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Whether the presence of Candida spp. in lower respiratory tract (LRT) secretions is a marker of underlying disease, intensive care unit (ICU) treatment and antibiotic therapy or contributes to poor clinical outcome is unclear. We investigated healthy controls, patients with proposed risk factors for Candida growth in LRT (antibiotic therapy, ICU treatment with and without antibiotic therapy), ICU patients with pneumonia and antibiotic therapy and candidemic patients (for comparison of truly invasive and colonizing Candida spp.). Fungal patterns were determined by conventional culture based microbiology combined with molecular approaches (next generation sequencing, multilocus sequence typing) for description of fungal and concommitant bacterial microbiota in LRT, and host and fungal biomarkes were investigated. Admission to and treatment on ICUs shifted LRT fungal microbiota to Candida spp. dominated fungal profiles but antibiotic therapy did not. Compared to controls, Candida was part of fungal microbiota in LRT of ICU patients without pneumonia with and without antibiotic therapy (63% and 50% of total fungal genera) and of ICU patients with pneumonia with antibiotic therapy (73%) (p

Previous research on stabilization methods for microbiome investigations has largely focused on human fecal samples. There are a few studies using feces from other species, but no published studies investigating preservation of samples collected from cattle. Given that microbial taxa are differentially impacted during storage it is warranted to study impacts of preservation methods on microbial communities found in samples outside of human fecal samples. Here we tested methods of preserving bovine fecal respiratory specimens for up to 2 weeks at four temperatures (room temperature, 4°C, -20°C, and -80°C) by comparing microbial diversity and community composition to samples extracted immediately after collection. Importantly, fecal specimens preserved and analyzed were technical replicates, providing a look at the effects of preservation method in the absence of biological variation. We found that preservation with the OMNIgene®•GUT kit resulted in community structure most like that of fresh samples extracted immediately, even when stored at room temperature (~20°C). Samples that were flash-frozen without added preservation solution were the next most representative of original communities, while samples preserved with ethanol were the least representative. These results contradict previous reports that ethanol is effective in preserving fecal communities and suggest for studies investigating cattle either flash-freezing of samples without preservative or preservation with OMNIgene®•GUT will yield more representative microbial communities., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Pinnell et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Various agents including Ca. Piscichlamydia salmonis, Ca. Branchiomonas cysticola, Desmozoon lepeophtherii, Paramoeba perurans and salmon gill poxvirus may be associated with complex gill disease in Atlantic salmon. Co-infections involving two or more of these agents are common and histopathological interpretation of lesions is therefore challenging. In this study, we developed a semi-quantitative scoring system for examination of histopathological gill lesions in sea-farmed Atlantic salmon suffering from gill disease. Following qPCR analysis of gills sampled for Ca. P. salmonis, Ca. B. cysticola, D. lepeophtherii and P. perurans from 22 geographically spread outbreaks, five cases representing different infectious loads and combinations of agents were chosen for histopathological scoring. Twenty-eight histological features were evaluated and potential associations between individual pathological changes and the occurrence of individual agents studied. The inter-observer agreement in interpretation of histological parameters between the three pathologists involved, was calculated to validate robustness of the scoring scheme. Seventeen histological parameters met the criteria for inter-observer agreement analysis and were included in the calculation. The three most frequent findings were identification of subepithelial leukocytes, epithelial cell hyperplasia and mucus cell hyperplasia. While few findings could be specifically related to particular agents, necrosis in hyperplastic lesions, pustules and necrosis of subepithelial cells appeared to be associated with the presence of Ca. B. cysticola. Further, lesion profiles clearly support the previously identified association between P. perurans and pathological changes associated with AGD. Very few pathological changes were observed in the single case in which Ca. P. salmonis was the dominating agent. Some lesions were only very rarely observed e.g. chloride cell necrosis, epithelial cell apoptosis, lamellar deposition of melanin and haemophagocytosis. The scoring scheme developed and applied was robust and sensitive. A less extensive scheme for routine diagnostic use is proposed. [ABSTRACT FROM AUTHOR]

Next-generation sequencing methods are increasingly used to identify eukaryotic, unicellular and multicellular symbiont communities within hosts. In this study, we analyzed the non-specific reads obtained during a metabarcoding survey of the bacterial communities associated to three different tissues collected from 13 wild Mediterranean teleost fish species. In total, 30 eukaryotic genera were identified as putative parasites of teleosts, associated to skin mucus, gills mucus and intestine: 2 ascomycetes, 4 arthropods, 2 cnidarians, 7 nematodes, 10 platyhelminthes, 4 apicomplexans, 1 ciliate as well as one order in dinoflagellates (Syndiniales). These results highlighted that (1) the metabarcoding approach was able to uncover a large spectrum of symbiotic organisms associated to the fish species studied, (2) symbionts not yet identified in several teleost species were putatively present, (3) the parasitic diversity differed markedly across host species and (4) in most cases, the distribution of known parasitic genera within tissues is in accordance with the literature. The current work illustrates the large insights that can be gained by making maximum use of data from a metabarcoding approach. [ABSTRACT FROM AUTHOR]

Introduction: Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are forms of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). AAV most commonly affects the upper and lower respiratory tract as well as the kidneys. The first symptoms are often nonspecific, requiring careful differential diagnosis with infections and malignancies. Materials and methods: We analyzed the clinical and radiological data of 38 patients (20 females and 18 males) diagnosed with ANCA-associated vasculitis. Lung involvement was observed in 29 cases. Lung ultrasound (LUS) was performed on 21 patients from the study group and compared to chest CT. For 7 patients the examination was conducted repeatedly. Results: In total, 35 LUS and CT examinations were performed, revealing the following lesions: nodules, infiltrates with and without features of disintegration, caves (n = 17), diffuse alveolar hemorrhage (n = 3), and features of interstitial lung disease (ILD) with pulmonary fibrosis (PF) (n = 11). In 2 cases LUS and CT were negative. In 4 cases LUS was negative, despite a positive CT result. Conclusions: Both in CT and LUS, images of pulmonary lesions were consistent though highly variable. Therefore, further studies are required for a larger group of patients. [ABSTRACT FROM AUTHOR]

Deposition of polydisperse particles representing nasal spray application in a human nasal cavity was performed under transient breathing profiles of sniffing, constant flow, and breath hold. The LES turbulence model was used to describe the fluid phase. Particles were introduced into the flow field with initial spray conditions, including spray cone angle, insertion angle, and initial velocity. Since nasal spray atomizer design determines the particle conditions, fifteen particle size distributions were used, each defined by a log-normal distribution with a different volume mean diameter (Dv50). Particle deposition in the anterior region was approximately 80% when Dv50 > 50μm, and this decreased to 45% as Dv50 decreased to 10μ m for constant and sniff breathing conditions. The decrease in anterior deposition was countered with increased deposition in the middle and posterior regions. The significance of increased deposition in the middle region for drug delivery shows there is potential for nasal delivered drugs to reach the highly vascularised mucosal walls in the main nasal passages. For multiple targeted deposition sites, an optimisation equation was introduced where deposition results of any two targeted sites could be combined and a weighting between 0 to 1 was applied to each targeted site, representing the relative importance of each deposition site. [ABSTRACT FROM AUTHOR]

Infectious diseases are potential contributors to decline in Coho salmon (Oncorhynchus kisutch) populations. Although pathogens are theoretically considered to pose higher risk in high-density rearing environments like hatcheries, there is no direct evidence that hatchery-origin Coho salmon increase the transmission of infectious agents to sympatric wild populations. This study was undertaken to compare prevalence, burden, and diversity of infectious agents between hatchery-reared and wild juvenile Coho salmon in British Columbia (BC), Canada. In total, 2,655 juvenile Coho salmon were collected between 2008 and 2018 from four regions of freshwater and saltwater in BC. High-throughput microfluidics qPCR was employed for simultaneous detection of 36 infectious agents from mixed-tissue samples (gill, brain, heart, liver, and kidney). Thirty-one agents were detected at least once, including ten with prevalence >5%. Candidatus Brachiomonas cysticola, Paraneuclospora theridion, and Parvicapsula pseudobranchiocola were the most prevalent agents. Diversity and burden of infectious agents were substantially higher in marine environment than in freshwater. In Mainland BC, infectious burden and diversity were significantly lower in hatchery smolts than in wild counterparts, whereas in other regions, there were no significant differences. Observed differences in freshwater were predominantly driven by three parasites, Loma salmonae, Myxobolus arcticus, and Parvicapsula kabatai. In saltwater, there were no consistent differences in agent prevalence between hatchery and wild fish shared among the west and east coasts of Vancouver Island. Although some agents showed differential infectious patterns between regions, annual variations likely contributed to this signal. Our findings do not support the hypothesis that hatchery smolts carry higher burdens of infectious agents than conspecific wild fish, reducing the potential risk of transfer to wild smolts at this life stage. Moreover, we provide a baseline of infectious agents in juvenile Coho salmon that will be used in future research and modeling potential correlations between infectious profiles and marine survival. [ABSTRACT FROM AUTHOR]

Developmental anomalies of the thyroid gland lead to congenital malformations such as thyroglossal duct cysts and thyroid dysgenesis. However, the pathogenesis of thyroid dysgenesis remains unclear due to the lack of suitable animal models. This study demonstrated that Slc:Wistar/ST rats frequently developed unilateral thyroid dysgenesis, including hemiagenesis, characterized by the absence of one lobe. In Wistar/ST rats, each thyroid lobe was frequently different in size, and approximately 27% and 20% of the rats presented with hemihypoplasia and hemiagenesis of the thyroid gland, respectively. Dysgenesis was predominant on the left side in both sexes, without sex differences. At a young age, thyroid hemiagenesis did not alter body weight. In rats of both sexes with thyroid hemiagenesis, plasma total triiodothyronine and total triiodothyronine levels remained unchanged while plasma thyroid-stimulating hormone levels were significantly elevated in young rats. The remaining thyroid lobes increased in weight, but the follicular epithelial cells appeared normal in terms of their height and proliferating activities. On the side of thyroid dysgenesis, the parathyroid glands were normally localized and were situated at the same location as the contralateral glands. The ultimobranchial body remnants were localized at the level of the thyroid gland along with the cranial thyroid artery and vein, forming cell clusters or cystic structures and containing calcitonin-positive C-cells. In conclusion, Wistar/ST rats developed unilateral thyroid dysgenesis and may be novel and useful animal models for thyroid hemiagenesis in humans and for morphogenesis of pharyngeal pouch-derived organs. [ABSTRACT FROM AUTHOR]

Background: Children and young people with neuromuscular disorders (NMD), such as Duchenne Muscular Dystrophy (DMD), develop progressive respiratory muscles weakness and pulmonary restriction. Pulmonary function monitoring of the decline in lung function allows for timely intervention with cough assist techniques and nocturnal non-invasive ventilation (NIV). NMD may find the measurement of lung function difficult using current techniques. Structured Light Plethysmography (SLP) has been proposed as a novel, non-contact, self-calibrating, non-invasive method of assessing lung function. The overarching aim of this study was to investigate the use of SLP as a novel method for monitoring respiratory function in children with neuromuscular disease. Methods: SLP thoraco-abdominal (TA) displacement was correlated with forced vital capacity measurements recorded by spirometry and the repeatability of the measurements with both methods examined. SLP tidal breathing parameters were investigated to assess the range and repeatability of regional right and left side TA displacement and rib cage and abdominal wall displacement. Results: The comparison of the FVC measured with SLP and with spirometry, while having good correlation (R = 0.78) had poor measurement agreement (95% limits of agreement: -1.2 to 1.2L) The mean relative contribution of right and left TA displacement in healthy controls was 50:50 with a narrow range. Repeatability of this measure with SLP was found to be good in healthy controls and moderate in NMD children with/without scoliosis but with a wider range. The majority of the control group displayed a predominant rib cage displacement during tidal breathing and those who displayed predominant abdominal wall displacement showed displacement of both regions close to 50:50 with similar results for the rib cage and abdomen. In comparison, children with NMD have a more variable contribution for all of these parameters. In addition, SLP was able to detect a reduction in abdominal contribution to TA displacement with age in the DMD group and detect paradoxical breathing in children with NMD. Using SLP tracings during tidal breathing we were able to identify three specific patterns of breathing amongst healthy individuals and in children with NMD. Conclusions: SLP is a novel method for measuring lung function that requires limited patient cooperation and may be especially useful in children with neuromuscular disorders. Measuring the relative contributions of the right and left chest wall and chest versus abdominal movements allows a more detailed assessment. [ABSTRACT FROM AUTHOR]

Olfactory and trigeminal chemosensory systems reside in parallel within the mammalian nose. Psychophysical studies in people indicate that these two systems interact at a perceptual level. Trigeminal sensations of pungency mask odour perception, while olfactory stimuli can influence trigeminal signal processing tasks such as odour localization. While imaging studies indicate overlap in limbic and cortical somatosensory areas activated by nasal trigeminal and olfactory stimuli, there is also potential cross-talk at the level of the olfactory epithelium, the olfactory bulb and trigeminal brainstem. Here we explored the influence of olfactory and trigeminal signaling in the nasal cavity. A forced choice water consumption paradigm was used to ascertain whether trigeminal and olfactory stimuli could influence behaviour in mice. Mice avoided water sources surrounded by both volatile TRPV1 (cyclohexanone) and TRPA1 (allyl isothiocyanate) irritants and the aversion to cyclohexanone was mitigated when combined with a pure odorant (rose fragrance, phenylethyl alcohol, PEA). To determine whether olfactory-trigeminal interactions within the nose could potentially account for this behavioural effect we recorded from single trigeminal sensory axons innervating the nasal respiratory and olfactory epithelium using an isolated in vitro preparation. To circumvent non-specific effects of chemical stimuli, optical stimulation was used to excite olfactory sensory neurons in mice expressing channel-rhodopsin (ChR2) under the olfactory marker protein (OMP) promoter. Photoactivation of olfactory sensory neurons produced no modulation of axonal action potential conduction in individual trigeminal axons. Similarly, no evidence was found for collateral branching of trigeminal axon that might serve as a conduit for cross-talk between the olfactory and respiratory epithelium and olfactory dura mater. Using direct assessment of action potential activity in trigeminal axons we observed neither paracrine nor axon reflex mediated cross-talk between olfactory and trigeminal sensory systems in the rodent nasal cavity. Our current results suggest that olfactory sensory neurons exert minimal influence on trigeminal signals within the nasal cavity. [ABSTRACT FROM AUTHOR]

Background: Auscultation is one of the first examinations that a patient is subjected to in a GP’s office, especially in relation to diseases of the respiratory system. However it is a highly subjective process and depends on the physician’s ability to interpret the sounds as determined by his/her psychoacoustical characteristics. Here, we present a cross-sectional assessment of the skills of physicians of different specializations and medical students in the classification of respiratory sounds in children. Methods and findings: 185 participants representing different medical specializations took part in the experiment. The experiment comprised 24 respiratory system auscultation sounds. The participants were tasked with listening to, and matching the sounds with provided descriptions of specific sound classes. The results revealed difficulties in both the recognition and description of respiratory sounds. The pulmonologist group was found to perform significantly better than other groups in terms of number of correct answers. We also found that performance significantly improved when similar sound classes were grouped together into wider, more general classes. Conclusions: These results confirm that ambiguous identification and interpretation of sounds in auscultation is a generic issue which should not be neglected as it can potentially lead to inaccurate diagnosis and mistreatment. Our results lend further support to the already widespread acknowledgment of the need to standardize the nomenclature of auscultation sounds (according to European Respiratory Society, International Lung Sounds Association and American Thoracic Society). In particular, our findings point towards important educational challenges in both theory (nomenclature) and practice (training). [ABSTRACT FROM AUTHOR]

Objective: In addition to rhinoscopy, computed tomography of paranasal sinuses (CT) may be performed on patients with primary unknown cause of severe epistaxis (SE) or recurrent epistaxis (RE) to further assess the potential cause of bleeding. The aim of this study was to evaluate CT findings during the work-up of intractable epistaxis patients. Methods: 6937 patients were treated in our emergency department with acute epistaxis between 2009–2018. 304/6937 patients underwent CT and rhinoscopy due to intractable SE or RE. 33 patients presented with head trauma prior to epistaxis and were excluded from the final analysis. In 271 cases the primary causes of SE (n = 252) or RE (n = 19) remained unknown. Two observers retrospectively evaluated CT scans for potential sources of epistaxis. Disagreement was settled by consensus. CT and rhinoscopy findings were compared. Results: In 247/271 (91.1%) SE patients no related pathology was found on CT. A possible cause for epistaxis was found in all RE patients, but only in 5/252 (1.9%) patients with SE. Most tumours (10/11) and inflammatory conditions (9/10) were found in patients with RE. In three SE cases, a tumour was suspected on CT, from which two suspicions were refuted during rhinoscopy. CT revealed 10 cases of inflammatory conditions of the sinus and anatomical variant as potential cause of bleeding. Conclusion: For patients with unknown causes of epistaxis, supplementary CT imaging may be a useful diagnostic add-on to rhinoscopy in the event of RE, tumour suspicion or inflammation of the paranasal sinuses. However, in most cases of first-time SE, CT does not necessarily add to the diagnosis. In these cases, the marginal benefit of CT needs to be weighed carefully against its risks. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to evaluate three dimensionally the effect of the combined maxillary expansion and protraction treatment on oropharyngeal airway in children with non-syndromic cleft palate with or without cleft lip (CP/L). Methods: CBCT data of 18 preadolescent individuals (ages, 8.4 ± 1.7 years) with CP/L, who underwent Phase I orthodontic maxillary expansion with protraction, were compared before and after treatment. The average length of treatment was 24.1± 7.6 months. The airway volume and minimal cross-sectional area (MCA) were determined using 3DMD Vultus imaging software with cross-sectional areas calculated for each 2-mm over the entire length of the airway. A control group of 8 preadolescent individuals (ages, 8.7 ± 2.6 years) with CP/L was used for comparison. Results: There was a statistically significant increase in pharyngeal airway volume after phase I orthodontic treatment in both groups, however, there was no statistically significant change in minimal cross-sectional area in neither study nor control group. Conclusion: The findings showed that maxillary expansion and protraction did not have a significant effect on increasing oropharyngeal volume and MCA in patients with CP/L. [ABSTRACT FROM AUTHOR]

Calreticulin (CRT) is an important molecular chaperon crucial to survival of organisms under adverse conditions. In this study, the potential roles of CRT in the mud crab, Scylla paramamosain, were investigated. Firstly, SpCRT gene expression was detected in various tissues of S. paramamosain with the highest expression found in the hepatopancreas. To evaluate potential role of SpCRT in cold adaption, sub-adult crabs were subjected to temperatures of 10, 15, 20 and 25°C and the profiles of SpCRT gene were determined in the hepatopancreas, chela muscle and gills. The results showed that the expressions of SpCRT mRNA in these tissues were significantly higher for those crabs exposed to low temperatures of 10 and 15°C as compared to those exposed to the higher temperatures, indicating SpCRT was involved in cold adaptation—probably through facilitating protein folding. When low temperature 10°C or 15°C was further combined with high and low salinity stress, the expression of SpCRT mRNA at low salinity (10 ppt) was in most cases significantly higher than that at high salinity (35 ppt), suggesting that under low temperatures, low salinity may represents a more stressful condition to the crab than high salinity. It was also shown that when crabs challenged by 10°C, Ca2+ concentration increased rapidly in the hepatopancreas and an in vitro experiment further showed that the expression of SpCRT mRNA increased concurrently with added Ca2+ concentration; these results together imply that Ca2+ probably plays a major role in low temperature signaling, which induces expression of genes related to cold adaption, such as CRT. [ABSTRACT FROM AUTHOR]

The olfactory epithelium is continuously exposed to exogenous chemicals, including odorants. During the past decade, the enzymes surrounding the olfactory receptors have been shown to make an important contribution to the process of olfaction. Mammalian xenobiotic metabolizing enzymes, such as cytochrome P450, esterases and glutathione transferases (GSTs), have been shown to participate in odorant clearance from the olfactory receptor environment, consequently contributing to the maintenance of sensitivity toward odorants. GSTs have previously been shown to be involved in numerous physiological processes, including detoxification, steroid hormone biosynthesis, and amino acid catabolism. These enzymes ensure either the capture or the glutathione conjugation of a large number of ligands. Using a multi-technique approach (proteomic, immunocytochemistry and activity assays), our results indicate that GSTs play an important role in the rat olfactory process. First, proteomic analysis demonstrated the presence of different putative odorant metabolizing enzymes, including different GSTs, in the rat nasal mucus. Second, GST expression was investigated in situ in rat olfactory tissues using immunohistochemical methods. Third, the activity of the main GST (GSTM2) odorant was studied with in vitro experiments. Recombinant GSTM2 was used to screen a set of odorants and characterize the nature of its interaction with the odorants. Our results support a significant role of GSTs in the modulation of odorant availability for receptors in the peripheral olfactory process. [ABSTRACT FROM AUTHOR]

Knodus nuptialis n. sp. is described from the Rio Curuá drainage, Rio Xingu basin, Brazil. It can be diagnosed from its congeners by having dentary teeth decreasing gradually in size posteriorly, outer premaxillary teeth row with five cusps, 12–15 branched anal-fin rays and a single humeral spot. The species presents notable sexual dimorphism consisting of densely concentrated nuptial tubercles on head, body, and fins, gill-gland, and bony hooks in the anal fin of mature males. It was found that these sexually dimorphic features are useful and functional in males of the new species only during the reproductive season and after this period, they become atrophied, and eventually disappear. The list of characiform species presenting breeding tubercles is updated and nine species and two genera of the Characidae, Deuterodon and Bryconacidnus, are for the first time reported to have breeding tubercles. [ABSTRACT FROM AUTHOR]

Our previous study demonstrated that predominant feeding inhibitory effects were found in the crude extracts of foregut and midgut of the silkworm Bombyx mori larvae. To address the entero-intestinal control crucial for the regulation of insect feeding behavior, the present study identified and functionally characterized feeding inhibitory peptides from the midgut of B. mori larvae. Purification and structural analyses revealed that the predominant inhibitory factors in the crude extracts were allatotropin (AT) and GSRYamide after its C-terminal sequence. In situ hybridization revealed that AT and GSRYamide were expressed in enteroendocrine cells in the posterior and anterior midgut, respectively. Receptor screening using Ca2+-imaging technique showed that the B. mori neuropeptide G protein-coupled receptor (BNGR)-A19 and -A22 acted as GSRYamide receptors and BNGR-A5 acted as an additional AT receptor. Expression analyses of these receptors and the results of the peristaltic motion assay indicated that these peptides participated in the regulation of intestinal contraction. Exposure of pharynx and ileum to AT and GSRYamide inhibited spontaneous contraction in ad libitum-fed larvae, while exposure of pharynx to GSRYamide did not inhibit contraction in non-fed larvae, indicating that the feeding state changed their sensitivity to inhibitory peptides. These different responses corresponded to different expression levels of their receptors in the pharynx. In addition, injection of AT and GSRYamide decreased esophageal contraction frequencies in the melamine-treated transparent larvae. These findings strongly suggest that these peptides exert feeding inhibitory effects by modulating intestinal contraction in response to their feeding state transition, eventually causing feeding termination. [ABSTRACT FROM AUTHOR]

The study of early development in Neotropical Leiuperinae frogs (Anura, Leptodactylidae) has been addressed by several works in recent times. However, a comparative developmental approach under a phylogenetic context was not available. Herein we analyzed the morphological and ontogenetic diversity of embryos belonging to 22 species of the three largest genera in Leiuperinae. We find that in most cases, variations fit with the phylogeny at the inter- and intrageneric levels. Embryo kyphosis and whitish color are synapomorphies for the clade grouping Physalaemus and Engystomops. The presence of a third lower tooth row on the oral disc is plesiomorphic for Leiuperinae, only changing in derived clades. The configurations and developmental trajectories of the lower lip are exceptionally diverse. The developmental sequences optimized on the phylogenetic tree recover an early differentiated first lower tooth row a synapomorphy of Pseudopaludicola and Physalaemus, and an early differentiated second row as synapomorphy of Pleurodema. On the other hand, few features are highly conserved in the subfamily, such as the adhesive glands universally present in a type-C configuration. Our results also suggest that the morphology and ontogeny of embryos is in some cases associated to the environment where they develop. A large body size, poorly developed transient respiratory structures, large yolk provision and delayed development of the digestive tract occur convergently in embryos inhabiting cold, oxygenated environments. Embryos that develop in warmer water bodies in xeric environments show more complex and persistent transient respiratory structures and an early onset of hind limbs development. Our survey highlights that morphology and early development of anurans can be a valuable source of information for phylogenetic studies, and provide fundamental bases to explore and discuss how evolutionary changes can be shaped by environmental conditions. [ABSTRACT FROM AUTHOR]

Background: Liposomal amphotericin B (L-AMB) has been used for mucosal leishmaniasis (ML), but comparative studies on L-AMB and other drugs used for the treatment of ML have not been conducted. The present study aimed to evaluate the outcome of patients with ML who were treated with L-AMB. Methods: This is a 15-year retrospective study of Brazilian patients with a confirmed diagnosis of ML. The therapeutic options for the treatment of ML consisted of L-AMB, amphotericin B lipid complex (ABLC), deoxycholate amphotericin B (d-AMB), itraconazole, antimonial pentavalent, or pentamidine. Healing, cure rate and adverse effects (AEs) associated with the drugs used to treat this condition were analyzed. Results: In 71 patients, a total of 105 treatments were evaluated. The outcome of the treatment with each drug was compared, and results showed that L-AMB was superior to other therapeutic regimens (P = 0.001; odds ratio [OR] = 4.84; 95% confidence interval [CI] = 1.78–13.17). d-AMB had worse AEs than other treatment regimens (P = 0.001, OR = 0.09; 95% CI = 0.09–0.43). Approximately 66% of the patients presented with AEs during ML treatment. Although L-AMB was less nephrotoxic than d-AMB, it was associated with acute kidney injury compared with other drugs (P <0.05). Conclusion: L-AMB was more effective than other therapies for the treatment of ML. However, a high incidence of toxicity was associated with its use. Therapeutic choices should be reassessed, and the development of new drugs is necessary for the treatment of ML. [ABSTRACT FROM AUTHOR]

Background: Area-level indices are widely used to assess the impact of socio-environmental characteristics on cancer outcomes. While area-level measures of socioeconomic status (SES) have been previously used in cancer settings, fewer studies have focused on evaluating the impact of area-level health services supply (HSS) characteristics on cancer outcomes. Moreover, there is significant variation in the methods and constructs used to create area-level indices. Methods: In this study, we introduced a psychometrically-induced, reproducible approach to develop area-level HSS and SES indices. We assessed the utility of these indices in detecting the effects of area-level characteristics on prostate, breast, and lung cancer incidence and stage at diagnosis in the US. The information on county-level SES and HSS characteristics were extracted from US Census, County Business Patterns data and Area Health Resource Files. The Surveillance, Epidemiology, and End Results database was used to identify individuals diagnosed with cancer from 2010 to 2012. SES and HSS indices were developed and linked to 3-year age-adjusted cancer incidence rates. SES and HSS indices empirically summarized the level of employment, education, poverty and income, and the availability of health care facilities and health professionals within counties. Results: SES and HSS models demonstrated good fit (TLI = 0.98 and 0.96, respectively) and internal consistency (alpha = 0.85 and 0.95, respectively). Increasing SES and HSS were associated with increasing prostate and breast cancer and decreasing lung cancer incidence rates. The results varied by stage at diagnosis and race. Conclusion: Composite county-level measures of SES and HSS were effective in ranking counties and detecting gradients in cancer incidence and stage at diagnosis. Thus, these measures provide valuable tools for monitoring geographic disparities in cancer outcomes. [ABSTRACT FROM AUTHOR]

Infection of rainbow trout with the parasitic ciliate Ichthyopthirius multifiliis induces differential responses in gills, skin and spleen. A controlled experimental infection was performed and expression of immune-relevant genes in skin, gills, and spleen were recorded by qPCR at day 1 and 8 after parasite exposure. Infection induced a marked reaction involving regulation of innate and adaptive immune genes in rainbow trout at day 8 post-infection. The expression level of a total of 22 out of 24 investigated genes was significantly higher in gills compared to skin reflecting the more sensitive and delicate structure of gills. Especially pro-inflammatory cytokines IL-6, IL-17 C1, regulatory cytokines IL-4/13A, IL-10, TGFβ, complement factor C5, chemokines CK10, CK12, acute phase proteins (precerebellin, hepcidin) and immunoglobulins (IgM, IgT) displayed differential expression levels. The spleen, a central immune organ with no trace of the parasite, showed elevated expression of IgM, IgT, complement factor C5 and chemokine CK10 (compared to skin and gills directly exposed to the parasite), indicating an interaction between the infected surface sites and central immune organs. This communication could be mediated by chemokines CK10 and CK12 and cytokine IL-4/13A and may at least partly explain the establishment of a systemic response in rainbow trout against the parasite. [ABSTRACT FROM AUTHOR]

Avian pathogenic Escherichia coli (APEC) causes great economic loss to the poultry industry worldwide. Chicken type II pneumocytes (CP II cells) secrete surfactants and modulate lung immunity to decrease the infection of the invading pathogen. Nevertheless, the pathogenesis of CP II cells to APEC infection remains poorly understood. Therefore, we conducted global gene expression profiling of CP II cells after APEC-O78 infection to explore the host-pathogen interaction. The differentially expressed genes of CP II cells to APEC infection were characterized by RNA-seq with EB-seq algorithm. In consequence, the mRNA of 18996 genes was identified, and CP II cells responded to APEC infection with marked changes in the expression of 1390 genes. Among them, there are 803 down-regulated mRNAs and 587 up-regulated mRNAs. The KEGG prediction and Gene Ontology terms analysis revealed that the major enriched pathways were related to NF-κB signaling pathway, apoptosis pathway, tight junction, and cytokine-cytokine receptor interaction and other pathways. We adopted qRT-PCR to verify the validity of the selected gene expression. The fold induction of qPCR was similar to the RNA-seq results. These results provide a better understanding of the pathogenesis of APEC, especially apoptosis pathway involved in APEC infection. [ABSTRACT FROM AUTHOR]

Ferlaviruses are important pathogens in snakes and other reptiles. They cause respiratory and neurological disease in infected animals and can cause severe disease outbreaks. Isolates from this genus can be divided into four genogroups–A, B, and C, as well as a more distantly related sister group, “tortoise”. Sequences from large portions (5.3 kb) of the genomes of a variety of ferlavirus isolates from genogroups A, B, and C, including the genes coding the surface glycoproteins F and HN as well as the L protein were determined and compared. In silico analyses of the glycoproteins of genogroup A, B, and C isolates were carried out. Three isolates representing these three genogroups were used in transmission studies with corn snakes (Pantherophis guttatus), and clinical signs, gross and histopathology, electronmicroscopic changes in the lungs, and isolation of bacteria from the lungs were evaluated. Analysis of the sequences supported the previous categorization of ferlaviruses into four genogroups, and criteria for definition of ferlavirus genogroups and species were established based on sequence identities (80% resp. 90%). Analysis of the ferlavirus glycoprotein models showed parallels to corresponding regions of other paramyxoviruses. The transmission studies showed clear differences in the pathogenicities of the three virus isolates used. The genogroup B isolate was the most and the group A virus the least pathogenic. Reasons for these differences were not clear based on the differences in the putative structures of their respective glycoproteins, although e.g. residue and consequential structure variation of an extended cleavage site or changes in electrostatic charges at enzyme binding sites could play a role. The presence of bacteria in the lungs of the infected animals also clearly corresponded to increased pathogenicity. This study contributes to knowledge about the structure and phylogeny of ferlaviruses and lucidly demonstrates differences in pathogenicity between strains of different genogroups. [ABSTRACT FROM AUTHOR]

Background: Children with oropharyngeal dysphagia have impaired airway protection mechanisms and are at higher risk for pneumonia and other pulmonary complications. Aspiration of gastric contents is often implicated as a cause for these pulmonary complications, despite being supported by little evidence. The goal of this study is to determine the relative contribution of oropharyngeal and gastric microbial communities to perturbations in the lung microbiome of children with and without oropharyngeal dysphagia and aspiration. Methods: We conducted a prospective cohort study of 220 patients consecutively recruited from a tertiary aerodigestive center undergoing simultaneous esophagogastroduodenoscopy and flexible bronchoscopy. Bronchoalveolar lavage, gastric and oropharyngeal samples were collected from all recruited patients and 16S sequencing was performed. A subset of 104 patients also underwent video fluoroscopic swallow studies to assess swallow function and were categorized as aspiration/no aspiration. To ensure the validity of the results, we compared the microbiome of these aerodigestive patients to the microbiome of pediatric patients recruited to a longitudinal cohort study of children with suspected GERD; patients recruited to this study had oropharyngeal, gastric and/or stool samples available. The relationships between microbial communities across the aerodigestive tract were described by analyzing within- and between-patient beta diversities and identifying taxa which are exchanged between aerodigestive sites within patients. These relationships were then compared in patients with and without aspiration to evaluate the effect of aspiration on the aerodigestive microbiome. Results: Within all patients, lung, oropharyngeal and gastric microbiomes overlap. The degree of similarity is the lowest between the oropharynx and lungs (median Jensen-Shannon distance (JSD) = 0.90), and as high between the stomach and lungs as between the oropharynx and stomach (median JSD = 0.56 for both; p = 0.6). Unlike the oropharyngeal microbiome, lung and gastric communities are highly variable across people and driven primarily by person rather than body site. In patients with aspiration, the lung microbiome more closely resembles oropharyngeal rather than gastric communities and there is greater prevalence of microbial exchange between the lung and oropharynx than between gastric and lung sites (p = 0.04 and 4x10−5, respectively). Conclusions: The gastric and lung microbiomes display significant overlap in patients with intact airway protective mechanisms while the lung and oropharynx remain distinct. In patients with impaired swallow function and aspiration, the lung microbiome shifts towards oropharyngeal rather than gastric communities. This finding may explain why antireflux surgeries fail to show benefit in pediatric pulmonary outcomes. [ABSTRACT FROM AUTHOR]

Purpose: To determine the impact of Sequential Organ Failure Assessment (SOFA) organ sub-scores for hospital mortality risk stratification in a contemporary cardiac intensive care unit (CICU) population. Materials and methods: Adult CICU admissions between January 1, 2007 and December 31, 2015 were reviewed. The SOFA score and organ sub-scores were calculated on CICU day 1; patients with missing SOFA sub-score data were excluded. Discrimination for hospital mortality was assessed using area under the receiver-operator characteristic curve (AUROC) values, followed by multivariable logistic regression. Results: We included 1214 patients with complete SOFA sub-score data. The mean age was 67 ± 16 years (38% female); all-cause hospital mortality was 26%. Day 1 SOFA score predicted hospital mortality with an AUROC of 0.72. Each SOFA organ sub-score predicted hospital mortality (all p <0.01), with AUROC values of 0.53 to 0.67. On multivariable analysis, only the cardiovascular, central nervous system, renal and respiratory SOFA sub-scores were associated with hospital mortality (all p <0.01). A simplified SOFA score containing the cardiovascular, central nervous system and renal sub-scores had an AUROC of 0.72. Conclusions: In CICU patients with complete SOFA sub-score data, risk stratification for hospital mortality is determined primarily by the cardiovascular, central nervous system, renal and respiratory SOFA sub-scores. [ABSTRACT FROM AUTHOR]

Objectives: The effect a wind instrument has on lung function is a much-discussed topic with inconclusive data, not least because existing studies combine all wind instruments as one entity. The aim of this study was to investigate the effect of playing a trumpet/cornet/flugelhorn on lung function. Methods: A prospective, multicentre, cross-sectional, case-control study. Participants were recruited from wind orchestra or brass bands throughout Switzerland. Inclusion criteria: aged 16 or older, reporting at least one year of playing a trumpet/cornet/flugelhorn. Controls were members of an orchestra, who had never played a wind instrument. The primary end-point of the study was the difference in FEV1%predicted between trumpet/cornet/flugelhorn players and controls. Results: 147 subjects were included in the study. Controls (n = 48) were significantly younger, more commonly male, current smokers and had a lower body mass index compared to trumpet/cornet/flugelhorn players (n = 99). There was no significant difference in FEV1%predicted (91.9% vs 94.2%; p = 0.316) or FVC %predicted (89.4% vs 92.6%; p = 0.125) between controls and trumpet/cornet/flugelhorn players, respectively, in crude and adjusted analyses. However, there was a significant negative association between the number of years playing a trumpet/cornet/flugelhorn and FVC %predicted after adjusting for smoking status, gender, and height. Trumpet/cornet/flugelhorn players had a similar amount of respiratory symptoms to controls (questionnaire score 3.2±3.2 vs 2.8±2.4, p = 0.717). Conclusion: Lung function in trumpet/cornet/flugelhorn players was similar to controls. However, the number of years playing a trumpet/cornet/flugelhorn seems to have an adverse effect on forced vital capacity. [ABSTRACT FROM AUTHOR]

Background: In patients with neuromuscular disorders, assessment of respiratory function relies on forced vital capacity (FVC) measurements. Providing complementary respiratory outcomes may be useful for clinical trials. Diaphragm sniff ultrasound (US) is a noninvasive technique that can assess diaphragm function that may be affected in patients with neuromuscular disorders. Purpose: We aimed to provide normal values of sniff diaphragm ultrasound, to assess the relationship between sniff diaphragm US, vital capacity (VC) and sniff nasal pressure. Additionally, we aimed to evaluate the diagnostic accuracy of sniff diaphragm US for predicting restrictive pulmonary insufficiency. Materials and methods: We included patients with neuromuscular disorders that had been tested with a sniff diaphragm US and functional respiratory tests. Healthy subjects were also included to obtain normal diaphragm sniff ultrasound. We performed diaphragm tissue Doppler imaging (TDI) and time movement (TM) diaphragm echography combined with sniff maneuver. Results: A total of 89 patients with neuromuscular diseases and 27 healthy subjects were included in our study. In patients, the median age was 32 years [25; 50] and the median FVC was 34% of predicted [18; 55]. Sniff diaphragm motion using TM ultrasound was significantly associated with sniff nasal pressure, both for the right hemidiaphragm (r = 0.6 p <0.0001) and the left hemidiaphragm (r = 0.63 p = 0.0008). Right sniff peak TDI velocity was also significantly associated with FVC (r = 0.72, p<0.0001) and with sniff nasal pressure (r = 0.66 p<0.0001). Sniff diaphragm ultrasound using either TM mode or TDI displayed significant accuracy for predicting FVC<60% with an area under curve (AUC) reaching 0.93 (p<0.0001) for the right sniff diaphragm ultrasound in TM mode and 0.86 (p<0.001) for right peak diaphragm TDI velocity. Conclusion: Sniff diaphragm TM and TDI measures were significantly associated with sniff nasal pressure. Sniff diaphragm TM and TDI had a high level of accuracy to reveal respiratory involvement in patients with neuromuscular disorders. This technique is useful to assess and follow up diaphragm function in patients with neuromuscular disorders. It may be used as a respiratory outcome for clinical trials. [ABSTRACT FROM AUTHOR]

Microstomidae (Platyhelminthes: Macrostomorpha) diversity has been almost entirely ignored within recent years, likely due to inconsistent and often old taxonomic literature and a general rarity of sexually mature collected specimens. Herein, we reconstruct the phylogenetic relationships of the group using both previously published and new 18S and CO1 gene sequences. We present some taxonomic revisions of Microstomidae and further describe 8 new species of Microstomum based on both molecular and morphological evidence. Finally, we briefly review the morphological taxonomy of each species and provide a key to aid in future research and identification that is not dependent on reproductive morphology. Our goal is to clarify the taxonomy and facilitate future research into an otherwise very understudied group of tiny (but important) flatworms. [ABSTRACT FROM AUTHOR]

Objective: Extra nodal natural killer/T-cell lymphoma (ENKTL), nasal type is a rare and highly aggressive type of non-Hodgkin's lymphoma (NHL) commonly presented in the nasal cavity or lymphatic system. However, the common causes of mortality in ENKTL remain unclear. We conducted a retrospective population-based cohort study to elucidate the different causes of mortality in ENKTL and illustrate the main causal and associated risk factors leading to death. Methods: The study included patients diagnosed with ENKTL from 1987 to 2014 in the Surveillance, Epidemiology, and End Results (SEER) program. Univariate survival analysis was conducted using Kaplan-Meier analysis, and multivariate analyses were performed using Cox proportional hazards regression model. Competing-risks regression model was applied to estimate specific risks associated with mortality. Results: The analysis demonstrated increased mortality in males and patients diagnosed at older age and higher disease stage. NHL was the most common cause of mortality in patients with ENKTL, accounting for 74.13% of deaths in the cohort, followed by other malignant cancers, heart diseases, and infection. However, NHL-specific death events were fewer in patients diagnosed with advanced disease stage compared with incidences of death by other causes such as disease of heart and infections. Significant difference was seen between patients diagnosed earlier than 2000, who showed a higher probability of dying from NHL, and those diagnosed later, who showed propensity to die from other malignant tumors and infection. No differences were found when comparing sex or age at diagnosis. Conclusion: The most common cause of mortality in cases with ENKTL-NT is NHL. The female sex, diagnosis at young age and early stage are associated with improved prognosis. Further, the classification of Ann Arbor stage and year of diagnosis can provide references of specific causes of death, which might help decrease the mortality rate. [ABSTRACT FROM AUTHOR]

Background: Pulmonary hypoplasia, characterized by incomplete alveolar development, remains a major cause of mortality and morbidity in congenital diaphragmatic hernia. Recently demonstrated to differentiate from a common bipotent progenitor during development, the two cell types that line the alveoli type 1 and type 2 alveolar cells have shown to alter their relative ratio in congenital diaphragmatic hernia lungs. Objective: We used the nitrofen/bisdiamine mouse model to induce congenital diaphragmatic hernia and accurately assess the status of alveolar epithelial cell differentiation in relation to the common bipotent progenitors. Study design: Pregnant Swiss mice were gavage-fed with nitrofen/bisdiamine or vehicle at embryonic day 8.5. The administered dose was optimized by assessing the survival, congenital diaphragmatic hernia and facial abnormality rates of the exposed mouse pups. NanoCT was performed on embryonic day 11.5 and 16.5 to assess the embryonic and early canalicular stages of lung development. At embryonic day 17.5 corresponding to late canalicular stage, congenital diaphragmatic hernia lungs were characterized by measuring the lung weight/body weight ratio, morphometry, epithelial cell marker gene expression levels and alveolar cell type quantification. Results: Nitrofen/bisdiamine associated congenital diaphragmatic hernia lungs showed delayed development, hypoplasia with morphologic immaturity and thickened alveolar walls. Expression levels of distal epithelial progenitor marker Id2 increased, alveolar type 1 cell markers Pdpn and Hopx decreased, while type 2 cell markers pro-SPC and Muc1 remained constant during the canalicular stage. The number of Pdpn+ type 1 alveolar cells also decreased in congenital diaphragmatic hernia lungs. Conclusion: The mouse nitrofen/bisdiamine model is a potential model allowing the study of congenital diaphragmatic hernia lung development from early stages using a wide array of methods. Based on this model, the alveolar epithelium showed a decrease in the number of alveolar type 1 cell in congenital diaphragmatic hernia lungs while type 2 cell population remains unchanged. [ABSTRACT FROM AUTHOR]

Chlorothalonil is a thiol-reactive antifoulant that disperses widely and has been found in the marine environment. However, there is limited information on the deleterious effects of chlorothalonil in marine mollusks. In this study, we evaluated the effects of chlorothalonil on the gill tissues of the Pacific oyster, Crassostrea gigas and the blue mussel, Mytilus edulis after exposure to different concentrations of chlorothalonil (0.1, 1, and 10 μg L−1) for 96 h. Following exposure to 1 and/or 10 μg L−1 of chlorothalonil, malondialdehyde (MDA) levels significantly increased in the gill tissues of C. gigas and M. edulis compared to that in the control group at 96 h. Similarly, glutathione (GSH) levels were significantly affected in both bivalves after chlorothalonil exposure. The chlorothalonil treatment caused a significant time- and concentration-dependent increase in the activity of enzymes, such as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GR), in the antioxidant defense system. Furthermore, 10 μg L−1 of chlorothalonil resulted in significant inhibitions in the enzymatic activity of Na+/K+-ATPase and acetylcholinesterase (AChE). These results suggest that chlorothalonil induces potential oxidative stress and changes in osmoregulation and the cholinergic system in bivalve gill tissues. This information will be a useful reference for the potential toxicity of chlorothalonil in marine bivalves. [ABSTRACT FROM AUTHOR]

Objective: To investigate the feasibility of CT-based quantitative airway and air-trapping measurements and to assess their correlation with pulmonary function in children with post-infectious bronchiolitis obliterans (PIBO). Materials and methods: This retrospective study approved by the institutional review board included chest CT scans and pulmonary function tests (PFT) completed between January 2005 and December 2016 in children diagnosed with PIBO. The quantitative analysis of segmental and subsegmental bronchi was performed on each chest CT scan, measuring the areas or diameters of lumens, walls, or the entire airway. The air-trapping volume (ATV), the volume of lung area exhibiting lower attenuation than the mean attenuation of normal and air-trapping areas, was also measured in each lobe. Comparison analyses between CT parameters and PFT results were performed with Pearson or Spearman correlation. Results: In total, 23 patients were enrolled (mean age 7.0 ± 3.3 years; range, 4–15 years). We successfully measured 89.6% of all segmental bronchi. In the airway analysis, wall area showed a negative correlation with forced expiratory volume in one second (FEV1) in the majority of the pulmonary lobes. Air-trapping analyses demonstrated that ATV was negatively correlated with FEV1 and positively correlated with reactance at 5 Hz. Conclusion: Quantitative airway and air-trapping measurements from chest CT are feasible and correlate with pulmonary function in pediatric PIBO patients. [ABSTRACT FROM AUTHOR]

Infectious laryngotracheitis (ILT) is a respiratory disease that affects chickens. It is caused by the alphaherpesvirus, infectious laryngotracheitis virus (ILTV). This virus undergoes lytic replication in the epithelial cells of the trachea and upper respiratory tract (URT) and establishes latent infection in the trigeminal ganglia (TG) and trachea. Live attenuated vaccines are widely used to control ILT. At least one of these vaccines can establish latent infections in chickens, but this has not been demonstrated for all vaccines. The aim of the current study was to determine the capacity of three commercially available vaccines (SA2, A20 and Serva) and a glycoprotein G deletion mutant vaccine candidate (ΔgG ILTV) to establish latent infection in the TG of specific pathogen free (SPF) chickens. Five groups of 7-day-old SPF chickens were eye-drop vaccinated with either one of the vaccine strains or mock-vaccinated with sterile media and followed until 20 or 21 days post-vaccination (dpv). ILTV DNA was detected at 20–21 dpv in the TG of 23/40 (57.5%) vaccinated SPF chickens (SA2 = 10/10; A20 = 6/10; Serva = 3/10; ΔgG = 4/10) by PCR, but virus could not be reactivated from TG co-cultivated with primary chicken embryo kidney cells. In the birds from which ILTV DNA was detected in the TG, ILTV DNA could not be detected in the URT or trachea of 3 birds in each of the SA2, A20 and Serva vaccinated groups, and in 4 birds in the ΔgG vaccinated group, indicating that these birds were latently infected in the absence of active lytic replication and virus shedding. Results from this study demonstrate the capacity of commercial ILTV vaccines to establish latent infections and underline their importance in the epidemiology of this disease. [ABSTRACT FROM AUTHOR]

Background and objective: The idiopathic interstitial pneumonias (IIPs) are diffuse parenchymal lung disorders that are associated with substantial morbidity and mortality. Early diagnosis and disease stratification of IIP patients are important because these are related with the treatment and prognosis. Idiopathic pulmonary fibrosis (IPF) and nonspecific interstitial pneumonia (NSIP) are two major distinctive pathologic patterns of pulmonary fibrosis. We researched the application of the fluid-structure interaction (FSI) to the respiratory system and compared the pulmonary acinus mechanics and functions in healthy and IIP models. Methods: The human pulmonary alveolus is idealized by a three-dimensional honeycomb-like geometry, and a fluid-structure interaction analysis is performed to study the normal and diseased breathing mechanics. The computational domain consists of two generations of alveolar ducts within the pulmonary acinus, with alveolar geometries approximated as closely packed 14-sided polygons. Findings: In a normal breathing cycle, the flow rate of the healthy model is significantly larger than that of the NSIP and IPF models. Similar trends are observed for the volume change and the maximum pressure drop. The flow rate and the volume change of the NSIP are almost the same as those of IPF. The maximum pressure drop of NSIP is 5.5% larger than that of IPF. There is a 47% decrease in the pulmonary acinus compliance for the NSIP and IPF compared with that of the healthy model. The acinus resistances of NSIP and IPF are higher than those of the healthy lung by 6.4~11.2%. In particular, the pulmonary acinus resistance of the NSIP lung is higher than that of the IPF lung by 4.5%. Conclusions: Our study demonstrates the differences of air flow and lung function in the pulmonary acinus between the healthy and the IIP models. These changes in the lung are important considerations for early diagnosis and disease stratification in patients. Patient-based geometry can to be included in the computational models in future studies. [ABSTRACT FROM AUTHOR]

Little information exists on the microbiomes of livestock workers. A cross-sectional, epidemiological study was conducted enrolling 59 participants (26 of which had livestock contact) in Iowa. Participants were enrolled in one of four ways: from an existing prospective cohort study (n = 38), from the Iowa Department of Natural Resources Animal Feeding Operations database (n = 17), through Iowa county fairs (n = 3), and through snowball sampling (n = 1). We collected swabs from the nares and oropharynx of each participant to assess the microbiome via 16s rRNA sequencing. We observed livestock workers to have greater diversity in their microbiomes compared to those with no livestock contact. In the nares, there were 27 operational taxonomic units found to be different between livestock workers and non-livestock workers with the greatest difference seen with Streptococcus and Proteobacteria. In the oropharynx, livestock workers with swine exposure were more likely to carry several pathogenic organisms. The results of this study are the first to characterize the livestock worker nasal and oropharyngeal microbiomes. [ABSTRACT FROM AUTHOR]

Background: A better understanding of sickle cell anemia (SCA) and improvements in drug therapy and health policy have contributed to the emergence of a large population of adults living with this disease. The mechanisms by which SCA produces adverse effects on the respiratory system of these patients are largely unknown. Fractional-order (FrOr) models have a high potential to improve pulmonary clinical science and could be useful for diagnostic purposes, offering accurate models with an improved ability to mimic nature. Part 2 of this two-part study examines the changes in respiratory mechanics in patients with SCA using the new perspective of the FrOr models. These results are compared with those obtained in traditional forced oscillation (FOT) parameters, investigated in Part 1 of the present study, complementing this first analysis. Methodology/Principal findings: The data consisted of three categories of subjects: controls (n = 23), patients with a normal spirometric exam (n = 21) and those presenting restriction (n = 24). The diagnostic accuracy was evaluated by investigating the area under the receiver operating characteristic curve (AUC). Initially, it was observed that biomechanical changes in SCA included increased values of fractional inertance, as well as damping and hysteresivity (p<0.001). The correlation analysis showed that FrOr parameters are associated with functional exercise capacity (R = -0.57), pulmonary diffusion (R = -0.71), respiratory muscle performance (R = 0.50), pulmonary flows (R = -0.62) and airway obstruction (R = 0.60). Fractional-order modeling showed high diagnostic accuracy in the detection of early respiratory abnormalities (AUC = 0.93), outperforming spirometry (p<0.03) and standard FOT analysis (p<0.01) used in Part 1 of this study. A combination of machine learning methods with fractional-order modeling further improved diagnostic accuracy (AUC = 0.97). Conclusions: FrOr modeling improved our knowledge about the biomechanical abnormalities in adults with SCA. Changes in FrOr parameters are associated with functional exercise capacity decline, abnormal pulmonary mechanics and diffusion. FrOr modeling outperformed spirometric and traditional forced oscillation analyses, showing a high diagnostic accuracy in the diagnosis of early respiratory abnormalities that was further improved by an automatic clinical decision support system. This finding suggested the potential utility of this combination to help identify early respiratory changes in patients with SCA. [ABSTRACT FROM AUTHOR]

Olfactory ensheathing cells are thought to support regeneration and remyelination of damaged axons when transplanted into spinal cord injuries. Following transplantation, improved locomotion has been detected in many laboratory models and in dogs with naturally-occurring spinal cord injury; safety trials in humans have also been completed. For widespread clinical implementation, it will be necessary to derive large numbers of these cells from an accessible and, preferably, autologous, source making olfactory mucosa a good candidate. Here, we compared the yield of olfactory ensheathing cells from the olfactory mucosa using 3 different techniques: rhinotomy, frontal sinus keyhole approach and rhinoscopy. From canine clinical cases with spinal cord injury, 27 biopsies were obtained by rhinotomy, 7 by a keyhole approach and 1 with rhinoscopy. Biopsy via rhinoscopy was also tested in 13 cadavers and 7 living normal dogs. After 21 days of cell culture, the proportions and populations of p75-positive (presumed to be olfactory ensheathing) cells obtained by the keyhole approach and rhinoscopy were similar (~4.5 x 106 p75-positive cells; ~70% of the total cell population), but fewer were obtained by frontal sinus rhinotomy. Cerebrospinal fluid rhinorrhea was observed in one dog and emphysema in 3 dogs following rhinotomy. Blepharitis occurred in one dog after the keyhole approach. All three biopsy methods appear to be safe for harvesting a suitable number of olfactory ensheathing cells from the olfactory mucosa for transplantation within the spinal cord but each technique has specific advantages and drawbacks. [ABSTRACT FROM AUTHOR]

In phytophagous sap-sucking insects, the precibarial valve plays an important role in sap ingestion. We used light and electron microspcopy to study the morphology and the ultrastructure of the precibarial valve of the meadow spittlebug, Philaenus spumarius (Hemiptera, Aphrophoridae), in order to better understand the operative mechanism of this structure. The precibarial valve revealed to be a complex structure with a bell-like invagination in the middle of the precibarium (on the epipharynx). Unlike the current hypothesis, we propose that the valve opens by dilator muscles and closes through cuticular and fluid tensions, the latter leading to morphological changes to the plane of the valve based on sap flow. Moreover, the presence of a precibarial secretory structure is described for the first time for auchenorrhynchan insects. In light of these observations, functions are hypothesized and discussed for this secretory structure. [ABSTRACT FROM AUTHOR]

Background: Epidemiological data suggests that obstructive sleep apnea (OSA) is associated with increased cancer incidence and mortality. We investigate the effects of cyclical intermittent hypoxia (CIH), akin to the underlying pathophysiology of OSA, on lung cancer progression and metastatic profile in a mouse model. Methods: Intrathoracic injection of Ad5CMVCre virus into a genetically engineered mouse (GEM) KrasG12D+/-; p53fl/fl; myristolated-p110αfl/fl-ROSA-gfp was utilized to induce a solitary lung cancer. Male mice were then exposed to either CIH or Sham for 40–41 days until harvest. To monitor malignant progression, serial micro CT scans with respiratory gating (no contrast) was performed. To detect spontaneous metastases in distant organs, H&E and immunohistochemistry were performed. Results: Eighty-eight percent of injected Ad5CMVCre virus was recovered from left lung tissue, indicating reliable and accurate injections. Serial micro CT demonstrated that CIH increases primary lung tumor volume progression compared to Sham on days 33 (p = 0.004) and 40 (p<0.001) post-injection. In addition, CIH increases variability in tumor volume on day 19 (p<0.0001), day 26 (p<0.0001), day 33 (p = 0.025) and day 40 (p = 0.004). Finally, metastases are frequently detected in heart, mediastinal lymph nodes, and right lung using H&E and immunohistochemistry. Conclusions: Using a GEM mouse model of metastatic lung cancer, we report that male mice with solitary lung cancer have accelerated malignant progression and increased variability in tumor growth when exposed to cyclical intermittent hypoxia. Our results indicate that cyclical intermittent hypoxia is a pathogenic factor in non-small cell lung cancer that promotes the more rapid growth of developing tumors. [ABSTRACT FROM AUTHOR]

Objectives: Chronic otitis media with effusion (COME) in children can cause prolonged hearing loss, which is associated with an increased risk of learning delays and behavioural problems. Dispersal of bacterial pathogens from the nasal passages to the middle ear is implicated in COME. We sought to determine whether there is an association between nasal microbial composition and COME in children. Methods: A case-control study of children aged 3 and 4 years was conducted. Cases undergoing placement of tympanostomy tubes for COME were compared to healthy controls. Nasal swabs were collected and a questionnaire was administered. The V1-3 region of the 16S rRNA gene was amplified, and sequenced on the Illumina MiSeq. Results: 73 children with COME had a lower Shannon diversity index than 105 healthy controls (1.62 [.80] versus 1.88 [.84], respectively; P = .046). The nasal microbiota of cases and controls differed in composition using Bray-Curtis dissimilarity (p = 0.002). Children with COME had a higher abundance of otopathogens and lower abundance of commensals including alpha haemolytic Streptococci and Lactococcus. Cluster analysis revealed 4 distinct nasal microbial profiles. Profiles that were Corynebacterium-dominated (aOR 4.18 [95%CI, 1.68–10.39], Streptococcus-dominated (aOR 3.12 [95%CI, 1.08–9.06], or Moraxella-dominated (aOR 4.70 [95%CI, 1.73–12.80] were associated with COME, compared to a more mixed microbial profile when controlling for age, ethnicity, and recent antibiotics use. Conclusions: Children with COME have a less diverse nasal microbial composition with a higher abundance of pathogens, compared to healthy children who have a more mixed bacterial profile with a higher abundance of commensals. Further research is required to determine how nasal microbiota may relate to the pathogenesis or maintenance of COME, and whether modification of the nasal microbiota can prevent or treat children at risk of COME. [ABSTRACT FROM AUTHOR]

Diplozoidae infects the gills of cyprinid fishes in Africa, Europe, and Asia. Traditionally the hardened internal structures, crucial for identification of diplozoid species, are studied using light microscopy. Recently, the sclerotised haptoral structures of an African diplozoid, Paradiplozoon vaalense, were successfully isolated and visualised using scanning electron microscopy (SEM). In this paper, the haptoral sclerites of three diplozoid species are compared using SEM for the first time. Paradiplozoon ichthyoxanthon and Paradiplozoon vaalense occur on Labeobarbus and Labeo species, respectively, in the Vaal River system, South Africa, while Diplozoon paradoxum is widely-distributed in Europe and Asia, infecting several host species. Diplozoon paradoxum is a well-studied species, as well as being the type species of the family and ideal for inclusion in an exploratory study for comparative purposes. SEM study of D. paradoxum and P. ichthyoxanthon provided valuable information regarding surface morphology of the attachment structures hitherto not observed. Elaborate morphometric study of the haptoral hooks were incorporated, adding 12 point-to-point measurements to current morphometric characteristics. The results were analysed statistically, and significant differences support absolute separation (100.00%) of the three species following discriminant analysis. These point-to-point measurements could also be used for light microscopical study in the future and aid species delimitation within the Diplozoidae. [ABSTRACT FROM AUTHOR]

Background: Velopharyngeal structure augmentation methods are used as alternatives to velopharyngeal plasty. Anatomic sites of implantation/injection vary widely due to a lack of standardized criteria. Here, we experimentally investigated optimal sites of velopharyngeal structure augmentation via saline injection in dogs as they naturally exhibit velopharyngeal insufficiency (VPI). Methods: Velopharyngeal structure augmentation was performed on 10 beagles (age range: 20–24 months; weight range: 9–12 kg). Saline containing 1/80,000 epinephrine was injected intraorally in 1-mL increments into the nasal mucosa of the soft palate (n = 4), posterior pharyngeal wall (n = 3), or bilateral pharyngeal walls (n = 3) of each dog. Nasal air leakage was measured under rebreathing until velopharyngeal closure was achieved; the measurement was performed using flow meter sensors on both nasal apertures, and the oral cavity was filled with alginate impression material to prevent oral air leakage. Results: Pre-injection, the dogs exhibited an average of 0.455 L/s air leakage from the nasal cavity. The dogs with saline injected into the nasal mucosa of the soft palate achieved steady augmentation, and nasal air leakage disappeared under rebreathing following 6-mL saline injection. Conversely, nasal air leakage remained in the dogs with saline injected in the posterior pharyngeal wall or bilateral pharyngeal walls. Conclusions: During VPI treatment in dogs, augmentation was most effective at the nasal mucosa of the soft palate. Improvement in nasal air leakage was highly dependent on the saline injection volume. Although velopharyngeal structures vary between dogs and humans, velopharyngeal closure style is similar. Thus, our results may aid in the treatment of VPI patients. [ABSTRACT FROM AUTHOR]

The study aims to examine drug-induced sleep endoscopy (DISE) in the decision-making process of pediatric obstructive sleep apnea (OSA) patients with small tonsils. This was a retrospective study of children who underwent awake flexible endoscopy, DISE, and adenoidectomy with/without tonsillectomy at the Shanghai Children’s Medical Center between 03/2015 and 12/2016. Tonsillectomy was performed for tonsillar obstruction found by DISE. Adenoidectomy was performed for all children. Cardio-pulmonary coupling (CPC) and oximetry were observed before/after surgery. The study included 126 children: 56 (44.4%) with grade 2 tonsils and 70 (55.6%) with grade 1. Mean age was 5.7±3.2 (range, 2.8–10.4) years and mean BMI of 15.7±5.5 kg/m2. Unexpectedly, DISE showed tonsillar obstruction in 57 (45.2%) children, including 44 (78.6%) with grade 2 tonsils and 13 (18.6%) with grade 1. Therefore, DISE-directed tonsillectomy was performed for 57 patients. There was an improvement in respiratory disturbance index (RDI) and oxygen saturation nadir in the DISE (P = 0.0007, P = 0.037) and control (P = 0.001, P = 0.023) groups 6 months after surgery, but RDI improvement was better in the DISE group compared with controls 1 year after surgery (P = 0.042). DISE is a good way to determine the necessity of tonsillectomy in pediatric OSA patients with small tonsils. [ABSTRACT FROM AUTHOR]

Multifocal micronodular pneumocyte hyperplasia (MMPH) is a rare pulmonary disease, generally manifesting as a tuberous sclerosis complex (TSC), characterised by multiple, small ground-glass nodular shadows on chest computed tomography (CT). Histological examination typically reveals multicentric, well-demarcated, nodular type II pneumocystic growth. Herein, we describe three cases of this rare pulmonary disease occurring within one family. Using reverse transcription polymerase chain reaction (RT-PCR) and direct DNA sequencing, we identified a novel germline mutation, a point mutation in TSC1 intron 5, which yielded a splice variant and loss of function of TSC1. Furthermore, immunohistochemical staining indicated the expression of phospho-p70S6K and phospho-4E-BP1, suggesting that TSC1 function was impaired by the novel gene mutation in MMPH cells. [ABSTRACT FROM AUTHOR]

Background: Mouth breathing could induce not only dry throat and eventually upper respiratory tract infection, but also snoring and obstructive sleep apnea, while nasal breathing is protective against those problems. Thus, one may want to explore an approach to modify habitual mouth breathing as preferable to nasal breathing. The aim of this study was to investigate the physiological effects of our newly developed mask on facilitation of nasal breathing. Methods: Thirty seven healthy male volunteers were enrolled in a double blind, randomized, placebo-controlled crossover trial. Participants wore a newly developed heated humidification mask or non-heated-humidification mask (placebo) for 10-min each. Subjective feelings including dry nose, dry throat, nasal obstruction, ease to breathe, relaxation, calmness, and good feeling were asked before and after wearing each mask. In addition, the effects of masks on nasal resistance, breathing pattern, and heart rate variability were assessed. Results: Compared with the placebo mask, the heated humidification mask improved all components of subjective feelings except for ease to breathe; moreover, decreased nasal resistance and respiratory frequency accompanied a simultaneous increase in a surrogate maker for tidal volume. However, use of the heated humidification mask did not affect heart rate variability Conclusion: Adding heated humidification to the nasopharynx could modulate breathing patterns with improvement of subjective experience and objective nasal resistance. [ABSTRACT FROM AUTHOR]

Symbiosis between Bathymodiolus and Gammaproteobacteria allows these deep-sea mussels to live in toxic environments such as hydrothermal vents and cold seeps. The quantity of endosymbionts within the gill-bacteriocytes appears to vary according to the hosts environment; however, the mechanisms of endosymbiont population size regulation remain obscure. We investigated the possibility of a control of endosymbiont density by apoptosis, a programmed cell death, in three mussel species. Fluorometric TUNEL and active Caspase-3-targeting antibodies were used to visualize and quantify apoptotic cells in mussel gills. To control for potential artefacts due to depressurization upon specimen recovery from the deep-sea, the apoptotic rates between mussels recovered unpressurised, versus mussels recovered in a pressure-maintaining device, were compared in two species from hydrothermal vents on the Mid-Atlantic Ridge: Bathymodiolus azoricus and B. puteoserpentis. Results show that pressurized recovery had no significant effect on the apoptotic rate in the gill filaments. Apoptotic levels were highest in the ciliated zone and in the circulating hemocytes, compared to the bacteriocyte zone. Apoptotic gill-cells in B. aff. boomerang from cold seeps off the Gulf of Guinea show similar distribution patterns. Deep-sea symbiotic mussels have much higher rates of apoptosis in their gills than the coastal mussel Mytilus edulis, which lacks chemolithoautotrophic symbionts. We discuss how apoptosis might be one of the mechanisms that contribute to the adaptation of deep-sea mussels to toxic environments and/or to symbiosis. [ABSTRACT FROM AUTHOR]

We present a single center’s experience of treatment outcomes and dosimetric parameters for breast cancer patients treated with hypofractionated Helical TomoTherapy (HT). This is a retrospective study of one hundred and thirty-six patients with invasive breast cancer treated between March 2012 and October 2016. Dosimetric parameters and 3-year loco-regional failure free survival (LRFFS) were analyzed. Dose to ipsilateral lung, heart and contralateral breast as well as acute and late toxicities were recorded. The median follow-up time is 45 months (range: 5–83). Two patients had loco-regional failure. The 3-year LRFFS was 99%. Acute grade 1 and 2 skin toxicities occurred in 95% and 1%, respectively. Coverage of the target volumes was achieved with the mean ± standard deviation (SD) of homogeneity and conformity index being 0.1 ± 0.04, and 0.8 ± 0.07, respectively. Dose to ipsilateral lung, contralateral breast, and heart was also within the limited constraints regardless of the complexity of target volumes. Only two percent of patients experienced late grade 2 skin toxicity. No late grade 2 subcutaneous tissue toxicity was found. Nine percent of patients developed late grade 1 lung toxicity. Hypofractionated radiotherapy using Helical TomoTherapy in breast irradiation provides excellent 3-year LRFFS and minimal acute and late toxicities. A careful, longer follow-up of healthy tissue effects to lung, heart, and contralateral breast is warranted. [ABSTRACT FROM AUTHOR]

Background: Exhaled aerosols from lungs have unique patterns, and their variation can be correlated to the underlying lung structure and associated abnormities. However, it is challenging to characterize such aerosol patterns and differentiate their difference because of their complexity. This challenge is even greater for small airway diseases, where the disturbance signals are weak. Objectives and methods: The objective of this study is exploiting different feature extraction algorithms to develop a practical classifier to diagnose obstructive lung diseases using exhaled aerosol images. These include proper orthogonal decomposition (POD), principal component analysis (PCA), dynamic mode decomposition (DMD), and DMD with control (DMDC). Aerosol images were generated via physiology-based simulations in one normal and four diseased airway models in G7-9 bronchioles. The image data were classified using both the support vector machine (SVM) and random forest (RF) algorithms. The effectiveness of different features was evaluated by classification accuracy and misclassification rate. Findings: Results show a significantly higher performance using dynamic feature extractions (DMD and DMDC) than static algorithms (POD and PCA). Adding the control variables to DMD further improved classification accuracy. Comparing the classification methods, RF persistently outperformed SVM for all types of features considered. While the performance of RF constantly increased with the number of features retained, the performance of SVM peaked at 50 and decreased thereafter. The 5-class classification accuracy was 94.8% using the DMDC-RF model and 93.0% using the DMD-RF model, both of which were higher than 87.0% in the previous study that used fractal dimension features. Conclusion: Considering that disease progression is inherently a dynamic process, DMD(C)-based feature extraction preserves temporal information and is preferred over POD and PCA. Compared with hand-crafted features like fractals, feature extraction by DMD and DMDC is automatic and more accurate. [ABSTRACT FROM AUTHOR]

Background: Cystic echinococcosis is caused by the metacestode of the zoonotic flatworm Echinococcus granulosus. Within the viscera of the intermediate host, the metacestode grows as a unilocular cyst known as hydatid cyst. This cyst is comprised of two layers of parasite origin: germinal and laminated layers, and one of host origin: the adventitial layer, that encapsulates the parasite. This adventitial layer is composed of collagen fibers, epithelioid cells, eosinophils and lymphocytes. To establish itself inside the host, the germinal layer produces the laminated layer, and to continue its life cycle, generates protoscoleces. Some cysts are unable to produce protoscoleces, and are defined as infertile cysts. The molecular mechanisms involved in cyst fertility are not clear, however, the host immune response could play a crucial role. Methodology/Principal findings: We collected hydatid cysts from both liver and lungs of slaughtered cattle, and histological sections of fertile, infertile and small hydatid cysts were stained with haematoxylin-eosin. A common feature observed in infertile cysts was the disorganization of the laminated layer by the infiltration of host immune cells. These infiltrating cells eventually destroy parts of laminated layer. Immunohistochemical analysis of both parasite and host antigens, identify these cells as cattle macrophages and are present inside the cysts associated to germinal layer. Conclusions/Significance: This is the first report that indicates to cell from immune system present in adventitial layer of infertile bovine hydatid cysts could disrupt the laminated layer, infiltrating and probably causing the infertility of cyst. [ABSTRACT FROM AUTHOR]

Agricultural intensification and shifts in precipitation regimes due to global climate change are expected to increase nutrient concentrations in aquatic ecosystems. However, the direct effects of nutrients widely present in wastewaters, such as nitrate, are poorly studied. Here, we use multiple indicators of fish health to experimentally test the effects of three ecologically relevant nitrate concentrations (<10, 50 and 250 mg NO3-/l) on wild-collected mosquitofish (Gambusia holbrooki), a species widely introduced for mosquito biocontrol in often eutrophic waters. Overall, biomarkers (histopathology, feeding assays, growth and caloric content and stable isotopes as indicators of energy content) did not detect overt signs of serious disease in juveniles, males or females of mosquitofish. However, males reduced food intake at the highest nitrate concentration compared to the controls and females. Similarly, juveniles reduced energy reserves without significant changes in growth or food intake. Calorimetry was positively associated with the number of perivisceral fat cells in juveniles, and the growth rate of females was negatively associated with δ15N signature in muscle. This study shows that females are more tolerant to nitrate than males and juveniles and illustrates the advantages of combing short- and long-term biomarkers in environmental risk assessment, including when testing for the adequacy of legal thresholds for pollutants. [ABSTRACT FROM AUTHOR]