Mucus threads from surface goblet cells clear particles from the airways.

BACKGROUND: The mucociliary clearance system driven by beating cilia protects the airways from inhaled microbes and particles. Large particles are cleared by mucus bundles made in submucosal glands by parallel linear polymers of the MUC5B mucins. However, the structural organization and function of the mucus generated in surface goblet cells are poorly understood. METHODS: The origin and characteristics of different mucus structures were studied on live tissue explants from newborn wild-type (WT), cystic fibrosis transmembrane conductance regulator (CFTR) deficient (CF) piglets and weaned pig airways using video microscopy, Airyscan imaging and electron microscopy. Bronchoscopy was performed in juvenile pigs in vivo. RESULTS: We have identified a distinct mucus formation secreted from the surface goblet cells with a diameter less than two micrometer. This type of mucus was named mucus threads. With time mucus threads gathered into larger mucus assemblies, efficiently collecting particles. The previously observed Alcian blue stained mucus bundles were around 10 times thicker than the threads. Together the mucus bundles, mucus assemblies and mucus threads cleared the pig trachea from particles. CONCLUSIONS: These results demonstrate that normal airway mucus is more complex and has a more variable structural organization and function than was previously understood. These observations emphasize the importance of studying young objects to understand the function of a non-compromised lung.

Mucus-producing 3D cell culture models.

In vitro cell-based models have been used for a long time since they are normally easily obtained and have an advantageous cost-benefit. Besides, they can serve a variety of ends, from studying drug absorption and metabolism to disease modeling. However, some in vitro models are too simplistic, not accurately representing the living tissues. It has been shown, mainly in the last years, that fully mimicking a tissue composition and architecture can be paramount for cellular behavior and, consequently, for the outcomes of the studies using such models. Because of this, 3D in vitro cell models have been gaining much attention, since they are able to better replicate the in vivo environment. In this review we focus on 3D models that contain mucus-producing cells, as mucus can play a pivotal role in drug absorption. Being frequently overlooked, this viscous fluid can have an impact on drug delivery. Thus, the aim of this review is to understand to which extent can mucus affect mucosal drug delivery and to provide a state-of-the-art report on the existing 3D cell-based mucus models.

Variations in mucous cell numbers in gills of Atlantic salmon (Salmo salar) presmolt in commercial freshwater farms in Norway.

Fish gills are heavily exposed to the external milieu and may react against irritants with different cellular responses. We describe variations in mucous cell counts in gills from healthy Atlantic salmon (Salmo salar) presmolts in five recirculating aquaculture system (RAS) farms and one flow-through farm. Based on certain criteria, mucous cells were histologically quantified in a defined lamellar region of the gills and the counts were analysed. Immunohistochemistry (IHC) was used to investigate epithelial responses. The median number of total mucous cells in the defined region was 59 per fish. Between the farms, the medians varied from 31 to 101 with the lowest in the flow-through farm. A regression model was fitted with "total mucous cells" as the dependent variable and with "fish length" and "fish farm" as independent variables. The proportion of variation in mucous cell counts explained by the model was twice as high when "fish farm" was included compared to only "fish length." IHC revealed proliferative responses in coherence with high mucous cell numbers. Conclusively, the variation in mucous cell counts depends on combined farm-related factors. Establishing a baseline for mucous cell counts is fundamental in the development of high-throughput monitoring programmes of gill health in farmed fish.

Protein Turnover in Epithelial Cells and Mucus along the Gastrointestinal Tract Is Coordinated by the Spatial Location and Microbiota.

The gastrointestinal tract is covered by a single layer of epithelial cells that, together with the mucus layers, protect the underlying tissue from microbial invasion. The epithelium has one of the highest turnover rates in the body. Using stable isotope labeling, high-resolution mass spectrometry, and computational analysis, we report a comprehensive dataset of the turnover of more than 3,000 and the expression of more than 5,000 intestinal epithelial cell proteins, analyzed under conventional and germ-free conditions across five different segments in mouse intestine. The median protein half-life is shorter in the small intestine than in the colon. Differences in protein turnover rates along the intestinal tract can be explained by distinct physiological and immune-related functions between the small and large intestine. An absence of microbiota results in an approximately 1 day longer protein half-life in germ-free animals.

Why antiplectic metachronal cilia waves are optimal to transport bronchial mucus.

The coordinated beating of epithelial cilia in human lungs is a fascinating problem from the hydrodynamics perspective. The phase lag between neighboring cilia is able to generate collective cilia motions, known as metachronal waves. Different kinds of waves can occur, antiplectic or symplectic, depending on the direction of the wave with respect to the flow direction. It is shown here, using a coupled lattice Boltzmann-immersed boundary solver, that the key mechanism responsible for their transport efficiency is a blowing-suction effect that displaces the interface between the periciliary liquid and the mucus phase. The contribution of this mechanism on the average flow generated by the cilia is compared to the contribution of the lubrication effect. The results reveal that the interface displacement is the main mechanism responsible for the better efficiency of antiplectic metachronal waves over symplectic ones to transport bronchial mucus. The conclusions drawn here can be extended to any two-layer fluid configuration having different viscosities, and put into motion by cilia-shaped or comb-plate structures, having a back-and-forth motion with phase lags.

Bacteria evoke alarm behaviour in zebrafish.

When injured, fish release an alarm substance (Schreckstoff) that elicits fear in members of their shoal. Although Schreckstoff has been proposed to be produced by club cells in the skin, several observations indicate that these giant cells function primarily in immunity. Previous data indicate that the alarm substance can be isolated from mucus. Here we show that mucus, as well as bacteria, are transported from the external surface into club cells, by cytoplasmic transfer or invasion of cells, including neutrophils. The presence of bacteria inside club cells raises the possibility that the alarm substance may contain a bacterial component. Indeed, lysate from a zebrafish Staphylococcus isolate is sufficient to elicit alarm behaviour, acting in concert with a substance from fish. These results suggest that Schreckstoff, which allows one individual to unwittingly change the emotional state of the surrounding population, derives from two kingdoms and is associated with processes that protect the host from bacteria.

Histochemical distribution of four types of enzymes and mucous cells in the intestine of koi carp (Cyprinus carpio var. koi).

The main purpose of this study was to investigate the distribution of acid phosphatase (ACP), alkaline phosphatase (ALP), non-specific esterase (NSE), peroxidase (POD), and mucous cells in the intestine of the koi carp Cyprinus carpio var. koi. ACP activity was located in the striated border, enterocytes, and lamina propria of the anterior and middle intestines. The ACP activity in the anterior intestine was higher than that in the middle and posterior intestines. ALP existed in the striated border of enterocytes and lamina propria, serosa, muscular layer, and the junction between muscular layer and submucosa layer of the intestine. The ALP activity in the anterior intestine was higher than that in the middle and posterior intestines. NSE activity was localized in the cytoplasm of enterocytes in the whole intestine, and the middle intestine showed the lower NSE activity than the anterior and posterior intestines. POD activity was localized in the blood cells of the lamina propria and cytoplasm of enterocytes in all intestinal segments. The POD activity among the anterior, middle, and posterior intestines was non-significantly different. Alcian blue periodic acid-Schiff histochemical results revealed three types of mucous cells in the intestine. The total number of mucous cells and percentage of type I cells among the anterior, middle, and posterior intestines were non-significantly different. The percentage of the type II cells was the highest in the posterior intestine, while the lowest in the anterior intestine. The percentage of the type III cells was the highest in the anterior intestine, while the lowest in the posterior intestine.

The structure of the skin, types and distribution of mucous cell of yangtze sturgeon ( Acipenser dabryanus ) / La estructura de la piel, los tipos y distribución de las células mucosas del esturión yangtze ( Acipenser dabryanus )

The structural characteristics of the skin, types and distribution of mucous cells of Yangtze sturgeon (Acipenser dabryanus) were studied at the light microscope level, stained with Haematoxylin-eosin (HE) and Alcian blue-periodie acid Schiff (ABPAS). The skin of both was composed of epidermis and dermis. The dermis was divided into stratum spongiosum and stratum compactum. The stained color of stratum compactum was stained more deeply than that of stratum spongiosum. The skin thickness displayed differences in the fish at different body positions. The thickest of epidermis layer was on the dorsal region for Yangtze sturgeon, reversely, the thinnest was the mandibular region; Stratum spongiosum on the mandibular region was the thickest, the stratum spongiosum of the maxillary region was not obvious. In summary, keratinized spines, a kind of keratin derivative, are widely distributed in the mandibular, ventral, dorsal, and caudal peduncle skin surface for Yangtze sturgeon, and some pit organs mainly present in the skin surface of the maxillary and ventral regions. In short, the small amount of mucous cells in the skin of Yangtze sturgeon and the type of mucous cell were main Type IV, nevertheless there was a distribution of a few Type III.

Se estudiaron las características estructurales de la piel, los tipos y la distribución de las células mucosas del esturión Yangtze (Acipenser dabryanus) con microscopio de luz, teñidas con hematoxilina-eosina (HE) y azul alcián-ácido de Schiff (AB-PAS). La piel estaba compuesta por epidermis y dermis. La dermis se dividía en estrato esponjoso y estrato compacto. El grosor de la piel mostró diferencias en los peces en diferentes posiciones del cuerpo. La capa más gruesa de la epidermis se observó en la región dorsal del esturión Yangtze; a la inversa, la más delgada en la región mandibular. El estrato esponjoso en la región mandibular era el más grueso, el estrato esponjoso de la región maxilar no era visualizado. En resumen, las espinas queratinizadas, un tipo derivado de la queratina, estaban ampliamente distribuidas en la superficie de la piel del pedúnculo mandibular, ventral, dorsal y caudal en el esturión Yangtze, y algunos órganos en fosas, presentes principalmente en la superficie de la piel de las regiones mandibular y ventral. En resumen, la pequeña cantidad de células mucosas en la piel del esturión Yangtze y el tipo de célula mucosa eran células principales tipo IV, sin embargo, se observaron algunas células tipo III.

Using 3D gastrointestinal tract in vitro models with microfold cells and mucus secreting ability to assess the hazard of copper oxide nanomaterials.

BACKGROUND: Copper oxide nanomaterials (CuO NMs) are exploited in many products including inks, cosmetics, textiles, wood preservatives and food contact materials. Their incorporation into these products may enhance oral exposure in consumer, environmental and occupational settings. Undifferentiated and differentiated monocultures of Caco-2 cells are commonly used to assess NM toxicity to the intestine in vitro. However, the integration of other cell types into Caco-2 in vitro models increases their physiological relevance. Therefore, the aim of this study is to evaluate the toxicity of CuO NMs and copper sulphate (CuSO4) to intestinal microfold (M) cell (Caco-2/Raji B) and mucus secreting (Caco-2/HT29-MTX) co-culture in vitro models via assessment of their impact on barrier integrity, viability and interleukin (IL)-8 secretion. The translocation of CuO NMs and CuSO4 across the intestinal barrier was also investigated in vitro. RESULTS: CuO NMs and CuSO4 impaired the function of the intestinal barrier in the co-culture models [as indicated by a reduction in transepithelial electrical resistance (TEER) and Zonular occludens (ZO-1) staining intensity]. Cu translocation was observed in both models but was greatest in the Caco-2/Raji B co-culture. CuO NMs and CuSO4 stimulated an increase in IL-8 secretion, which was greatest in the Caco-2/HT29-MTX co-culture model. CuO NMs and CuSO4 did not stimulate a loss of cell viability, when assessed using light microscopy, nuclei counts and scanning electron microscopy. CuO NMs demonstrated a relatively similar level of toxicity to CuO4 in both Caco-2/Raji B and Caco-2/HT29-MTX co- culture models. CONCLUSIONS: The Caco-2/Raji B co-culture model was more sensitive to CuO NM and CuSO4 toxicity than the Caco-2/HT29-MTX co-culture model. However, both co-culture models were less sensitive to CuO NM and CuSO4 toxicity than simple monocultures of undifferentiated and differentiated Caco-2 cells, which are more routinely used to investigate NM toxicity to the intestine. Obtained data can therefore feed into the design of future studies which assess the toxicity of substances (e.g. NMs) and pathogens to the intestine (e.g. by informing model and endpoint selection). However, more testing with a wider panel of NMs would be beneficial in order to help select which in vitro models and endpoints to prioritise when screening the safety of ingested NMs. Comparisons with in vivo findings will also be essential to identify the most suitable in vitro model to screen the safety of ingested NMs.

Mucus Architecture and Near-Surface Swimming Affect Distinct Salmonella Typhimurium Infection Patterns along the Murine Intestinal Tract.

Mucus separates gut-luminal microbes from the tissue. It is unclear how pathogens like Salmonella Typhimurium (S.Tm) can overcome this obstacle. Using live microscopy, we monitored S.Tm interactions with native murine gut explants and studied how mucus affects the infection. A dense inner mucus layer covers the distal colon tissue, limiting direct tissue access. S.Tm performs near-surface swimming on this mucus layer, which allows probing for colon mucus heterogeneities, but can also entrap the bacterium in the dense inner colon mucus layer. In the cecum, dense mucus fills only the bottom of the intestinal crypts, leaving the epithelium between crypts unshielded and prone to access by motile and non-motile bacteria alike. This explains why the cecum is highly infection permissive and represents the primary site of S.Tm enterocolitis in the streptomycin mouse model. Our findings highlight the importance of mucus in intestinal defense and homeostasis.

CT and Functional MRI to Evaluate Airway Mucus in Severe Asthma.

BACKGROUND: Intraluminal contributor(s) to airflow obstruction in severe asthma are patient-specific and must be evaluated to personalize treatment. The occurrence and functional consequence of airway mucus in the presence or absence of airway eosinophils remain undetermined. OBJECTIVE: The objective of this study was to understand the functional consequence of airway mucus in the presence or absence of eosinophils and to identify biomarkers of mucus-related airflow obstruction. METHODS: Mucus plugs were quantified on CT scans, and their contribution to ventilation heterogeneity (using MRI ventilation defect percent [VDP]) was evaluated in 27 patients with severe asthma. Patients were dichotomized based on sputum eosinophilia such that the relationship between mucus, eosinophilia, and ventilation heterogeneity could be investigated. Fractional exhaled nitric oxide (Feno) and related cytokines in sputum were measured. RESULTS: Mucus plugging was present in 100% of asthma patients with sputum eosinophils and 36% of those without sputum eosinophils (P = .0006) and was correlated with MRI VDP prebronchodilator (r = 0.68; P = .0001) and postbronchodilator (r = 0.72; P < .0001). In a multivariable regression, both mucus and eosinophils contributed to the prediction of postbronchodilator MRI VDP (R2 = 0.75; P < .0001). Patients with asthma in whom the mucus score was high had raised Feno (P = .03) and IL-4 (P = .02) values. Mucus plugging correlated with Feno (r = 0.63; P = .005). CONCLUSIONS: Both airway eosinophils and mucus can contribute to ventilation heterogeneity in patients with severe asthma. Patients in whom mucus is the dominant cause of airway obstruction have evidence of an upregulated IL-4/IL-13 pathway that could be identified according to increased Feno level.

Investigating the correlation between mucus cytokine levels, inflammatory cell counts, and baseline quality-of-life measures in chronic rhinosinusitis.

BACKGROUND: It is hypothesized that uncontrolled inflammation is responsible for many of the manifestations and symptoms of chronic rhinosinusitis (CRS). Although earlier work has demonstrated an association between olfactory loss and mucus cytokines, the impact on other symptoms is unknown. In this study we investigated the relationship between cytokines, inflammatory cell counts, and patient-reported outcomes measures to better understand how the inflammatory microenvironment correlates with CRS symptomatology. METHODS: The 22-item Sino-Nasal Outcome Test (SNOT-22) and 8-item Short Form Health Survey (SF-8) were administered to 76 patients undergoing endoscopic sinus surgery for CRS. Mucus was collected intraoperatively from the middle meatus and tested for 17 cytokines using a multiplex flow cytometric bead assay. Eosinophil/neutrophil counts were obtained from histopathologic slide review. Spearman correlations between cytokines, cell counts, and quality-of-life subdomain scores were assessed without multiple comparisons correction due to the small sample size. RESULTS: Interleukin-4 (IL-4) correlated significantly with the Rhinologic domain (Rs = 0.25, p = 0.03), whereas eosinophil and neutrophil counts were inversely correlated with the Extranasal Rhinologic domain (Rs = -0.32, p = 0.01; and Rs = -0.27, p = 0.03). Subgroup analysis for nasal polyposis (CRSwNP) showed significant correlations between IL-6 and Total SF-8 (Rs = 0.35, p = 0.02), General Health (Rs = 0.34, p = 0.03), and Emotional (Rs = 0.47, p = 0.002) scores. In patients without polyps (CRSsNP), IL-21 correlated positively with Extranasal Rhinologic Symptoms domain (Rs = 0.41, p = 0.01). CONCLUSION: This pilot study identifies possible pairwise correlations between mucus cytokine levels and baseline quality-of-life measures that need confirmation in larger, targeted studies. Due to the exploratory methodology, positive results may be spurious and should only be used as a starting point for future confirmatory work.

Oral administration of viable Bifidobacterium pseudolongum strain Patronus modified colonic microbiota and increased mucus layer thickness in rat.

This study aimed at evaluating the alteration of the colonic microbiota and the changes in the mucus layer thickness induced by oral administration of living bifidobacteria in rats. The study was performed on rats fed with Bifidobacterium pseudolongum strain Patronus (1010 bacteria per day for 7 days). This bacterial administration led to a large increase of mucus thickness (57%, P < 0.05). Both quantitative PCR and high-throughput sequencing of bacterial 16S rRNA gene revealed a significant increase of the amount of the Bifidobacterium genus in the microbiota of rats fed with the strain Patronus, associated with a decrease of Akkermansia muciniphila. The increase in mucus thickness could be due to an increase of the bifidobacteria per se or via the decrease of A. muciniphila, a major mucin-degrading species. As the mucus layer plays an essential role in gut protection, our data enlighten the importance of studying mucus-degrading bacteria for understanding the underlying etiology of diseases such as intestinal bowel diseases and to implement new therapeutic strategies.

Management and prognosis of low-grade appendiceal mucinous neoplasms: A clinicopathologic analysis of 50 cases.

BACKGROUND: Low-grade appendiceal mucinous neoplasms (LAMN) are poorly understood lesions characterized by their potential to spread to the peritoneal cavity as pseudomyxoma peritonei (PMP). The purpose of this study was to investigate the clinical and pathologic features and management of these tumors. METHODS: This was a retrospective study of consecutive patients with LAMN who underwent surgery by a surgical team at the First Affiliated Hospital of China Medical University between 2005 and 2016. Subgroup analyses were performed for patients with PMP. RESULT: The study included 50 LAMN patients, 13 of them with PMP. There were no significant differences in age (p = 0.293) or gender (p = 0.196) at diagnosis between the two groups. There was no significant difference in their presentation (p = 0.700). Although 5 patients with PMP had perforation of the appendiceal mucinous, acute peritonitis was uncommon. Microscopic examination detected that PMP without any obvious perforation in tumors shown mucin and/or mucinous epithelium herniating into the appendiceal wall, or as islands within these tissues. The patients underwent appendectomy, caecectomy and right hemicolectomy according to the intraoperative situation. The median follow-up period was 53 months (range 11-146 months). None of the patients developed clinical progression in either group during the follow-up period. CONCLUSION: The age of LAMN at presentation was almost 60 years (56.7) and there was no clear gender predilection. When LAMN was treated surgically with resection of the primary site in early stage disease or with pushing invasion, there was an excellent prognosis and expanded surgical procedures were unnecessary.

Behaviour during transportation predicts stress response and lower airway contamination in horses.

This study aimed to document the effects of an eight hour journey on behavioural, clinical, haematological, environmental and respiratory parameters, and to identify possible associations between factors. Twelve horses underwent clinical examination, respiratory endoscopy with tracheal wash (TW) aspiration, and collection of venous and arterial blood before (BJ) and after the journey (AJ). TW were submitted for conventional quantitative bacteriological evaluation and genetic microbiome analyses. Behaviour was assessed in stables prior to transportation and throughout the journey. Transportation caused mild, but significant, effects on fluid and electrolyte balance and an acute phase response, characterized by neutrophilia, hyperfibrinogenaemia and hyperglobulinaemia. The proportion of neutrophils in TW, tracheal mucus and TW bacterial concentration was increased AJ, with preferential replication of Pasteurellaceae. Horse behaviour en route predicted clinical and respiratory outcomes. The frequency of stress related behaviours was greatest in the first hour of the journey, and balance-related behaviours were most common in the final hour of the journey. Horses which lowered their heads less frequently en route and showed more stress-related behaviours had higher physiological stress (serum cortisol and heart rate on arrival), increased tracheal mucus and inflammation scores, and higher TW bacterial concentration AJ (P<0.05). Six horses with abnormal lung auscultation AJ proved to have had higher tracheal inflammation scores at preloading (P = 0.017), an overall higher concentration of bacteria in their TW (P = 0.013), and an increased percentage of neutrophils in TW at five days AJ (P = 0.003) in comparison to the other horses. While transport-related health problems are multifactorial, clinical examination, including auscultation and endoscopic inspection of the lower respiratory tract before and after journey, and behavioural observation en route may identify animals at increased risk of transport associated respiratory disease.

Lactobacillus spp. belonging to the Casei group display a variety of adhesins.

BACKGROUND: n. Adhesion of bacteria from the genus Lactobacillus to the gastrointestinal epithelium is, to a considerable degree, dependent on the interactions between adhesins found on the surface of bacterial cells and elements found within the epithelium. A significant role in these interactions is played by bacterial pro teins exposed to the cell wall surface, which are capable of binding to molecules of substances comprising the extracellular matrix of the intestinal epithelium. METHODS: In order to analyze the extracellular proteome of intestinal bacteria in terms of the presence of cell adhesion molecules, a total of twenty strains from the Lactobacillus spp. group Casei were tested. The analyses were conducted using SDS PAGE, 2-D electrophoresis, Western blot and mass spectrometry. An experiment was also conducted to assess the adhesion capacity of the tested strains to cervical epithelial cells (HeLa). RESULTS: The tested strains varied in their adhesion efficiency to HeLa cells, ranging from 0.5% to 29%. Us- ing electrophoretic methods a total of 54 extracellular protein fractions were distinguished in these strains, additionally identifying potential adhesion molecules (e.g. a surface antigen of the NLP/P60 family and a small heat shock protein/chaperonin). CONCLUSIONS: The identification of these proteins in the extracellular proteome of Latobacillus spp. isolates may suggest that they serve currently unknown functions on the cell surface, including those connected with the interactions between bacteria and the intestinal epithelium. Such analyses may provide insight into new factors promoting probiotic adhesion to various types of epithelial cells.

The biology of mucus: Composition, synthesis and organization.

In this review we discuss mucus, the viscoelastic secretion from goblet or mucous producing cells that lines the epithelial surfaces of all organs exposed to the external world. Mucus is a complex aqueous fluid that owes its viscoelastic, lubricating and hydration properties to the glycoprotein mucin combined with electrolytes, lipids and other smaller proteins. Electron microscopy of mucosal surfaces reveals a highly convoluted surface with a network of fibers and pores of varying sizes. The major structural and functional component, mucin is a complex glycoprotein coded by about 20 mucin genes which produce a protein backbone having multiple tandem repeats of Serine, Threonine (ST repeats) where oligosaccharides are covalently O-linked. The N- and C-terminals of this apoprotein contain other domains with little or no glycosylation but rich in cysteines leading to dimerization and further multimerization via SS bonds. The synthesis of this complex protein starts in the endoplasmic reticulum with the formation of the apoprotein and is further modified via glycosylation in the cis and medial Golgi and packaged into mucin granules via Ca2+ bridging of the negative charges on the oligosaccharide brush in the trans Golgi. The mucin granules fuse with the plasma membrane of the secretory cells and following activation by signaling molecules release Ca2+ and undergo a dramatic change in volume due to hydration of the highly negatively charged polymer brush leading to exocytosis from the cells and forming the mucus layer. The rheological properties of mucus and its active component mucin and its mucoadhesivity are briefly discussed in light of their importance to mucosal drug delivery.

A new index for characterizing micro-bead motion in a flow induced by ciliary beating: Part I, experimental analysis.

Mucociliary clearance is one of the major lines of defense of the respiratory system. The mucus layer coating the pulmonary airways is moved along and out of the lung by the activity of motile cilia, thus expelling the particles trapped in it. Here we compare ex vivo measurements of a Newtonian flow induced by cilia beating (using micro-beads as tracers) and a mathematical model of this fluid flow, presented in greater detail in a second companion article. Samples of nasal epithelial cells placed in water are recorded by high-speed video-microscopy and ciliary beat pattern is inferred. Automatic tracking of micro-beads, used as markers of the flow generated by cilia motion, enables us also to assess the velocity profile as a function of the distance above the cilia. This profile is shown to be essentially parabolic. The obtained experimental data are used to feed a 2D mathematical and numerical model of the coupling between cilia, fluid, and micro-bead motion. From the model and the experimental measurements, the shear stress exerted by the cilia is deduced. Finally, this shear stress, which can easily be measured in the clinical setting, is proposed as a new index for characterizing the efficiency of ciliary beating.

Diagnostic utility of arborizing stromal meshwork fragments in mucinous tumors.

INTRODUCTION: Arborizing stromal meshwork fragments (ASMFs) have been proposed as a useful clue to differentiate mucin associated with mucinous adenocarcinoma from contaminating mucus during endobronchial ultrasound-guided transbronchial needle aspiration. Our aim was to retrospectively review cytology cases with mucinous material to determine the utility of ASMFs in diagnosing mucinous tumors. MATERIAL AND METHODS: Diff-Quik stained smears from archival cytology cases (N = 40) were reviewed, including adenocarcinomas with mucinous features, cystic mucinous neoplasms, and control cases with mucin contamination. Specimens were procured by image-guided fine needle aspiration (FNA) (16 cases), endoscopic ultrasound-guided FNA (22 cases), pathologist-performed FNA (1 case), and fluid drainage (1 case). All cases were reviewed for ASMFs, which were defined as metachromatic, spidery extensions with frayed edges within a background of mucinous material. RESULTS: ASMFs were identified in 4 (10% of cases, 14% of adenocarcinomas) cases of metastatic gastrointestinal mucinous adenocarcinomas in various locations (liver, lymph node, lung, and bone), but absent in mucin contamination. ASMFs in Diff-Quik stained smears were magenta-colored and corresponded to intervening stroma between dissecting mucin in the tumor. Nonarborizing desmoplastic stroma, inspissated mucus, cartilage fragments, transgressing vessels in renal cell carcinoma, and mucus-like material in pancreatic pseudocysts can morphologically mimic ASMFs. CONCLUSION: These data show that ASMFs may be encountered in some (14%) cases of adenocarcinoma with mucinous differentiation. When present, ASMFs can be diagnostically helpful to differentiate adenocarcinoma with mucinous features from contaminating mucus, if reliably distinguished from mimics. Diagn. Cytopathol. 2016;44:805-810. © 2016 Wiley Periodicals, Inc.