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Do you get red and itchy rashes that just do not seem to go away? You may have atopic dermatitis, sometimes called eczema, the most common skin disease in children and teenagers. In this article, we describe how to recognize eczema and what causes it. Then we discuss the various treatments for eczema and strategies to help prevent it. Finally, we discuss the impact eczema can have on a person’s life.

The coronavirus disease 2019 (COVID-19) pandemic necessitated shifts in education delivery, forcing professional development specialists toward alternative learning delivery methods. Members of an academic-practice partnership at a Midwestern hospital collaboratively designed virtual evidence-based education modules for staff onboarding. We describe the transition from in-person education to online professional development. [ J Contin Educ Nurs . 2021;52(9):404–406.]

The COVID-19 pandemic has caused significant shifts in patient care including a steep decline in ambulatory visits and a marked increase in the use of telemedicine. Infantile hemangiomas (IH) can require urgent evaluation and risk stratification to determine which infants need treatment and which can be managed with continued observation. For those requiring treatment, prompt initiation decreases morbidity and improves long-term outcomes. The Hemangioma Investigator Group has created consensus recommendations for management of IH via telemedicine. FDA/EMA-approved monitoring guidelines, clinical practice guidelines, and relevant, up-to-date publications regarding initiation and monitoring of beta-blocker therapy were used to inform the recommendations. Clinical decision-making guidelines about when telehealth is an appropriate alternative to in-office visits, including medication initiation, dosage changes, and ongoing evaluation, are included. The importance of communication with caregivers in the context of telemedicine is discussed, and online resources for both hemangioma education and propranolol therapy are provided.

Statistically Speaking Lecture Series sponsored by the Biostatistics Collaboration Center (BCC). Presented virtually on May 11, 2020.

The African Region is committed to measles elimination by 2020 but coverage with the first dose of measles-containing vaccine was only 70% in 2017. Several obstacles to achieving high coverage with measles and rubella vaccines exist, some of which could be overcome with new vaccine delivery technologies. Microarray array patches (MAPs) are single-dose devices used for transcutaneous administration of molecules, including inactivated or attenuated vaccines, that penetrate the outer stratum corneum of the skin, delivering antigens to the epidermis or dermis. MAPs to deliver measles and rubella vaccines have the potential to be a transformative technology to achieve elimination goals in the African Region. MAPs for measles and rubella vaccination have been shown to be safe, immunogenic and thermostable in preclinical studies but results of clinical studies in humans have not yet been published. This review summarizes the current state of knowledge of measles and rubella MAPs, their potential advantages for immunization programs in the African Region, and some of the challenges that must be overcome before measles and rubella MAPs are available for widespread use.

A key challenge for entrepreneurs is to raise investments into their business, and a common narrative in literatures on entrepreneurship and social influence more broadly is that such investments a...

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social interaction and the presence of stereotypic behaviors or restricted interests. To explore possible consequences of an excitatory/inhibitory (E/I) imbalance on the visual system in ASD, we investigated spatial suppression in 16 children with ASD and 16 neurotypical comparison children from 6 - 12 years of age using a visual motion processing task during high-density electroencephalography (EEG) recording in order to derive the N1 event related potential (ERP). Consistent with prior behavioral research, neurotypical participants displayed spatial suppression in conditions of large, high-contrast sinusoidal gratings as indexed by delayed N1 response latency. As predicted, children with ASD displayed weakened surround suppression, i.e. shorter N1 response latency to large, high-contrast sinusoidal gratings. However, this study also unexpectedly revealed that children with ASD showed longer N1 latencies in response to small, high-contrast sinusoidal gratings as compared to neurotypical control children. Although there were no statistically significant differences between children with ASD and NT children for N1 peak amplitude, there was a strong negative correlation between N1 amplitude represented in absolute values for large, high-contrast sinusoidal gratings and hyper-responsiveness item mean scores on the Sensory Experiences Questionnaire for children with ASD, but not for NT children. As predicted, no significant differences were found within or between groups in the low-contrast experiment. Our results are indicative of weakened spatial suppression and deficits in contrast gain in children with ASD, suggestive of an underlying E/I imbalance in ASD.

Aging and inflammation are independent risk factors for thrombosis and for the development of cardiovascular disease (CVD). Both conditions are characterized by varying degrees of chronic inflammation, mostly due to elevated levels of proinflammatory cytokines such as TNF-α, IL-1ß and IL-6. Furthermore, a significant proportion of thrombotic events associated with these conditions contribute to the elevated morbidity and mortality in this age group. With an expected significant rise in the proportion of older adults over 65 years of age within the next 30 years, it is important to identify the mechanisms by which aging-associated inflammation promotes thrombosis and worsens CVD. Our work has focused on the identification of key aging-associated factors that impact platelet development and function and that result in platelet hyperreactivity. We hypothesize that aging-associated inflammation promotes megakaryocyte reprogramming and results in the development of platelet hyperreactivity increasing the thrombotic risk during aging. Functional characterization of platelets by flow cytometry and microfluidic assay from young (mean age 35± 5 years of age) and aged frail adults (mean age 78±8) as well as from young (2 months) and old (>18 months) mice showed that platelets from old mice and humans are more reactive, demonstrated by increased aIIbb3 activation and phosphatidylserine exposure, and form larger thrombi under flow conditions when compared to platelets from young mice and human. Moreover, this platelet hyperreactive phenotype can be promoted in young mice after daily injections of TNF-α. In addition, TNF-α receptors I and II deficient mice (p55/p65 KO) do not develop platelet hyperreactivity after being injected with TNF-α, suggesting that sustained inflammation by TNF-α is a key promoter of platelet hyperreactivity in acute and chronic TNF-driven inflammation. Similarly, age-associated platelet hyperreactivity in old mice can be abrogated by the use of anti-TNF-α antibodies in vivo. Single-cell RNA-seq analysis of native megakaryocytes from young and old mice revealed significant differences in metabolic and mitochondrial gene pathways. Top differentially regulated pathways between young and old megakaryocytes are: a) protein ubiquitination; b) mitochondrial dysfunction and c) oxidative phosphorylation. Further investigations showed that platelets from old mice exhibit significant mitochondrial dysfunction characterized by elevated mitochondrial mass and oxygen consumption during activation. Finally, we show that platelets from patients with myeloproliferative neoplasms (MPN), characterized by somatic mutations that favor clonal hematopoiesis, elevated TNF-α levels, increased incidence of thrombo-hemorrhagic events and often, thrombocytosis, exhibit a similar mitochondrial phenotype as the one observed in aged murine platelets, suggesting that the high TNF-α levels associated with MPNs may play a significant role in the previously described platelet hyperreactivity of MPN. Disclosures No relevant conflicts of interest to declare.

The production of Secretory Aspartyl Proteases (Sap) is an important virulence factor of Candida albicans. Many studies have shown that a challenge with sub-inhibitory concentrations of antifungals lead species of Candida to the secretion of higher concentrations of Sap. Nevertheless, published studies only reported the secretion of such enzymes by cells growing in planktonic phase, with few mention of biofilms. The present study evaluated the alterations in the secretion of Sap by C. albicans grown in biofilms and exposed to sub-inhibitory concentrations of fluconazole. The MICs for fluconazole of seven clinical strains were determined for planktonic cells. Biofilm and planktonic cells were grown in the presence of 1/2 MIC, 1/4 MIC, and no medication (control). The relative metabolic activity, indirectly related to cell loads, were estimated by the absorbance of reduced XTT and the Sap activity was evaluated by bovine albumin test. It was observed that 72h-old biofilms under the influence of 1/2 MIC had fewer cells than 1/4 MIC and control. The production of Sap was inversely proportional to the cell content, with higher secretion in 1/2 MIC, followed by 1/4 MIC and control. Biofilms of C. albicans challenged by sub-MICs of fluconazole tend to secrete higher quantities of Sap.

To examine relationships between subgingival biofilm composition and levels of gingival crevicular fluid (GCF) cytokines in periodontal health and generalized aggressive periodontitis (GAP).Periodontal parameters were measured in 25 periodontally healthy and 31 GAP subjects. Subgingival plaque and GCF samples were obtained from 14 sites from each subject. Forty subgingival taxa were quantified using checkerboard DNA-DNA hybridization and the concentrations of eight GCF cytokines were measured using Luminex. Cluster analysis was used to define sites with similar subgingival microbiotas in each clinical group. Significance of differences in clinical, microbiological and immunological parameters among clusters was determined using the Kruskal-Wallis test.GAP subjects had statistically significantly higher GCF levels of interleukin-1beta (IL-1beta) (p0.001), granulocyte-macrophage colony-stimulating factor (GM-CSF) (p0.01) and IL-1beta/IL-10 ratio (p0.001) and higher proportions of Red and Orange complex species than periodontally healthy subjects. There were no statistically significant differences in the mean proportion of cytokines among clusters in the periodontally healthy subjects, while the ratio IL-1beta/IL-10 (p0.05) differed significantly among clusters in the aggressive periodontitis group.Different subgingival biofilm profiles are associated with distinct patterns of GCF cytokine expression. Aggressive periodontitis subjects were characterized by a higher IL-1beta/IL-10 ratio than periodontally healthy subjects, suggesting an imbalance between pro- and anti-inflammatory cytokines in aggressive periodontitis.

Biofilms are aggregates of microorganisms living in multilayered structures inside polymeric matrices onto surfaces. These biofilms may subvert the physiological properties of adjacent tissues causing morphofunctional failure. Many studies have shown that the expression of virulence attributes is maximized when microbes form such communities. This study evaluated the differential phospholipasic activity of Candida albicans SC5314 grown in planktonic phase and in biofilm. We propose two distinct protocols for the colorimetric evaluation of phosphatidylcholine hydrolysis in neutral and acidic conditions. The results showed that both protocols are suitable for the proposed intention and that 72 h-old planktonic cultures of C. albicans SC5314 secrete higher quantities of neutral (6.42-fold) and acidic (3.85-fold) phospholipases than biofilms.

This study aimed to evaluate the influence of different redox potentials (Eh) on cell growth, whole-cell protein profile and cell surface hydrophobicity (CSH) of Candida albicans SC5314. The yeast was grown in YNB broth enriched with reducing (158mM sodium sulfite, 4mM sodium sulfite, 2.5mM sodium metabisulfite, 1.3mM 2-mercaptoethanol, 5.5mM thioglycolic acid, and 3.2mM l-cysteine hydrochloride) and oxidizing agents (15mM ammonium persulfate and 80mM potassium ferricyanide) and incubated in normoxic and anoxic atmospheres at 37°C, for 48h. Pre- and post-incubation Eh values were determined and cytoplasm proteins were extracted. Proteins were parted by SDS-PAGE and their profiles were compared. 3.2mM l-cysteine and 1.3mM 2-mercaptoethanol promoted and maintained negative Eh values during incubation. No differences were detected among SDS-PAGE profiles. CSH differences only were observed with 4mM sodium sulfite and 3.2mM l-cysteine. Results showed that 3.2mM l-cysteine is a reducing agent that allows maintenance of negative Eh in both anoxic and normoxic conditions and it seems not to interfere in the global expression of plasmatic proteins.

The phenotypic pressure exerted by non-steroidal anti-inflammatory drugs (NSAIDs) on autochthonous and pathogenic microbiota remains sparsely known. In this study, we investigated if some NSAIDs increment or diminish the secretion of aspartyl-proteases (Sap) by Candida albicans grown under different phenotypes and oxygen availability using a set of SAP knock-out mutants and other set for genes (EFG1 and CPH1) that codify transcription factors involved in filamentation and protease secretion. Pre-conditioned cells were grown under planktonic and biofilm phenotypes, in normoxia and anoxia, in the presence of plasma concentrations of acetylsalicylic acid, diclofenac, indomethacin, nimesulide, piroxicam, ibuprofen, and acetaminophen. For diclofenac, indomethacin, nimesulide, and piroxicam the secretion rates of Sap by SAP1-6, EFG1, and CPH1 mutants were similar or, even, inferior to parental wild-type strain. This suggests that neither Sap 1-6 isoenzymes nor Efg1/Cph1 pathways may be entirely responsible for protease release when exposed to these NSAIDs. Ibuprofen and acetaminophen enhanced Sap secretion rates in three environmental conditions (normoxic biofilm, normoxic planktonic and anoxic planktonic). In other hand, aspirin seems to reduce the Sap-related pathogenic behavior of candidal biofilms. Modulation of Sap activity may occur according to candidal phenotypic state, oxygen availability, and type of NSAID to which the cells are exposed.

The production of Secretory Aspartyl Proteases (Sap) is an important virulence factor of Candida albicans. Many studies have shown that a challenge with sub-inhibitory concentrations of antifungals lead species of Candida to the secretion of higher concentrations of Sap. Nevertheless, published studies only reported the secretion of such enzymes by cells growing in planktonic phase, with few mention of biofilms. The present study evaluated the alterations in the secretion of Sap by C. albicans grown in biofilms and exposed to sub-inhibitory concentrations of fluconazole. The MICs for fluconazole of seven clinical strains were determined for planktonic cells. Biofilm and planktonic cells were grown in the presence of ½ MIC, ¼ MIC, and no medication (control). The relative metabolic activity, indirectly related to cell loads, were estimated by the absorbance of reduced XTT and the Sap activity was evaluated by bovine albumin test. It was observed that 72 h-old biofilms under the influence of ½ MIC had fewer cells than ¼ MIC and control. The production of Sap was inversely proportional to the cell content, with higher secretion in ½ MIC, followed by ¼ MIC and control. Biofilms of C. albicans challenged by sub-MICs of fluconazole tend to secrete higher quantities of Sap.

Material and methods: Fifty nine elders wearing complete dentures and living in retirement homes in Curitiba (southern Brazil), were divided into two groups: group #1, 26 patients with denture-induced stomatitis and group #2, 33 patients without denture-induced stomatitis. The two groups were evaluated in relation to the degree of denture-induced stomatitis, salivary fungal loads, and secretion of some histolytic enzymes. Results: Patients from group #1 showed higher degrees of colonisation by Candida albicans (p = 0.031). Candida krusei, Candida tropicalis, and Candida parapsilosis were also isolated, but there were no differences between the groups (p > 0.05). Secretory aspartyl protease (Sap) and chondroitinase did not show significant differences among the isolated Candida spp. in the two groups. Phospholipase secretion rates were higher among the strains of C. albicans from group #2 (p = 0.036). The same behaviour was not detected for non-albicans Candida species. Conclusions: The results could infer that differences in the secretion rates of candidal histolytic enzymes should not be imputed as imperative for the progress of denture-induced stomatitis.

430 Background: mTOR inhibitors (mTORi) are an important class of targeted therapies for mRCC that may act through regulation of mTOR as well as hypoxia-inducible factor and its resultant downstream angiogenesis pathways. FDA approval was based on efficacy in poor risk patients in the first-line setting for temsirolimus (T) and in sunitinib- and sorafenib-refractory patients for everolimus (E). Little is known about T’s effectiveness in good and intermediate risk patients and E’s outcomes in the first-line setting. Methods: We evaluated our international mRCC database to evaluate the outcomes of patients who received mTORi as their first-line targeted therapy. Results: Of the 2,370 patients in the database, 49 received a first-line mTORi (7 E, 42 T). Median age was 61 years and median KPS was 80%. 63% had clear cell and 37% had non-clear cell histology. 65% had prior nephrectomy. Of the 38 patients with available Heng prognostic risk criteria, 21%, 21%, and 58% were good, intermediate, and poor risk respectively. Median PFS and OS are detailed below. Objective responses and disease stabilization were achieved in 5% and 58%. Second-line therapy was administered in 21 patients of which 17 received VEGF inhibitors. Conclusions: Outcomes for good and intermediate risk patients treated with first-line mTORi were lower than historically expected for patients treated with VEGF targeted therapies. These results may be due to inclusion of non-clear cell histologies, treatment biases, small sample size, or other undefined confounders that need further exploration. Greater data capture of this important cohort of patients to confirm these results is planned and will be presented. [Table: see text]

4538 Background: Patients with mRCC have variable courses in terms of survival and response to targeted therapy. The patients at the two extremes of the survival spectrum need to be characterized. Methods: 2,161 patients with mRCC treated with targeted therapy were examined. 152 patients who survived 4 years or more after the initiation of targeted therapy (long-term) were compared with 218 patients who survived 6 months or less (short-term) over the same time period (2004-2007). Results: Long-term survivors had fewer poor prognostic factors (PFs) such as Karnofsky performance status (KPS)