O câncer é uma doença caracterizada pelo crescimento exacerbado das células podendo alastrar-se para outros órgãos e tecidos (metástase). O câncer de pele não melanoma é o tipo de câncer mais comum no Brasil contendo como uns dos fatores de risco a idade e a exposição prolongada ao sol. Os idosos, mediante a longevidade, apresentam maior suscetibilidade para adquirir o câncer de pele. Em face dessa realidade, faz-se necessário a intervenção da enfermagem direcionada a prevenção, com a disseminação da informação, atuação na detecção precoce de sinais indicativos da doença, bem como proceder pela orientação adequada. Trata-se de uma revisão narrativa da literatura por meio de abordagem qualitativa tendo como principais resultados: os idosos possuem sistema imune e tegumentar diferente, além de sofrerem consequências de fatores ambientais como exposição ao sol; a enfermagem deve intervir por meio da educação em saúde na Atenção Básica, além de oferecer uma assistência humanizada; possuir conhecimento de lesões pré-malignas para obtenção de prevenção considerável e utilização da regra ABCDE por intermédio do exame físico.

Background Human herpes-virus 8-negative/idiopathic multicentric Castleman disease (iMCD) is a rare inflammatory disorder involving multicentric lymphadenopathy with characteristic histopathology. Clinical presentation is heterogenous and includes cytokine-driven constitutional symptoms, cytopenias, systemic inflammation, and multi-organ dysfunction. International consensus treatment guidelines are based on a large cohort of case studies and a few clinical trials, but the available evidence is limited. Siltuximab, an anti-IL-6 therapy, is the only FDA-approved treatment for iMCD; 34% of patients achieved durable symptomatic and tumor response in the phase II trial. Tocilizumab, an anti-IL-6 receptor therapy, is frequently used off label and demonstrated promising results in an open-label study in Japan. The treatment guidelines recommend siltuximab ± corticosteroids (CS) as first-line therapy for all iMCD patients and tocilizumab as a substitute when siltuximab is not available. Rituximab, a CD20 antibody, is recommended as an alternate first-line therapy in patients who are non-severe and do not exhibit marked cytokine-driven symptoms. In all other patients, rituximab is recommended second-line; however, it has never been systematically evaluated in iMCD. Chemotherapies, immunosuppressants, and immunomodulators are recommended second- or third-line, but again, effectiveness is not well described. Better understanding of treatment effectiveness is urgently needed. Herein, we describe treatment and response in a real-world cohort of iMCD patients. Methods Data were collected and abstracted for 68 patients enrolled in an on-going IRB-approved natural history study of Castleman disease. Diagnosis is graded by an expert panel of clinicians and pathologists on an on-going basis; patients unlikely to have iMCD were excluded from analysis (N=12). Of the 56 patients included, 37 (66%) are expert panel-confirmed and 19 (34%) are awaiting confirmation. Durable response is defined as achieving ≥50% improvement in the proportion of abnormal iMCD minor clinical and laboratory diagnostic criteria sustained for ≥1 year. Small sample size prevented statistical comparisons. Results Median age at diagnosis is 33 years (range: 1-65 years). The cohort is 52.9% female, 63% white, and 4 (7%) patients died. Thirty-three unique drugs, including anti-IL-6 therapies, CS, chemotherapies, immunosuppressants, and others have been administered across the 56 patients. Rituximab is the most frequently used drug, administered to 39 (70%) patients. Siltuximab (29 patients, 52%) and tocilizumab (19 patients, 34%) are the next two most frequently used targeted therapies. There was a 52% response (15/29) to regimens inclusive of siltuximab, 50% response (9/18) to those inclusive of tocilizumab, and 25% response (9/26) to those inclusive of rituximab. Siltuximab±CS induced response in 15/24 (63%) patients, tocilizumab±CS in 4/7 (57%), and rituximab±CS in 2/13 (15%). Among the 37 expert-confirmed iMCD patients, we found a 58% response (11/19) to regimens inclusive of siltuximab, 47% (8/17) to those inclusive of tocilizumab, and 27% (7/26) to those inclusive of rituximab. Further, in these patients, siltuximab±CS induced response in 11/16 (69%), tocilizumab±CS in 3/6 (50%), and rituximab±CS in 1/6 (17%) patients. Of note, 3 of 4 deceased patients received both anti-IL-6 therapy and rituximab and all 4 received chemotherapies and immunosuppressants but did not respond to any drug. Discussion These data reveal that despite there being one FDA-approved treatment, iMCD is treated with a variety of agents. Among the full cohort, siltuximab±CS demonstrated a 63% durable response, which was higher than the response reported in the clinical trial (not statistically compared). This may reflect differences in response criteria and/or disease activity of patients in clinical trials versus real world settings. Siltuximab and tocilizumab have never been systematically compared; in this cohort they demonstrated similar response. Considering the morbidity and mortality of iMCD, these data suggest that current therapies demonstrate important activity. However, additional agents are needed for refractory patients, who have few options and are at risk of death due to disease progression. Further data are needed to compare groups and identify optimal treatment protocols. Liu: BridgeBio Pharma: Employment, Equity Ownership. Gibson:EUSA Pharma: Employment. Kanhai:EUSA Pharma: Employment. Martin:EUSA Pharma: Employment. Srkalovic:Takeda: Speakers Bureau; Janssen: Speakers Bureau; Foundation Medicine: Speakers Bureau; EUSA Pharma: Speakers Bureau. Uldrick:Patent: Patents & Royalties: co-inventor on US Patent 10,001,483 entitled ; Celgene: Other: research support from Celgene through a CRADA at the NCI; Roche: Other: commercial research support through a CTA with Fred Hutchinson Cancer Research Center; Merck: Other: drug for a clinical trial from Merck through a CRADA with the NCI. van Rhee:Takeda: Consultancy; Sanofi Genzyme: Consultancy; Karyopharm Therapeutics: Consultancy; EUSA: Consultancy; Adicet Bio: Consultancy; Kite Pharma: Consultancy; Castleman Disease Collaborative Network: Consultancy. Fajgenbaum:Janssen Pharmaceuticals: Research Funding. Tocilizumab, a monoclonal antibody directed against IL-6-receptor, is approved for use in rheumatoid arthritis in the US. It is frequently used off-label in idiopathic multicentric Castleman disease (iMCD) and is recommended as a substitute first-line therapy in the International Consensus iMCD treatment guidelines. Rituximab, a monoclonal antibody directed against CD20, is used in rheumatoid arthritis and other autoimmune and cancerous disorders. It is frequently used off-label in iMCD and is recommended as an alternate first-line or a second-line therapy in the International Consensus iMCD treatment guidelines. Corticosteroids are used broadly in iMCD and are recommended as needed as useful adjunctive therapy in the International Consensus iMCD treatment guidelines.

We have developed a precise dictionary between the spectrum of primordial density fluctuations and the parameters of the effective field theory (EFT) of inflation that determine the primordial power spectrum (PPS). At lowest order the EFT contains two parameters: the slow-roll parameter $\epsilon$, which acts as an order parameter, and the speed of sound $c_s$. Applying second-order perturbation theory, we provide maps from the PPS to the EFT parameters that are precise up to the cube of the fractional change in the PPS $(\Delta \mathcal{P}/\mathcal{P})^3$, or less than $1\%$ for spectral features that modulate the PPS by $20\%$. While such features are not required when the underlying cosmological model is assumed to be $\Lambda$CDM they are necessary for alternative models that have no cosmological constant/dark energy. We verify the dictionary numerically and find those excursions in the slow-roll parameter that reproduce the PPS needed to fit Planck data for both $\Lambda$ and no-$\Lambda$ cosmological models.

Abstract Despite the great progress made in neonatal and perinatal medicine over the last couple of decades, sepsis remains one of the main causes of morbidity and mortality. Sepsis in pediatric population was defined at the Pediatric Sepsis Consensus Conference in 2005. There is still no consensus on the definition of neonatal sepsis. Neonatal sepsis is a sepsis that occurs in the neonatal period. According to the time of occurrence, neonatal sepsis can be of early onset, when it occurs within the first 72 hours of birth and results from vertical transmission, and of late onset, in which the source of infection is found most often in the environment and occurs after the third day of life. The most common causes of early-onset sepsis are Group B Streptococcus (GBS) and E. coli. Risk factors can be mother-related and newborn-related. Clinical symptoms and signs of sepsis are quite unspecific. The dysfunction of different organs may imitate sepsis. On the other hand, infectious and non-infectious factors may exist simultaneously. The start of the antimicrobial therapy in any newborn with suspected sepsis should not be delayed. Pentoxifylline may have potential benefits in preterm newborns with sepsis. The only proven intervention that has been shown to reduce the risk of early-onset neonatal sepsis is intrapartum intravenous antibiotic administration to prevent GBS infection. It is still a great challenge to discontinue antibiotic treatment in non-infected newborns as soon as possible, because any extended antibiotic use may later be associated with other pathological conditions.

Pozegaca’ is the most important native plum genotype in southeast Europe. In this study, the phytochemical fruit composition of the ‘Pozegaca’ ecotype from four different growing regions was evaluated over three growing years. HPLC was used for identification and quantification of sugars, organic acids and phenolic compounds in the fruits. The total effects of growing years and regions on different phytochemical characteristics of ‘Pozegaca’ fruit were analysed using principal component analysis (PCA). Glucose, fructose, sucrose and sorbitol were detected as major sugars in ‘Pozegaca’ fruit. Malic, citric, fumaric and shikimic acids were identified in the studied plum ecotype. Glucose was the predominant sugar and malic acid was the predominant organic acid. A range of phenol compounds was identified, including hydroxycinnamic acids, flavonols, anthocyanins and flavan3-ols. The main factor affecting the fruit quality and phenol composition of the ‘Pozegaca’ plum ecotype in skin and pulp was the growing year. The geographical origin of the ‘Pozegaca’ ecotype appears to have no major influence on the phenol profile of ‘Pozegaca’ fruit. The results showed that air temperature has a strong correlation with sugar compounds (particularly with fructose and sucrose) and with some organic acids (fumaric, shikimic and citric). Related to the accumulation of phenol compounds, air temperature strongly correlated with flavanols (particularly with quercetin 3-rutinoside) and anthocyanins in pulp. Precipitation and altitude were strongly correlated with total phenols in pulp, chlorogenic acid in skin and pulp, neochlorogenic acid in pulp, and all three identified flavanols in pulp. The results showed that specific seasonal and geographic environmental conditions could significantly affect the content of secondary metabolites in ‘Pozegaca’ fruit.

Purpose The current challenges international charities face with regards to their deteriorating image, as a result of recent scandals (e.g. Oxfam, Save the Children), provide the impetus for this exploratory research, where the purpose of this paper is to examine the conceptualization and dimensionality of non-profit brand image across national cultures. Design/methodology/approach The study employs a quantitative research design, using multi-country samples from India, Bosnia and Herzegovina and the UK. The authors first examine the psychometric properties of the non-profit brand image scale via confirmatory factor analysis across countries, identifying the optimal model for invariance testing. Further, the authors use multi-group invariance analysis to evaluate whether non-profit brand image (using an 18-item scale and six factors) provides equivalent measurement across cultures. Findings The study shows that individuals in the three countries perceive non-profit brand image equally, and as consisting of perceptions of usefulness, efficiency, affect, dynamism, reliability and ethicality. However, the results also indicate that the means of the dimensions of non-profit brand image are not comparable across different cultures. Originality/value The study extends limited current literature on non-profit brand image in international contexts, deriving insightful suggestions for further theoretical approaches in this under-developed research domain. It also yields key implications for charities and other non-profit organizations operating internationally, as they can use non-profit brand image and its dimensions as actionable tools in their communication campaigns to shape their brand image.

The electrical properties of neural tissue are important in a range of different applications in biomedical engineering and basic science. These properties are characterized by the electrical admittivity of the tissue, which is the inverse of the specific tissue impedance. Objective. Here we derived analytical expressions for the admittivity of various models of neural tissue from the underlying electrical and morphological properties of the constituent cells. Approach. Three models are considered: parallel bundles of fibers, fibers contained in stacked laminae and fibers crossing each other randomly in all three-dimensional directions. Main results. An important and novel aspect that emerges from considering the underlying cellular composition of the tissue is that the resulting admittivity has both spatial and temporal frequency dependence, a property not shared with conventional conductivity-based descriptions. The frequency dependence of the admittivity results in non-trivial spatiotemporal filtering of electrical signals in the tissue models. These effects are illustrated by considering the example of pulsatile stimulation with a point source electrode. It is shown how changing temporal parameters of a current pulse, such as pulse duration, alters the spatial profile of the extracellular potential. In a second example, it is shown how the degree of electrical anisotropy can change as a function of the distance from the electrode, despite the underlying structurally homogeneity of the tissue. These effects are discussed in terms of different current pathways through the intra- and extra-cellular spaces, and how these relate to near- and far-field limits for the admittivity (which reduce to descriptions in terms of a simple conductivity). Significance. The results highlight the complexity of the electrical properties of neural tissue and provide mathematical methods to model this complexity.

The response to metformin, the most commonly used drug for the treatment of type 2 diabetes (T2D), is highly variable. The common variant rs7903146 C>T within the transcription factor 7 like 2 gene (TCF7L2) is the strongest genetic risk factor associated with T2D to date. In this study we explored the effects of TCF7L2 rs7903146 genotype on metformin response in T2D. The study included 86 newly diagnosed patients with T2D, incident users of metformin. Levels of fasting glucose, insulin, HbA1c, total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, and anthropometric parameters were measured prior to metformin therapy, and 6 and 12 months after the treatment. Genotyping of TCF7L2 rs7903146 was performed by the Sequenom MassARRAY® iPLEX® platform. At baseline, the diabetes risk allele (T) showed an association with lower triglyceride levels (p = 0.037). After 12 months of metformin treatment, the T allele was associated with 25.9% lower fasting insulin levels (95% CI 10.9-38.3%, p = 0.002) and 29.1% lower HOMA-IR index (95% CI 10.1-44.1%, p = 0.005), after adjustment for baseline values. Moreover, the T allele was associated with 6.7% lower fasting glucose levels (95% CI 1.1-12.0%, p = 0.021), adjusted for baseline glucose and baseline HOMA-%B levels, after 6 months of metformin treatment. This effect was more pronounced in TT carriers who had 16.8% lower fasting glucose levels (95% CI 7.0-25.6%, p = 0.002) compared to the patients with CC genotype. Our results suggest that TCF7L2 rs7903146 variant affects markers of insulin resistance and glycemic response to metformin in newly diagnosed patients with T2D within the first year of metformin treatment.