Impetigo‐Like Tinea Faciei Around the Nostrils Caused by Arthroderma vanbreuseghemii Identified Using Polymerase Chain Reaction–Based Sequencing of Crusts

We report a case of Arthroderma vanbreuseghemii (a teleomorph of Trichophyton interdigitale) infection around the nostrils in a 3‐year‐old girl. The culture was negative, so the pathogenic agent was identified using polymerase chain reaction–based sequencing of the crusts taken from the lesion on the nostril. Treatment with oral itraconazole and topical 1% naftifine/0.25% ketoconazole cream after a topical wash with ketoconazole shampoo was effective.     

Socialization Patterns and Their Associations with Unprotected Anal Intercourse,HIV, and Syphilis Among High-Risk Men Who Have Sex with Men and Transgender Women in Peru

The association of socialization patterns with unprotected anal intercourse (UAI) and HIV/STI prevalence remains underexplored in men who have sex with men (MSM) and transgender women (TW) in developing country settings. We evaluated the correlation of UAI, HIV, and syphilis with MSM/TW venue attendance and social network size among high-risk MSM and TW in Peru according to self-reported sexual identity. Frequency of venue attendance and MSM/TW social network size were lowest among heterosexual MSM and highest among TW respondents. Attendance (frequent or occasional) at MSM/TW venues was associated with increased odds of insertive UAI among heterosexual participants. Frequent venue attendance was associated with increased odds of receptive UAI among gay/homosexual, bisexual, and TW participants. Further investigation of the differing socialization patterns and associations with HIV/STI transmission within subgroups of Peruvian MSM and TW will enable more effective prevention interventions for these populations.     

Cytochrome P450-generated metabolites derived from ω-3 fatty acids attenuate neovascularization

Ocular neovascularization, including age-related macular degeneration (AMD), is a primary cause of blindness in individuals of industrialized countries. With a projected increase in the prevalence of these blinding neovascular diseases, there is an urgent need for new pharmacological interventions for their treatment or prevention. Increasing evidence has implicated eicosanoid-like metabolites of long-chain polyunsaturated fatty acids (LCPUFAs) in the regulation of neovascular disease. In particular, metabolites generated by the cytochrome P450 (CYP)–epoxygenase pathway have been shown to be potent modulators of angiogenesis, making this pathway a reasonable previously unidentified target for intervention in neovascular ocular disease. Here we show that dietary supplementation with ω-3 LCPUFAs promotes regression of choroidal neovessels in a well-characterized mouse model of neovascular AMD. Leukocyte recruitment and adhesion molecule expression in choroidal neovascular lesions were down-regulated in mice fed ω-3 LCPUFAs. The serum of these mice showed increased levels of anti-inflammatory eicosanoids derived from eicosapentaenoic acid and docosahexaenoic acid. 17,18-epoxyeicosatetraenoic acid and 19,20-epoxydocosapentaenoic acid, the major CYP-generated metabolites of these primary ω-3 LCPUFAs, were identified as key lipid mediators of disease resolution. We conclude that CYP-derived bioactive lipid metabolites from ω-3 LCPUFAs are potent inhibitors of intraocular neovascular disease and show promising therapeutic potential for resolution of neovascular AMD.Angiogenesis plays a central role in many diseases, including age-related macular degeneration (AMD), a leading cause of blindness. Advanced AMD exists in two forms, “atrophic” and “neovascular,” which are defined by the absence or presence of choroidal neovascularization (CNV), respectively (1). Neovascular AMD is characterized by the formation of abnormal blood vessels that grow from the choroidal vasculature, through breaks in Bruch’s membrane, toward the outer retina (1). These vessels generally are immature in nature and leak fluid below or within the retina (2). Although growth factors are thought to play an important role in the late stage of neovascular AMD progression, they likely do not contribute to the underlying cause of the disease. The current standard of care for individuals with neovascular AMD is based on the targeting of VEGF, which promotes both angiogenesis and vascular permeability (3). However, although VEGF-targeted therapy attenuates angiogenesis and vascular permeability, it does not lead to complete vascular regression or disease resolution (3).The ω-3 and ω-6 long-chain polyunsaturated fatty acids (LCPUFAs) are two classes of dietary lipids that are essential fatty acids and have opposing physiological effects. The ω-6 LCPUFA, arachidonic acid (AA), and its cytochrome P450 (CYP)-generated metabolites (epoxyeicosatrienoic acids, EETs) recently have attracted much attention as a result of increasing evidence that they play a role in cancer as well as in cardiovascular disease (4–9). EETs are part of the VEGF-activated signaling cascade leading to angiogenesis (10) and promote tumor growth and metastasis (11). The major dietary ω-3 LCPUFAs are docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), which are highly enriched in the central nervous system including the retina (12). The ω-3 LCPUFAs have antithrombotic, antiangiogenic, and anti-inflammatory properties, and they compete with ω-6 LCPUFAs as substrates for synthesis of downstream metabolites by CYP enzymes, cyclooxygenases (COX), and lipoxygenases (LOX) (6, 13–15). Moreover, dietary enrichment with ω-3 LCPUFAs has been shown to protect against pathological angiogenesis-associated cancer and retinopathy (2, 16–19). Of the three main pathways (COX, LOX, and CYP) involved in eicosanoid biosynthesis, the lipid mediators derived from the CYP branch are the most susceptible to changes in dietary fatty acid composition (20–23). The ω-3 double bond that distinguishes DHA and EPA from their ω-6 counterparts provides a preferred epoxidation site for specific CYP family members (20, 22). In fact, most CYP isoforms can metabolize EPA and DHA with significantly higher catalytic efficiency than AA, making them uniquely susceptible to variations in the availability of these lipids (19–22). CYP epoxygenases target the ω-3 double bond, resulting in an accumulation of 17,18-epoxyeicosatetraenoic acid (17,18-EEQ) derived from EPA and 19,20-epoxydocosapentaenoic acid (19,20-EDP) from DHA (20, 22). Very recently, it was recognized that19,20-EDP inhibits angiogenesis, tumor growth, and metastasis (24). Thus, it appears that the CYP–epoxygenase pathway has the capacity to produce proangiogenic metabolites from ω-6 LCPUFAs (10, 11) and antiangiogenic metabolites from ω-3 LCPUFAs (24). This unique feature of the CYP enzymes may provide a previously unidentified mechanistic link between the ω-6/ω-3 ratio of dietary LCPUFAs and pathological angiogenesis; however, their roles in ocular angiogenesis have been largely unexplored to date.We now show that dietary enrichment with ω-3 LCPUFAs suppresses CNV, vascular leakage, and immune cell recruitment to the lesion site in a mouse model of laser-induced CNV. We characterized the CYP-dependent pathway by which dietary ω-3 LCPUFAs promote resolution of choroidal neovessels in this model and identified CYP-generated metabolites 17,18-EEQ and 19,20-EDP as mediators of disease resolution. Furthermore, we show that expression of adhesion molecules at the CNV site was down-regulated in association with inhibition of leukocyte recruitment in mice receiving ω-3 LCPUFAs.     

Variables Associated with Stress Ulcer Prophylaxis Misuse: A Retrospective Analysis

Background

Stress ulcer prophylaxis (SUP) is commonly used in hospitals. Although its indications are better delineated for intensive care unit (ICU) patients, its use in non-ICU settings is somewhat arbitrary and based on judgment.

Objective

We attempted to assess the extent of SUP overuse in our hospital. We also carefully collected and analyzed several variables to detect associations governing this flawed behavior and its financial burden on the hospital’s budget.

Materials and Methods

We retrospectively analyzed charts of patients admitted to the medical floor of a tertiary referral university hospital over a 1 year period. All adult patients admitted to the medical ward who received at least one dose of SUP were included and reviewed for a multitude of variables in addition to the appropriateness of acid suppression therapy (AST).

Results

We included 320 charts and found that 92% of patients admitted during that period were not eligible for SUP. The total inappropriateness of SUP was noted to be 58% (p = 0.015). Increasing age and male gender were found to be significant variables in AST misuse (p = 0.045 and p = 0.010), much like duration of hospital stay (p = 0.008). Comorbidities was also found to be a defining variable for AST overuse (odds ratio [OR] = 3.27). Patients with two or more minor risk factors were also subjected more to SUP inappropriately (OR = 3.53), in addition to patients of certain specialties (Neurology, Infectious Diseases, etc.). Our calculated financial burden was more than $23,000 per year for the medical floor.

Conclusion

This retrospective study confirmed the growing suspicion that SUP misuse is evident on the medical floors. We also delineated several factors and variables associated with and affecting SUP overuse.     

Metabolic syndrome in Spain: prevalence and coronary risk associated with harmonized definition and WHO proposal. DARIOS study

Introduction and objectives

To update the prevalence of metabolic syndrome and associated coronary risk in Spain, using the harmonized definition and the new World Health Organization proposal (metabolic premorbid syndrome), which excludes diabetes mellitus and cardiovascular disease.

Methods

Individual data pooled analysis study of 24 670 individuals from 10 autonomous communities aged 35 to 74 years. Coronary risk was estimated using the REGICOR function.

Results

Prevalence of metabolic syndrome was 31% (women 29% [95% confidence interval, 25%-33%], men 32% [95% confidence interval, 29%-35%]). High blood glucose (P=.019) and triglycerides (P<.001) were more frequent in men with metabolic syndrome, but abdominal obesity (P<.001) and low high-density lipoprotein cholesterol (P=.001) predominated in women. Individuals with metabolic syndrome showed moderate coronary risk (8% men, 5% women), although values were higher (P<.001) than in the population without the syndrome (4% men, 2% women). Women and men with metabolic syndrome had 2.5 and 2 times higher levels of coronary risk, respectively (P<.001). Prevalence of metabolic premorbid syndrome was 24% and the increase in coronary risk was also proportionately larger in women than in men (2 vs 1.5, respectively; P<.001).

Conclusions

Prevalence of metabolic syndrome is 31%; metabolic premorbid syndrome lowers this prevalence to 24% and delimits the population for primary prevention. The increase in coronary risk is proportionally larger in women, in both metabolic syndrome and metabolic premorbid syndrome.Full English text available from:www.revespcardiol.org     

β-Cell Lipotoxicity in Response to Free Fatty Acid Elevation in Prepubertal Youth: African American Versus Caucasian Contrast

Prepubertal African American (AA) youth compared with their Caucasian (C) peers have higher insulin secretion, which correlates positively with free fatty acid (FFA) concentration. In our continued efforts to explain the racial disparity in insulinemia, and because FFAs modulate insulin secretion, we hypothesized that AA youth would have a greater response to FFA-induced β-cell insulin secretion than C youth. We compared the short-term effects of FFA elevation on fasting and glucose-stimulated C-peptide–modeled insulin secretion in prepubertal normal-weight AA versus C peers during a 2-h hyperglycemic clamp (12.5 mmol/L) on two occasions: 1) infusion of normal saline and 2) infusion of 20% intralipid (IL). During IL infusion, insulin sensitivity (IS) declined comparably in AA and C youth. Glucose sensitivity of first- and second-phase insulin secretion showed a significant condition × race interaction being higher in AA youth. Disposition index, β-cell function relative to IS, declined with IL infusion in AA and C youth, with a significantly greater decrease in Cs compared with AAs. In conclusion, AA and C prepubertal youth both demonstrated a decline in β-cell function relative to IS during IL infusion, indicative of acute lipotoxicity. The greater decline in C youth compared with AAs may suggest that C youth are more susceptible to β-cell lipotoxicity than AA youth, or alternatively, that AA youth are hypersensitive to FFA stimulation of β-cell insulin secretion, consistent with our theory.Short-term exposure to elevated free fatty acid (FFA) concentrations has a stimulatory effect on β-cell function in in vitro and in vivo animal and human studies (1–8). On the other hand, chronic exposure to sustained elevations in FFAs has been shown to decrease insulin secretion and result in β-cell lipotoxicity in in vitro rat and human islet experiments (4,9,10) and in vivo human experiments (1,5,7,11,12).We previously found that prepubertal African American (AA) youth have higher insulin secretion and an upregulated β-cell function relative to insulin sensitivity (IS) compared with their Caucasian (C) peers (13). The hyperinsulinemic response in AA youth appears to be greater than the compensatory response to their lower IS, because the disposition index (DI), which is insulin secretion relative to IS, was ∼75% higher in AA than in C youth (13). Furthermore, first- and second-phase insulin concentrations during the hyperglycemic clamp correlated positively and significantly with fasting FFA levels in AAs but not Cs, despite similar plasma FFA concentrations (13). We therefore hypothesized that the higher insulin secretion in AA prepubertal youth could be driven by a greater sensitivity to the stimulatory effects of FFA on insulin secretion and β-cell function. Thus, in the present investigation we examined the effects of FFA elevation on glucose-stimulated insulin secretion in AA and C prepubertal normal-weight children, expecting to observe a heightened response in AA children.