A solitary red nodule on the wrist: bacillary angiomatosis in a patient with lymphoplasmacytic lymphoma

A 54-year-old male with well-controlled human immunodeficiency virus (HIV) presented with fevers and a red nodule on the wrist. Two weeks previous, he was scratched by his cat. His medical history included lymphoplasmacytic lymphoma (LPL) with Waldenstrom macroglobulinemia. A solitary 1.7cm red nodule was present on the right wrist (Figure 1). He was febrile to 103F. A complete blood count showed baseline anemia and thrombocytopenia. The complete metabolic panel was unremarkable. His CD4+ T-cell count was 466 cells/mm3 (reference 410-961 cells/mm3), and his HIV viral load was undetectable. Historically, the patient's CD4 nadir was 274 cells/mm3. The patient underwent shave removal of the visible nodule. Histopathologic examination of the nodule demonstrated diffuse dermal vascular proliferation (Figure 2). Gram, Gomori methenamine silver, acid-fast bacillus, and human herpesvirus-8 stains were negative. There was focal uptake within the dermis with Warthin-Starry stain (Figure 3). Tissue and blood cultures were negative. Polymerase chain reaction (PCR) from the tissue sample was positive for Bartonella henselae DNA, consistent with a diagnosis of bacillary angiomatosis (BA). The patient was started on a 3-month course of doxycycline. At his follow-up appointment one month later, he continued to be afebrile. The biopsy site healed with a circular scar without recurrence.Lisa Ishii (MD, Department of Dermatology, Vanderbilt University Medical Center, Nashville, TN, USA), Alan S. Boyd (MD, Department of Pathology, Vanderbilt University Medical Center, Nashville, TN, USA)Includes bibliographical reference

Development of warfarin-induced, non-uremic calciphylaxis following recovery from COVID-19 infection with acute renal injury -- a report of a case.

Herein we report a case of an obese female presenting with calciphylaxis after a prolonged hospital course due to COVID-19, with multiple complications including now-recovered acute renal failure and deep venous thrombosis requiring treatment with warfarin. Two months after discharge, she presented with new, painful, ulcerated plaques on the thighs and was diagnosed with calciphylaxis. Throughout the COVID-19 pandemic, cutaneous manifestations of SARS-CoV-2 infection have been increasingly characterized, yet non-uremic calciphylaxis is infrequently observed. Despite its rarity, our case highlights the importance of clinician awareness of the potential association of COVID-19 as an additional trigger for calciphylaxis, especially in patients with multiple risk factors. We also urge physicians to be aware of delayed onset in the presentation of calciphylaxis after renal recovery.Briana Halle (BA, Vanderbilt University School of Medicine, Nashville, Tennessee, USA), Lisa Ishii (MD, Department of Dermatology, Vanderbilt University Medical Center, Nashville, Tennessee, USA), Jeffrey P. Zwerner (MD, PhD, Department of Dermatology, Vanderbilt University Medical Center, Nashville, Tennessee, USA), Eva Rawlings Parker (MD, Department of Dermatology, Vanderbilt University Medical Center, Nashville, Tennessee, USA)Includes bibliographical reference

Differential induction of nuclear factor-like 2 signature genes with toll-like receptors stimulation

Inflammation is associated with production of reactive oxygen species (ROS) and results in the induction of thioredoxin (TXN) and peroxiredoxins (PRDXs) and activation of nuclear factor-like 2 (Nrf2). In this study we have used the mouse RAW 264.7 macrophage and the human THP-1 monocyte cell line to investigate the pattern of expression of three Nrf2 target genes, PRDX1, TXN reductase (TXNRD1) and heme oxygenase (HMOX1), by activation of different Toll-like receptors (TLR). We found that, while the TLR4 agonist lipopolysaccharide (LPS) induces all three genes, the pattern of induction with agonists for TLR1/2, TLR3, TLR2/6 and TLR7/8 differs depending on the gene and the cell line. In all cases, the extent of induction was HMOX1>TXNRD1>PRDX1. Since LPS was a good inducer of all genes in both cell lines, we studied the mechanisms mediating LPS induction of the three genes using mouse RAW 264.7 cells. To assess the role of ROS we used the antioxidant N-acetylcysteine (NAC). Only LPS induction of HMOX1 was inhibited by NAC while that of TXNRD1 and PRDX1 was unaffected. These three genes were also induced by phorbol myristate acetate (PMA), a ROS-inducer acting by activation of protein kinase C (PKC). The protein kinase inhibitor staurosporine inhibited the induction of all three genes by PMA but only that of HMOX1 by LPS. This indicates that activation of these genes by inflammatory agents is regulated by different mechanisms involving either ROS or protein kinases, or both

Identification of transcriptional networks responding to pyrroloquinoline quinone dietary supplementation and their influence on thioredoxin expression, and the JAK/STAT and MAPK pathways

PQQ (pyrroloquinoline quinone) improves energy utilization and reproductive performance when added to rodent diets devoid of PQQ. In the present paper we describe changes in gene expression patterns and transcriptional networks that respond to dietary PQQ restriction or pharmacological administration. Rats were fed diets either deficient in PQQ (PQQ−) or supplemented with PQQ (approx. 6 nmol of PQQ/g of food; PQQ+). In addition, groups of rats were either repleted by administering PQQ to PQQ− rats (1.5 mg of PQQ intraperitoneal/kg of body weight at 12 h intervals for 36 h; PQQ−/+) or partially depleted by feeding the PQQ− diet to PQQ+ rats for 48 h (PQQ+/−). RNA extracted from liver and a Codelink® UniSet Rat I Bioarray system were used to assess gene transcript expression. Of the approx. 10000 rat sequences and control probes analysed, 238 were altered at the P<0.01 level by feeding on the PQQ− diet for 10 weeks. Short-term PQQ depletion resulted in changes in 438 transcripts (P<0.01). PQQ repletion reversed the changes in transcript expression caused by PQQ deficiency and resulted in an alteration of 847 of the total transcripts examined (P<0.01). Genes important for cellular stress (e.g. thioredoxin), mitochondriogenesis, cell signalling [JAK (Janus kinase)/STAT (signal transducer and activator of transcription) and MAPK (mitogen-activated protein kinase) pathways] and transport were most affected. qRT-PCR (quantitative real-time PCR) and functional assays aided in validating such processes as principal targets. Collectively, the results provide a mechanistic basis for previous functional observations associated with PQQ deficiency or PQQ administered in pharmacological amounts

Apšvietimas kaip architektūros modernumo simbolis

The paper is designed to reveal the aesthetics of artificial lighting and its influence on the architecture of the 20th century. The main topics discussed are electric lighting, which appeard in our history at the end of the 19th century, and the technical development of lighting till the middle of the 20th century. Connections of artificial lighting with visual arts, its influence on advertisement, building architecture and the whole city are analysed. An idea is proposed that although lighting by nature was purely functional, very soon it acquired symbolic ambitions to represent architecture. In modern times architects understood that lighting was both a technological development and a symbol of a new era, when there appeared an independent field of creation - lighting architecture. Santrauka Straipsnyje nagrinėjama dirbtinio apšvietimo estetika ir jos įtaka XX a. architektūrai. Išryškinta XIX a. pabaigoje atsiradusio elektrinio apšvietimo svarba ir atskleista apšvietimo techninė raida iki XX a. vidurio. Nagrinėjamos dirbtinio apšvietimo sąsajos su vizualiaisiais menais, apšvietimo įtaka reklamai, pastatų architektūrai bei visam miestui. Straipsnyje keliama idėja, kad nors apšvietimo prigimtis pradžioje buvo grynai funkcionali, ji greitai įgavo simbolinių ambicijų – reprezentuoti architektūrą. Architektai į apšvietimą žvelgė ne tik kaip į technologinę pažangą, tai buvo naują erą ženklinantis simbolis, erą, kurioje atsiranda didelės įtakos visoms kūrybinėms idėjoms turinti nauja savarankiška kūrybos sritis – šviesos architektūra. First Published Online: 22 May 2013 Reikšminiai žodžiai: meninis, dirbtinis, elektrinis apšvietimas, stiklo, šviesos architektūra, modernumas

Enhanced Platelet-activating Factor synthesis facilitates acute and delayed effects of ethanol intoxicated thermal burn injury

Thermal burn injuries in patients alcohol intoxicated result in greater morbidity and mortality. Murine models combining ethanol and localized thermal burn injury reproduce the systemic toxicity seen in human subjects, which consists of both acute systemic cytokine production with multiple organ dysfunction, as well as a delayed systemic immunosuppression. However, the exact mechanisms for these acute and delayed effects are unclear. These studies sought to define the role of the lipid mediator Platelet-activating factor (PAF) in the acute and delayed effects of intoxicated burn injury. Combining ethanol and thermal burn injury resulted in increased enzymatic PAF generation in a keratinocyte cell line in vitro, human skin explants ex vivo, as well as in murine skin in vivo. Further, the acute increase in inflammatory cytokines such as IL-6, and the systemic immunosuppressive effects of intoxicated thermal burn injury, were suppressed in mice lacking PAF receptors. Together, these studies provide a potential mechanism and novel treatment strategies for the augmented toxicity and immunosuppressive effects of thermal burn injury in the setting of acute ethanol exposure, which involves the pleotropic lipid mediator PAF

Distinct Roles of Bcl-2 and Bcl-Xl in the Apoptosis of Human Bone Marrow Mesenchymal Stem Cells during Differentiation

Background: Adult mesenchymal stem cells (MSCs) can be maintained over extended periods of time before activation and differentiation. Little is known about the programs that sustain the survival of these cells. Principal Findings: Undifferentiated adult human MSCs (hMSCs) did not undergo apoptosis in response to different cell death inducers. Conversely, the same inducers can readily induce apoptosis when hMSCs are engaged in the early stages of differentiation. The survival of undifferentiated cells is linked to the expression of Bcl-Xl and Bcl-2 in completely opposite ways. Bcl-Xl is expressed at similar levels in undifferentiated and differentiated hMSCs while Bcl-2 is expressed only in differentiated cells. In undifferentiated hMSCs, the down-regulation of Bcl-Xl is associated with an increased sensitivity to apoptosis while the ectopic expression of Bcl-2 induced apoptosis. This apoptosis is linked to the presence of cytoplasmic Nur 77 in undifferentiated hMSCs. Significance: In hMSCs, the expression of Bcl-2 depends on cellular differentiation and can be either pro- or anti-apoptotic. Bcl-Xl, on the other hand, exhibits an anti-apoptotic activity under all conditions

Disgust sensitivity relates to attitudes toward gay men and lesbian women across 31 nations

Previous work has reported a relation between pathogen-avoidance motivations and prejudice toward various social groups, including gay men and lesbian women. It is currently unknown whether this association is present across cultures, or specific to North America. Analyses of survey data from adult heterosexuals ( N = 11,200) from 31 countries showed a small relation between pathogen disgust sensitivity (an individual-difference measure of pathogen-avoidance motivations) and measures of antigay attitudes. Analyses also showed that pathogen disgust sensitivity relates not only to antipathy toward gay men and lesbians, but also to negativity toward other groups, in particular those associated with violations of traditional sexual norms (e.g., prostitutes). These results suggest that the association between pathogen-avoidance motivations and antigay attitudes is relatively stable across cultures and is a manifestation of a more general relation between pathogen-avoidance motivations and prejudice towards groups associated with sexual norm violations