Patients' willingness to accept adverse event and cost tradeoffs from oral nicotinamide for reduced risk of non-melanoma skin cancer.

Background: Non-immunosuppressed patients with a history of multiple non-melanoma skin cancers (NMSCs) taking oral nicotinamide supplementation experienced a 23% decrease in annual NMSC risk in a randomized clinical trial. Patient preferences for risks and costs associated with nicotinamide are unknown.

Objectives: To understand how patients prioritize NMSC reduction, infection risk, and cost.

Collagenolysis-dependent DDR1 signalling dictates pancreatic cancer outcome.

Pancreatic ductal adenocarcinoma (PDAC) is a highly desmoplastic, aggressive cancer that frequently progresses and spreads by metastasis to the liver. Cancer-associated fibroblasts, the extracellular matrix and type I collagen (Col I) support or restrain the progression of PDAC and may impede blood supply and nutrient availability. The dichotomous role of the stroma in PDAC, and the mechanisms through which it influences patient survival and enables desmoplastic cancers to escape nutrient limitation, remain poorly understood.

The Association between Parents and Children Meeting Physical Activity Guidelines.

Purpose: To examine the association between parents and children meeting physical activity (PA) guidelines, by gender, among 8-12 year old children with BMI ≥75th percentile DESIGN AND METHODS: This was a secondary analysis of baseline data from a school-based healthy weight management intervention in Minnesota for 8-12 year old children. Survey data about PA participation were collected from 2014 through 2018. Analyses entailed descriptive statistics and multivariate logistic regression controlling for child age, race/ethnicity, BMIz, child's perception of parent support for activity, and number of sports played.

Biomolecular Analysis of Beta Dose-Dependent Cutaneous Radiation Injury in a Porcine Model.

While cutaneous radiation injury (CRI) is generally referenced as a consequence of a nuclear attack, it can also be caused by less dangerous events such as the use of dirty bombs, industrial radiological accidents, or accidental overexposure of beta (β) particle or gamma (γ) radiation sources in medical procedures. Although the gross clinical consequences of these injuries have been well documented, relatively little is known about the molecular changes underlying the progression of pathology. Here we describe a porcine model of cutaneous radiation injury after skin was exposed to strontium-90 b particle at doses of 16-42 Gy and characterize the anatomical and molecular changes over 70 days.

Pilot study of mitochondrial bioenergetics in subjects with acute porphyrias.

Background And Aims: The acute porphyrias are characterized by defects in heme synthesis, particularly in the liver. In some affected patients, there occurs a critical deficiency in a regulatory heme pool within hepatocytes that leads to up-regulation of 5-aminolevulinic acid [ALA] synthase-1, which is the first and normally rate-controlling enzyme in the pathway. In earlier work, we described defects in mitochondrial functions in cultured skin fibroblasts from patients with acute intermittent porphyria [AIP].

Safety of Intradermal/Subcutaneous Lidocaine With Epinephrine Use in Dermatologic Surgery.

Background: Recently, the safety of lidocaine plus epinephrine use in outpatient surgery has come under scrutiny despite its long history of use in outpatient dermatologic procedures and surgeries.

Objective: To assess the frequency of crash cart and other emergency interventions during Mohs micrographic surgery when lidocaine plus epinephrine is used as a local anesthetic and evaluate patient comorbidities associated with these events.

Materials And Methods: A retrospective chart review was conducted in an outpatient Mohs micrographic surgery clinic.

Alfalfa-derived HSP70 administered intranasally improves insulin sensitivity in mice.

Heat shock protein (HSP) 70 is an abundant cytosolic chaperone protein that is deficient in insulin-sensitive tissues in diabetes and unhealthy aging, and is considered a longevity target. It is also protective in neurological disease models. Using HSP70 purified from alfalfa and administered as an intranasal solution, we tested in whether the administration of Hsp70 to diet-induced diabetic mice would improve insulin sensitivity.

Identification and SAR of selective inducible nitric oxide synthase (iNOS) dimerization inhibitors.

We have identified and synthesized a series of imidazole containing dimerization inhibitors of inducible nitric oxide synthase (iNOS). The necessity of key imidazole and piperonyl functionality was demonstrated and SAR studies led to the identification of compound 35, which showed a dose dependant inhibition in multiple pain models, including tactile allodynia induced by spinal nerve ligation (Chung model).

Bridging the Gap Between Validation and Implementation of Non-Animal Veterinary Vaccine Potency Testing Methods.

In recent years, technologically advanced high-throughput techniques have been developed that replace, reduce or refine animal use in vaccine quality control tests. Following validation, these tests are slowly being accepted for use by international regulatory authorities. Because regulatory acceptance itself has not guaranteed that approved humane methods are adopted by manufacturers, various organizations have sought to foster the preferential use of validated non-animal methods by interfacing with industry and regulatory authorities.

KD5170, a novel mercaptoketone-based histone deacetylase inhibitor that exhibits broad spectrum antitumor activity in vitro and in vivo.

Histone deacetylase (HDAC) inhibitors have garnered significant attention as cancer drugs. These therapeutic agents have recently been clinically validated with the market approval of vorinostat (SAHA, Zolinza) for treatment of cutaneous T-cell lymphoma. Like vorinostat, most of the small-molecule HDAC inhibitors in clinical development are hydroxamic acids, whose inhibitory activity stems from their ability to coordinate the catalytic Zn2+ in the active site of HDACs.

Inhibition of inducible nitric oxide synthase expression by a novel small molecule activator of the unfolded protein response.

The transcription of inducible nitric oxide synthase (iNOS) is activated by a network of proinflammatory signaling pathways. Here we describe the identification of a small molecule that downregulates the expression of iNOS mRNA and protein in cytokine-activated cells and suppresses nitric oxide production in vivo. Mechanistic analysis suggests that this small molecule, erstressin, also activates the unfolded protein response (UPR), a signaling pathway triggered by endoplasmic reticulum stress.

Ovarian pregnancy after in vitro fertilization.

We report a rare ovarian pregnancy after in vitro fertilization and transcervical embryo transfer. Ultrasound guidance of embryo transfer does not eliminate the risk of this potentially lethal complication.

Matrix metalloproteinase (MMP)-7 activates MMP-8 but not MMP-13.

Matrix Metalloproteinases (MMPs) are a class of zinc-dependent enzymes that degrade extracellular matrix components, particularly collagen. MMPs have been implicated in a diverse list of pathological processes, including cancer and cardiovascular disease. Recent efforts to bring MMP inhibitors to clinical trials, however, have proved disappointing.

Dual roles for Mcm10 in DNA replication initiation and silencing at the mating-type loci.

Recent studies linking DNA replication proteins to transcriptional silencing suggest that some of the same mechanisms that facilitate the initiation of replication at origins might be involved in establishing repressed chromatin at silencer elements. Our ongoing studies of several mutants of the replication initiation factor Mcm10 of budding yeast revealed an associated defect in the production of mating type pheromones. This observation prompted us to look more directly at the effect of MCM10 mutations on the expression of a reporter gene in the mating type locus and to assay for physical interactions between Mcm10 and known silencing factors.

HIF-1 in cell cycle regulation, apoptosis, and tumor progression.

Cells in a low oxygen, or hypoxic, microenvironment must have the ability to sense oxygen levels in the nucleus in order to maintain oxygen homeostasis by gene regulation. Hypoxia inducible factor-1 (HIF-1) serves as a molecular bridge between the sensation and utilization of oxygen, and thus functions as a key player in oxygen homeostasis. HIF-1 is a heterodimeric transcription factor and is composed of two subunits, the oxygen-sensitive HIF-1alpha and constitutively expressed HIF-1beta.

Morphological changes in blood vessels produced by hyperosmotic agents and measured by optical coherence tomography.

Optical tissue clearing by hyperosmotic chemical agents significantly increases light depth penetration in skin and may improve light-based therapeutics such as laser treatment of cutaneous vascular lesions. A feasibility study was conducted to evaluate the potential role of optical clearing by glycerol in laser treatment of cutaneous vessels. Optical imaging was performed to investigate the morphological effects of glycerol on blood vessels of skin.

Using nursing students to enhance one college's immunization program.

In New York State, all college students who were born on or after January 1, 1957, are required to show proof of immunity against measles, mumps, and rubella (MMR) before the 1st day of classes. Colleges have established immunization programs so that those students who do not have the required proof can be given the necessary injections. Often, our health service office does not have enough staff to administer the MMR shots during the registration period, resulting in long lines of students waiting to be immunized.

Photofrin photodynamic therapy for treatment of AIDS-related cutaneous Kaposi's sarcoma.

Objective: Kaposi's sarcoma, the most common malignancy in AIDS patients, often presents with painful cutaneous lesions that are difficult to treat effectively despite a wide variety of therapeutic approaches. We used photodynamic therapy in an attempt to provide effective palliative treatment for this disease.

Methods: Photodynamic therapy utilizes the activation by light of a photosensitizing drug that preferentially accumulates in tumor tissue such as Kaposi's sarcoma.

Bacteriology of inflamed and uninflamed epidermal inclusion cysts.

Objective: To determine whether inflamed and uninflamed epidermoid cysts differ in the number and/or type of bacteria inhabiting them.

Design: A controlled study. We obtained aerobic and anaerobic bacterial culture specimens from 25 inflamed and 25 uninflamed epidermoid cysts.

Beachfront screening for skin cancer in Texas Gulf coast surfers.

Skin cancer screening programs may attract the "worried well," while those at greatest risk for skin cancer are less likely to attend. Our purpose was to compare the results of skin cancer screening examinations between persons participating in the 1992 American Academy of Dermatology-sponsored free skin cancer screening and surfers participating in a free beachfront skin cancer screening held in conjunction with a regional surfing competition. The hypothesis was that screening an at-risk population (ie, surfers) would be more productive in terms of incidence of clinically diagnosed malignant skin lesions.

Lymphoepithelioma-like carcinoma of the skin treated by Mohs micrographic surgery.

Background: Lymphoepithelioma-like carcinoma of the skin (LELCS) is a rare malignant tumor thought to be of adnexal origin. Because of its rarity, treatment parameters have not been defined.

Objective: To examine the role and success of Mohs micrographic surgery in the treatment of LELCS versus other forms of treatment previously documented in the literature.

Development of human papillomavirus type 16 associated squamous cell carcinoma of the scrotum in a patient with Darier's disease treated with systemic isotretinoin.

In contrast to squamous cell carcinoma of the penis, scrotal carcinoma has historically been associated with exposure to environmental or industrial carcinogens and has only rarely been correlated with human papillomavirus. We report on a patient with squamous cell carcinoma of the scrotum in which human papillomavirus type 16 was integrated into the tumor cell genome, suggesting a causal role of human papillomavirus in the development of squamous cell carcinoma of the scrotum. Other unique features of our case include the presence of Darier's disease, an uncommon genodermatosis, and treatment with oral retinoids, which have prophylactic value in the prevention of cutaneous malignancies.