Procedures and operating instructions for diagnosis in vascular anomalies and pathology

In the last 30 years a revolution has occurred in the diagnosis and management of vascular anomalies. The great changes began with Mulliken and Glowacki separation of hemangiomas and vascular anomalies. Their work has now morphed into the ISSVA classification. Subsequently the discovery of the significance of the presence of GLUT-1 in the diagnosis of the hemangiomas of infancy gave us a new marker in our quest for accurate classification. Now genetic breakthroughs have led us into a \u201cStar Wars\u201d like environment in the experimental laboratory. During all these events the critical role of the pathologist has become more evident. Understanding the histopathology of anomalies has greatly aided in our approach to therapies. Moreover, genetic findings do not have full significance without the morphologic framework

The effect of farming system on dairy cow cleanliness in the UK and implications to udder health

The cleanliness of dairy cows was assessed using a 20 point hygiene score system at different times in the year on 14 organic and 14 conventional farms in the UK. Overall, cows were dirtier during winter housing compared to summer grazing. Farming system had no effect on cow cleanliness when cows were at grass, but when housed in the winter, organic cows were more likely to be cleaner. There was a link between cow hygiene scores and milk hygiene, with herds having lower bulk tank somatic cell counts (BTSCC) tending to have cleaner cows. This relationship was strongest for the organic herds. There was no significant link between hygiene score and Bactoscan (BS) count or mastitis incidence

Láser y luz pulsada intensa en el tratamiento de hemangiomas infantiles y malformaciones vasculares

The use of the indications of the laser in treating vascular malformations and infantile haemangiomas is based on the theory of selective photothermolysis, in which the oxyhaemoglobin is the target chromophore on which the light of the laser acts, thus avoiding damage to neighbouring tissues. The pulsed dye laser is the most employed and at present is the treatment of choice in capillary malformations (port-wine stains). A variable response is obtained, with a substantial clearing of the colour of the lesion after several sessions. Application at early ages seems to improve the results. Venous malformations, especially those localised in the mucosa, respond better to the Nd:YAG laser; lymphatic malformations to the CO2 laser. Arteriovenous malformations rarely respond. Use of the pulsed dye laser in the phase of proliferation of the haemangiomas is subject to controversy, except where there is ulceration. A rapid re-epithelialization is obtained in these cases following its use. In the involution phase, patients with residual vascular lesions can benefit from other lasers such as KTP or Nd:YAG. If they show an atrophic surface and scars these complications improve with the CO2 laser or Er:YAG. New treatment modalities are emerging, such as photodynamic therapy, whose efficacy and safety, both in the treatment of haemangiomas and vascular malformations, have yet to be confirmed

Implementing Archaeological Conservation During American Nation-Building Efforts

This thesis seeks to define best practices for implementing the conservation of archaeological sites as part of a broader system of cultural heritage protection within the framework of United States nation-building efforts. The ransacking of the Baghdad Museum, plus the widespread looting of the Iraq’s archaeological sites, makes it clear that measures for cultural property protection within the United States government military framework deserve a critical analysis. First, the importance of protecting cultural property during armed conflict will be examined from a historical and military perspective. Next, previous American nation building attempts are discussed to give a sense of the general circumstances within which conservation activities are to be conducted. Specifically, Iraq will be analyzed as a prime example of the necessity of cultural heritage protection and the damage that can be inflicted on archaeological heritage when such protection is not included as part of larger operational planning framework. Then, what the United States has done and is currently doing in response to the ratification of the Hague Convention and the destruction of cultural property in Iraq are explored. After that, internationally-accepted best practices of archaeological conservation are provided as a framework for evaluating current endeavors and planning those for the future. Finally, recommendations will be made on how the government, specifically the Department of Defense and the State Department, can institute measures for the conservation of archaeological heritage during the planning process of nation building operations

procedures and operating instructions for diagnosis in vascular anomalies and pathology

In the last 30 years a revolution has occurred in the diagnosis and management of vascular anomalies. The great changes began with Mullikenand Glowacki separation of hemangiomas and vascular anomalies. Their work has now morphed into the ISSVA classification. Subsequentlythe discovery of the significance of the presence of GLUT-1 in the diagnosis of the hemangiomas of infancy gave us a new markerin our quest for accurate classification. Now genetic breakthroughs have led us into a "Star Wars" like environment in the experimental laboratory.During all these events the critical role of the pathologist has become more evident. Understanding the histopathology of anomalieshas greatly aided in our approach to therapies. Moreover, genetic findings do not have full significance without the morphologic framewor

Isolation, characterization, and in vitro propagation of infantile hemangioma stem cells and an in vivo mouse model

<p>Abstract</p> <p>Background</p> <p>Infantile hemangiomas (IH) are the most common benign tumors of infancy. The typical clinical course consists of rapid growth during the first year of life, followed by natural and gradual involution over a multi-year time span through unknown cellular mechanisms. Some tumors respond to medical treatment with corticosteroids or beta-blockers, however, when this therapy fails or is incomplete, surgical extirpation may be necessary. Noninvasive therapies to debulk or eliminate these tumors would be an important advance. The development of an <it>in vitro </it>cell culture system and an animal model would allow new insights into the biological processes involved in the development and pathogenesis of IH.</p> <p>Results</p> <p>We observed that proliferative stage IH specimens contain significantly more SALL4+ and CD133+ cells than involuting tumors, suggesting a possible stem cell origin. A tumor sphere formation assay was adapted to culture IH cells <it>in vitro</it>. Cells in IH tumor spheres express GLUT1, indicative of an IH cell of origin, elevated levels of VEGF, and various stem/progenitor cell markers such as SALL4, KDR, Oct4, Nanog and CD133. These cells were able to self-renew and differentiate to endothelial lineages, both hallmarks of tumor stem cells. Treatment with Rapamycin, a potent mTOR/VEGF inhibitor, dramatically suppressed IH cell growth <it>in vitro</it>. Subcutaneous injection of cells from IH tumor spheres into immunodeficient NOD-SCID mice produced GLUT1 and CD31 positive tumors with the same cellular proliferation, differentiation and involution patterns as human hemangiomas.</p> <p>Conclusions</p> <p>The ability to propagate large numbers of IH stem cells <it>in vitro </it>and the generation of an <it>in vivo </it>mouse model provides novel avenues for testing IH therapeutic agents in the future.</p

High levels of SARS-CoV-2 specific T-cells with restricted functionality in patients with severe course of COVID-19

Patients infected with SARS-CoV-2 differ in the severity of disease. In this study, SARS-CoV-2 specific T-cells and antibodies were characterized in patients with different COVID-19 related disease severity. Despite severe lymphopenia affecting all major lymphocyte subpopulations, patients with severe disease mounted significantly higher levels of SARS-CoV-2 specific T-cells as compared to convalescent individuals. SARS-CoV-2 specific CD4 T-cells dominated over CD8 T-cells and closely correlated with the number of plasmablasts and SARS-CoV-2 specific IgA- and IgG-levels. Unlike in convalescents, SARS-CoV-2 specific T-cells in patients with severe disease showed marked alterations in phenotypical and functional properties, which also extended to CD4 and CD8 T-cells in general. Given the strong induction of specific immunity to control viral replication in patients with severe disease, the functionally altered phenotype may result from the need for contraction of specific and general immunity to counteract excessive immunopathology in the lung

High levels of SARS-CoV-2-specific T cells with restricted functionality in severe courses of COVID-19

BACKGROUND. Patients infected with severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) differ in the severity of disease. We hypothesized that characteristics of SARS-CoV-2– specific immunity correlate with disease severity. METHODS. In this study, SARS-CoV-2–specific T cells and antibodies were characterized in uninfected controls and patients with different coronavirus disease 2019 (COVID-19) disease severity. SARS-CoV-2–specific T cells were flow cytometrically quantified after stimulation with SARS-CoV-2 peptide pools and analyzed for expression of cytokines (IFN-γ, IL-2, and TNF-α) and markers for activation, proliferation, and functional anergy. SARS-CoV-2–specific IgG and IgA antibodies were quantified using ELISA. Moreover, global characteristics of lymphocyte subpopulations were compared between patient groups and uninfected controls. RESULTS. Despite severe lymphopenia affecting all major lymphocyte subpopulations, patients with severe disease mounted significantly higher levels of SARS-CoV-2–specific T cells as compared with convalescent individuals. SARS-CoV-2–specific CD4+ T cells dominated over CD8+ T cells and closely correlated with the number of plasmablasts and SARS-CoV-2–specific IgA and IgG levels. Unlike in convalescent patients, SARS-CoV-2–specific T cells in patients with severe disease showed marked alterations in phenotypical and functional properties, which also extended to CD4+ and CD8+ T cells in general. CONCLUSION. Given the strong induction of specific immunity to control viral replication in patients with severe disease, the functionally altered characteristics may result from the need for contraction of specific and general immunity to counteract excessive immunopathology in the lung. FUNDING. The study was supported by institutional funds to MS and in part by grants of Saarland University, the State of Saarland, and the Rolf M. Schwiete Stiftung

Apocrine-Eccrine Carcinomas: Molecular and Immunohistochemical Analyses

Apocrine-eccrine carcinomas are rare and associated with poor prognosis. Currently there is no uniform treatment guideline. Chemotherapeutic drugs that selectively target cancer-promoting pathways may complement conventional therapeutic approaches. However, studies on genetic alterations and EGFR and Her2 status of apocrine-eccrine carcinomas are few in number. In addition, hormonal studies have not been comprehensive and performed only on certain subsets of apocrine-eccrine carcinomas. To investigate whether apocrine-eccrine carcinomas express hormonal receptors or possess activation of oncogenic pathways that can be targeted by available chemotherapeutic agent we performed immunohistochemistry for AR, PR, ER, EGFR, and HER2 expression; fluorescence in situ hybridization (FISH) for EGFR and ERBB2 gene amplification; and molecular analyses for recurrent mutations in 15 cancer genes including AKT-1, EGFR, PIK3CA, and TP53 on 54 cases of apocrine-eccrine carcinomas. They include 10 apocrine carcinomas, 7 eccrine carcinomas, 9 aggressive digital papillary adenocarcinomas, 10 hidradenocarcinomas, 11 porocarcinomas, 1 adenoid cystic carcinoma, 4 malignant chondroid syringomas, 1 malignant spiradenoma, and 1 malignant cylindroma. AR, ER, PR, EGFR and HER2 expression was seen in 36% (19/53), 27% (14/51), 16% (8/51), 85% (44/52) and 12% (6/52), respectively. Polysomy or trisomy of EGFR was detected by FISH in 30% (14/46). Mutations of AKT-1, PIK3CA, and TP53 were detected in 1, 3, and 7 cases, respectively (11/47, 23%). Additional investigation regarding the potential treatment of rare cases of apocrine-eccrine carcinomas with PI3K/Akt/mTOR pathway inhibitors, currently in clinical testing, may be of clinical interest