Functional Closure Research Articles

Molecular Mechanisms for Regulating Postnatal Ductus Arteriosus Closure.

The ductus arteriosus (DA) connects the main pulmonary artery and the aorta in fetal circulation and closes spontaneously within days after birth in normal infants. Abnormal patent DA (PDA) causes morbidities and mortality, especially in preterm infants. Closure of the DA is a complex interactive process involving two events: functional and anatomic closure. Functional closure by smooth muscle contraction was achieved through the regulatory factors of vaso-reactivity. These factors include oxygen sensing system, glutamate, osmolality, prostaglandin E2, nitric oxide, and carbon monoxide. Anatomic closure by vascular remodeling involved several vascular components including endothelium, extracellular matrix, smooth muscle cells, and intraluminal blood cells. Despite advances in understanding of PDA pathogenesis, the molecular mechanism for regulation of DA closure is complex and not fully understood. In this article we review recent evidence regarding the molecular mechanisms of DA closure.

Colour Flow Mapping examination: An useful screening test for the early diagnosis of ductus venosus patency in canine newborns.

Ductus venosus (DV) closure plays a key role in hepatic circulation adaptation to postnatal metabolic function, and DV patency might develop a congenital portosystemic shunt (CPSS). The noninvasive Color Flow Mapping (CFM) examination, a validated method to diagnose CPSS in adult dogs, is routinely performed to assess DV closure after birth in humans. This study aimed to describe the feasibility of the ultrasonographic evaluation of the DV after birth and to determine its closure time in healthy Great Dane neonates. Patency of DV in serial Color Flow Mapping (CFM) examinations and bodyweight (BW) were recorded on Days 0-3-6-9 in 24 neonates that were classified as having patent (PDV) or closed ductusvenosus (CDV) basing on CFM signal presence/absence. Since the 3rd day, DV diameter was recorded. Data were analysed by ANOVA (p<0.05). All dogs resulted healthy 1year later. The number of PDV and CDV puppies at birth was not different on Day 3 (24 and 0 vs. 22 and 2, PDV and CDV, respectively), whereas it resulted different on Days 6 (24 and 0 vs. 14 and 10) and 9 (24 and 0 vs. 0 and 24); on Day 3, it was different compared to Days 6 and 9; on Day 6, it was different from Day 9. Reduction of DV diameter resulted positively related to neonatal BW growth. The CFM evaluation of DV closure after birth in Great Dane puppies represents a feasible technique. Present results suggest the time of functional closure in normal neonates within 9days after birth. Thus, CFM examination, as an early screening test for DV patency evaluation, performed 10days after birth, may identify suspicious dogs at risk that would require further investigations. Further studies are needed to deepen the role of a delayed closure in low bodyweight and preterm puppies.

Total Cheek Reconstruction Using the Pre-Expanded Medial Arm Flap With Functional and Aesthetic Donor Site Closure.

This clinical study aimed at introducing a reconstructive method for total cheek soft tissue defects using the pre-expanded medial arm flap and to maximally reduce donor site morbidities simultaneously. A retrospective review of data was performed for 3 patients requiring the pre-expanded medial arm flap to reconstruct total cheek defects. The donor site in the medial arm was primarily closed using a pedicle parascapular or thoracodorsal artery perforator flap. All patients had a total unilateral cheek defect after lesion removal. Three pre-expanded medial arm flaps measuring 17 × 11 cm, 22 × 15 cm, and 20 × 15 cm were separately used for cheek defect reconstruction. The donor sites in the medial arm were closed using a pedicle parascapular flap, measuring 22 × 9.5 cm, and 2 pedicle thoracodorsal artery perforator flaps, measuring 22 × 10 cm and 23 × 10 cm. No major complications occurred in any patient. Patients were followed up for 3, 12, and 18 months. Patients (and/or their family members) were satisfied with the final outcomes. Total cheek defect reconstruction using a pre-expanded medial arm flap, with the donor site closed using a pedicle axial back flap, can not only provide sufficient tissue for cheek resurfacing, but also guarantee primary donor site closure and could be an alternative reconstructive option for patients who have a total cheek defect.

Using functional dependency and node closure to detect communities from the sparse network

Community structure is one of the most important features of complex networks, a large number of methods have been proposed to extract community structures from networks. However, some of those methods suffer from the high time complexity, and some of them cannot obtain the acceptable results. In this paper, we borrow the idea from the database theory, and propose the concepts of functional dependency (FD) between nodes and node closure first, then we utilize these concepts to extract communities. This method takes both effectiveness and efficiency into consideration, the community detection process can be accomplished with O(m) time consumption. We conducted extensive experiments both on some synthetic networks and on some real-world networks, the experimental results demonstrate that the method can detect communities from a given network successfully.

Probability Based Most Informative Gene Selection From Microarray Data

Microarray datasets have a wide application in bioinformatics research. Analysis to measure the expression level of thousands of genes of this kind of high-throughput data can help for finding the cause and subsequent treatment of any disease. There are many techniques in gene analysis to extract biologically relevant information from inconsistent and ambiguous data. In this paper, the concepts of functional dependency and closure of an attribute of database technology are used for finding the most important set of genes for cancer detection. Firstly, the method computes similarity factor between each pair of genes. Based on the similarity factors a set of gene dependency is formed from which closure set is obtained. Subsequently, conditional probability based interestingness measurements are used to determine the most informative gene for disease classification. The proposed method is applied on some publicly available cancerous gene expression dataset. The result shows the effectiveness and robustness of the algorithm.

The Role of Na+/Ca2+ Exchanger 1 in Maintaining Ductus Arteriosus Patency

Patency of the ductus arteriosus (DA) is crucial for both fetal circulation and patients with DA-dependent congenital heart diseases (CHD). The Na+/Ca2+ exchanger 1 (NCX1) protein has been shown to play a key role in the regulation of vascular tone and is elevated in DA-dependent CHD. This current study was conducted to investigate the mechanisms underpinning the role of NCX1 in DA patency. Our data showed NCX1 expression was up-regulated in the DA of fetal mice. Up-regulation of NCX1 expression resulted in a concomitant decrease in cytosolic Ca2+ levels in human DA smooth muscle cells (DASMCs) and an inhibition of the proliferation and migration capacities of human DASMCs. Furthermore, treatment of DASMCs with KB-R7943, which can reduce Ca2+ influx, resulted in the inhibition of both cell proliferation and migration. These findings indicate that NCX1 may play a role in maintaining patent DA not only by preventing DA functional closure through reducing cytosolic Ca2+ level in DASMC but also by delaying the anatomical closure process. The latter delay is facilitated by the down-regulation of human DASMC proliferation and migration. It is also likely that a reduction in cytosolic Ca2+ levels inhibits the proliferation and migration capacities of human DASMCs in vitro.

The Utility of Assessing Nonverbal Communication in the Psychiatric Evaluation

The Utility of Assessing Nonverbal Communication in the Psychiatric Evaluation

Theoretical Conversation and Conceptual Transplants Between Economics and Systems Theory: Towards an Interpretative Passe-partout of Functional Systems

General systems theory is based on functional differentiation and operational closure, which make autopoiesis possible. However, in the current complex framework, the model proposed by Luhmann seems to need some supplements in order to explain the evolutionary dynamics of world society. While adopting a systemic approach and using its related theoretical tools, the focus is shifted from the inside of a system to its boundaries. The thesis proposed is the integration between the principle of functional differentiation and that of functional connectivity. To prove such an assumption and overcome the limitations of operational closure, the Luhmannian concept of ‘structural coupling’ is used, but theoretical tools borrowed from economics (trade-off, optimal point) are also employed. This interdisciplinary integration makes it possible to argue the shift of the sociological paradigm from ‘functionalism of differences’ towards ‘functionalism of links’. Constitutive and evolutionary dynamics seem to be connected with the optimum combination of the system’s openness and closure and the ability to establish intersystemic communication channels, where the latter determines resilience to the change factors of the environment. And it is this constant disposition to change that enables the reproduction of the social system. JEL: Z Other special topics: (Social System Theory)

Tidal airway closure in asthma and COPD

Functional closure of small airways can occur during tidal breathing above functional residual capacity (FRC) both in asthma and COPD patients, especially during exacerbations. Such event has several noxious consequences on gas exchange, airway hyperresponsiveness and mechanical stress and strain within lung tissue and airway wall, mostly due to increase in ventilation heterogeneity. The availability of simple functional tests based on sequential measurements of lung volumes (i.e.: FRC), by plethysmography and dilutional techniques may reveal and monitor easily tidal airway closure that can be and should be treated with the aim of abolishing or at least reducing this dangerous condition.

Failed Primary Bladder Exstrophy Closure with Osteotomy: Multivariable Analysis of a 25-Year Experience

Successful primary bladder exstrophy closure provides the best opportunity for patients to achieve a functional closure and urinary continence regardless of the method of repair. Use of osteotomy during initial closure has significantly improved success rates. However, failures can still occur. We identify factors that contribute to a failed primary exstrophy closure with osteotomy. We reviewed a prospectively maintained institutional database for classic bladder exstrophy cases primarily closed with osteotomy at our institution or referred after primary closure between 1990 and 2015. Data were collected regarding patient gender, closure, osteotomy, immobilization, orthopedics and perioperative pain control. Univariate and multivariable analyses were performed to determine predictors of failure. A total of 156 patients met inclusion criteria. Overall failure rate was 30% (13% from our institution and 87% from referrals). On multivariable analysis use of Buck traction (OR 0.11, 95% CI 0.02-0.60, p = 0.011) and immobilization time greater than 4 weeks (OR 0.19, 95% CI 0.04-0.86, p = 0.031) had significantly lower odds of failure. Osteotomy performed by general orthopedic surgeons had significantly higher odds of failure (OR 23.47, 95% CI 1.45-379.19, p = 0.027). Type of osteotomy and use of epidural anesthesia did not significantly impact failure rates. Proper immobilization with modified Buck traction and external fixation, immobilization time greater than 4 weeks and undergoing osteotomy performed by a pediatric orthopedic surgeon are crucial factors for successful primary closure with osteotomy.

A DYNAMIC DENSITY FUNCTIONAL THEORY APPROACH TO DIFFUSION IN WHITE DWARFS AND NEUTRON STAR ENVELOPES

ABSTRACT We develop a multicomponent hydrodynamic model based on moments of the Born–Bogolyubov–Green–Kirkwood–Yvon hierarchy equations for physical conditions relevant to astrophysical plasmas. These equations incorporate strong correlations through a density functional theory closure, while transport enters through a relaxation approximation. This approach enables the introduction of Coulomb coupling correction terms into the standard Burgers equations. The diffusive currents for these strongly coupled plasmas is self-consistently derived. The settling of impurities and its impact on cooling can be greatly affected by strong Coulomb coupling, which we show can be quantified using the direct correlation function.

Free groin flap for aesthetic and functional donor-site closure of the anterolateral thigh flap

Better methods for anterolateral thigh flap donor-site reconstruction are desirable in cases when direct closure is impossible. Multiple surgical strategies have been attempted, and each has its shortcomings. The use of a contralateral free groin flap to repair the anterolateral thigh flap donor site is investigated in this report. From October 2015 to February 2016, free groin flaps were harvested on six patients for aesthetic and functional donor-site closure of the anterolateral thigh flap, which could not be directly closed. In these cases, the reverse-flow distal portion of the descending branch of the lateral circumflex femoral artery and vein were used as recipient vessels and anastomosed to the superficial circumflex iliac artery and vein, respectively. One flap had presented a few blisters on the distal margin; the other five flaps fully survived without any complications. Patients were highly satisfied with the aesthetic outcomes of both the anterolateral thigh area and the groin site. Although with theoretical risks of compromised venous blood flow, free groin flaps are an effective strategy for closure of massive anterolateral donor-site defects and can be safely performed with thoughtful planning and meticulous microsurgical techniques.

Esthetic rehabilitation with minimally invasive feldspathic ceramic veneers: 30 months of clinical follow-up

Diastemas among maxillary incisors and gingival contour disharmony are common findings among patients in dental practice. Ceramic veneers are indicated for esthetic rehabilitation of anterior diastemas due their predictable results, optical characteristics, fracture resistance and tooth structure conservation. However, because it is a friable material and have a brittle behavior, fractures occurrences are related to trauma, oclusal overload, parafunctional habits and material fatigue. This article describes 30 months follow-up of an esthetic and functional rehabilitation diastemas closure using feldspathic veneers associated with periodontal surgery and a ceramic repair with composite resin. Gingivectomy and frenectomy needs were found and the surgical procedures performed guided by new anatomic aspects of the crowns. Mock-up was performed after waxing and reverse planning. All anterior teeth underwent minimally invasive preparation. Feldspathic ceramic veneers were made, tried using try in paste and luted with light-cure resin cement. After 24 months, a fracture occurred on the right maxillary canine veneer. The ceramic restoration repair was performed with nano-hybrid composite resin, after the conditioning with 5% hydrofluoric acid, 37% phosphoric acid and silane couple agent. The combination between ceramic veneers and gingivectomy enables to obtain conservative treatments and esthetic success. After six months of the repair, resulting 30 months of follow-up, the anterior restorations were aesthetically and functionally satisfactory.

Lipopolysaccharide Delays Closure of the Rat Ductus Arteriosus by Induction of Inducible Nitric Oxide Synthase But Not Prostaglandin E&lt;sub&gt;2&lt;/sub&gt;

The incidence of patent ductus arteriosus is known to be higher in premature neonates with infection than in those without infection. However, the detailed mechanism has not been investigated. Lipopolysaccharide (LPS; 100 μg/kg) was injected into timed-pregnant Wistar rats on day 18 and 19 of pregnancy. The fetuses were delivered by cesarean section on gestational day 21. Using a rapid whole-body freezing method, it was found that closure of the ductus arteriosus (DA) was significantly delayed in neonates from LPS-injected rats after birth. Histological analysis demonstrated that there was no difference in vascular remodeling of the DA. Quantitative reverse transcriptase-polymerase chain reaction analysis showed that the tumor necrosis factor α and inducible nitric oxide synthase (iNOS) mRNA expression level was significantly increased, but there was no difference in cyclooxygenase 2 and prostaglandin receptor, EP4, mRNA expression in the DA from LPS-injected rats. Moreover, the NOS inhibitor,Nω-Nitro-L-arginine methyl ester hydrochloride, significantly prevented the delayed closure of the DA after birth in neonates from LPS-injected rats. The present study demonstrated that LPS-mediated infection delayed closure of the rat DA without apparent histological changes. iNOS, but not prostaglandin E2, may play a primary role in delayed functional closure of the DA. (Circ J 2016; 80: 703-711).

Loss of Notch2 and Notch3 in vascular smooth muscle causes patent ductus arteriosus

The overlapping roles of the predominant Notch receptors in vascular smooth muscle cells, Notch2 and Notch3, have not been clearly defined in vivo. In this study, we use a smooth muscle-specific deletion of Notch2 together with a global Notch3 deletion to produce mice with combinations of mutant and wild-type Notch2/3 alleles in vascular smooth muscle cells. Mice with complete loss of Notch3 and smooth muscle-expressed Notch2 display late embryonic lethality and subcutaneous hemorrhage. Mice without smooth muscle-Notch2 and only one wild-type copy of Notch3 die within one day of birth and present with vascular defects, most notably patent ductus arteriosus (DA) and aortic dilation. These defects were associated with decreased expression of contractile markers in both the DA and aorta. These results demonstrate that Notch2 and Notch3 have overlapping roles in promoting development of vascular smooth muscle cells, and together contribute to functional closure of the DA.

A Method for Recording Urethral Pressure Profiles in Female Rats

AimsUrethral pressure profile (UPP) and leak-point pressure (LPP) measurements as well as external urethral sphincter (EUS) electromyography (EMG) and videourodynamic analyses are the primary methods for evaluating urethral function in humans. However, UPP recording in female rats, a widely used animal model, is challenging due to their small body sizes. This study reports a novel method for recording UPP in female rats.Materials and MethodsSeventeen anesthetized female rats were studied. LPP data for 14 rats were included. The other 3 rats were excluded because of death or abnormal urogenital organs. UPP curves were recorded using a modified water-perfusion catheter system, with the lateral hole facing the 3-, 6-, 9-, and 12-o’clock positions in a randomized sequence. LPP, functional urethral length (FUL) and maximum urethral closure pressure (MUCP) were analyzed.ResultsThe mean LPP was 64.39 ± 20.29 cm H2O. The mean FUL and MUCP values at the 3-, 6-, 9-, and 12-o’clock positions were 12.90 ± 1.20, 16.70 ± 1.95, 13.90 ± 2.42, and 11.60 ± 0.97 mm, respectively, and 38.70 ± 11.85, 33.90 ± 11.82, 37.40 ± 11.95, and 71.90 ± 23.01 cm H2O, respectively. The FUL at the 6-o’clock position and MUCP at the 12-o’clock position were significantly greater than those at the other 3 positions. The FUL and MUCP of repeated UPP recordings were not significantly different than those of the first recordings.ConclusionsUPP recording using a modified method based on a water-perfusion catheter system is feasible and replicable in female rats. It produces UPP curves that sensitively and appreciably reflect detailed pressure changes at different points within the urethra and thus provides opportunity to evaluate urethral structures, especially the urethral sphincter, in detail. These results may enhance the utility of female rat models in research of urinary sphincter mechanisms.

Prostaglandin E-mediated molecular mechanisms driving remodeling of the ductus arteriosus.

The ductus arteriosus (DA), a fetal arterial connection between the pulmonary arteries and aorta, normally closes after birth. Persistent DA patency usually has life-threatening consequences. In certain DA-dependent congenital heart diseases, however, patient survival depends on maintaining DA patency. Complete closure of the DA involves both functional closure, induced by muscle contraction, and anatomical closure, achieved through morphological and molecular remodeling. Anatomical closure of the DA is associated with the formation of intimal thickening, which is characterized by deposition of extracellular matrix in the subendothelial region, sparse elastic fiber formation, and migration of medial smooth muscle cells into the subendothelial space. In addition, fetal molecular remodeling that is suitable for postnatal muscle contraction has been observed in the DA. After the second trimester, high concentration of prostaglandin E2 (PGE2) causes the DA to dilate through the remainder of the fetal period. Emerging evidence from studies using pharmacological approaches and genetically modified mice suggests that, in addition to its vasodilatory effect, this chronic exposure to PGE2 promotes DA-specific anatomical and molecular remodeling through EP4, one of four receptor subtypes for PGE2. Signals that are downstream of PGE2-EP4, such as cyclic AMP (cAMP)-protein kinase A (PKA), exchange protein activated by cAMP (Epac), phospholipase C, and Wnt/β-catenin, may be involved in the regulation of intimal thickening, elastogenesis, and contraction-related genes. Understanding the physiological role of PGE2 in DA remodeling could enable more effective regulation of PDA, both in isolation and in the context of congenital cardiac anomalies.

Can abnormal ductus venosus peak velocity index for veins in normal fetuses predict failure of functional closure of the foramen ovale in the postnatal period?

To investigate whether ductus venosus (DV) wave velocities and/or DV peak velocity index for veins (DV-PVIV) can predict failure of functional closure of the foramen ovale in the postnatal period. Fetal echocardiography was performed in 455 healthy women with uneventful pregnancies between the 20-24th gestational weeks. DV blood flow and DV-PVIV data were collected prospectively. Echocardiography was repeated in healthy subjects on the 30th postnatal day. Four hundred patients met the study criteria. Newborns with clearly visible foraminal flaps, interatrial septal defects smaller than 5 mm and right-to-left shunting through the defect were accepted as patent foramen ovale (PFO) (n=91). Newborns without PFO (n=309) comprised the control group. A statistically significant difference was detected between the groups with and without PFO in terms of mean DV-PVIV values, DV-D and DV-a wave velocities (p<0.05 for all). ROC analysis showed that increased DV-PVIV values were related to and predictive of PFO (AUC=0.75; p<0.001) and that a threshold value of 0.62, had a sensitivity of 86.8% (95% CI 78.1-93.0%) and a specificity of 51.7% (95% CI 46.1-57.5%). DV-PVIV values above 0.62 at the time of fetal echocardiographic examination can predict failure of functional closure of the foramen ovale in the postnatal period.

Effects of Advancing Gestation and Non-Caucasian Race on Ductus Arteriosus Gene Expression

To identify genes affected by advancing gestation and racial/ethnic origin in human ductus arteriosus (DA). We collected 3 sets of DA tissue (n = 93, n = 89, n = 91; total = 273 fetuses) from second trimester pregnancies. We examined four genes, with DNA polymorphisms that distribute along racial lines, to identify "Caucasian" and "non-Caucasian" DA. We used real time polymerase chain reaction to measure RNA expression of 48 candidate genes involved in functional closure of the DA, and used multivariable regression analyses to examine the relationships between advancing gestation, "non-Caucasian" race, and gene expression. Mature gestation and non-Caucasian race are significant predictors for identifying infants who will close their patent DA when treated with indomethacin. Advancing gestation consistently altered gene expression in pathways involved with oxygen-induced constriction (eg, calcium-channels, potassium-channels, and endothelin signaling), contractile protein maturation, tissue remodeling, and prostaglandin and nitric oxide signaling in all 3 tissue sets. None of the pathways involved with oxygen-induced constriction appeared to be altered in "non-Caucasian" DA. Two genes, SLCO2A1 and NOS3, (involved with prostaglandin reuptake/metabolism and nitric oxide production, respectively) were consistently decreased in "non-Caucasian" DA. Prostaglandins and nitric oxide are the most important vasodilators opposing DA closure. Indomethacin inhibits prostaglandin production, but not nitric oxide production. Because decreased SLCO2A1 and NOS3 expression can lead to increased prostaglandin and decreased nitric oxide concentrations, we speculate that prostaglandin-mediated vasodilation may play a more dominant role in maintaining the "non-Caucasian" patent DA, making it more likely to close when inhibited by indomethacin.

Oxygenation decreases elastin secretion from rat ductus arteriosus smooth muscle cells.

The ductus arteriosus (DA), a fetal arterial connection between the main pulmonary artery and the descending aorta, normally closes immediately after birth. The oxygen concentration in the blood rises after birth, and in the DA this increase in oxygen concentration causes functional closure, which is induced by smooth muscle contraction. Previous studies have demonstrated that hypoxia and/or oxygenation affect vascular remodeling of various vessels. Therefore, we hypothesized that the rise in oxygen concentration would affect the vascular structure of the DA due to production of proteins secreted from DA smooth muscle cells (SMC). Liquid chromatography-tandem mass spectrometry was used to comprehensively investigate the secreted proteins in the supernatant of rat DA SMC harvested under hypoxic conditions (1% oxygen) or under normoxic conditions (21% oxygen). We found that the rise in oxygen concentration reduced the secretion of elastin from DA SMC. On reverse transcription-polymerase chain reaction, the expression of elastin mRNA was not significantly changed in DA SMC from hypoxic to normoxic conditions. Given that elastin forms internal elastic lamina and elastic fibers in the vascular muscle layers, and that a rise in oxygen concentration reduced the secretion of elastin, this suggests that the rise in blood oxygen concentration after birth reduces the secretion of elastin, and therefore may play a role in DA structural remodeling after birth.