Synthetic opioids such as fentanyl contribute to the vast majority of opioid-related overdose deaths, but fentanyl use remains broadly understudied. Like other substances with misuse potential, opioids cause lasting molecular adaptations to brain reward circuits, including neurons in the ventral tegmental area (VTA). The VTA contains numerous cell types that play diverse roles in opioid use and relapse; however, it is unknown how fentanyl experience alters the transcriptional landscape in specific subtypes.
View Article and Find Full Text PDFAlthough many viral infections are linked to the development of neurological disorders, the mechanism governing virus-induced neuropathology remains poorly understood, particularly when the virus is not directly neuropathic. Using a mouse model of Zika virus (ZIKV) infection, we found that the severity of neurological disease did not correlate with brain ZIKV titers, but rather with infiltration of bystander activated NKG2DCD8 T cells. Antibody depletion of CD8 or blockade of NKG2D prevented ZIKV-associated paralysis, suggesting that CD8 T cells induce neurological disease independent of TCR signaling.
View Article and Find Full Text PDFSynthetic opioids such as fentanyl contribute to the vast majority of opioid-related overdose deaths, but fentanyl use remains broadly understudied. Like other substances with misuse potential, opioids cause lasting molecular adaptations to brain reward circuits, including neurons in the ventral tegmental area (VTA). The VTA contains numerous cell types that play diverse roles in opioid use and relapse, however it is unknown how fentanyl experience alters the transcriptional landscape in specific subtypes.
View Article and Find Full Text PDFFollowing the recent outbreak of Zika virus (ZIKV) infections in Latin America, ZIKV has emerged as a global health threat due to its ability to induce neurological disease in both adults and the developing fetus. ZIKV is largely mosquito-borne and is now endemic in many parts of Africa, Asia, and South America. However, several reports have demonstrated persistent ZIKV infection of the male reproductive tract and evidence of male-to-female sexual transmission of ZIKV.
View Article and Find Full Text PDFDrug addiction is thought to be driven by negative reinforcement, and it is thought that a shift from positive affect upon initial exposure to negative affect after chronic exposure to a drug is responsible for maintaining self-administration (SA) in addicted individuals. This can be modeled in rats by analyzing ultrasonic vocalizations (USVs), a type of intraspecies communication indicative of affective state based on the frequency of the emission: calls in the 22 kHz range indicate negative affect, whereas calls in the 50 kHz range indicate positive affect. We employed a voluntary chronic, long-access model of fentanyl SA to analyze affective changes in the response to chronic fentanyl exposure.
View Article and Find Full Text PDFBackground: Keratoacanthomas (KAs) are common tumors of squamous cell origin that grow rapidly and may regress; however, differentiation from an aggressive squamous cell carcinoma is problematic.
Objective: To report the authors' experience in managing KA with intralesional methotrexate (MTX) or surgical excision.
Materials And Methods: The authors collected data on 157 tumors (136 patients) over 6 months from a single institution.
Cancer stem-like cells are hypothesized to be the major tumor-initiating cell population of human cutaneous squamous cell carcinoma (cSCC), but the landscape of molecular alterations underpinning their signaling and cellular phenotypes as drug targets remains undefined. In this study, we developed an experimental pipeline to isolate a highly enriched CD133CD31CD45CD61CD24 (CD133) cell population from primary cSCC specimens by flow cytometry. The CD133 cells show enhanced stem-like phenotypes, which were verified by spheroid and colony formation and tumor generation Gene expression profiling of CD133 cells was compared and validated, and differentially expressed gene signatures and top pathways were identified.
View Article and Find Full Text PDFDermatomyositis is an idiopathic inflammatory myopathy with characteristic skin manifestations. Although the disorder is rare, with a prevalence of one to 10 cases per million in adults and one to 3.2 cases per million in children, early recognition and treatment are important ways to decrease the morbidity of systemic complications.
View Article and Find Full Text PDFWe studied the safety and immunogenicity of a Shigella flexneri 2a vaccine comprising native S. flexneri 2a lipopolysaccharide (LPS) complexed to meningococcal outer membrane proteins-proteosomes-in normal, healthy adults. A two-dose series of immunizations was given by intranasal spray, and doses of 0.
View Article and Find Full Text PDFTranscutaneous immunization, a topical vaccine application, combines the advantages of needle-free delivery while targeting the immunologically rich milieu of the skin. In animal studies, this simple technique induces robust systemic and mucosal antibodies against vaccine antigens. Here, we demonstrate safe application of a patch containing heat-labile enterotoxin (LT, derived from Escherichia coli) to humans, resulting in robust LT-antibody responses.
View Article and Find Full Text PDFJ Am Acad Dermatol
August 2000
Sunscreen loses efficacy when used with the insect repellent N,N -diethyl-3-methylbenzamide (diethyltoluamide; deet). A previous study demonstrated a 33.3% decrease in sun protection factor when insect repellent and sunscreen were applied sequentially to the skin.
View Article and Find Full Text PDFBackground: The pursestring suture (PSS) utilizes a circumferentially placed intradermal suture to decrease the size of a defect. Its primary application in dermatologic surgery has been to allow placement of a smaller full-thickness skin graft and to enhance secondary intention wound healing.
Objective: To present our experience with 3 variations of the PSS.
Background: Primary aldosteronism (PA) is a disease associated with hypersecretion of aldosterone caused by an aldosterone-producing adrenal adenoma, bilateral adrenal hyperplasia, and, although rarely, by adrenal carcinoma. Arterial hypertension induces several cardiovascular alterations that yield a high cardiovascular risk. It has been shown that reduced myocardial perfusion at rest, assessed by thallium-201 myocardial scintigraphy, was greater in PA than in essential hypertension (EH).
View Article and Find Full Text PDFBackground: Confluent and reticulated papillomatosis (CRP) of Gougerot and Carteaud is an uncommon disorder of unknown cause for which a variety of treatments have been proposed.
Objective: We attempted to evaluate the effectiveness of oral minocycline.
Methods: Nine patients with CRP were treated with oral minocycline, 50 mg twice a day, for 6 weeks.
J Am Acad Dermatol
November 1995
Superficial papillary adenomatosis of the nipple is a benign tumor of the ductal epithelium that clinically resembles Paget's disease. Histologically, the tumor is characterized by proliferating ductal structures lined by a double layer of columnar epithelium. Keratin cysts and apical intraluminal projections are commonly found.
View Article and Find Full Text PDFPerianal dermatitis has been reported to be caused by group A beta-hemolytic Streptococcus. We present a case caused by Staphylococcus aureus. A clinical clue pointing to this organism was the presence of satellite pustules.
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