The mitophagy receptor NIX induces vIRF-1 oligomerization and interaction with GABARAPL1 for the promotion of HHV-8 reactivation-induced mitophagy.

Recently, viruses have been shown to regulate selective autophagy for productive infections. For instance, human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus (KSHV), activates selective autophagy of mitochondria, termed mitophagy, thereby inhibiting antiviral innate immune responses during lytic infection in host cells. We previously demonstrated that HHV-8 viral interferon regulatory factor 1 (vIRF-1) plays a crucial role in lytic replication-activated mitophagy by interacting with cellular mitophagic proteins, including NIX and TUFM. However, the precise molecular mechanisms by which these interactions lead to mitophagy activation remain to be determined. Here, we show that vIRF-1 binds directly to mammalian autophagy-related gene 8 (ATG8) proteins, preferentially GABARAPL1 in infected cells, in an LC3-interacting region (LIR)-independent manner. Accordingly, we identified key residues in vIRF-1 and GABARAPL1 required for mutual interaction and demonstrated that the interaction is essential for mitophagy activation and HHV-8 productive replication. Interestingly, the mitophagy receptor NIX promotes vIRF-1-GABARAPL1 interaction, and NIX/vIRF-1-induced mitophagy is significantly inhibited in GABARAPL1-deficient cells. Moreover, a vIRF-1 variant defective in GABARAPL1 binding substantially loses the ability to induce vIRF-1/NIX-induced mitophagy. These results suggest that NIX supports vIRF-1 activity as a mitophagy mediator. In addition, we found that NIX promotes vIRF-1 aggregation and stabilizes aggregated vIRF-1. Together, these findings indicate that vIRF-1 plays a role as a viral mitophagy mediator that can be activated by a cellular mitophagy receptor.

Generation and characterization of a humanized ACE2 mouse model to study long-term impacts of SARS-CoV-2 infection.

Although the COVID-19 pandemic has officially ended, the persistent challenge of long-COVID or post-acute COVID sequelae (PASC) continues to impact societies globally, highlighting the urgent need for ongoing research into its mechanisms and therapeutic approaches. Our team has recently developed a novel humanized ACE2 mouse model (hACE2ki) designed explicitly for long-COVID/PASC research. This model exhibits human ACE2 expression in tissue and cell-specific patterns akin to mouse Ace2. When we exposed young adult hACE2ki mice (6 weeks old) to various SARS-CoV-2 lineages, including WA, Delta, and Omicron, at a dose of 5 × 105 PFU/mouse via nasal instillation, the mice demonstrated distinctive phenotypes characterized by differences in viral load in the lung, trachea, and nasal turbinate, weight loss, and changes in pro-inflammatory cytokines and immune cell profiles in bronchoalveolar lavage fluid. Notably, no mortality was observed in this age group. Further, to assess the model's relevance for long-COVID studies, we investigated tau protein pathologies, which are linked to Alzheimer's disease, in the brains of these mice post SARS-CoV-2 infection. Our findings revealed the accumulation and longitudinal propagation of tau, confirming the potential of our hACE2ki mouse model for preclinical studies of long-COVID.

Tapping into non-English-language science for the conservation of global biodiversity.

The widely held assumption that any important scientific information would be available in English underlies the underuse of non-English-language science across disciplines. However, non-English-language science is expected to bring unique and valuable scientific information, especially in disciplines where the evidence is patchy, and for emergent issues where synthesising available evidence is an urgent challenge. Yet such contribution of non-English-language science to scientific communities and the application of science is rarely quantified. Here, we show that non-English-language studies provide crucial evidence for informing global biodiversity conservation. By screening 419,679 peer-reviewed papers in 16 languages, we identified 1,234 non-English-language studies providing evidence on the effectiveness of biodiversity conservation interventions, compared to 4,412 English-language studies identified with the same criteria. Relevant non-English-language studies are being published at an increasing rate in 6 out of the 12 languages where there were a sufficient number of relevant studies. Incorporating non-English-language studies can expand the geographical coverage (i.e., the number of 2° × 2° grid cells with relevant studies) of English-language evidence by 12% to 25%, especially in biodiverse regions, and taxonomic coverage (i.e., the number of species covered by the relevant studies) by 5% to 32%, although they do tend to be based on less robust study designs. Our results show that synthesising non-English-language studies is key to overcoming the widespread lack of local, context-dependent evidence and facilitating evidence-based conservation globally. We urge wider disciplines to rigorously reassess the untapped potential of non-English-language science in informing decisions to address other global challenges. Please see the Supporting information files for Alternative Language Abstracts.

Overlapping Intravelar Veloplasty Improves the Speech Outcomes in Submucous Cleft Palate.

BACKGROUND: Submucous cleft palate (SMCP) is a subgroup of cleft palate that can present as velopharyngeal insufficiency due to muscle displacement. The pharyngeal flap and Furlow palatoplasty have been introduced to correct SMCP patient with velopharyngeal insufficiency. However, pharyngeal flap and Furlow palatoplasty can occur various complications. We consider the overlapping intravelar veloplasty (IVVP) can overcome these complications. Therefore, we present the speech outcomes of overlapping IVVP for the treatment of patients with SMCP. METHODS: We retrospectively reviewed 12 patients with SMCP underwent overlapping IVVP between April 2016 and October 2018. The patients who underwent speech evaluation, nasometry, and nasoendoscopy before and after surgery and who were followed up for >18 months were enrolled in this study. RESULTS: The average age of the patients was 5 years (range, 3-11 years) and the postoperative follow-up period ranged from 18 to 24 months (mean, 20 months). The preoperative perceptual speech evaluation was moderate and the postoperative evaluation was normal ( P < 0.01). The preoperative and postoperative nasalance scores obtained using a nasometer were 37.00 and 12.50, respectively, ( P < 0.01). Preoperative and postoperative velopharyngeal movements were grades 3 and 0, respectively, ( P < 0.01). CONCLUSIONS: Our study showed that overlapping IVVP could provide successful correction of velopharyngeal insufficiency in patients with SMCP, including relatively old patients.

Speech Outcomes of Treatment for Velopharyngeal Insufficiency: Combined Use of an Overlapping Intravelar Veloplasty and Dynamic Sphincter Pharyngoplasty.

BACKGROUND: Velopharyngeal insufficiency involving a large velopharyngeal gap and poor lateral wall movement is referred to as a "black hole" and remains a challenging problem for cleft surgeons. The effect of the pharyngeal flap on this form of velopharyngeal insufficiency is still debatable because a wide pharyngeal flap is associated with a high incidence of airway obstruction. The present study aimed to evaluate the speech outcomes of combined overlapping intravelar veloplasty and dynamic sphincter pharyngoplasty for the treatment of velopharyngeal insufficiency. METHODS: Between March 2016 and June 2019, 15 patients with velopharyngeal insufficiency were treated with a combination of overlapping intravelar veloplasty and dynamic sphincter pharyngoplasty. Preoperative speech evaluation was performed on the basis of perceptual speech evaluation, nasometry, and nasoendoscopy. Postoperative speech evaluation using the same approach as that used preoperatively was performed after completion of speech therapy. RESULTS: All 15 patients achieved satisfactory velopharyngeal port closure and speech phonation after completion of speech therapy. No additional procedures were performed to improve velopharyngeal port closure and speech production. The preoperative and postoperative results of perceptual speech evaluation, nasometry, and nasoendoscopy evaluation were significantly different (P < 0.01). CONCLUSION: Combined treatment with overlapping intravelar veloplasty and dynamic sphincter pharyngoplasty can correct the velopharyngeal insufficiency "black hole" with highly reliable results and minimal risk of airway obstruction.

Comparison of Effectiveness and Safety of a Botulinum Toxin Monotherapy and a Combination Therapy with Hyaluronic Acid Filler for Improving Glabellar Frown.

BACKGROUND: Among numerous cosmetic procedures for face rejuvenation performed all over the world, botulinum toxin type A (BoNT-A) for wrinkles is one of the most widely practiced procedures. However, for severe frowns, the application of botulinum toxin is often insufficient. In this study, the effects of hyaluronic acid filler combination therapy and the BoNT-A alone were evaluated. METHODS: Forty subjects with 2 or higher points (moderate to severe) of a facial wrinkle scale (FWS) when frowning in the glabellar area were assigned to 2 group: Botulinum toxin type A monotherapy group and a combination regimen of the toxin and hyaluronic acid filler group. Subjects visited outpatient department every 4 weeks until 28 weeks after the injection, and the assessment of the efficacy using FWS, subject satisfaction at both resting and maximum frowning and safety analysis were performed. RESULTS: Subjects of both group was administered 18U of BoNT-A and the subjects of the combination group received additional 0.45mL of hyaluronic acid filler regimen. Both at rest and maximum frown, the combination group scored lower FWS than the toxin and showed significance in the week-20 and week-28. And at final visit, subject satisfaction score of the combination was higher than that of toxin group. CONCLUSION: For patients with moderate to severe glabellar frown, the combined administration of BoNT-A and hyaluronic acid filler could be a considerable treatment for improving wrinkles. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

"Fasting: An Effective Preconditioning Method to Increase Fat Graft Survival".

BACKGROUND: Most preconditioning techniques before fat grafting require external manipulation. Since nutrition is the main factor maintaining the balance of lipogenesis and lipolysis, we hypothesized that fasting before undergoing autologous fat grafting may increase lipolysis and reduce adipocyte size, thereby improving the fat graft survival rate. METHODS: C57BL/6 mice were divided into 24 h starved or fed groups. Adipose tissue lipolysis, adipogenesis, and angiogenesis-related gene expression, in fat from both groups, were analyzed. The volume and weight of the grafted fat at 4-8 weeks postoperatively were measured using micro-computed tomography. Immunohistochemistry staining and mRNA expression analysis were also performed to evaluate the effect of fasting on fat graft survival. RESULTS: Fasting decreased adipocyte size by inducing adipose tissue lipolysis. Adipogenesis-related genes were remarkably downregulated while lipolysis-related genes and angiogenesis inducer genes were significantly upregulated in the starved adipose tissue. The mice grafted with the fat from the 24 h starved group had approximately 20% larger volumes and considerably heavier weights than those from the fed group. Increased viable adipocytes and vessels, and reduced macrophages in the fat grafts obtained from the 24 h starved group were also observed. CONCLUSIONS: Fasting for 24 h before harvesting fat increased the retention volume of fat graft by increasing angiogenesis via VEGF induction. Therefore, fasting would be a novel and reliable preconditioning strategy to improve graft survival in autologous fat grafting. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Mechanical Stress Improves Fat Graft Survival by Promoting Adipose-Derived Stem Cells Proliferation.

Cell-assisted lipotransfer (CAL), defined as co-transplantation of aspirated fat with enrichment of adipose-derived stem cells (ASCs), is a novel technique for cosmetic and reconstructive surgery to overcome the low survival rate of traditional fat grafting. However, clinically approved techniques for increasing the potency of ASCs in CAL have not been developed yet. As a more clinically applicable method, we used mechanical stress to reinforce the potency of ASCs. Mechanical stress was applied to the inguinal fat pad by needling . Morphological and cellular changes in adipose tissues were examined by flow cytometric analysis 1, 3, 5, and 7 days after the procedure. The proliferation and adipogenesis potencies of ASCs were evaluated. CAL with ASCs treated with mechanical stress or sham control were performed, and engraftment was determined at 4 weeks post-operation. Flow cytometry analysis revealed that mechanical stress significantly increased the number as well as the frequency of ASC proliferation in fat. Proliferation assays and adipocyte-specific marker gene analysis revealed that mechanical stress promoted proliferation potential but did not affect the differentiation capacity of ASCs. Moreover, CAL with cells derived from mechanical stress-treated fat increased the engraftment. Our results indicate that mechanical stress may be a simple method for improving the efficacy of CAL by enhancing the proliferation potency of ASCs.

Nasal Reconstruction of a Frontonasal Dysplasia via Septal L-Strut Reconstruction Using Costal Cartilage.

OBJECTIVE: Frontonasal dysplasia (FND) is a rare congenital condition. Its major features include hypertelorism, a large and bifid nasal tip, and a broad nasal root. We present our technique of septal L-strut reconstruction using costal cartilage. DESIGN: Retrospective review from June 2008 and August 2017. METHODS: Under general anesthesia, 6 patients with FND underwent septal reconstruction using costal cartilage via open rhinoplasty. We reconstructed the nasal and septal cartilaginous framework by placing columellar struts and cantilever-type grafts. RESULTS: The patients ranged in age from 6 to 13 years old. All were female. The follow-up period ranged from 8 months to 2 years; we encountered no postoperative complications (infection, nasal obstruction, or recurrence). All patients were satisfied with their nasal appearance. CONCLUSIONS: Although the results were not entirely satisfactory from an esthetic point of view, we found that FND can be treated via septal reconstruction with costal cartilage and that the clinical outcomes are reliable and satisfactory. Our approach is a useful option for FND patients.

Introduction of Non-Native Ticks Collected from Fresh Migratory Bird Carcasses on a Stopover Island in the Republic of Korea.

When free-ranging birds are accidentally killed or die, there may be greater potential for their associated ticks to detach, seek alternate hosts, and become established. We examined 711 carcasses of 95 avian species for ticks at a stopover island of migratory birds in the Republic of Korea where only Ixodes nipponensis and I. persulcatus were previously reported from local mammals and vegetation. A total of 16 ticks, I. turdus and Haemaphysalis flava, were collected from 8 fresh carcasses belonging to 5 avian species. Despite their known abundance on migratory birds and mainland Korea, these species had not colonized the isolated insular ecosystem possibly due to the low abundance and diversity of local hosts. The results imply that increasing human impact, such as the anthropogenic mortality of migratory birds and the introduction of non-native mammalian hosts, will increase the potential invasion and colonization risk of ticks. This finding also suggests that tick surveillance consisting of fresh carcasses of dead migratory birds may provide additional information, often ignored in surveillance of ticks on live birds, for the potential introduction of non-native ticks and associated pathogens affecting animal and human health.

The Effectiveness of Early Combined CO2 Ablative Fractional Laser and 595-nm Pulsed Dye Laser Treatment After Scar Revision.

ABSTRACT: Scars are significant complications of wound healing and associated with negative physical, psychological, and cosmetic effects. Scar revision and laser treatment have been used over the past century to improve many different types of scars. Here, we evaluated the effectiveness of early combined carbon dioxide ablative fractional laser (AFL) and pulsed dye laser (PDL) treatment after scar revision. Fourteen patients who underwent scar revision were enrolled. All patients were treated with both a 10,600-nm AFL and a 595-nm PDL commencing 2 weeks after scar revision and continuing at 4-week intervals for a total of 4 treatments. Vancouver Scar Scale scores were evaluated before treatment and 5 months after the final treatment. All Vancouver Scar Scale scores improved significantly except that of scar height. We encountered no adverse complications (wound disruption, or hyper- or hypopigmentation) during follow-up. Early combined carbon dioxide AFL and PDL treatment after scar revision effectively and safely minimized scar formation.

The Effects of Alar Base Augmentation in Secondary Unilateral Cleft Lip Nasal Deformity.

ABSTRACT: In unilateral cleft lip and palate patients, the alar base is displaced inferoposterolaterally due to the depression of the pyriform aperture in the cleft side, and the drooping of the nostril rim is provoked by displacement of the alar base. This study was conducted between May 1998 and December 2012. In total, 82 patients with secondary unilateral cleft lip nasal deformities were treated using alar base augmentation. The patients were divided into two groups according to the degree of their preoperative alar base asymmetry. Patients with alar base asymmetry <3 mm were treated with a soft tissue augmentation procedure. Those with alar base asymmetry >3 and <6 mm were treated with a bony augmentation procedure. Soft tissue augmentation was conducted in 42 patients, and bony augmentation was conducted in 40 patients. In the soft tissue augmentation group, the degree of alar base asymmetry was improved from 2.42 ±â€Š0.38 mm preoperatively to 0.45 ±â€Š0.21 mm postoperatively (P  < 0.05). In the bony augmentation group, the degree of alar base asymmetry was improved from 4.33 ±â€Š0.50 mm preoperatively to 0.81 ±â€Š0.20 mm postoperatively (P  < 0.05). In the amount of alar base augmentation, there were statistically significant differences between the soft tissue augmentation group and the bony augmentation group (P  < 0.05). This clinical study shows that secondary cleft lip nasal deformities can be corrected with alar base augmentation using soft tissue and bony augmentation and that these procedures can provide reliable, satisfactory, and safe clinical outcomes.

Volumetric Evaluation of Dead Space in Ischial Pressure Injuries Using Magnetic Resonance Imaging: A Case Series.

OBJECTIVE: To establish a preoperative evaluation procedure by measuring the volume of dead space using MRI in patients with ischial pressure injuries. METHODS: Patients with spinal cord injury and ischial pressure injuries who underwent treatment between August 2016 and November 2019 were included in the study. Preoperative MRI scan was conducted on all patients. The volume estimation and three-dimensional (3D) reconstruction were performed based on MRI data using a 3D Slicer. Based on the resulting volume, a muscle flap that could fit the dead space was selected. Surgery was performed with the selected muscle flap, and a fasciocutaneous flap was added, if necessary. RESULTS: A total of eight patients with ischial pressure injuries were included in the study. The mean patient age was 59.0 ± 11.0 years. The mean body mass index was 26.62 ± 3.89 kg/m2. The mean volume of dead space was 104.75 ± 81.05 cm3. The gracilis muscle was the most selected muscle flap and was used in four patients. In five of eight cases, a fasciocutaneous flap was used as well. The mean follow-up period was 16 months, and by that point, none of the patients evinced complications that required surgery. CONCLUSIONS: To the authors' knowledge, this is the first report on volumetric evaluation of dead space in ischial pressure injuries. The authors believe that the 3D reconstruction process would enable adequate dead space obliteration in ischial pressure injuries. The authors propose that preoperative MRI scans in patients with ischial pressure injury should become an essential part of the process.

Favorable Crisscrossing Pattern With Polydioxanone: Barbed Thread Lifting in Constructing Fibrous Architecture.

BACKGROUND: The longevity of polydioxanone (PDO)-barbed lifting threads remains controversial. OBJECTIVES: The authors sought to assess the longevity extension effect of a crisscross implantation pattern in PDO-barbed thread lifting. METHODS: To acquire the desired outcome in PDO-barbed thread lifting, the authors suggested a paradigm shift to incorporate biochemical factors in enforcing the physico-mechanical lift. A nude mouse model was employed to evaluate their theory to compare the conventional fan-shaped protocols in barbed thread lifting with an architectural construction of intersections of fibrous capsule in a crisscross pattern. Three fragments of monofilament PDO-barbed-lifting threads were implanted in the dorsal skin of 12 nude mice. The pattern of implantation was fan-shaped in the control group and crisscross in the experimental group. Tissue specimens containing tangential areas of threads were harvested, fixed, and paraffin-embedded. Samples were horizontally cut and histologically analyzed employing hematoxylin and eosin, Massons' Trichrome, and Sirius red staining. Fibrotic areas and the width of fibrosis from the thread were also analyzed. RESULTS: Fibrous capsulations around the barbed area of the PDO-barbed lifting threads were threefold greater than those around the barb-free areas of the threads. In the crisscross implantation pattern, width and density of the fibrotic areas were fivefold greater than those of the fan-shaped areas. Induction of fibrous capsules around the PDO-barbed thread was markedly condensed in the crisscross areas. CONCLUSIONS: This study provides the basis for a more logical implantation pattern in PDO-barbed lifting threads for facial rejuvenation. By generating controlled multiple crisscross patterns, we can create more intense fibrogenesis, reduce tension applied on each barbed thread, and, therefore, extend the longevity of the result.

Surgical Treatment of Mandible Fracture Using Unsintered Hydroxyapatite/Poly L-Lactide Composite Fixation System.

Recently, absorbable plates have been used for various types of facial fractures. However, in the case of mandibular fractures, a large amount of force is applied after fixation. Thus, a firm fixation is necessary. In particular, unfavorable fractures are more frequent in mandibular fractures. Therefore, plates should be strong enough to withstand forces at the time of surgery. The purpose of this study was to determine clinical efficacy and usefulness of unsintered hydroxyapatite (u-HA)/poly (L-lactide) (PLLA) composite system by clinical application and follow-up of fixation in patients with mandible fracture. A total of 13 patients with mandible fractures were assessed for compliance with the selection criteria. Fracture site was confirmed with radiographic findings including X-ray and facial computed tomography images. Subjects who fulfilled all criteria underwent operation using HA/PLLA composite fixation system (OSTEOTRANS; Takiron Co Ltd, Osaka, Japan). After reduction of fracture site through oral or skin incision, we placed OSTEOTRANS plates on fracture line and performed rigid fixation with OSTEOTRANS-MX screws. Follow-up was performed at 1 week, 1, 3, and 6 months after surgery. Occlusion and mouth opening were checked by physical examination and radiographic finding. We also confirmed bone approximation status, bony gap change, and bone union status. All patients finished every follow-up. They were satisfied with outcomes without complications such as malocclusion, foreign body sensation, or tenderness. This study confirms that OSTEOTRANS can be used appropriately for mandibular fractures.

Monitoring mRNA transcription of genes involved in early pregnancy from endometrium and peripheral blood mononuclear cells of pregnant pigs with different parity.

The reproductive success of mammals is largely dependent on the interaction between maternal and foetal interfaces during early pregnancy. Particularly, immune cells which reside at the maternal endometrium can modulate the conception and placental vascularization. In this study, we analysed the transcription of genes involved in early pregnancy from endometrium and peripheral blood mononuclear cells (PBMCs) of pregnant pigs with different parity. Briefly, three groups of female pigs were divided based on parity (0, 2 and 5) and each group was artificially inseminated. Within 30 days of gestation, the total RNA was isolated from the endometrium and PBMCs of sacrificed experimental pigs and the expression patterns of genes involved in early pregnancy were monitored by quantitative real-time RT-PCR. Results indicated absence of correlation between increased parity and the expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1-α (HIF-1α) mRNA in endometrium among the groups of pigs analysed. Yet, the mRNA levels of Fas, Fas ligand (FasL) and tumour necrosis factor-α (TNF-α) in the endometrium of parity 5 sows were much higher than those of pregnant gilts (parity 0), and the mRNA ratios of both TNF-α:interleukin-4 (IL-4) and IFN-γ (interferon-γ):interleukin-10 (IL-10) in PBMCs of pregnant pigs were augmented with increasing parity. Furthermore, the mRNA levels of TNF-α and IFN-γ in PBMCs of pregnant pigs were inversely correlated with litter size. These combined results may demonstrate that increased parity of pregnant pigs leads to enhance Th1-prone immunity within the maternal-foetal interface during early pregnancy.

Carboxytherapy-Induced Fat loss is Associated with VEGF-Mediated Vascularization.

BACKGROUND: Carboxytherapy is the transcutaneous administration of CO2 gas for therapeutic purposes. Although this non-surgical procedure has been widely used for reducing localized adiposity, its effectiveness on fat loss in obese patients and its underlying mechanisms remain unclear. METHODS: C57BL/6 mice were fed with a high-fat diet for 8 weeks to generate obese animal models. Obese mice were randomly assigned to two groups: One group was administered air to both inguinal fat pads (air/air), and the other group was treated with air to the left inguinal fat pad and with CO2 to the right inguinal fat pad (air/CO2). Each group was treated every other day for 2 weeks. Morphological changes and expression levels of genes associated with lipogenesis and vascularization in fat were determined by histological and qRT-PCR analyses. RESULTS: Mice treated with air/CO2 showed lower body weights and blood glucose levels compared to air/air-treated mice. Paired comparison analysis revealed that CO2 administration significantly decreased adipose tissue weights and adipocyte sizes compared to air treatment. Additionally, CO2 treatment markedly increased vessel numbers and expressions of Vegfa and Fgf1 genes in adipose tissues. The expressions of Fasn and Fabp4 genes were also modestly reduced in CO2-treated adipose tissue. Moreover, Ucp1 expression, the target gene of VEGF and a key regulator in energy expenditure, was significantly increased in CO2-treated adipose tissue. CONCLUSIONS: Carboxytherapy is effective in the reduction of localized fat in obese patients which is mechanistically associated with alteration of the vasculature involved in VEGF. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Pig tissue factor pathway inhibitor α fusion immunoglobulin inhibits pig tissue factor activity in human plasma moderately more efficiently than the human counterpart.

OBJECTIVE: To determine the efficacy of soluble pig tissue factor pathway inhibitor fusion immunoglobulin (TFPI-Ig) in blocking pig to human xenogeneic blood coagulation. RESULTS: To generate pig TFPI-Ig or human TFPI-Ig, expression vector containing cDNA encoding pig TFPIα or human TFPIα combined with human constant Ig heavy chain region was cloned and introduced into CHO cells. After purification of pig TFPI-Ig and human TFPI-Ig, the inhibition of each recombinant protein on pig tissue factor (TF)-mediated blood coagulation was examined in human plasma. Compared to human TFPI-Ig, pig TFPI-Ig inhibited pig TF activity and thrombin generation in human plasma more efficiently at certain concentrations. CONCLUSIONS: Pig TFPI-Ig will be be useful as a therapeutic protein to treat pig to human xenogeneic blood coagulation.

Molecular Cloning and Expression Analysis of Pig Cd90.

The CD90 (Thy-1) is a glycosylphosphatidylinositol (GPI)-anchored glycoprotein that transfers signals involved in many biological events including cell activation, cell migration, cell adhesion, and tumor suppression. In this study, we cloned pig CD90 cDNA and determined its complete cDNA sequence. Pig CD90 cDNA contained an open reading frame (486 bp) encoding 161 amino acids with three putative N-glycosylation sites and four well-conserved cysteine residues, which form a possible disulfide bond within the extracellular domain among mammalian species. Pig CD90 mRNA was detected in various tissues, indicating the multicellular functions of CD90 in pigs. Flow cytometry analyses demonstrated that anti-human CD90 antibody recognizes a pig CD90 on the cell surface. Moreover, immunohistochemistry analysis revealed that CD90 expression is widely diffused in several pig tissues. Further studies will be necessary to define the functional contribution of CD90 during specific infectious diseases in pigs.

Treatment of Symptomatic Osteoma on Eyebrow Using Adjacent Supraorbital Neuroperiosteal Flap.

Osteomas grow slowly, blocking or compressing adjacent structures, and frequently causing aesthetic deformity. Although most patients remain asymptomatic, development of facial pain and headaches due to compression of adjacent sensory nerves is not uncommon. Depending on the location of osteoma, many techniques were introduced to remove it. If the osteoma was located close to important structures such as nerves and vessels, surgeons can be concerned about damaging them resulting in unfavorable symptoms to patients. Osteoma is a benign slow-growing osteogenic lesion, composed of well-differentiated mature bone tissue, characterized by the proliferation of compact or cancellous bone, and found in the head and neck region. It is often slow growing and asymptomatic, diagnosed incidentally on radiographs. It can cause deformation of the bone and compression of the adjacent structures such as nerve compression. This case shows how symptomatic osteoma can be successfully extracted.