Dose and time effects of solar-simulated ultraviolet radiation on the in vivo human skin transcriptome.

BACKGROUND: Terrestrial ultraviolet (UV) radiation causes erythema, oxidative stress, DNA mutations and skin cancer. Skin can adapt to these adverse effects by DNA repair, apoptosis, keratinization and tanning. OBJECTIVES: To investigate the transcriptional response to fluorescent solar-simulated radiation (FSSR) in sun-sensitive human skin in vivo. METHODS: Seven healthy male volunteers were exposed to 0, 3 and 6 standard erythemal doses (SED). Skin biopsies were taken at 6 h and 24 h after exposure. Gene and microRNA expression were quantified with next generation sequencing. A set of candidate genes was validated by quantitative polymerase chain reaction (qPCR); and wavelength dependence was examined in other volunteers through microarrays. RESULTS: The number of differentially expressed genes increased with FSSR dose and decreased between 6 and 24 h. Six hours after 6 SED, 4071 genes were differentially expressed, but only 16 genes were affected at 24 h after 3 SED. Genes for apoptosis and keratinization were prominent at 6 h, whereas inflammation and immunoregulation genes were predominant at 24 h. Validation by qPCR confirmed the altered expression of nine genes detected under all conditions; genes related to DNA repair and apoptosis; immunity and inflammation; pigmentation; and vitamin D synthesis. In general, candidate genes also responded to UVA1 (340-400 nm) and/or UVB (300 nm), but with variations in wavelength dependence and peak expression time. Only four microRNAs were differentially expressed by FSSR. CONCLUSIONS: The UV radiation doses of this acute study are readily achieved daily during holidays in the sun, suggesting that the skin transcriptional profile of 'typical' holiday makers is markedly deregulated. What's already known about this topic? The skin's transcriptional profile underpins its adverse (i.e. inflammation) and adaptive molecular, cellular and clinical responses (i.e. tanning, hyperkeratosis) to solar ultraviolet radiation. Few studies have assessed microRNA and gene expression in vivo in humans, and there is a lack of information on dose, time and waveband effects. What does this study add? Acute doses of fluorescent solar-simulated radiation (FSSR), of similar magnitude to those received daily in holiday situations, markedly altered the skin's transcriptional profiles. The number of differentially expressed genes was FSSR-dose-dependent, reached a peak at 6 h and returned to baseline at 24 h. The initial transcriptional response involved apoptosis and keratinization, followed by inflammation and immune modulation. In these conditions, microRNA expression was less affected than gene expression.

Next-generation sequencing of the basal cell carcinoma miRNome and a description of novel microRNA candidates under neoadjuvant vismodegib therapy: an integrative molecular and surgical case study.

BACKGROUND: MicroRNAs (miRNAs) have been identified as key players in posttranscriptional gene regulation and have a significant impact on basal cell carcinoma (BCC) development. The Sonic hedgehog pathway inhibitor vismodegib has been approved for oral therapy of metastatic or advanced BCC. Here, a high-throughput miRNA sequencing analysis was carried out to identify differentially expressed miRNAs and possible novel miRNA candidates in vismodegib-treated BCC tissue. Additionally, we described our surgical experience with neoadjuvant oral vismodegib therapy. PATIENTS AND METHODS: A punch biopsy (4 mm) from a patient with an extensive cranial BCC under oral vismodegib therapy and a corresponding nonlesional epithelial skin biopsy were harvested. Total RNA was isolated, after which a sequencing cDNA library was prepared, and cluster generation was carried out, which was followed by an ultra-high-throughput miRNA sequencing analysis to indicate the read number of miRNA expression based on miRBase 21. In addition to the identification of differentially expressed miRNAs from RNA sequencing data, additional novel miRNA candidates were determined with a tool for identifying new miRNA sequences (miRDeep2). RESULTS: We identified 33 up-regulated miRNAs (fold change ≥2) and 39 potentially new miRNA candidates (miRDeep scores 0-43.6). A manual sequence analysis of the miRNA candidates on the genomic locus of chromosome 1 with provisional IDs of chr1_1913 and chr1_421 was further carried out and rated as promising (chr1_1913) and borderline (chr1_421). Histopathology revealed skip lesions in clinically healthy appearing skin at the tumor margins, which were the cause of seven re-excisions by micrographic controlled surgery to achieve tumor-free margins. CONCLUSION: miRNA sequencing revealed novel miRNA candidates that need to be further confirmed in functional Dicer knockout studies. Clinically, on the basis of our surgical experience described here, neoadjuvant vismodegib therapy in BCC appears to impede histopathologic evaluations with effects on surgical therapy. Thus, larger studies are necessary, but are not preferable at this time if other options are available.

MicroRNA expression profiling in blood from fragile X-associated tremor/ataxia syndrome patients.

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder associated with FMR1 gene premutation alleles (55-200 CGG repeats). Fragile X-associated tremor/ataxia syndrome clinical core features include action tremor, gait ataxia, cognitive deficits progressing to dementia, and frequently parkinsonism. Although the pathogenic molecular mechanism of FXTAS is not completely understood, the restriction of the phenotype to the FMR1 premutation range has given rise to a model based on a RNA toxic gain-of-function. Since the identification of the first microRNAs (miRNAs) and their role in normal development, several studies have associated them with neurodegenerative diseases such as Parkinson, Alzheimer and Huntington diseases, suggesting that they play a key role in brain development, as well as in its morphogenesis. Herein, we present the characterization of miRNA expression profiles in FXTAS male patients using deep sequencing-based technologies and microarray technology. Deep sequencing analysis evidenced 83 miRNAs that were significantly deregulated whereas microarray analysis showed 31. When comparing these results, 14 miRNAs were found deregulated in FXTAS patients. MiR-424 and miR-574-3p showed significant fold change adjusted P-values in both platforms in FXTAS patients. MiR-424 has been founded substantially and specifically enriched in human cerebral cortical white matter of Alzheimer disease patients, which, together with cerebral atrophy, is a prominent imaging finding in individuals with FXTAS. The study provides the first systematic evidence of differential miRNA expression changes in FXTAS blood samples. Although further studies are necessary to better characterize the miRNA function in FXTAS disorder, our results suggest that they might contribute to its pathogenesis.

[An institutional evaluation design]. / Um design de avaliação institucional.

This study aims at describing the design used in the evaluation of technical nursing courses in São Paulo State's Education System by means of quantitative and qualitative institutional performance indicators. Such indicators, established by former students and by the labor market, showed to be useful in the evaluation and demonstrated the need for increasing, by means of similar evaluation studies, parameters related to the academic staff's performance as well as that of practical teaching fields. It is concluded that the use of a reasonable number of indicators allowed the articulation among data and a better understanding of the evaluated institutions.

[The importance of the word "comfort" from the viewpoint of patients with acute myocardial infarct]. / Os significados da palavra conforto segundo a perspectiva do paciente com infarto agudo do miocárdio.

This investigation included 25 male adult patients with Acute Myocardial Infarction admitted in a Coronary Disease Unit located in the Municipality of São Paulo, Brazil. It aimed at identifying the meaning those patients give to the word comfort. Data collection was carried using a specific form and manually processed; answers to open questions were treated using the BARDIN's content analysis method and the results were basically analysed in absolute numbers and percentages and organized in tables and figures. Comfort was expressed by several ways, from material and financial conditions, enjoyment of personal interactions, sense of physical, psychological, and spiritual well-being to normal functioning which means recovery expectations, disease-freedom and capacity to perform usual activities. Material and financial conditions (29,4%) and personal interactions (21,6%) were emphasized. In addition to the conclusions directly related to the objective, the results showed that: (a) viewing the multidimensional aspects related to comfort, it should not be exclusively considered as dependent of nursing care; (b) various indicators identified suggested that the same meaning for comfort was expressed or described in most varied ways.

[Advantages of nursing laboratory teaching]. / Vantagens do ensino no laboratório de enfermagem.

Reviewing the literature, the author describes some advantages of the psychomotor skill teaching at nursing laboratory as a previous training to the clinical service setting. The arguments herein presented are related, first to the ethics (questioning the mistakes made by the trainee on the patient); second, to the psychological nature by pointing out the trainee, the patient and the teacher's conflicts, as well as aspects on the cost-benefit obtained with this preliminary training; and third, to the pedagogy. These last mentioned aspects are supported on the psychomotor learning theories which confirm the importance of a nursing laboratory.

[The specific characteristics of the physical exam performed by the nurse]. / Características específicas do exame físico realizado pelo enfermeiro.

The purpose of this work is focused on the physical examinations made by the nurse, identifying four basic assumption originated from the performance of this procedure. It also suggests indicative guidelines of specificity to the nursing physical examinations.

[Psychomotor skills versus intelligence and affectivity]. / Habilidade psicomotora versus inteligência e afetividade.

It is an study, based on specific Bibliography, which purpose is to divulge up dated knowledge capable of establishing the importance of psychomotor skills. The article also describes the relation between the action and mental capabilities, both in the phylogenesis and ontogenesis level. The notion of relationship between all aspects that make up the human being and the environment with which man interacts, confirms the new global conceptions of the modern pedagogy.

[Incentives that aid training in the nursing laboratory: the opinion of professors and students]. / Estímulos que favorecem o treinamento em laboratório de enfermagem: opinião de professores e alunos.

The authors developed a survey on a population of 5 professors and 48 students on the reasons, that can to stimulate or to disfavour the voluntary attendance of the students to practice the psychomotor ability in the nursing laboratory. The results showed positive and negative reasons expected by professors and students to evaluate nursing laboratory training.

[Incentives that favor laboratory training in nursing: a review of the literature]. / Estímulos que favorecem o treinamento no laborató rio de enfermagem: revisão de literatura.

This article is a review of literature related to what motivates nursing graduates to attend freely a laboratory to better develop practical skills. It concluded that the literature indicates conditions that stimulate or discourage training of practical skills. These conditions are related to the professor, to techniques or procedures, to laboratory conditions, to evaluating systems and to the student himself.