bluuebunny/crossref_metadata_2025_split huggingface dataset:
Jagged 1 is Necessary for Palatal Arterial Development
Authors: Humphreys J. Ryan , Goudy Steven L 
Published: August 2008

ProblemPalatal development is a complex process of growth, elongation, and fusion of paired palatal shelves. We hypothesize that arterial formation is necessary for normal palatal growth and development. Alagille's syndrome, a recently categorized genetic syndrome, is linked to genetic mutations in Jagged 1, a Notch signaling ligand necessary for vascular development. The cranial neural crest (CNC) cells are a well known cell population crucial in palate formation. To test our hypothesis, we have selectively removed Jagged 1 in the CNC population.MethodsWe identified the normal pattern of Jagged 1 expression in the palate using in situ hybridization and immunohistochemistry. We selectively removed Jagged 1 from the craniofacial mesenchyme using Cre‐Lox technology, mutant Wnt1‐cre Jagged 1 f/f selective knockouts. Mutant embryos were harvested at e13, e14, and e15 (critical time points in palatal development). To visualize the vascular development, we used platelet endothelial cell adhesion molecule (PECAM) antibody staining and utilized immunoflouresence with confocal microscopy.ResultsJagged 1 gene and protein expression was found throughout the midface and palate. The expression of Jagged 1 was concentrated in the perivascular tissue in the palatal mesenchyme. As palatal development occurs, there is a concomitant increase in Jagged 1 expression. Wnt1‐cre Jagged1 f/f mice were found viable. However, the mutant mice died in the neonatal period secondary to severe midface hypoplasia. Mutant mice had a significantly hypoplastic osseous palate and irregularly spaced palatal rugae. Examination of e15 mutant palatal shelves, using PECAM immunoflouresence and confocal microscopy, demonstrated a complete absence of mature vasculature.ConclusionJagged1 is required for palatal vascular development. The absence of Jagged1 in the CNC leads to severe palatal hypoplasia and neonatal death.SignificanceCleft lip and palate is the most common craniofacial congenital deformity occurring in 1:1000 live births. Clefting in conjunction with vascular syndromes, such as Alagille's, is a common observation.
Effectiveness of Honey on S.aureus and P.aeruginosa Biofilms
Authors: Alandejani Talal , Marsan Joseph G , Ferris Wendy , Robert Slinger , Chan Frank 
Published: August 2008

ProblemBiofilms formed by Pseudomonas aeruginosa (PA) and Staphylococcus aureus (SA) have been shown to be an important factor in the pathophysiology of chronic rhinosinusitis (CRS). Growth in biofilms increases bacterial resistance to antibiotics, which may explain why CRS responds poorly to antibiotic therapy. Honey has been used as an effective topical antimicrobial agent in the treatment of antibiotic‐resistant bacterial wound infections. To our knowledge, no research has studied the effect of honey on biofilms.MethodsWe used a previously established biofilm model to assess antibacterial activity of Manuka honey from New Zealand and Sidr honey from Yemen. These were tested at a 1 in 2 dilution against 11 isolates of methicillin‐susceptible SA (MSSA), 11 methicillin‐resistant SA (MRSA), and 11 PA isolates. Honeys were tested against both planktonic (broth) and biofilm‐grown bacteria.ResultsBoth honeys were effective in killing 100% of the isolates in the planktonic form. Biofilm‐grown bacteria were less susceptible to the honeys, but honey still had significant bactericidal activity. The bactericidal rate for the Sidr and Manuka honeys against MSSA MRSA and PA were 63%, 73%, 91% and 82%, 63% and 91%, respectively. These rates were significantly higher (p<0.001) than those seen with single antibiotics commonly used against MSSA and MRSA (e.g. cloxacillin and vancomycin) in a previous study done on the same bacterial isolates.ConclusionHoney, which is a natural, non‐toxic and inexpensive product, is effective in killing SA and PA bacterial biofilms.SignificanceThis intriguing observation may have important clinical implications and could lead to a new approach for treating refractory CRS.
Electrophysiologic Features of Freshly Excised Nasal Tissue
Authors: Cho Do‐Yeon , Beate Illek , Horst Fischer , Hwang Peter H 
Published: August 2008

ProblemEpithelial ion transport regulates hydration of respiratory mucosal surfaces, which promotes effective mucociliary clearance. Activators of chloride ion (Cl‐) secretion, such as ascorbic acid (Vitamin C), may enhance the rheologic properties of mucus. Altered ion transport could play a role in the pathogenesis of chronic rhinosinusitis (CRS). The purpose of this study is to assess the electrophysiologic characteristics and role of vitamin C on the nasal mucosa of CRS patients.MethodsNasal tissues (uncinate process, inferior turbinate, nasal septum) were obtained from five CRS patients during sinus surgery and mounted on disks with open areas of 0.03cm2 to 0.71cm2 between Ussing hemichambers. Short‐circuit current (Isc) was continuously recorded, and at 50‐s intervals transepithelial voltage was clamped from 0 to 2mV. Serosa‐to‐mucosa‐directed Cl‐ gradient was applied to increase the electrochemical driving force for Cl‐ exit across the apical membrane.ResultsIsc decreased when the epithelial Na+ channel blocker (amiloride) was added to the luminal side of the chamber indicating that the tissues were Na+ absorbing. Addition of the cAMP‐elevating agonist forskolin induced a Cl‐ secretory response and exposure of the apical airway surface to vitamin C(600uM) stimulated the transepithelial Cl‐ secretion to 60% of the forskolin‐stimulated Isc. The contribution of the Na+/K+/2Cl‐ cotransporter to the Cl‐ secretory response was verified by addition of bumetamide. Glybenclamide was used to probe for the CFTR‐Cl‐ conductance. These results were observed in all specimens.ConclusionFreshly excised human nasal epithelium is easily accessible and its bioelectric measurements can be applied as a functional measurement of ion transport in epithelial diseases. Vitamin C may serve as a biological regulator of CFTR‐mediated Cl‐ secretion in human nasal epithelia.SignificanceVitamin C in human nasal epithelia may represent a potential target for the complementary treatment of thickened mucus secretions by enhancing epithelial fluid secretion in diseases, such as CRS or cystic fibrosis.
In Vitro Study of Interleukin‐5,‐13,VCAM‐1 in CRS
Authors: Sauter Alexander , Stern‐Straeter Jens , Hörmann Karl , Naim Ramin 
Published: August 2008

ProblemThe pathogenesis of eosinophilic chronic rhino‐sinusitis (ECRS) is still unclear. Paranasal mucosa inflammation might be related to eosinophil infiltration. Eosinophil infiltration seems to induce changes in the expression of cell adhesion molecules, such as VCAM‐1. Futhermore Mediators such as Interleukin 5 and 13 (IL‐5, IL‐13) are considered to be key factors for eosinophilic accumulation and activation. The E ‐ Cadherin – β ‐ catenin complex maintain the integrity of epithelium. Down‐regulation of β‐catenin and E‐cadherin is a pivotal factor for loose integrity and progressive cell growth. This study aimed to assess which cytokines regulate the expression of the adhesion molecule E‐cadherin and the multifunctional protein β‐catenin, playing an essential role in the cadherin‐mediated anchoring, in ECRS.MethodsECRS cell cultures were incubated with IL‐5, IL‐13 and VCAM‐1 and β‐catenin / E‐cadherin levels were analysed after 8–72 hours using cytokine immunoassay and immuno‐histochemistry.ResultsWe could ascertain a significant increase in β‐catenin expression in eosinophilic paranasal cell culture after IL‐13 administration compared to non‐eosinophilic culture. Stimulation with IL‐5 did demonstrate an alteration of E‐cadherin expression. Incubation with VCAM‐1 could induce a significant increase in E‐cadherin expression in fibroblast cell cultures. Immuno‐staining for β‐catenin was restricted to the membrane of the cells.ConclusionIn regard to the increased mural expression of β‐catenin, we presume that a fibrotic reaction similar to asthma and chronic obstructive pulmonary disease is taking place in patients suffering from CRS.SignificanceThe tissue remodelling during chronic eosinophilic inflammation offers new insight into pathogenesis of ECRS.
Safety of Ethmoid Sinus Drug‐Eluting Catheter Insertion
Authors: Melroy Christopher T , Kuhn Frederick A 
Published: August 2008

ProblemThe objective is to develop an instrument which allows a drug‐eluting catheter to be safely and reproducibly inserted into the ethmoid sinuses.MethodsA trochar‐based insertion device was designed to allow delivery of a drug‐eluting catheter into the anterior and posterior ethmoid sinuses. It was inserted into 12 cadaveric ethmoid sinuses under endoscopic and fluoroscopic guidance. CT scans were performed pre‐, intra‐, and post‐procedure. The device's position was analyzed and the proximity to the skull base, lamina papyracea, and ethmoid face was measured. The specimens were then dissected and evaluated for skull base, sphenoid face, or lamina papyracea injury.ResultsThe drug eluting catheter system was successfully inserted into the ethmoid sinuses of all 12 cadaver sides without injury to either the medial orbital wall or the skull base as confirmed by post‐procedure CT scan and dissection. The final position of the distal tip of the stent averaged 8.1mm (RMS = 3.3) from the skull base, 5.6mm (RMS=3.5) from the sphenoid face, and 5.0mm (RMS=3.5) from the lamina papyracea; the proximal tip was at the face of the ethmoid bulla and 17.1mm (RMS=3.5) below the skull base.ConclusionThis study demonstrates that a trochar‐based instrument can safely and reproducibly introduce a drug‐eluting catheter into the ethmoid sinuses without skull base or lamina papyracea injury. This device may allow safe topical drug delivery into the ethmoid sinuses and provide chronic ethmoid sinusitis patients an alternative to ethmoidectomy.SignificanceThe primary surgical therapy for chronic ethmoid sinusitis is ethmoidectomy; topical therapy has been widely used in the management of chronic ethmoid sinusitis only after ethmoidectomy. This study shows a drug‐eluting catheter can be safely and reliably inserted into virgin ethmoid sinuses in order to allow the topical elution of medications into the ethmoids without ethmoidectomy.SupportAcclarent supplied cadaveric specimens.
The Impact of Olfactory Stimulation on Dreams
Authors: Stuck Boris A , Desislava Atanasova , Grupp Kathrin Frauke , Schredl Michael 
Published: August 2008

ProblemOnly a limited number of trials is available regarding the impact of external and internal stimuli on human dreams. Current research focuses on the question whether these stimuli (acoustic or mildly painful stimuli e.g.) are incorporated into dreams and whether they influence their emotional coloring. In a recently published trial we were able to demonstrate that isolated olfactory stimulation does not lead to arousals. Aim of the present study was to investigate whether olfactory stimuli of different hedonic characteristics influence dreams in humans.Methods15 young healthy female volunteers were investigated during 30 nights of testing. Standardized awakenings were performed during REM sleep. During REM phases, subjects were exposed to non‐odorous control, a positive odor (PEA, 20%) and a negative odor (H2S, 4 ppm) for 10 seconds each in a randomized fashion using a computer olfactometer. After the awakening, subjects were advised to report the content of their dream in a standardized fashion and to assess the emotional coloration (positive and negative) on a four digit scale (0/1/2/3: no / little / moderate / strong feelings) to calculate the overall emotional coloration.ResultsIn all subjects, three REM awakenings were performed. For 40 out of 45 awakenings, a dream was reported by the subjects. Mean emotional coloration after control stimulation was slightly positive (+0.5). After negative stimulation, the mean emotional coloration was shifted to negative values (‐0.4) while the mean emotional coloration was significantly more positive after positive stimulation (+1.2).ConclusionStandardized REM awakenings can be performed successfully even under the conditions of an olfactory laboratory with intransal stimulation. With olfactory stimulation, the emotional coloration of dreams can be significantly influenced in accordance with the hedonic aspect of the stimulant.SignificanceThe study opens a potential field of therapeutic intervention with nocturnal olfactory stimulation.
R400 – Effects of Silicone Gel Sheeting on Scar Formation
Authors: Aminpour Shervin , Tollefson Travis T 
Published: August 2008

ProblemThe treatment of keloids and hypertrophic scars has long been a concern for facial plastic surgeons. There are a wide variety of over‐the‐counter products that claim to improve hypertrophic scarring. Post‐surgical patients often inquire as to which of these products will give the best cosmetic result. Silicone gel sheeting is reported to provide positive outcomes with respect to a reduction in scar hypertrophy and an improvement in color differences. The exact mechanism is unknown. Micropore (3M) tape, a cheaper and more readily available product, has also been reported to reduce scar hypertrophy. This study will evaluate the differences and effectiveness of silicone gel sheeting and micropore tape in the reduction of scar hypertrophy in an animal model of scarring.MethodsHypertrophic scar formation was induced in an established rabbit model that parallels human skin. Treatment of the animals' scars was divided into 3 study groups: silicone gel sheeting, micropore tape, or no treatment. 80 total scars were treated for 30 days after the complete reepithelialization of the created scars. Both photometric and histologic analysis was performed on the scars. Scar hypertrophy was analyzed with blinded observers using a visual analog scale. Histological analysis was performed using the Scar Elevation Index, a ratio of the scar height over normal skin.ResultsBoth photographic and histological analysis showed there was a statistically significant improvement (p<0.05) in scar hypertrophy after use of either silicone gel sheeting and micropore tape when compared with controls.ConclusionSilicone Gel Sheeting and Micropore Tape are equally effective in the reduction of hypertrophic scarring.SignificanceFacial plastic surgeons should consider covering facial incisions with micropore tape for 30 days after surgery to minimize the risk of hypertrophic scarring.
R401 – Anti‐Aging Compounds and Epidermal Effects on Mouse Skin
Authors: Bhattacharyya Tapan K , Higgins Natalie P , Sebastian J Scott , Thomas J Regan 
Published: August 2008

ProblemTo compare topical effects of 5 anti‐aging agents on epidermal histology in the non‐irradiated hairless mouse.MethodsFemale retired breeders (SKH‐1 hairless mouse) were treated topically on the dorsal skin with 5 commercially available agents as a daily treatment for 2 weeks. The agents used were retinoic acid, glycolic acid, estrogen, soy, and vitamin C. Skin sections were analyzed in the light microscope to acquire morphometric data of keratinocyte proliferation (Index of Proliferating Cell Nuclear Antigen), epidermal thickness, and nuclear volume of cells from three epidermal layers. Quantitative data were analyzed with SPSS 14.0 statistical software to detect significant difference between the means of control and 5 experimental groups.ResultsEpidermal stimulation was observed with all cosmeceuticals but most pronounced effects resulted from the application of glycolic acid, and estrogen, and retinoic acid to a somewhat lesser degree. Soy and vitamin C produced significant cellular changes of lesser magnitude.ConclusionReported studies of many of these agents were conducted in the irradiated mice, and their effects on the intact animal skin have been rarely documented. These data will be useful for our contemplated studies of photo aging in the same species. Agents like retinoic acid derivatives, or glycolic acid are popular rejuvenating compounds, but have been reported to produce annoying side effects. Milder compounds like Vitamin C or soy may cause reversal of detrimental aging changes without cutaneous side effects.SignificanceThis study may be helpful to pinpoint therapeutic advantages of popular anti‐wrinkle compounds, and devise clinical strategies to combat photo aging.SupportThis research has been supported by the 2007 Leslie Bernstein Grant from the AAFPRS Foundation.
R402 – Profilometry and Skin Histology with Anti‐wrinkle Agents
Authors: Bhattacharyya Tapan K , Linton Jeannie , Mei Lily , Thomas J Regan 
Published: August 2008

ProblemTo investigate whether topical anti‐aging compounds can reduce wrinkle depth as seen by replica profilometry with comparable changes in histological parameters in murine skin.MethodsFemale hairless mice were exposed to topical application of a retinoic acid cream, a peptide lotion, and a soy cream on the dorsal skin areas for 4 weeks. Silicone negative replicas of treated and untreated skin surface were photographed using Optimus V6.5 image processing system (CuDerm Corporation, Texas), and evaluated for traditional surface roughness parameters (Rz, Ra, FSpace, and DL). Skin samples were also processed for histomorphometry, and immunohistochemistry of proliferating cell antigen (PCNA). Quantitative light microscopic data were acquired from tissue sections for estimating DNA replication in epidermal keratinocytes (PCNA index), epidermal thickness, depth of dermal collagen bundles.ResultsAll quantitative data were analyzed for comparing means with one‐way analysis of variance (ANOVA) using SPSS 14.0 statistical software, and significant changes in all the parameters were noted. Augmented keratinocyte proliferation and thickening of viable epidermis was observed with all three compounds although a greater effect was seen in the retinoic acid and peptide treatment groups. A similar trend was noted in respect of widening of dermal collagen layer. Epidermal surface roughness manifested maximum smoothening effect following treatment with the peptide compound.ConclusionRetinoic acid effects have been reported in literature but reports of comparison with soy and peptide preparation in this laboratory model are lacking. The pronounced effects seen with all the compounds indicate topical agents other than retinoic acid may have beneficial regenerating effects on photo aged skin without irritating effects reported for retinoic acid.SignificanceThese results may be helpful in defining clinical strategies for topical non‐invasive improvement of aging facial skin.SupportThis study was supported by the 2007 Leslie Bernstein Grant from the AAFPRS Foundation.
R403 – Epidermal Proliferating Cell Nuclear Antigen in Aging Rats
Authors: Bhattacharyya Tapan K , Jackson Paula , Thomas J Regan 
Published: August 2008

ProblemTo determine if epidermal cell proliferation in colony‐raised Fischer 344 rats changes with age and diet.MethodsFischer 344 rats fed ad libitum and calorie‐restricted (CR) diets were obtained from the NIA colonies, and young, young adult, and old animals from both groups were used for this study (six in each group). Tissue sections from the dorsal skin (DS) and foot plate (FP) were used for immunohistochemical staining of proliferating cell nuclear antigen (PCNA). The proliferation index (PCNA‐I) was computed from counts of stained and total number of keratinocytes. Simultaneous measurements of epidermal thickness were obtained from same sections. Data were analyzed with Excel and SPSS 14.0 software for statistics.ResultsTwo‐way analysis of variance (ANOVA) was applied to the data to probe the effect of age, diet, and age‐diet interaction. A significant effect of age was noticed in the two parameters i.e., DS PCNA (F 3.96, P. 011), FP epidermal width (F 3.37, P. 021) and FP PCNA‐I (F 9.0, P. 000). A significant correlation between DS width and PCNA values was also noted (r 0.5, P. 01).ConclusionThere is a trend of reduction of PCNA positive cells with increasing age irrespective of thickness of epidermis, and this trend is more apparent in CR rats.SignificanceThis cell proliferation study has implications in relation to CR effect on age‐related disease conditions, and biogerontology.SupportThe study was partially funded by the 2007 Leslie Bernstein grant from AAFPRS foundation.
R404 – Regulatory T Cells and Clinical Outcome in HNSCC Patients
Authors: Alhamarneh Osama , Stafford Nicholas D. , Greenman John 
Published: August 2008

ProblemTo determine the correlation between peripheral blood CD4+CD25high regulatory T cells (Treg), a suppressor cell population that dampen the immune response, and clinical outcome and survival in HNSCC patients.MethodsTreg cell numbers in the peripheral blood of newly‐presenting, untreated HNSCC patients (n=65) were determined pre‐operatively, 4–6 weeks after treatment (n=30) and in a cohort of healthy controls (n=35) of similar age and sex, after Treg cell isolation using magnetic microbeads (Miltenyi Biotec) by flow cytometry. The Mann‐Whitney U test was used to analyse the correlations between Treg cell levels and clinical outcome.ResultsTreg cells were significantly higher in patients pre‐operatively vs. controls (p=0.002). After treatment, patients showed a significant rise compared with their pre‐treatment levels (p=0.022). Pre‐treatment Treg cells levels did not correlate with survival or any of the other conventional clinicopathological parameters. However, higher Treg cells levels were discovered in the advanced disease stages (III/IV vs. I/II, median 6.3 vs 4.3) in the pre‐treatment group that turned into significantly higher levels in the early disease stages post treatment (I/II vs. III/IV, median 10.8 vs. 5.67 p=0.044).ConclusionAlthough peripheral blood Treg cells levels were higher in patients when compared to controls, no correlation was found between this cell population and clinical outcome or survival. In contrast with gastric, colorectal and ovarian tumors, Treg cell levels did not normalize 4–6 weeks after curative treatment in this cohort of HNSCC patients. Studies into Treg cell function are thus required to try and elucidate the apparent paradox in Treg cell levels observed in HNSCC.SignificanceThe presence of Regulatory T cells in the peripheral blood of HNSCC patients may be detrimental to host defence against tumor. Further studies are needed to explore their role in the tumor microenvironment and their correlation with clinical outcome.
R405 – Laser Welded Transluminal Repair of Rabbit Esophageal Injury
Authors: Bleier Benjamin Saul , Gratton Michael Anne , Leibowitz Jason M , Palmer James N , Newman Jason G , Cohen Noam A 
Published: August 2008

ProblemTo test the feasibility of Laser Tissue Welding in creating an endoscopic transluminal repair of esophageal perforation.MethodsA diode laser was used to create an endoluminal rabbit esophageal perforation repair. Burst pressures were compared to open incision, external suture, and external laser augmented suture closure. Comparisons were performed 5 times and analyzed using Kruskal‐Wallis ANOVA and a post‐hoc Dunn's Method.ResultsThe burst threshold of the endoluminal weld (54.78mHg) was significantly higher than the open incision (6.5mmHg) and not significantly different than the external suture (37.18mmHg) or the laser augmented suture group (71.60mmHg).ConclusionLaser welding is a feasible method of creating endoluminal repairs with burst strengths comparable to external suture repair.SignificanceThis is the first report of Laser Tissue Welding for endoscopic closure of iatrogenic esophageal perforation which may allow a subset of these patients to avoid traditional open approaches.