMPRSS2). Trypsin inhibitors inhibited the infection of Huh7‐25‐CD81 cells with cell‐culture–derived HCV (HCVcc) of Japanese fulminant hepatitis 1 isolate at the postbinding and entry step, and trypsin enhanced HCVcc infection at an early stage of infection. Several major transmembrane serine proteases, in particular, furin and hepsin, were detected in Huh7‐25‐CD81 cells, but TMPRSS2 was not. Huh7‐25‐CD81 cell clones stably expressing TMPRSS2‐ WT (wild type) and inactive TMPRSS2‐mutant genes showed positive and negative enhancement of their susceptibility to HCVcc infection, respectively. The enhanced susceptibility of TMPRSS2‐WT Huh7‐25‐CD81 cells was confirmed by knockdown of TMPRSS2 using small interfering RNA. The cell‐surface protease activity of TMPRSS2‐WT cells was markedly active in the cleavage of QAR and QGR, corresponding to amino acid residues at P3 to P1. Conclusion: The cell‐surface activity of a trypsin‐like serine protease, such as TMPRSS2, activates HCV infection at the postbinding and entry stage. Host transmembrane serine proteases may be involved in the sensitivity, persistence, and pathogenesis of HCV infection and be possible targets for antiviral therapy. (Hepatology 2015;61:438‐447)


Vaccine Protects Against SARS In Mice


Flavivirus‐Induced Up‐regulation of MHC Class I Antigens; Implications for the Induction of CD8(+) T‐Cell‐Mediated Autoimmunity


title: Preventing healthcare‐associated infection: risks, healthcare systems and behaviour

text: More than 177 000 potentially preventable healthcare‐associated infections (HAIs) occur per annum in Australia with sizable attributable mortality. Organizational systems to protect against HAI in hospitals in Australia are relatively poorly developed. Awareness and practice of infection control by medical and other healthcare staff are often poor. These lapses in practice create significant risk for patients and staff from HAI. Excessive patient exposure to antimicrobials is another key factor in the emergence of antibiotic‐resistant bacteria and Clostridium difficile infection. Physicians must ensure that their interactions with patients are safe from the infection prevention standpoint. The critical preventative practice is hand hygiene in accord with the World Health Organization 5 moments model. Improving the use of antimicrobials, asepsis and immunization also has great importance. Hospitals should measure and feed back HAI rates to clinical teams. Physicians as leaders, role models and educators play an important part in promoting adherence to safe practices by other staff and students. They are also potentially effective system engineers who can embed safer practices in all elements of patient care and promote essential structural and organizational change. Patients and the public in general are becoming increasingly aware of the risk of infection when entering a hospital and expect their carers to adhere to safe practice. Poor infection control practice will be regarded in a negative light by patients and their families, regardless of any other manifest skills of the practitioner.


Immune‐Mediated Encephalitis: On the Role of Antigen‐Presenting Cells in Brain Tissue