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Since the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, over 103214008 cases have been reported, with more than 2231158 deaths as of January 31, 2021. Although the gold standard for diagnosis of this disease remains the reverse-transcription polymerase chain reaction of nasopharyngeal and oropharyngeal swabs, its false-negative rates have ignited the use of medical imaging as an important adjunct or alternative. Medical imaging assists in identifying the pathogenesis, the degree of pulmonary damage, and the characteristic features in each imaging modality. This literature review collates the characteristic radiographic findings of COVID-19 in various imaging modalities while keeping the preliminary focus on chest radiography, computed tomography (CT), and ultrasound scans. Given the higher sensitivity and greater proficiency in detecting characteristic findings during the early stages, CT scans are more reliable in diagnosis and serve as a practical method in following up the disease time course. As research rapidly expands, we have emphasized the CO-RADS classification system as a tool to aid in communicating the likelihood of COVID-19 suspicion among healthcare workers. Additionally, the utilization of other scoring systems such as MuLBSTA, Radiological Assessment of Lung Edema, and Brixia in this pandemic are reviewed as they integrate the radiographic findings into an objective scoring system to risk stratify the patients and predict the severity of disease. Furthermore, current progress in the utilization of artificial intelligence via radiomics is evaluated. Lastly, the lesson from the first wave and preparation for the second wave from the point of view of radiology are summarized.

Irreversible denervation atrophy remains an unsolved clinical problem, and the role of skeletal muscle stem cell (MuSC, satellite cell) depletion in this process is unclear. We investigated the ability of MuSCs to regenerate muscle in the context of denervation. Three to 12 months following sciatic denervation in mice, MuSC number, size, EdU uptake, rate of division, and mitochondrial activity were increased. Following acute myotoxin injury, denervated muscles formed new muscle fibers in situ. MuSCs isolated via flow cytometry from denervated mouse muscle, or from atrophic denervated gluteus maximus muscles of humans with complete spinal cord injuries two decades prior, formed new muscle fibers and reoccupied the anatomic niche after transplantation into uninjured muscle. Our results show unequivocally that, even after prolonged denervation, MuSCs retain intrinsic regenerative potential similar to that of uninjured MuSCs. Treatment of denervation atrophy will require elucidating the non-MuSC environmental changes in muscle that prevent functional regeneration.

White matter lesions (WML) underlie multiple brain disorders, and automatic WML segmentation is crucial to evaluate the natural disease course and effectiveness of clinical interventions, including drug discovery. Although recent research has achieved tremendous progress in WML segmentation, accurate detection of subtle WML present early in the disease course remains particularly challenging. Here we propose an approach to automatic WML segmentation of mild WML loads using an intensity standardisation technique, gray level co-occurrence matrix (GLCM) embedded clustering technique, and random forest (RF) classifier to extract texture features and identify morphology specific to true WML. We precisely define their boundaries through a local outlier factor (LOF) algorithm that identifies edge pixels by local density deviation relative to its neighbors. The automated approach was validated on 32 human subjects, demonstrating strong agreement and correlation (excluding one outlier) with manual delineation by a neuroradiologist through Intra-Class Correlation (ICC = 0.881, 95% CI 0.769, 0.941) and Pearson correlation (r = 0.895, p-value

3D imaging data necessitate 3D reference atlases for accurate quantitative interpretation. Existing computational methods to generate 3D atlases from 2D-derived atlases result in extensive artifacts, while manual curation approaches are labor-intensive. We present a computational approach for 3D atlas construction that substantially reduces artifacts by identifying anatomical boundaries in the underlying imaging data and using these to guide 3D transformation. Anatomical boundaries also allow extension of atlases to complete edge regions. Applying these methods to the eight developmental stages in the Allen Developing Mouse Brain Atlas (ADMBA) led to more comprehensive and accurate atlases. We generated imaging data from 15 whole mouse brains to validate atlas performance and observed qualitative and quantitative improvement (37% greater alignment between atlas and anatomical boundaries). We provide the pipeline as the MagellanMapper software and the eight 3D reconstructed ADMBA atlases. These resources facilitate whole-organ quantitative analysis between samples and across development., eLife digest The research community needs precise, reliable 3D atlases of organs to pinpoint where biological structures and processes are located. For instance, these maps are essential to understand where specific genes are turned on or off, or the spatial organization of various groups of cells over time. For centuries, atlases have been built by thinly ‘slicing up’ an organ, and then precisely representing each 2D layer. Yet this approach is imperfect: each layer may be accurate on its own, but inevitable mismatches appear between the slices when viewed in 3D or from another angle. Advances in microscopy now allow entire organs to be imaged in 3D. Comparing these images with atlases could help to detect subtle differences that indicate or underlie disease. However, this is only possible if 3D maps are accurate and do not feature mismatches between layers. To create an atlas without such artifacts, one approach consists in starting from scratch and manually redrawing the maps in 3D, a labor-intensive method that discards a large body of well-established atlases. Instead, Young et al. set out to create an automated method which could help to refine existing ‘layer-based’ atlases, releasing software that anyone can use to improve current maps. The package was created by harnessing eight atlases in the Allen Developing Mouse Brain Atlas, and then using the underlying anatomical images to resolve discrepancies between layers or fill out any missing areas. Known as MagellanMapper, the software was extensively tested to demonstrate the accuracy of the maps it creates, including comparison to whole-brain imaging data from 15 mouse brains. Armed with this new software, researchers can improve the accuracy of their atlases, helping them to understand the structure of organs at the level of the cell and giving them insight into a broad range of human disorders.

Objective The aim of this study was to evaluate which mesh type yields lower recurrence and complication rates after ventral hernia repair. Summary background data More than 400,000 ventral hernia repairs are performed annually in the United States. Although the most effective method for repairing ventral hernias involves using mesh, whether to use biologic mesh versus synthetic mesh is controversial. Methods Single-blind, randomized, controlled, pragmatic clinical trial conducted from March 2014 through October 2018; 165 patients enrolled with an average follow up of 26 months. Patients were randomized 1:1 to have their ventral hernias repaired using either a biologic (porcine) or synthetic (polypropylene) mesh. The primary study outcome measure was hernia recurrence at 2 years. Results A total of 165 patients (68 men), mean age 55 years, were included in the study with a mean follow-up of 26 months. An intention-to-treat analysis noted that hernias recurred in 25 patients (39.7%) assigned to biologic mesh and in 14 patients (21.9%) assigned to synthetic mesh (P = 0.035) at 2 years. Subgroup analysis identified an increased rate of hernia recurrence in the biologic versus the synthetic mesh group under contaminated wound conditions (50.0% vs 5.9%; P for interaction = 0.041). Postoperative complication rates were similar for the 2 mesh types. Conclusions The risk of hernia recurrence was significantly higher for patients undergoing ventral hernia repair with biologic mesh compared to synthetic mesh, with similar rates of postoperative complications. These data indicate that the use of synthetic mesh over biologic mesh to repair ventral hernias is effective and can be endorsed, including under contaminated wound conditions. Trial registration ClinicalTrials.gov Identifier: NCT02041494.

The healthcare industry has placed significant effort on reducing pressure injuries as they often occur while patients are seeking treatment for an unrelated condition, lengthen the stay of the patient, impact treatment options, are extremely painful, and can result in death. Current work has shown that an increase in nursing care can reduce pressure injury occurrence, but increased nursing care is not sustainable. The Braden Scale is the current method of stratifying patients by risk of forming a pressure injury, but previous work has shown that the Braden Scale is not an accurate predictor of pressure injury formation. We present an objective mobility measure of pressure injury risk that can be used in addition to the Braden Scale using a wearable pressure-sensing device. By assessing the current pressure readings in real-time we can determine when a patient is mobile and present this data to the clinic. In future we aim to use this mobility measurement in a Cloud-based system that can compare the mobility measurements to similar patients to assess risk with increased accuracy.

Open abdominal surgery is frequently complicated by the subsequent development of an incisional hernia. Consequently, more than 400,000 incisional hernia repairs are performed each year, adding over $15 billion per year to U.S. health-care expenditures. While the vast majority of studies have focused on improved surgical techniques or prosthetic materials, we examined the use of metallic silver microparticles to prevent incisional hernia formation through enhanced wound healing.A rodent incisional hernia model was used. Eighty-two rats were randomly placed into two control groups (saline alone and silver microparticles alone), and three experimental groups (0 mg/cm, 2.5 mg/cm, and 25 mg/cm of silver microparticles applied with a fibrin sealant). Incisional hernia incidence and size, tensile strength, and tissue histology were assessed after 28 days.A significant reduction of both incisional hernia incidence and hernia size was observed between the control groups and 2.5 mg/cm group, and between the control and 25 mg/cm group by nearly 60% and 90%, respectively (P 0.05). Histological samples showed a noticeable increase in new fibrosis in the treated animals as compared with the controls, whereas the tensile strength between the groups did not differ.The novel approach of using silver microparticles to enhance wound healing appears to be a safe and effective method to prevent incisional hernias from developing and could herald a new era of medicinal silver use.

Incisional hernia is a frequent complication of midline laparotomy and enterostomal creation and is associated with high morbidity, decreased quality of life, and high costs. The International Symposium on Incisional Hernia Prevention was held October 19 –20, 2017, at the InterContinental Hotel in San Francisco, CA, hosted by the Department of Surgery, University of California, San Francisco. One hundred and three attendees included general and plastic surgeons from 9 countries, including principal participants for several of the seminal studies in the field. Over the course of the 2-day meeting, there were 38 oral presentations, 3 keynote lectures, and 2 panel discussions. The Symposium was a combination of new information but also a comprehensive review of the existing data so as to assess the current state of the field and to set the stage for future research. Further, the Symposium sought to increase awareness and thus emphasize the importance of preventing the formation of incisional and enterostomal hernias. pre-print 443 KB

BACKGROUND: Uncomplicated skin abscesses are common, yet the appropriate management of the condition in the era of community-associated methicillin-resistant Staphylococcus aureus (MRSA) is unclear. METHODS: We conducted a multicenter, prospective, double-blind trial involving outpatient adults and children. Patients were stratified according to the presence of a surgically drainable abscess, abscess size, the number of sites of skin infection, and the presence of nonpurulent cellulitis. Participants with a skin abscess 5 cm or smaller in diameter were enrolled. After abscess incision and drainage, participants were randomly assigned to receive clindamycin, trimethoprim–sulfamethoxazole (TMP-SMX), or placebo for 10 days. The primary outcome was clinical cure 7 to 10 days after the end of treatment. RESULTS: We enrolled 786 participants: 505 (64.2%) were adults and 281 (35.8%) were children. A total of 448 (57.0%) of the participants were male. S. aureus was isolated from 527 participants (67.0%), and MRSA was isolated from 388 (49.4%). Ten days after therapy in the intention-to-treat population, the cure rate among participants in the clindamycin group was similar to that in the TMP-SMX group (221 of 266 participants [83.1%] and 215 of 263 participants [81.7%], respectively; P = 0.73), and the cure rate in each active-treatment group was higher than that in the placebo group (177 of 257 participants [68.9%], P

Rapamycin, a specific inhibitor for mTOR complex 1, is an FDA-approved immunosuppressant for organ transplant. Recent developments have raised the prospect of using rapamycin to treat cancer or diabetes and to delay aging. It is therefore important to assess how rapamycin treatment affects glucose homeostasis. Here, we show that the same rapamycin treatment reported to extend mouse life span significantly impaired glucose homeostasis of aged mice. Moreover, rapamycin treatment of lean C57B/L6 mice reduced glucose-stimulated insulin secretion in vivo and ex vivo as well as the insulin content and beta cell mass of pancreatic islets. Confounding the diminished capacity for insulin release, rapamycin decreased insulin sensitivity. The multitude of rapamycin effects thus all lead to glucose intolerance. As our findings reveal that chronic rapamycin treatment could be diabetogenic, monitoring glucose homeostasis is crucial when using rapamycin as a therapeutic as well as experimental reagent.

Background: CXCL12 is a chemokine involved in postinjury leukocyte chemotaxis, migration, and homing of stem cells. We hypothesized that by increasing the level of the chemokine CXCL12 in wounds of diabetic mice, we would increase stem cell recruitment to the wound and, thus, accelerate time to wound closure. Methods: Eighteen Lepr db-/db- (B6.Cg-m +/+ Leprdb/J; Jackson Labs, Bar Harbor, ME) and their nondiabetic littermates were wounded and treated either with an empty plasmid or a plasmid containing the CXCL12 gene. Wounds were measured approximately every 5 days until they closed completely and were analyzed using planimetry. Wounds were harvested, and relative expression of CXCL12 mRNA was measured using an ABI Prism SDS 7000. To study stem cells affected by this, the plasmid's affect on stem cell recruitment, we used flow cytometry. Results: The diabetic wounds contain a significantly decreased level of CXCL12 mRNA at day 7 postwounding, and these wounds take 55 days to heal. Application of a CXCL12 plasmid to diabetic wounds significantly increases CXCL12 mRNA at day 7, and these wounds heal in 23 days. Conclusions: Lack of CXCL12 in diabetic wounds contributes to delayed wound healing and can be reversed via single application of a CXCL12-containing plasmid.

Tuberous sclerosis (TSC) is an autosomally dominant neurocutaneous disease notable for its high comorbidity with autism in human patients. Studies of murine models of tuberous sclerosis have found defects in cognition and learning, but thus far have not uncovered deficits in social behaviors relevant to autism. To explore social communication and interaction in TSC2 heterozygous mice, we recorded ultrasonic vocalizations (USV) and found that although both wild-type (WT) and heterozygous pups born to WT dams showed similar call rates and patterns, baseline vocalization rates were elevated in pups born to heterozygous dams. Further analysis revealed several robust features of maternal potentiation in all but WT pups born to heterozygous dams. This lack of potentiation is suggestive of defects in mother–pup social interaction during or before the reunion period between WT pups and heterozygous dams. Intriguingly, male pups of both genotypes born to heterozygous dams showed particularly heightened call rates and burst patterns. Because our maternal retrieval experiments revealed that TSC2 +/− dams exhibited improved defensive reactions against intruders and highly efficient pup retrieval performance, the alterations in their pups’ USVs and maternal potentiation do not appear to result from poor maternal care. These findings suggest that a pup's interaction with its mother strongly influences the pup's vocal communication, revealing an intriguing dependence of this social behavior on TSC2 gene dosage of both parties involved. Our study of this murine model thus uncovers social abnormalities that arise from TSC haploinsufficiency and are suggestive of autism.

Impaired wound healing in diabetic patients is associated with deficiencies in the production of factors involved in cell proliferation and migration, such as vascular endothelial growth factor. However, it remains unclear how the transcriptional regulation of the genes encoding these factors is affected by the diabetic environment. Hypoxia-inducible factor-1alpha (Hif-1alpha), the regulatory subunit of the Hif-1 transcription factor, plays an important role in activating many of these genes. Therefore, we tested whether Hif-1alpha function is impaired in the diabetic wound environment and whether restoring Hif-1 function improves wound healing. Here, we show that Hif-1alpha protein levels are dramatically reduced in wounds of leptin receptor-deficient diabetic mice compared with nondiabetic littermates. Reduction in Hif-1alpha levels results in decreased DNA-binding activity and in decreased expression of several Hif-1 target genes, including vascular endothelial growth factor, heme oxygenase-1, and inducible nitric oxide synthase. Furthermore, we demonstrate that sustained expression of Hif-1alpha in leptin receptor-deficient diabetic wounds restores expression of these factors, enhances angiogenesis, and significantly accelerates wound healing. Taken together, these results suggest that Hif-1alpha function plays a significant role in wound healing and reduced levels of Hif-1alpha may contribute to impaired healing.

When pressure is applied to a localized area of the body for an extended time, the resulting loss of blood flow and subsequent reperfusion to the tissue causes cell death and a pressure ulcer develops. Preventing pressure ulcers is challenging because the combination of pressure and time that results in tissue damage varies widely between patients, and the underlying damage is often severe by the time a surface wound becomes visible. Currently, no method exists to detect early tissue damage and enable intervention. Here we demonstrate a flexible, electronic device that non-invasively maps pressure-induced tissue damage, even when such damage cannot be visually observed. Using impedance spectroscopy across flexible electrode arrays in vivo on a rat model, we find that impedance is robustly correlated with tissue health across multiple animals and wound types. Our results demonstrate the feasibility of an automated, non-invasive 'smart bandage' for early detection of pressure ulcers.

Genotypic and phenotypic analyses were carried out to clarify the taxonomic position of the naturally transformable Acinetobacter sp. strain ADP1. Transfer tDNA-PCR fingerprinting, 16S rRNA gene sequence analysis, and selective restriction fragment amplification (amplified fragment length polymorphism analysis) indicate that strain ADP1 and a second transformable strain, designated 93A2, are members of the newly described species Acinetobacter baylyi . Transformation assays demonstrate that the A. baylyi type strain B2 T and two other originally identified members of the species (C5 and A7) also have the ability to undergo natural transformation at high frequencies, confirming that these five strains belong to a separate species of the genus Acinetobacter , characterized by the high transformability of its strains that have been cultured thus far.

The genetic and physiological properties of Acinetobacter baylyi strain ADP1 make it an inviting subject for investigation of the properties underlying its nutritional versatility. The organism possesses a relatively small genome in which genes for most catabolic functions are clustered in several genetic islands that, unlike pathogenicity islands, give little evidence of horizontal transfer. Coupling mutagenic polymerase chain reaction to natural transformation provides insight into how structure influences function in transporters, transcriptional regulators, and enzymes. With appropriate selection, mutants in which such molecules have acquired novel function may be obtained. The extraordinary competence of A. baylyi for natural transformation and the ease with which it expresses heterologous genes make it a promising platform for construction of novel metabolic systems. Steps toward this goal should take into account the complexity of existing pathways in which transmembrane trafficking plays a significant role.

The Social Democratic Federation (S.D.F.) was one of the founding elements of the Labour party in Britain. Many activists who would later become prominent in the labour movement and parliamentary politics obtained their introduction to political life through the S.D.F. This article aims to provide a membership profile of the London region, an area where the S.D.F. had some influence. The data gathered make possible an analysis of the branch size and turnover as well as of gender, age and occupational structure. They also illustrate in general the development of the socialist and labour movement of the capital in this period.

The aim of this article is to present a structure for the historical study of party activism. Based on research carried out on the activities of the Social Democratic Federation (SDF) between 1884 and 1911, the article puts forward the case that current understandings of that organisation should be reassessed to include the notion of the ‘political journeys’ of the activists. Instead of focusing exclusively on ideology, the article suggests that other poles or features such as locality and collective biography should be used. If the organisation is viewed from a wider perspective and with a longer exposure time, then, this article argues, a clearer picture presents itself.

Diabetic wound healing is characterized by deficiencies in both growth factor and collagen production. We have observed that expression of homeobox D3 (HoxD3), a collagen-inducing transcription factor, and expression of collagen are reduced in an established animal model of diabetic wound repair, the leptin-deficient diabetic (db/db) mouse. We sought to evaluate whether the diminished expression of collagen and HoxD3 would be maintained once fibroblasts were removed from the diabetic wound environment. Fibroblasts were isolated from both wild-type and diabetic animals and expression of HoxD3 and collagen assessed. We found that when removed from the diabetic wound environment, HoxD3 and type I collagen expression are increased in diabetic fibroblasts when compared to wild-type fibroblasts. The increase in type I collagen is not related to increased production or activation of transforming growth factor-beta1. However, when the diabetic fibroblasts are cultured in a 3D collagen matrix, expression of type I collagen and HoxD3 is markedly reduced and reflects the pattern of gene expression observed in the in vivo diabetic wound environment. Thus, although diabetic fibroblasts can regain the capacity to express high levels of collagen and HoxD3 once removed from the diabetic wound environment, culturing cells in the presence of a 3D collagen matrix is sufficient to revert these fibroblasts to their previous nonsynthetic state.

We give a brief overview of the GGMRES method, the MGMRES method, and the LAN/MGMRES method, which are generalizations and modifications of the Generalized Minimum Residual (GMRES) method.

Hydroxycinnamates are ubiquitous in the environment because of their contributions to the structure and defense mechanisms of plants. Additional plant products, many of which are formed in response to stress, support the growth of Acinetobacter sp. strain ADP1 through pathways encoded by genes in the dca - pca-qui - pob chromosomal cluster. In an appropriate genetic background, it was possible to select for an Acinetobacter strain that had lost the ability to grow with caffeate, a commonly occurring hydroxycinnamate. The newly identified mutation was shown to be a deletion in a gene designated hcaC and encoding a ligase required for conversion of commonly occurring hydroxycinnamates (caffeate, ferulate, coumarate, and 3,4-dihydroxyphenylpropionate) to thioesters. Linkage analysis showed that hcaC is linked to pobA . Downstream from hcaC and transcribed in the direction opposite the direction of pobA transcription are open reading frames designated hcaDEFG . Functions of these genes were inferred from sequence comparisons and from the properties of knockout mutants. HcaD corresponded to an acyl coenzyme A (acyl-CoA) dehydrogenase required for conversion of 3,4-dihydroxyphenylpropionyl-CoA to caffeoyl-CoA. HcaE appears to encode a member of a family of outer membrane proteins known as porins. Knockout mutations in hcaF confer no discernible phenotype. Knockout mutations in hcaG indicate that this gene encodes a membrane-associated esterase that hydrolyzes chlorogenate to quinate, which is metabolized in the periplasm, and caffeate, which is metabolized by intracellular enzymes. The chromosomal location of hcaG , between hcaC (required for growth with caffeate) and quiA (required for growth with quinate), provided the essential clue that led to the genetic test of HcaG as the esterase that produces caffeate and quinate from chlorogenate. Thus, in this study, organization within what is now established as the dca - pca-qui - pob - hca chromosomal cluster provided essential information about the function of genes in the environment.

Background Reported 10-year patient survival after liver transplantation is nearing 70 percent, with similar trends seen for kidney transplantation. With increasing life expectancy, these patients have an increased need for posttransplant reconstructive surgery. Thus, plastic surgeons must know the effects of immunosuppressive medications on outcomes in microvascular reconstruction. Methods A retrospective review was performed on all immunosuppressed solid-organ transplant patients who underwent subsequent free tissue transfer of all types, over an 8-year period. Patient demographics, type of solid organ transplant, immunosuppressive regimen, anticoagulation regimen, associated medical comorbidities, and complication rates were analyzed. Results Twenty-four microvascular free tissue transfers were performed over an 8-year period on immunosuppressed patients, for head and neck and lower extremity reconstruction. Fifteen patients (63 percent) underwent prior kidney transplant, seven (29 percent) underwent prior liver transplant, and two (8 percent) underwent prior lung transplant. Prednisone (79 percent of patients), cyclosporine (33 percent), and tacrolimus (33 percent) were the most commonly used immunosuppressive medications. Complications included one total flap loss (4 percent), three intraoperative arterial thromboses (13 percent), and two postoperative venous thromboses (8 percent). Univariate analysis illustrated a statistically significant association between prednisone and overall complication rate (p = 0.032). Conclusions Microvascular free tissue transfer is a challenge in immunosuppressed patients. Univariate analysis showed prednisone to correlate statistically with operative morbidity. Transplant patients receiving prednisone at the time of their elective free flap procedure will require additional care to lower the additional risk of delayed wound healing, partial flap loss, and anastomotic thrombosis. Clinical question/level of evidence Therapeutic IV.

Ion channels are important integral membrane proteins that allow charged ions to pass into and out of a cell. Many ion channels are evolutionarily related, and small mutations may be responsible for the observed diversity in channel gating and ion selectivity. Ion channels can be gated by the movement of a charged voltage sensor through the lipid bilayer, the pull of a calcium-gating ring, the interaction with calmodulin proteins, the binding of G-protein subunits, or the detection of ATP by auxiliary subunits. Any of these events deforms the channel protein, physically distorting the gate to allow ion permeation. Ion selectivity in pore-loop potassium, sodium, and calcium channels is achieved by protein-ion interactions that dehydrate ions as they move through the pore. The energetics involved in the unfavorable removal of water molecules from an ion’s hydration shell ensure that ions of the correct size and charge are selectively conducted through the pore.

Background: As the elderly population continues to expand, it becomes increasingly important to develop treatments to improve wound healing in the elderly. One problem limiting the research is the lack of appropriate animal models for wound healing in elderly patients. We hypothesized that the Klotho mouse of premature aging is a suitable animal model to shed light on many of the biological processes involved in aging skin. Methods: Klotho mice (kl/kl), Klotho-heterozygous mice (kl/+), and wild-type mice (+/+) were wounded, and the area of the wound was measured every 3 days until the wound was healed. To compare the klotho phenotype with wild-type mice, wounds were also harvested at 4 and 7 days after wounding. For histological examination, paraffin-embedded sections were stained with hematoxylin and eosin and Masson trichrome. Collagen expression in the wound was also studied by analyzing messenger RNA using real-time polymerase chain reaction. Results: Klotho mice showed a significantly slower rate of wound closure compared with Klotho-heterozygous mice and wild-type mice. Histology showed substantial less healing and collagen deposition in the wounds of the Klotho mice. The expression of collagen messenger RNA in Klotho mice was also less than that in heterozygous and wild-type mice. The Klotho mice exhibited significant phenotypic similarities with aged skin, such as atrophy and delayed wound healing. Conclusion: These preliminary data suggest that the Klotho mouse may be a model to further investigate wound healing in the elderly.

Background. Without angiogenesis, tumor growth is limited to a few millimeters, the limit of diffusion. Vascular endothelial growth factor (VEGF) is an endothelial-specific mitogen and a major regulator of angiogenesis. Methods. To investigate the relationship between VEGF and thyroid tumor angiogenesis, we xenografted human dermal matrix inoculated with FTC-133 cells into nude mice or directly injected FTC-133 cells subcutaneously. To block the function of VEGF, the neutralizing anti-VEGF monoclonal antibody A.4.6.1 (mAb A.4.6.1) was injected intraperitoneally twice weekly. As control, an antibody of the same isotype (Ab 5B6) or phosphate buffer saline solution (PBS) was used. To evaluate the dermal matrix as a model for angiogenesis studies, recombinant human VEGF was inoculated into the dermal matrix pocket and xenografted into mice. Results. In the dermal matrix angiogenesis model, the number of blood vessels paralleled the concentration of recombinant human VEGF and was highest at 100 ng/mL. Mice that were treated with the mAb A4.6.1 developed fewer blood vessels (mean, 6.6 per HPF) than control mice (18 per HPF in Ab 5B6 and 22 per HPF in PBS; P