Endoscopic laryngotracheal cleft repair without tracheotomy or intubation.

OBJECTIVES: The objectives of this study are to present the technique and results of endoscopic repair of laryngotracheoesophageal clefts (LTEC) extending caudally to the cricoid plate into the cervical trachea and to revisit the classification of LTEC. METHODS: The authors conducted a retrospective case analysis consisting of four infants with complete laryngeal clefts (extending through the cricoid plate in three cases and down into the cervical trachea in one case) treated endoscopically by CO2 laser incision of the mucosa and two-layer endoscopic closure of the cleft without postoperative intubation or tracheotomy. RESULTS: All four infants resumed spontaneous respiration without support after a mean postoperative period of 3 days with continuous positive airway pressure (CPAP). They accepted oral feeding within 5 postoperative days (range, 3-11 days). No breakdown of endoscopic repair was encountered. After a mean follow up of 48 months (range, 3 mos to 7 y), all children have a good voice, have no sign of residual aspiration, but experience a slight exertional dyspnea. CONCLUSION: This limited experience on the endoscopic repair of extrathoracic LTEC shows that a minimally invasive approach sparing the need for postoperative intubation or tracheotomy is feasible and safe if modern technology (ultrapulse CO2 laser, endoscopic suturing, and postoperative use of CPAP in the intensive care unit) is available.

The rare cancer network: ongoing studies and future strategy.

The Rare Cancer Network (RCN) was formed in the early 1990's to create a global network that could pool knowledge and resources in the studies of rare malignancies whose infrequency prevented both their study with prospective clinical trials. To date, the RCN has initiated 74 studies resulting in 46 peer reviewed publications. The First International Symposium of the Rare Cancer Network took place in Nice in March of 2014. Status updates and proposals for new studies were heard for fifteen topics. Ongoing studies continue for cardiac sarcomas, thyroid cancers, glomus tumors, and adult medulloblastomas. New proposals were presented at the symposium for primary hepatic lymphoma, solitary fibrous tumors, Rosai-Dorfman disease, tumors of the ampulla of Vater, salivary gland tumors, anorectal melanoma, midline nuclear protein in testes carcinoma, pulmonary lymphoepithelioma-like carcinoma, adenoid cystic carcinoma of the trachea, osteosarcomas of the mandible, and extra-cranial hemangiopericytoma. This manuscript presents the abstracts of those proposals and updates on ongoing studies, as well a brief summary of the vision and future of the RCN.

Congenital tracheal anomalies.

Congenital tracheal lesions are rare, but important, causes of morbidity in infants and children. Consequently, experience in their management is limited and dispersed. Given its small diameter, the juvenile trachea is obstructed easily by various natural causes, or following a surgical intervention. The diagnosis of a congenital, tracheal, obstructive anomaly is based on a high degree of suspicion in infants and children with respiratory distress accompanied by retraction. In this article, the authors discuss the various causes of these conditions, their diagnostic features, and the treatment possibilities.

Identificació de nous gens que participen en la remodelació del sistema traqueal de Drosophila melanogaster

Un dels organismes model més utilitzats en experimentació genètica és la Drosophila melanogaster ja que la facilitat de manipulació genètica i la seva simplicitat permeten estudiar processos biològics amb múltiples aplicabilitats en diferents àmbits d’estudi com el desenvolupament embrionari i la morfogènesis. La morfogènesi es un dels esdeveniments més importants durant el desenvolupament embrionari que permet la formació dels diferent teixits i òrgans, i que depèn de l'expressió genètica i de l'activació i coordinació de diferents vies de senyalització. Entendre com es coordinen aquest processos es fonamental per conèixer com es forma un òrgan. Així, l’objectiu principal d’aquest Treball de Final de Grau és identificar nous gens implicats en la formació del sistema traqueal (el nostre òrgan model) mitjançant un mini-­‐cribratge funcional de gens que s’expressen en la tràquea, a més de generar eines per a l'estudi de la via de senyalització FGF/Bnl durant la remodelació del sistema traqueal mitjançant la tècnica de knock in. Per a dur-­‐ho a terme, amb el suport de la base de dades de Gens i Genomes de Drosophila melanogaster (mod-­‐ENCODE Tissue Expression Data) s’han seleccionat gens candidats expressats a la tràquea en estat larvari. Un cop identificats, s'ha estudiat la seva possible funció en el desenvolupament de les tràquees mitjançant el seu silenciament amb el sistema UAS-­‐Gal4. Així hem vist que Vein (CG10491), CG17098, No Ocelli (CG4491) i Peptidasa (CG4017) presenten diversos fenotips que afecten la formació dels traqueoblasts. També hem vist que Vein, lligand de la via EGF és necessari per a la proliferació i supervivència de les cèl·∙lules traqueals del sac aeri. Finalment s’ha iniciat la generació d'un knock in en el gen branchless (bnl). Per aquest motiu s'han amplificat les regions 5’ i 3’ de l’exó 2 del gen Bnl i s'ha iniciat la seva clonació dirigida al vector de destí pTV-­‐Cherry. Aquesta tècnica generarà eines que permetran entendre la funció del gen bnl durant la remodelació del sistema traqueal.

Modified method for bronchial suture by Ramirez Gama compared to separate stitches suture: experimental study

OBJECTIVE: To experimentally compare two classic techniques described for manual suture of the bronchial stump.METHODS: We used organs of pigs, with isolated trachea and lungs, preserved by refrigeration. We dissected 30 bronchi, which were divided into three groups of ten bronchi each, of 3mm, 5mm, and 7mm, respectively. In each, we performed the suture with simple, separated, extramucosal stitches in five other bronchi, and the technique proposed by Ramirez and modified by Santos et al in the other five. Once the sutures were finished, the anastomoses were tested using compressed air ventilation, applying an endotracheal pressure of 20mmHg.RESULTS: the Ramirez Gama suture was more effective in the bronchi of 3, 5 and 7 mm, and there was no air leak even after subjecting them to a tracheal pressure of 20mmHg. The simple interrupted sutures were less effective, with extravasation in six of the 15 tested bronchi, especially in the angles of the sutures. These figures were not significant (p = 0.08).CONCLUSION: manual sutures of the bronchial stumps were more effective when the modified Ramirez Gama suture was used in the caliber bronchi arms when tested with increased endotracheal pressure.

Importance of flexible bronchoscopy in decannulation of tracheostomy patients

OBJECTIVE: To evaluate the importance of flexible bronchoscopy in tracheostomy patients in the process of decannulation to assess the incidence and types of laryngotracheal injury and compare the presence of such lesions with clinical criteria used for decannulation. METHODS: We studied 51 tracheostomized patients aged between 19 and 87 years, with tracheal stent for a mean of 46 ± 28 days and with clinical criteria for decannulation. They were submitted to tracheostomy tube occlusion tolerance testfor 24 hours, and then to flexible bronchoscopy. We described and classified the diagnosed laryngotracheal changes. We compared the clinical criteria for decannulation indication with the bronchoscopy-diagnosed laryngotracheal injuries that contraindicated decannulation. We identified the factors that could interfere in decannulation and evaluated the importance of bronchoscopy as part of the process. RESULTS: Forty (80.4%) patients had laryngotracheal alterations. Of the 40 patients considered clinically fit to decannulation, eight (20%) (p = 0.0007) presented with laryngotracheal injuries at bronchoscopy that contraindicated the procedure. The most frequent laryngeal alteration was vocal cords lesion, in 15 (29%) individuals, and granuloma, the most prevalent tracheal lesion, in 14 (27.5%) patients. CONCLUSION: flexible bronchoscopy showed a large number of laryngotracheal injuries, the most frequent being the vocal cords injury in the larynx and the granuloma in the trachea, which contributed to increase the decannulation procedure safety.

Thoracic and heart biometrics of non-anesthetized agouti (Dasyprocta primnolopha Wagler, 1831) measured on radiographic images

The agouti is a species intensively hunted throughout the Amazon and the semi-arid regions of northeastern Brazil. Considering the current trend in conservation management of wild species, the aim of this study was to determine the morphometric reference to the heart of agouti raised in captivity, based on thoracic and cardiac measurements in these animals. Thirty adult agoutis, 1 to 3 years of age, without clinical signs of cardiac disease were selected. The animals were physically restrained and radiographies in laterolateral (LL) and ventrodorsal (VD) recumbence were produced. The following measures were taken: the apicobasilar length of the heart (at the most cranial height of the Carina region to the heart apex) (AB), maximum width of the heart perpendicular to AB (CD), heart inclination angle (AIC), trachea inclination angle (AIT), distance from the right heart wall (DPTd), distance from the left heart wall (DPTe) and vertical depth of the thorax, and the ventral face of the vertebral column to the dorsal border of the sternum at the level of the trachea bifurcation (H). The ratios between AB/CD, AB/H and CD/H were also analyzed. To calculate the vertebral heart scale (VHS), the AB and CD measurements were laid over the thoracic vertebra starting at T4. Radiographic evaluation showed values consistent with those reported in small animals and some wild and exotic species. The main biometric values in the chest cavity and heart of agouti are arranged as follows: (1) The ratios between AB/H ratio and CD/H were not sensitive for identifying heart increases (p>0.05), while the ratio AB/CD was more sensitive in this identification (p<0.05); (2) AIC: 21.2±6.4º (mean between male and famale); (3) AIT for males and females: 9.93±3.23° and 8.4±3.94°; (4) DPTd and DPTe for males: 0.97±0.40cm and 0.7±0.30cm; (5) DPTd and DPTe for females: 1.12±0.42cm and 01.02±0.43cm; (6) VHS for males and females: 7.75±0.48v e 7.61±0.34v; (7) The caudal vena cava (CVC) was visualized dorsal-cranially and located right of the midline. The data obtained allowed the acquisition of the first reference values for biometry of the heart of agoutis, contributing to better understanding of cardiac morphology and identification of cardiomyopathy in these animals.

Outbreak of infectious laryngotracheitis in large multi-age egg layer chicken flocks in Minas Gerais, Brazil

A recent (November 2010) outbreak of infectious laryngotracheitis (ILT) in a multi-age laying hen facility in Minas Gerais state, Brazil, is described. Previous ILT outbreak in laying hens was only notified in São Paulo state, Brazil, in 2002. In the outbreak described here, the affected population was approximately eight million hens, with flock sizes ranging from 100,000 to 2,900,000 chickens. The average mortality ranged from 1 to 6%, and morbidity was around 90% (most of the twenty seven farms of the area were positive for ILT virus). Three multi-age laying farms from one company were selected for this report. Clinical signs included prostration, dyspnea, conjunctivitis, occasional swelling of the paranasal sinuses and bloody mucous nasal discharge. Severely affected chickens presented with dyspnea, gasping and became cyanotic before death. At necropsy, these chickens had fibrinous exudate blocking the larynx and the lumen of cranial part of the trachea. In addition, conjunctivitis with intense hyperemia, edema and sinuses with caseous exudate were present. On histopathology, there were marked necrosis and desquamation of respiratory ephitelium and conjunctiva with numerous syncytial cells formation and fibrinous exudate. Moderate to marked non suppurative (especially lymphocytes and plasma cells) infiltration in the lamina propria also was observed. Sixteen out of 20 examined chickens, eosinophilic intranuclear inclusion bodies were observed in the syncytial cells. The DNA extracted from larynx and trachea produced positive PCR results for ILT virus (ILTV) DNA using formalin-fixed, paraffin embedded (FFPE) samples. Amplicons from a small region of ICP4 gene were submitted to sequencing and showed 100% identity with ILTV EU104910.1 (USA strain), 99% with ILTV JN596963.1 (Australian strain) and 91% with ILTV JN580316.1 (Gallid herpesvirus 1 CEO vaccine strain) and JN580315.1 (Gallid herpesvirus 1 TCO vaccine strain).

Increased expression of Interleukin-6 related to nephritis in chickens challenged with an Avian infectious bronchitis virus variant

A Brazilian field isolate (IBV/Brazil/PR05) of avian infectious bronchitis virus (IBV), associated with development of nephritis in chickens, was previously genotyped as IBV variant after S1 gene sequencing. The aim of this study was to evaluate the levels of IL-6 in kidneys and trachea of birds vaccinated and challenged with IBV/Brazil/PR05 strain, correlating these results with scores of microscopic lesions, specific IBV antigen detection and viral load. The up-regulation of IL-6 and the increased levels of viral load on renal and tracheal samples were significantly correlated with scores of microscopic lesions. Reduced levels of viral load were detected in kidneys of birds previously vaccinated and challenged, compared to non-vaccinated challenged group, although markedly microscopic lesions were observed for both groups. The expression of IL-6, present both in the kidney and in the tracheas, was dependent on the load of the virus present in the tissue, and the development of lesions was related with IL-6 present in the tissues. These data suggest that variant IBV/Brazil/PR05 can induce the expression of proinflammatory cytokines in a manner correlated with viral load and increased IL-6 is involved in the tissue with the influx of inflammatory cells and subsequent nephritis. This may contribute with a model to the development of immunosuppressive agents of IL-6 to prevent acute inflammatory processes against infection with IBV and perhaps other coronaviruses, as well as contribute to the understanding of the immunopathogenesis of IBV nephropatogenic strains.

The effect of L-arginine on guinea-pig and rabbit airway smooth muscle function in vitro

We have investigated the effects of L-arginine, D-arginine and L-lysine on airway smooth muscle responsiveness to spasmogens in vitro. Both L-arginine and D-arginine (100 mM) significantly reduced the contractile potency and maximal contractile response to histamine but not to methacholine or potassium chloride in guinea-pig epithelium-denuded isolated trachea. Similarly, the contractile response to histamine was significantly reduced by L-arginine (100 mM) in rabbit epithelium-denuded isolated bronchus. The amino acid L-lysine (100 mM) failed to significantly alter the contractile potency of histamine in guinea-pig isolated trachea (P>0.05). In guinea-pig isolated trachea precontracted with histamine, both L-arginine and D-arginine produced a concentration-dependent relaxation which was not significantly altered by epithelium removal or by the presence of the nitric oxide synthase inhibitor, NG-nitro L-arginine methyl ester (L-NAME; 50 µM). Thus, at very high concentrations, arginine exhibit a non-competitive antagonism of histamine-induced contraction of isolated airway preparations that was independent of the generation of nitric oxide and was not dependent on charge. These observations confirm previous studies of cutaneous permeability responses and of contractile responses of guinea-pig isolated ileal smooth muscle. Taken together, the data suggest that high concentrations of arginine can exert an anti-histamine effect.

Toxicity of a cyanobacterial extract containing microcystins to mouse lungs

Toxic cyanobacteria in drinking water supplies can cause serious public health problems. In the present study we analyzed the time course of changes in lung histology in young and adult male Swiss mice injected intraperitoneally (ip) with a cyanobacterial extract containing the hepatotoxic microcystins. Microcystins are cyclical heptapeptides quantified by ELISA method. Ninety mice were divided into two groups. Group C received an injection of saline (300 µl, ip) and group Ci received a sublethal dose of microcystins (48.2 µg/kg, ip). Mice of the Ci group were further divided into young (4 weeks old) and adult (12 weeks old) animals. At 2 and 8 h and at 1, 2, 3, and 4 days after the injection of the toxic cyanobacterial extract, the mice were anesthetized and the trachea was occluded at end-expiration. The lungs were removed en bloc, fixed, sectioned, and stained with hematoxylin-eosin. The percentage of the area of alveolar collapse and the number of polymorphonuclear (PMN) and mononuclear cell infiltrations were determined by point counting. Alveolar collapse increased from C to all Ci groups (123 to 262%) independently of time, reaching a maximum value earlier in young than in adult animals. The amount of PMN cells increased with time of the lesion (52 to 161%). The inflammatory response also reached the highest level earlier in young than in adult mice. After 2 days, PMN levels remained unchanged in adult mice, while in young mice the maximum number was observed at day 1 and was similar at days 2, 3, and 4. We conclude that the toxins and/or other cyanobacterial compounds probably exert these effects by reaching the lung through the blood stream after ip injection.

Influence of renal denervation on blood pressure, sodium and water excretion in acute total obstructive apnea in rats

Obstructive apnea (OA) can exert significant effects on renal sympathetic nerve activity (RSNA) and hemodynamic parameters. The present study focuses on the modulatory actions of RSNA on OA-induced sodium and water retention. The experiments were performed in renal-denervated rats (D; N = 9), which were compared to sham (S; N = 9) rats. Mean arterial pressure (MAP) and heart rate (HR) were assessed via an intrafemoral catheter. A catheter was inserted into the bladder for urinary measurements. OA episodes were induced via occlusion of the catheter inserted into the trachea. After an equilibration period, OA was induced for 20 s every 2 min and the changes in urine, MAP, HR and RSNA were recorded. Renal denervation did not alter resting MAP (S: 113 ± 4 vs D: 115 ± 4 mmHg) or HR (S: 340 ± 12 vs D: 368 ± 11 bpm). An OA episode resulted in decreased HR and MAP in both groups, but D rats showed exacerbated hypotension and attenuated bradycardia (S: -12 ± 1 mmHg and -16 ± 2 bpm vs D: -16 ± 1 mmHg and 9 ± 2 bpm; P < 0.01). The basal urinary parameters did not change during or after OA in S rats. However, D rats showed significant increases both during and after OA. Renal sympathetic nerve activity in S rats increased (34 ± 9%) during apnea episodes. These results indicate that renal denervation induces elevations of sodium content and urine volume and alters bradycardia and hypotension patterns during total OA in unconscious rats.

Étude des interactions entre Haemophilus parasuis et des cellules endothéliales et épithéliales porcines: implications d’une composante bactérienne, le lipooligosaccharide (LOS)

Haemophilus parasuis est un pathogène porcin causant la maladie de Glässer caractérisée par de la polysérosite fibrineuse, polyarthrite, méningite et septicémie. La pathogenèse de l’infection et les facteurs de virulence sont encore mal connus. Le site de colonisation de Haemophilus parasuis dans le tractus respiratoire supérieur est controversé. Pour accéder à la circulation sanguine, H. parasuis doit envahir la muqueuse. H. parasuis adhère à des cellules épithéliales porcines de trachée (NPTr). Pour accéder au système nerveux central et causer la méningite, H. parasuis doit traverser la barrière hémato-méningée. H. parasuis adhère à et envahit des cellules endothéliales porcines de microvaisseaux cérébraux (PBMEC) provenant de la BBB. Le but de cette étude était d’étudier certaines interactions entre H. parasuis et son lipooligosccharide (LOS), et des cellules endothéliales et épithéliales porcines. Les résultats démontrent que l’adhésion de H. parasuis Nagasaki aux NPTr et aux PBMEC est en partie médiée par son LOS. H. parasuis induit l’apoptose des NPTr et des PBMEC, mais le LOS ne semble pas impliqué. H. parasuis, et à un niveau moindre son LOS, stimulent la sécrétion d’interleukine- (IL) 6 et d’IL-8. Différentes souches de H. parasuis sérotypes 4 et 5 (sérotypes les plus prévalents en Amérique du Nord) stimulent également les NPTr et PBMEC à produire IL-6 et IL-8. Les résultats suggèrent que le LOS de H. parasuis joue un certain rôle dans la pathogenèse de l’infection, mais d’autres composantes bactériennes sont également impliquées.

Expression des cofacteurs de transcription associés au SRF dans le muscle lisse respiratoire équin

L’hyperplasie et l’hypertrophie contribuent à l'augmentation de la masse de muscle lisse bronchique observée dans le souffle. Les cellules musculaires lisses (CML) présentent deux phénotypes; prolifératif ou contractile. Le serum response factor (SRF), un facteur de transcription impliqué dans l’activation de nombreux gènes, contribuerait à cette modulation phénotypique. Notamment, lorsqu'associé au cofacteur Elk-1, un phénotype prolifératif serait observé, alors qu'en présence de la myocardine (MYOCD) il y aurait induction d'un profil contractile. Récemment, il a été démontré que SRF est surexprimé dans les voies périphériques chez les chevaux atteints du souffle suite à une exposition antigénique. Cette étude vise à caractériser l'expression protéique et génique de SRF, Elk-1 et MYOCD dans les CML des voies respiratoires centrales et périphériques chez des chevaux atteints du souffle et des chevaux contrôles. L'évaluation de l’expression protéique de SRF, Elk-1 et MYOCD s’est effectuée par immunodétection sur des tissus provenant de biopsies thoracoscopiques ou endobronchiques, et ce, avant, à 1 et 30 jours du défi antigénique. L'expression génique a été étudiée par qPCR sur du muscle lisse disséqué de la trachée, et des bronches, ainsi que sur des voies respiratoires intermédiaires et périphériques. Les expressions génique et protéique de MYOCD sont augmentées uniquement dans les voies périphériques. L’expression génique de SRF et Elk-1 varient dans les voies centrales alors que le taux de protéines demeure stable. En conclusion, SRF et MYOCD pourraient être impliquées dans l’hypertrophie des voies respiratoires périphériques dans le souffle alors que l’hyperplasie ne semble pas être activée par Elk-1.

Not the outside but the inside matters : functional analysis of Capricious and Tartan during Drosophila tracheal morphogenesis

The tubular structures, which transport essential gases, liquids, or cells from one site to another, are shared among various divergent organisms. These highly organized tubular networks include lung, kidney, vasculature and mammary gland in mammals as well as trachea and salivary gland in Drosophila melanogaster. Many questions regarding the tubular morphogenesis cannot be addressed sufficiently by investigating the mammalian organs because their structures are extremely complex and therefore, systematic analyses of genetic and cellular programs guiding the development is not possible. In contrast, the Drosophila tracheal development provides an excellent model system since many molecular markers and powerful tools for genetic manipulations are available. Two mechanisms were shown to be important for the outgrowth of tracheal cells: the FGF signaling pathway and the interaction between the tracheal cells and the surrounding mesodermal cells. The Drosophila FGF ligand encoded by branchless (bnl) is localized in groups of cells near tracheal metameres. The tracheal cells expressing the FGF receptor breathless (btl) respond to these sources of FGF ligand and extend towards them. However, this FGF signaling pathway is not sufficient for the formation of continuous dorsal trunk, the only muticellular tube in tracheal system. Recently, it was found out that single mesodermal cells called bridge-cells are essential for the formation of continuous dorsal trunk as they direct the outgrowth of dorsal trunk cells towards the correct targets. The results in this PhD thesis demonstrate that a cell adhesion molecule Capricious (Caps), which is specifically localized on the surface of bridge-cells, plays an essential role in guiding the outgrowing dorsal trunk cells towards their correct targets. When caps is lacking, some bridge-cells cannot stretch properly towards the adjacent posterior tracheal metameres and thus fail to interconnect the juxtaposing dorsal trunk cells. Consequently, discontinuous dorsal trunks containing interruptions at several positions are formed. On the other hand, when caps is ectopically expressed in the mesodermal cells through a twi-GAL4 driver, these mesodermal cells acquire a guidance function through ectopic caps and misguide the outgrowing dorsal trunk cells in abnormal directions. As a result, disconnected dorsal trunks are formed. These loss- and gain-of-function studies suggest that Caps presumably establishes the cell-to-cell contact between the bridge-cells and the tracheal cells and thereby mediates directly the guidance function of bridge-cells. The most similar protein known to Caps is another cell adhesion molecule called Tartan (Trn). Interestingly, trn is expressed in the mesodermal cells but not in the bridge-cells. When trn is lacking, the outgrowth of not only the dorsal trunks but also the lateral trunks are disrupted. However, in contrast to the ectopic expression of caps, the misexpression of trn does not affect tracheal development. Whereas Trn requires only its extracellular domain to mediate the matrix function, Caps requires both its extracellular and intracellular domains to function as a guidance molecule in the bridge-cells. These observations suggest that Trn functions differently from Caps during tracheal morphogenesis. Presumably, Trn mediates a matrix function of mesodermal cells, which support the tracheal cells to extend efficiently through the surrounding mesodermal tissue. In order to determine which domains dictate the functional specificity of Caps, two hybrid proteins CapsEdTrnId, which contains the Caps extracellular domain and the Trn intracellular domain, and TrnEdCapsId, which consists of the Trn extracellular domain and the Caps intracellular domain, were constructed. Gain of function and rescue experiments with these hybrid proteins suggest on one hand that the extracellular domains of Caps and Trn are functionally redundant and on the other hand that the intracellular domain dictates the functional specificity of Caps. In order to identify putative interactors of Caps, yeast two-hybrid screening was performed. An in vivo interaction assay in yeast suggests that Ras64B interacts specifically with the Caps intracellular domain. In addition, an in vitro binding assay reveals a direct interaction between an inactive form of Ras64B and the Caps intracellular domain. ras64B, which encodes a small GTPase, is expressed in the mesodermal cells concurrently as caps. Finally, a gain-of-function study with the constitutively active Ras64B suggests that Ras64B presumably functions downstream of Caps. All these results suggest consistently that the small GTPase Ras64B binds specifically to the Caps intracellular domain and may thereby mediate the guidance function of Caps.