Pilot Study of the Effects of Paced Breathing on Measures of Convergent and Divergent Thinking.

BACKGROUND: The ability of the autonomic nervous system's stress response to impair aspects of cognitive flexibility is known. However, the ability to modulate the sympathetic response and improve these cognitive impairments via nonpharmacological intervention, such as paced breathing (PB), requires further investigation. OBJECTIVE: To better elucidate the effects of PB on cognition. METHOD: We employed a PB protocol in a total of 52 healthy men and women and measured performance on convergent and divergent cognitive tasks, perceived stress, and physiological measures (eg, blood pressure, heart rate). Participants attended two experimental sessions consisting of either PB or normal breathing followed by cognitive assessments including convergent (compound remote associate, anagram) and divergent (alternate use, fluency) tasks. Experiment 2 consisted of more difficult versions of cognitive tasks compared with Experiment 1. RESULTS: In Experiment 1, PB significantly reduced the female participants' systolic and diastolic blood pressure immediately after the breathing protocol without affecting their cognition. In Experiment 2, PB significantly reduced perceived stress immediately after the breathing protocol, regardless of sex. There was no effect on cognition in Experiment 2, but a correlation was observed between perceived stress change and anagram number solved change. CONCLUSION: While PB modulates sympathetic activity in females, there was a lack of improvement in cognitive flexibility performance. At least for a single trial of PB, cognitive flexibility did not improve.

Advanced basal cell carcinoma: What dermatologists need to know about treatment.

The treatment of advanced basal cell carcinoma (BCC) often requires therapies beyond local surgical excision or radiation due to the invasiveness of the tumor. Historically, cytotoxic chemotherapy was used to treat advanced BCC, but with limited data, no standard regimens were established. The discovery of cyclopamine, a natural inhibitor in the Hedgehog pathway, led to the development of the 2 currently approved Hedgehog inhibitors, vismodegib and sonidegib. Both agents are indicated for locally advanced BCC, while vismodegib is also indicated for metastatic BCC. In patients who progress on hedgehog inhibitors or cannot tolerate hedgehog inhibitors, the programmed cell death protein 1 inhibitor cemiplimab can be used to treat locally advanced or metastatic disease. Complex cases of locally advanced or metastatic BCC may be best discussed through a multidisciplinary approach in order to determine the optimal treatment approach for the individual patient.

Chemical Profiling of A-to-I RNA Editing Using a Click-Compatible Phenylacrylamide.

Straightforward methods for detecting adenosine-to-inosine (A-to-I) RNA editing are key to a better understanding of its regulation, function, and connection with disease. We address this need by developing a novel reagent, N-(4-ethynylphenyl)acrylamide (EPhAA), and illustrating its ability to selectively label inosine in RNA. EPhAA is synthesized in a single step, reacts rapidly with inosine, and is "click"-compatible, enabling flexible attachment of fluorescent probes at editing sites. We first validate EPhAA reactivity and selectivity for inosine in both ribonucleosides and RNA substrates, and then apply our approach to directly monitor in vitro A-to-I RNA editing activity using recombinant ADAR enzymes. This method improves upon existing inosine chemical-labeling techniques and provides a cost-effective, rapid, and non-radioactive approach for detecting inosine formation in RNA. We envision this method will improve the study of A-to-I editing and enable better characterization of RNA modification patterns in different settings.

Bim expression in endothelial cells and pericytes is essential for regression of the fetal ocular vasculature.

Apoptosis plays a central role in developmental and pathological angiogenesis and vessel regression. Bim is a pro-apoptotic Bcl-2 family member that plays a prominent role in both developmental and pathological ocular vessel regression, and neovascularization. Endothelial cells (EC) and pericytes (PC) each play unique roles during vascular development, maintenance and regression. We recently showed that germline deletion of Bim results in persistent hyaloid vasculature, increased retinal vascular density and prevents retinal vessel regression in response to hyperoxia. To determine whether retinal vascular regression is attributable to Bim expression in EC or PC we generated mice carrying a conditional Bim allele (BimFlox/Flox) and VE-cadherin-cre (BimEC mice) or Pdgfrb-cre (BimPC mice). BimEC and BimPC mice demonstrated attenuated hyaloid vessel regression and postnatal retinal vascular remodeling. We also observed decreased retinal vascular apoptosis and proliferation. Unlike global Bim -/- mice, mice conditionally lacking Bim in EC or PC underwent hyperoxia-mediated vessel obliteration and subsequent retinal neovascularization during oxygen-induced ischemic retinopathy similar to control littermates. Thus, understanding the cell autonomous role Bim plays in the retinal vascular homeostasis will give us new insight into how to modulate pathological retinal neovascularization and vessel regression to preserve vision.

A Retrospective Case-Matched Cost Comparison of Surgical Treatment of Melanoma and Nonmelanoma Skin Cancer in the Outpatient Versus Operating Room Setting.

BACKGROUND: To date, no study has used authentic billing data in a case-control matched fashion to examine the cost of treating skin cancer in different settings. OBJECTIVE: To compare the cost of surgical treatment of skin cancer in the outpatient versus operating room setting using matched cases based on patient and skin cancer characteristics. METHODS: ICD-9 diagnosis codes for skin cancers were used to find patients who had a malignant excision current procedural terminology code in the operating room setting during 2010 to 2014. Patient and skin cancer characteristics were used to match cases to those treated as an outpatient. A total of 36 cases (18 operating room and 18 outpatient) had the required information and characteristics to be matched and analyzed for cost. Health status was determined using the American Society of Anesthesiologists anesthesia grading scale. RESULTS: No statistically significant differences were found in the age (p > 0.9) or American Society of Anesthesiologists scores (p > 0.6) of the outpatient and operating room cases. The median cost for outpatient cases was $1,745. For operating room cases, the median cost was $11,323. This was a statistically significant difference (p < 0.001). CONCLUSION: The outpatient setting remains a cost-effective location to treat skin cancer compared with the operating room.

Endothelium Expression of Bcl-2 Is Essential for Normal and Pathological Ocular Vascularization.

Bcl-2 is an anti-apoptotic protein with important roles in vascular homeostasis and angiogenesis. Mice globally lacking Bcl-2 (Bcl-2 -/-) are small in stature and succumb to renal failure shortly after weaning as a result of renal hypoplasia/cystic dysplasia. We have shown that Bcl-2 -/- mice displayed attenuated retinal vascular development and neovascularization. In vitro studies indicated that in addition to modulating apoptosis, Bcl-2 expression also impacts endothelial and epithelial cell adhesion, migration and extracellular matrix production. However, studies delineating the cell autonomous role Bcl-2 expression plays in the endothelium during vascular development, pruning and remodeling, and neovascularization are lacking. Here we generated mice carrying a conditional Bcl-2 allele (Bcl-2Flox/Flox) and VE-cadherin-cre (Bcl-2EC mice). Bcl-2EC mice were of normal stature and lifespan and displayed some but not all of the retinal vascular defects previously observed in global Bcl-2 deficient mice. Bcl-2EC mice had decreased numbers of endothelial cells, decreased retinal arteries and premature primary branching of the retinal vasculature, but unlike the global knockout mice, spreading of the retinal superficial vascular layer proceeded normally. Choroidal neovascularization was attenuated in Bcl-2EC mice, although retinal neovascularization accompanying oxygen-induced ischemic retinopathy was not. Thus, Bcl-2 expression in the endothelium plays a significant role during postnatal retinal vascularization, and pathological choroidal but not retinal neovascularization, suggesting vascular bed specific Bcl-2 function in the endothelium.

Pruritic rash on trunk.

The patient had been treated with topical antifungals and steroids without relief, but a more detailed history suggested a serious infectious etiology.

Renal medullary carcinoma metastatic to the scalp.

A 40-year-old woman presented to the Brooke Army Medical Center Emergency Department complaining of 2 episodes of gross hematuria. Computed tomography and intravenous pyelogram revealed a right renal mass. A radical nephrectomy was performed with complete excision of the mass with negative margins on histological examination. The patient was diagnosed with renal medullary carcinoma, Fuhrman grade 4, based upon histological examination. A positron emission tomography scan revealed no other evidence of the disease. The pathologic stage was stage I renal medullary carcinoma. Four months after her nephrectomy, the patient developed a papule on her right frontal scalp. Initially thought to be a cyst, the papule increased in size over the course of 2 months and eventually ulcerated. At that time, she presented to the Wilford Hall Medical Center Dermatology Clinic with a 2.5-cm ulcerated tumor with pink rolled borders. A punch biopsy of the tumor revealed an infiltrating carcinoma with scattered glandular lumina and desmoplastic and mucinous stroma. The carcinoma was completely intradermal. Expert consultation confirmed the diagnosis of metastatic renal medullary carcinoma. Clear cell (conventional) and papillary renal cell carcinomas are known to metastasize to the skin, including the scalp. Renal medullary carcinoma commonly metastasizes to the regional lymph nodes, lung, liver, or adrenals. To our knowledge, this is the first report of a cutaneous metastasis of renal medullary carcinoma.

Subcutaneous nodules with sporotrichoid spread.

BACKGROUND: Mycobacterium marinum is an atypical mycobacterium found worldwide and associated with swimming pools and aquariums. Infections typically present with subcutaneous nodules and lymphangitis. CASE REPORT: A 61-year-old female presented with a two-month history of subcutaneous nodules. The patient had a significant recent history that included rose gardening and cleaning her aquarium at home. Biopsy for histology and tissue culture proved the presence of infection with Mycobacterium marinum and the patient was treated with minocycline. The nodules eventually healed and no new lesions appeared after initiation of treatment. CONCLUSION: Mycobacterium marinum is one of many entities that must be considered in a patient with ascending nodules along the lymphatic drainage of an extremity.

Mycobacterium marinum infection: a case report and review of the literature.

Mycobacterium marinum is a nontuberculous mycobacteria that is often acquired via contact with contaminated salt or fresh water. We present a case of a 67-year-old man who developed several solitary nontender nodules on his hands and forearm after working on the underside of his boat. In addition, we provide a review of the literature and discuss how this infection is acquired, the underlying pathogenesis, the cutaneous and histologic findings, the differential diagnosis, the diagnostic methods, and the various treatment options.