Serratia marcescens Necrotizing Fasciitis of the Ankle: A Case Report.

Necrotizing fasciitis is a devastating inflammatory infection requiring emergent medical treatment and surgical intervention. Even with timely management, the mortality rate of necrotizing fasciitis approaches 25%. The causative bacteria invade fascial planes and express toxins that advance rapidly. Here, we document a rare case of necrotizing fasciitis from Serratia marcescens infection. Serratia marcescens is capable of inducing a necrotizing inflammatory cascade mediated by extracellular cytotoxin and lipase. In this case report, a 90-year-old man presented to our emergency department from a long-term care facility with a relatively benign-appearing ulcer with surrounding cellulitis on the right ankle. Blood cultures and wound cultures confirmed the organism to be S marcescens. A multidisciplinary team was consulted for management. The patient received antibiotic therapy and medical support, but because of his comorbid conditions and social situation, the designated medical decision maker opted for comfort care rather than aggressive surgical debridement. The patient progressed through the clinical stages of necrotizing fasciitis. Within 36 hours, the patient died as result of sepsis-induced organ failure.

Mohs micrographic surgery: a treatment method for many non-melanocytic skin cancers.

Mohs micrographic surgery (MMS) is a breakthrough surgical technique that has changed the management of neoplasms in dermatology. Through continued practice and evolution, MMS now can successfully treat a variety of rare non-melanocytic cutaneous malignancies for which achieving remission and the optimal aesthetic result after surgery was previously challenging. Mohs micrographic surgery has utility for conditions besides melanoma. Herein, we discuss this versatility of Mohs micrographic surgery. Specifically, Mohs micrographic surgery can be successfully used for cases such as dermatofibrosarcoma protuberans, atypical fibroxanthomas, extramammary Paget disease, Merkel cell carcinoma, sebaceous carcinoma, and microcystic adnexal carcinoma.

Diet and acne: an exploratory survey study of patient beliefs.

BACKGROUND: In the past, medical literature reflected that diet was not a proven cause of acne. However, studies in recent years have substantiated a link between certain dietary factors and acne. It is unclear whether patients are aware of recent research findings. OBJECTIVES: Acne patients were surveyed to explore beliefs regarding the link between diet and acne, to determine whether these beliefs translated into behavior change and to identify health information sources. PATIENTS/METHODS: Upon Institutional Review Board (IRB) approval, surveys were administered to 50 acne patients at an academic dermatology clinic in 2014, with 49 completed in full and included in this analysis. RESULTS: Ninety-two percent of respondents believed that diet could affect acne. Seventy-one percent attempted to change their diet to improve acne. Seventy-one percent believed acne to be caused by fried or greasy foods, although chocolate (53%), dairy (47%), and soda drinks (35%) were highly implicated. Patients obtained information from Google searches (49%), dermatologists (43%), family members and TV (41% each), and medical websites (31%). CONCLUSIONS: In this exploratory study, patients reported utilizing a diversity of information sources, a majority from the Internet. In those surveyed, there was a persistence of long-held belief that fried/greasy foods and chocolate may serve as acne triggers, and less belief in trigger foods supported by recent research, including refined carbohydrates and sugar. Given the multiplicity of beliefs and utilized sources among acne patients in our survey, there is a need to establish up-to-date and reliable methods to educate patients on diet and acne.

Cutaneous Protothecosis in a Patient with Chronic Lymphocytic Leukemia: A Case Report and Literature Review.

Protothecosis is a rare infection, which has the potential to cause severe disease in patients with underlying immunosuppression. We describe a case of an elderly female with chronic lymphocytic leukemia (CLL), as well as other risk factors, who presented with pustular and erythematous plaques, initially presumed to be leukemia cutis. A biopsy with special stains revealed the lesions to be cutaneous protothecosis, thus presenting a most unusual concurrence of disease entities. The literature to date on this rare infection will be reviewed.

Chronic alcohol-induced hepatic insulin resistance and endoplasmic reticulum stress ameliorated by peroxisome-proliferator activated receptor-δ agonist treatment.

BACKGROUND AND AIM: Chronic alcoholic liver disease is associated with hepatic insulin resistance, dysregulated lipid metabolism with increased toxic lipid (ceramide) accumulation, lipid peroxidation, and oxidative and endoplasmic reticulum (ER) stress. Peroxisome-proliferator activated receptor (PPAR) agonists are insulin sensitizers that can restore hepatic insulin responsiveness in both alcohol and non-alcohol-related steatohepatitis. Herein, we demonstrate that treatment with a PPAR-δ agonist enhances insulin signaling and reduces the severities of ER stress and ceramide accumulation in an experimental model of ethanol-induced steatohepatitis. METHODS: Adult male Long Evans rats were pair fed with isocaloric liquid diets containing 0% or 37% ethanol (caloric) for 8 weeks. After 3 weeks on the diets, rats were treated with vehicle or PPAR-δ agonist twice weekly by i.p. injection. RESULTS: Ethanol-fed rats developed steatohepatitis with inhibition of signaling through the insulin and insulin-like growth factor-1 receptors, and Akt activated pathways. Despite continued ethanol exposure, PPAR-δ agonist co-treatments increased Akt activation, reduced multiple molecular indices of ER stress and steatohepatitis. CONCLUSIONS: These results suggest that PPAR-δ agonist rescue of chronic alcoholic liver disease is mediated by enhancement of insulin signaling through Akt/metabolic pathways that reduce lipotoxicity and ER stress.

Motor Function Deficits Following Chronic Prenatal Ethanol Exposure are Linked to Impairments in Insulin/IGF, Notch and Wnt Signaling in the Cerebellum.

BACKGROUND: Fetal alcohol spectrum disorder (FASD) is associated with deficits in cerebellar function that can persist through adolescence. Previous studies demonstrated striking inhibition of insulin and insulin-like growth factor (IGF) signaling in ethanol-exposed cerebella. OBJECTIVES: We sought to determine if FASD-induced impairments in motor function were associated with deficits in insulin/IGF signaling in juvenile cerebella. Given the growing evidence that insulin/IGF pathways cross-talk with Notch and Wnt to promote brain development and maturation; we also examined the integrity of canonical Wnt and Notch signaling networks in the brain following chronic prenatal ethanol exposure. METHODS: Pregnant Long Evans rats were fed isocaloric liquid diets containing 0% or 24% ethanol by caloric content from gestation day 6 through delivery. Pups were subjected to rotarod testing on postnatal days (P) 15-16 and sacrificed on P30. Cerebella were used for molecular and biochemical analysis of insulin/IGF-1, canonical Wnt, and Notch signaling mechanisms. RESULTS: Prenatal ethanol exposures impaired rotarod performance, inhibited signaling through insulin and IGF-1 receptors, IRS-1, and Akt, increased activation of GSK-3ß, and broadly suppressed genes mediating the canonical Wnt and Notch networks. CONCLUSIONS: Abnormalities in cerebellar function following chronic prenatal ethanol exposure are associated with inhibition of insulin/IGF, canonical Wnt, and Notch networks that cross-talk via GSK-3ß. Effective therapeutic measures for FASD may require multi-pronged support of interrelated signaling networks that regulate brain development.

Differences in the function of three conserved E-boxes of the muscle creatine kinase gene in cultured myocytes and in transgenic mouse skeletal and cardiac muscle.

The 1256-base pair enhancer-promoter of the mouse muscle creatine kinase gene includes three CAnnTG E-boxes that are conserved among mammals and have flanking and middle sequences conforming to consensus muscle regulatory factor binding sites. This study seeks to determine whether these E-boxes are critical for muscle creatine kinase expression in physiologically distinct muscles. Mutations of the "right" and "left" E-boxes in the enhancer decreased expression in cultured skeletal myocytes approximately 10- and 2-fold, respectively, whereas a "promoter" E-box mutation had little effect. In neonatal myocardiocytes, the left E-box mutation decreased expression approximately 3-fold, whereas right or promoter E-box mutations had no effect. Very different effects were seen in transgenic mice, where the promoter E-box mutation decreased expression in quadriceps, extensor digitorum longus, and soleus approximately 10-fold, and approximately 100-fold in distal tongue, diaphragm, and ventricle. The right E-box mutation, tested in the presence of the other two mutations, caused a significant decrease in distal tongue, but not in quadriceps, extensor digitorum longus, soleus, or ventricle. Mutation of the left E-box actually raised expression in soleus, suggesting a possible repressor role for this control element. The discrepancies between mutation effects in differentiating skeletal muscle cultures, neonatal myocardiocytes, and adult mice suggested that the E-boxes might play different roles during muscle development and adult steady-state function. However, transgenic analysis of embryonic and early postnatal mice indicated no positive role for these three E-boxes in early development, implying that differences in E-box function between adult muscle and cultured cells are the result of physiological signals.

Transgenic and tissue culture analyses of the muscle creatine kinase enhancer Trex control element in skeletal and cardiac muscle indicate differences in gene expression between muscle types.

The muscle creatine kinase (MCK) gene is expressed at high levels only in differentiated skeletal and cardiac muscle. The activity of the cloned enhancer-promoter has previously been shown to be dependent on the Trex element which is specifically bound by a yet unidentified nuclear factor, TrexBF. We have further characterized the function of the Trex site by comparing wild-type and Trex-mutated MCK transgenes in five mouse skeletal muscles: quadriceps, extensor digitorum longus (EDL), soleus, diaphragm, and distal tongue, as well as in heart ventricular muscle. Several types of statistical analysis including analysis of variance (ANOVA) and rank sum tests were used to compare expression between muscle types and between constructs. Upon mutation of the Trex site, median transgene expression levels decreased 3- to 120-fold in the muscles examined, with statistically significant differences in all muscles except the EDL. Expression in the largely slow soleus muscle was more affected than in the EDL, and expression in the distal tongue and diaphragm muscles was affected more than in soleus. Median expression of the transgene in ventricle decreased about 18-fold upon Trex mutation. Transfections into neonatal rat myocardiocytes confirmed the importance of the Trex site for MCK enhancer activity in heart muscle, but the effect is larger in transgenic mice than in cultured cells.