First report of trans-A2B-corrole derived from a lapachone derivative: photophysical, TD-DFT and photobiological assays.

In this work, the synthesis, characterization and photophysical assays of a new trans-A2B-corrole derivative from the naturally occurring quinone are described. ß-Lapachone is a naturally occurring quinoidal compound that provides highly fluorescent heterocyclic compounds such as lapimidazoles. The new trans-A2B-corrole compound was obtained from the reaction between 2,3,4,5,6-(pentafluorophenyl)dipyrromethane and the lapimidazole bearing an aldehyde group. The dyad was characterized by high-resolution mass spectrometry (HRMS), NMR spectroscopy (1H, COSY 2D, HMBC, 19F), FT-IR, UV-vis, steady-state and time-resolved fluorescence, electrochemical studies (CV), TD-DFT analysis and photobiological experiments, in which includes aggregation, stability in solution, photostability and partition coefficients assays. Finally, ROS generation assays were performed using 1,3-diphenylisobenzofuran (DPBF) method and the presented compound showed significant photostability and singlet oxygen production.

Sistematização da propedêutica de massas cervicais­da Atenção Primária à Terciária / Systematization of neck masses propaedeutics ­from Primary to Tertiary Care

Introdução: As massas cervicais são causas frequentes de encaminhamentos aos ambulatórios de otorrinolaringologia, muitas vezes com pouca abordagem na atenção primária à saúde. Sendo assim, a falta de uma rotina de manejo pode deixar o médico assistente inseguro e por vezes confuso quanto ao caminho de investigação a ser seguido, tornando-se necessário elaborar e aplicar uma rotina propedêutica que facilite e direcione o raciocínio clínico para diagnóstico de massas cervicais. Desenvolvimento: Através de revisão da literatura de artigos científicos coletados nos portais Medline, Lilacse PubMed,utilizando descritores específicos como: necklump; head and neck cancer; epidemiology of head and neck cancere consulta à literatura médica específica, foi elaborado um fluxograma para diagnóstico inicial das massas cervicais. Conclusão: Os autores elaboraram um fluxograma para a investigação e diagnóstico das massas cervicais de fácil memorização e aplicabilidade, adequado às condições estruturais de instituições públicas, e visando melhor atendimento, minimização de riscos, bem como qualificação dos profissionais. O fluxograma proposto visa ao diagnóstico diferencial entre doenças malignas e benignas, focando o que pode ser feito em nível de atenção primária à saúde.

Introduction: Neck masses are frequent causes of referrals to otorhinolaryngology clinics, often with a little approach in primary health care. Therefore, the lack of a usual approach can make the attending physician unsafe and prone to error, thus, it is necessary toelaborate a propaedeutic routine for the diagnosis of neck masses. Development: From a literature review of scientific articles collected on Medline, Lilacsand PubMedportals using specific descriptors such as: neck lump; head and neck cancer; epidemiology of head and neck cancer and using specific medical literature, a flowchart had been prepared for initial diagnosis of neck masses. Conclusion: The authors sought a practical form, easy to remember and applicable, appropriate to public institutions, aiming for better care, minimizing risks as well as the qualifications of professionals, targeting on the differential diagnosis between malignant and benign diseases, and what can be done at primary level of health care.

Cienciometria: uma ferramenta para inserção da Dermatologia brasileira na produção científica mundial / Scientometrics: a tool for the insertion of Brazilian Dermatology in the world scientific production

Introdução: foi verificada a produção científica brasileira em Dermatologia no cenário internacional pela Cienciometria (segmento da Sociologia sobre aspectos quantitativos da ciência). Objetivo: é plausível afirmar que a inserção do Brasil na produção científica internacional pode e deve ser realizada a partir de uma perspectiva mais estratégica, sendo necessário observar a produção de documentos indexados em Scopus na área de Dermatologia e temas relacionados de forma mais minuciosa. Métodos: por meio de pesquisa exploratória, quanti-quali indutiva na plataforma Scopus - plataforma digital que reúne mais de 25 mil artigos científicos e disponibiliza ferramentas analíticas para extrair resultados e tendências no campo da pesquisa -, foi possível obter dados quantitativos sobre a produção científica brasileira em Dermatologia geral e em seis dermatoses proeminentes. Resultados: foi possível extrair análise a fim de apontar as dermatoses mais importantes atualmente na literatura e os autores relacionados, comparar os dados brasileiros com os de outros países que se destacam na literatura científica em Dermatologia e elaborar e justificar as estratégias efetivas de inserção internacional da produção científica da Dermatologia brasileira

Introduction: The Brazilian scientific production in Dermatology in the international scenario was verified by scientometrics (Sociology segment on quantitative aspects of science). Objective: The insertion of Brazil in the international scientific production scenario can and should be conducted from a more strategic perspective, and it is necessary to observe the production of documents indexed in Scopus in the Dermatology area and related topics in a more detailed way. Methods: Through exploratory, inductive, quantitative, and qualitative research on the Scopus platform ­ a digital platform comprising more than 25 thousand scientific articles and analytical tools to extract results and trends in the field of research, it was possible to obtain quantitative data on Brazilian scientific production in General Dermatology and six prominent dermatoses. Results: It was possible to analyze and point out the most prominent dermatoses currently in the literature and the related authors, compare Brazilian data with those from other countries that stand out in the scientific literature in Dermatology, and elaborate and justify effective strategies for the international insertion of Brazilian Dermatology scientific production.

The pterygospinous foramen (Civinini) and the pterygoalar (crotaphitico-buccinatorius): laboratory findings / El foramen pterigoespinoso (Civinini) y el pterigoalar (crotafítico-buccinatorius): hallazgos de laboratorio

SUMMARY: The Pterygospinous foramen and pterygoalar foramen (crotaphitico-buccinatorius) are variant and atavic formations of the skull base and arise respectively from complete or incomplete idiopathic ossifications of the pterygospinous and pterygoalar ligaments. By proximity with areas of relevance for diagnosis and surgery, such as access pathways to the parapharyngeal and retropharyngeal spaces, it is necessary to be aware of these conditions due to the difficulties generated in surgical maneuvers and the promotion of compressive syndromes of mandibular nerve branches. This study was conducted on 45 samples of dry skulls and disarticulated sphenoid bones belonging to the collection of the Federal University of Juiz de Fora, Governador Valadares campus, Minas Gerais, Brazil. Our results indicated a total incidence of complete and incomplete pterygospinous and pterygoalar foramen (crotaphitico- buccinatorius) in 15, 5 % (7 skulls), with a higher incidence for the incomplete form of pterygospinous foramen (Civinini foramen) in 4 skulls (8.8 %), with 3 presenting unilaterally and 3 presenting bilaterally. The pterygoalar foramen (crotaphitico-buccinatorius or Hyrtl) was noted bilaterally in 1 of the skulls (2.2 %). The pterygospinous foramen and pterygoalar foramen are important findings, sometimes incidental, of an area of great anatomical expressiveness and pathological occurrences, besides the indispensable and unclear studies of phylogenetic order.

RESUMEN: El foramen pterigoespinoso y el foramen pterigoalar (crotafítico-buccinatorius) son formaciones variantes y atávicas de la base del cráneo y surgen respectivamente de osificaciones idiopáticas completas o incompletas, de los ligamentos pterigoespinoso y pterigoalar. Debido a la proximidad con áreas de relevancia para el diagnóstico y la cirugía, como las vías de acceso a los espacios parafaríngeo y retrofaríngeo, es necesario conocer estas condiciones por las dificultades que se generan en las maniobras quirúrgicas. Este estudio se realizó en 45 muestras de cráneos secos y huesos esfenoides desarticulados pertenecientes a la colección de la Universidad Federal de Juiz de Fora, campus Governador Valadares, Minas Gerais, Brasil. Nuestros resultados indicaron una incidencia total de foramen pterigoespinoso y pterigoalar completo e incompleto (crotafítico-buccinatorius) en el 15,5 % (7 cráneos), con una mayor incidencia de la forma incompleta de foramen pterigoespinoso (agujero de Civinini) en 4 cráneos (8,8 %), con 3 de presentación unilateral y 3 de presentación bilateral. El foramen pterigoalar (crotaphitico-buccinatorius o Hyrtl) se observó bilateralmente en 1 de los cráneos (2,2 %). El foramen pterigoespinoso y pterigoalar son hallazgos importantes, a veces incidentales, de un área de gran expresividad anatómica y ocurrencias patológicas, además de los estudios indispensables y poco claros de orden filogenético.

Análise de percepção da insulinoterapia em diabéticos tipo 1 no Serviço de Apoio e Assistência aos Diabéticos e seus Familiares / Analysis of type 1 diabetes patients' perception of insulin therapy at the service of care and support to diabetics and their family

Objetivo: Analisar a percepção dos diabéticos tipo 1 sobre a insulinoterapia. Métodos: Trata-se de estudo epidemiológico analítico de percepção, tendo sido realizado com pacientes de um Serviço de Apoio e Assistência aos Diabéticos e seus Familiares, no período de abril a agosto de 2018. Resultados: Os 33 diabéticos tipo 1 avaliados eram predominantemente do sexo feminino (60,6%) e a média de idade foi de 21±9 anos. A maioria afirmou portar o Cartão de Identificação do Diabético (78,8%). Mais de dois terços dos pacientes afirmaram saber quando aplicar a insulina de correção. A aferição da glicemia capilar foi relatada por 78,8%. Das insulinas utilizadas no esquema basal, a glargina e a NPH foram citadas como as mais utilizadas. Do total de pacientes, 97% referiram fazer autoaplicação, e 90,9% disseram posicionar a agulha corretamente sobre a pele. Quanto aos locais de aplicação, 84,8% realizavam rodízio. A maioria dos pacientes (78,8%) que aplicavam a insulina não referiu desconforto durante ou após a aplicação, e 69,7% mostraram conhecimento sobre o significado de distrofia. Conclusão: O serviço de educação continuada desenvolvido pelo Serviço de Apoio e Assistência aos Diabéticos e seus Familiares é efetivo na aquisição de bons hábitos e dos devidos cuidados para esses pacientes. A educação do indivíduo com diabetes tipo 1 e de sua família, bem como o acompanhamento por uma equipe multidisciplinar, é essencial para o bom controle da doença,

Objective: To analyze the perception of type 1 diabetes (DM 1) patients of insulin therapy. Methods: This is an epidemiological study of analysis of perception and was performed at the service for care and support of diabetes patients and their families from April to August 2018. Results: The 33 type 1 diabetes mellitus patients evaluated were predominantly female (60.6%) and the mean age was 21 years ± 9 years. Most reported having the diabetes medical ID card (78.8%). More than two thirds of the patients reported knowing when to apply the correction insulin. The capillary glycemia measurement was reported by 78.8%. Of the insulins used in the baseline regimen, Glargine and NPH were cited as the most used. Of the total patients, 97% reported self-application and 90.9% reported positioning the needle correctly on the skin. As for the application sites, 84.8% reported rotating sites. Most patients (78.8%) who applied insulin did not report discomfort during or after application, and 69.7% showed knowledge about the meaning of dystrophy. Conclusion: The continuing education service developed by the Service for Care and Support of Diabetics and their Families is effective in promoting good habits and the proper care of these patients for their disease.The education of the individual with type 1 diabetes and of his/her family, as well as follow-up by a multidisciplinary team, is essential for good disease control.

Trends in Bone Marrow Sampling and Core Biopsy Specimen Adequacy in the United States and Canada: A Multicenter Study.

OBJECTIVES: To assess bone marrow (BM) sampling in academic medical centers. METHODS: Data from 6,374 BM samples obtained in 32 centers in 2001 and 2011, including core length (CL), were analyzed. RESULTS: BM included a biopsy (BMB; 93%) specimen, aspirate (BMA; 92%) specimen, or both (83%). The median (SD) CL was 12 (8.5) mm, and evaluable marrow was 9 (7.6) mm. Tissue contraction due to processing was 15%. BMB specimens were longer in adults younger than 60 years, men, and bilateral, staging, and baseline samples. Only 4% of BMB and 2% of BMB/BMA samples were deemed inadequate for diagnosis. BM for plasma cell dyscrasias, nonphysician operators, and ancillary studies usage increased, while bilateral sampling decreased over the decade. BM-related quality assurance programs are infrequent. CONCLUSIONS: CL is shorter than recommended and varies with patient age and sex, clinical circumstances, and center experience. While pathologists render diagnoses on most cases irrespective of CL, BMB yield improvement is desirable.

Comparison of the yield of different diagnostic procedures for cellular differentiation and genetic profiling of non-small-cell lung cancer.

INTRODUCTION: As treatments for non-small-cell lung cancer (NSCLC) become personalized, cellular and molecular differentiation of the tumor is becoming the standard of care. Our objective is to compare the yield of different diagnostic procedures for cellular differentiation of NSCLC and analysis of epidermal growth factor receptor (EGFR) mutation. METHODS: We evaluated all patients diagnosed with NSCLC from January 2004 to September 2010 at the Jewish General Hospital, Montreal. Diagnostic procedures included surgical biopsies, nonsurgical histologic biopsies (endobronchial and core needle), transbronchial needle aspirate (TBNA) and transthoracic needle aspirate (TTNA), bronchoalveolar lavage (BAL), and pleural fluid samples. RESULTS: We included 702 subjects investigated for histopathologic differentiation of NSCLC. Of these, 269 were also investigated for EGFR mutation. Failure to ascertain the cellular subtype and EGFR mutation status was least likely with surgical specimens (0% and 1.8%, respectively); followed by TTNA (14% and 10%, respectively) and histologic biopsy (18% for both); and was frequent with TBNA (39% and 30%, respectively). Although BAL and pleural fluid specimens provided reasonable yield for cellular differentiation (20 % and 11%, respectively), their results were not accurate in 6% of their samples when compared with concurrent or subsequent surgical specimens (reference standard) performed in a subgroup of patients. CONCLUSION: Radiologically guided TTNA and histologic biopsies provided high yield for both molecular and histologic analyses. The yield of unguided TBNA was relatively low. Further studies are needed to assess the adequacy of BAL and pleural fluid samples for EGFR mutation analysis and accurate characterization of cellular subtypes of NSCLC.

Canadian anaplastic lymphoma kinase study: a model for multicenter standardization and optimization of ALK testing in lung cancer.

INTRODUCTION: Fluorescence in situ hybridization (FISH) is currently the standard for diagnosing anaplastic lymphoma kinase (ALK)-rearranged (ALK+) lung cancers for ALK inhibitor therapies. ALK immunohistochemistry (IHC) may serve as a screening and alternative diagnostic method. The Canadian ALK (CALK) study was initiated to implement a multicenter optimization and standardization of laboratory developed ALK IHC and FISH tests across 14 hospitals. METHODS: Twenty-eight lung adenocarcinomas with known ALK status were used as blinded study samples. Thirteen laboratories performed IHC using locally developed staining protocols for 5A4, ALK1, or D5F3 antibodies; results were assessed by H-score. Twelve centers conducted FISH using protocols based on Vysis' ALK break-apart FISH kit. Initial IHC results were used to optimize local IHC protocols, followed by a repeat IHC study to assess the results of standardization. Three laboratories conducted a prospective parallel IHC and FISH analysis on 411 consecutive clinical samples using post-validation optimized assays. RESULTS: Among study samples, FISH demonstrated 22 consensus ALK+ and six ALK wild type tumors. Preoptimization IHC scores from 12 centers with 5A4 and the percent abnormal cells by FISH from 12 centers showed intraclass correlation coefficients of 0.83 and 0.68, respectively. IHC optimization improved the intraclass correlation coefficients to 0.94. Factors affecting FISH scoring and outliers were identified. Post-optimization concurrent IHC/FISH testing in 373 informative cases revealed 100% sensitivity and specificity for IHC versus FISH. CONCLUSIONS: Multicenter standardization study may accelerate the implementation of ALK testing protocols across a country/region. Our data support the use of an appropriately validated IHC assay to screen for ALK+ lung cancers.

Non-Small Cell Lung Carcinoma Biomarker Testing: The Pathologist's Perspective.

Biomarker testing has become standard of care for patients diagnosed with non-small cell lung carcinoma (NSCLC). Although, it can be successfully performed in circulating tumor cells, at present, the vast majority of investigations are carried out using direct tumor sampling, either through aspiration methods, which render most often isolated cells, or tissue sampling, that could range from minute biopsies to large resections. Consequently, pathologists play a central role in this process. Recent evidence suggests that refining NSCLC diagnosis might be clinically significant, particularly in cases of lung adenocarcinomas (ADC), which in turn, has prompted a new proposal for the histologic classification of such pulmonary neoplasms. These changes, in conjunction with the mandatory incorporation of biomarker testing in routine NSCLC tissue processing, have directly affected the pathologist's role in lung cancer work-up. This new role pathologists must play is complex and demanding, and requires a close interaction with surgeons, oncologists, radiologists, and molecular pathologists. Pathologists often find themselves as the central figure in the coordination of a process, that involves assuring that the tumor samples are properly fixed, but without disruption of the DNA structure, obtaining the proper diagnosis with a minimum of tissue waste, providing pre-analytical evaluation of tumor samples selected for biomarker testing, which includes assessment of the proportion of tumor to normal tissues, as well as cell viability, and assuring that this entire process happens in a timely fashion. Therefore, it is part of the pathologist's responsibilities to assure that the samples received in their laboratories, be processed in a manner that allows for optimal biomarker testing. This article goal is to discuss the essential role pathologists must play in NSCLC biomarker testing, as well as to provide a summarized review of the main NSCLC biomarkers of clinical interest.

Lung cancer histologies associated with emphysema on computed tomography.

BACKGROUND: Multiple studies have demonstrated an increased risk of lung cancer in the presence of emphysema detected visually on computed tomography (CT) independent of smoking history and airflow obstruction. The relationship between emphysema and specific histologic subtypes of lung cancer remains uncertain. OBJECTIVE: To determine the extent to which emphysema on chest CT is associated with lung cancer histology. METHODS: Cross-sectional analysis of consecutive lung cancer patients referred to the Jewish General Hospital was performed (2001-2009). All those with demographic data, smoking history (pack-years), documented histology and chest CT were included. Emphysema was graded on CT by three readers, using a standardized rubric. Odds of each lung cancer subtype were compared between patients with and without emphysema, and adjusted for age, sex, physician diagnosed COPD and smoking history by multiple logistic regression. RESULTS: Complete data were available for 498 lung cancer patients (mean age 68 years; 44% female; 16% never smokers; 53% without emphysema on CT). The most common histologies were adenocarcinoma (242 [49%]), squamous (71 [14%]), undifferentiated (48 [10%]) and small cell carcinoma (42 [8%]). The presence of emphysema was associated with increased odds of squamous (OR 3.1; 95% CI 1.8-5.3) and small cell (OR 2.1; 95% CI 1.1-4.1) carcinoma. After adjustment for age, sex, COPD and smoking history, emphysema was associated with squamous (adjusted OR 2.6; 95% CI 1.4-4.8) but not small cell (adjusted OR 1.5; 95% CI 0.76-3.1) carcinoma. Sensitivity analysis was performed by sequential censoring of each histologic subtype yielding similar results. Adenocarcinoma was less common in the presence of emphysema relative to squamous and small cell carcinoma (adjusted OR 0.62; 95% CI 0.41-0.92). When these latter histologies were censored, no significant association between adenocarcinoma and emphysema was observed (adjusted OR 1.0; 95% CI 0.49-2.1). CONCLUSIONS: Relative to other histologic subtypes, the odds of squamous carcinoma were significantly increased among lung cancer patients with emphysema after adjustment for age, sex, COPD and smoking history. Other common subtypes were not independently associated with emphysema.

Epidermal growth factor receptor mutations detected by denaturing high-performance liquid chromatography in nonsmall cell lung cancer: impact on response to therapy with epidermal growth factor receptor-tyrosine kinase inhibitors.

BACKGROUND: Somatic mutations in the epidermal growth factor receptor (EGFR) kinase domain are associated with sensitivity to EGFR-tyrosine kinase inhibitors (EGFR-TKI) in patients with nonsmall cell lung cancer (NSCLC). METHODS: The authors tested the possibility that nucleotide sequencing may be poorly suited for detection of mutations in tumor samples and found that denaturing high-performance liquid chromatography (dHPLC) was an efficient and more sensitive method for screening. RESULTS: These results suggested that some reports based on standard DNA sequencing techniques may have underestimated mutation rates. In the present report, the authors examined the relationship between the presence and type of EGFR mutations detected by dHPLC and various clinicopathologic features of NSCLC, including response to therapy with EGFR-TKI. Among 251 patients with advanced disease, 100 individuals received EGFR-TKI. Those whose tumors harbored a detectable EGFR kinase mutation were much more likely to have a partial response (PR) or stable disease (SD) with EGFR-TKI therapy than patients whose tumor contained no mutation (80% vs 35%; P = .001). Among the individual genotype subgroups, the frequency of a PR or SD was significantly different between patients with an exon 19 deletion compared with those with no detectable mutation (86% vs 35%; P < .001). Furthermore, patients whose tumors expressed an exon 19 mutant EGFR isoform exhibited a trend toward better EGFR-TKI response (86% vs 67%; P = .171) and improved survival compared with patients whose tumors expressed an exon 21 mutation. CONCLUSIONS: Our findings warrant confirmation in large prospective trials and exploration of the biological mechanisms of the differences between mutation types.

Bilateral pulmonary alveolar infiltrate and prostate tumour in a 54-year-old man.

THIS CASE STUDY DESCRIBES THE ASSOCIATION BETWEEN TWO RARE ENTITIES: pulmonary alveolar proteinosis (PAP) and embryonic rhabdomyosarcoma of the prostate in a 54 year old male presenting with pulmonary symptoms and obstructive urinary symptoms. The prostate tumour was treated with a radical cystectomy and adjuvant chemotherapy and radiotherapy. The patient did not wish to have treatment for his pulmonary disease and died 1 year after surgery as a result of intra-abdominal spread of the neoplasm.

Grading follicular lymphomas in fine-needle aspiration biopsies: the role of ThinPrep slides and flow cytometry.

BACKGROUND: The World Health Organization (WHO) recommends a 3-tier grading system (Grades 1-3) for follicular lymphomas (FLs) based on the absolute number of centroblasts per high-power microscopic field (HPF) in 10 neoplastic follicles. Grades 1 and 2 FL are still managed as indolent FLs, whereas Grade 3 FL is thought to behave more aggressively. In this study, the feasibility of grading FL using ThinPrep (TP) slides and flow cytometry (FC) was evaluated. METHODS: Fifty-three cases of lymph node fine-needle aspiration (FNA) from patients with histologically confirmed FL (20 Grade 1, 17 Grade 2, and 16 Grade 3) were included. The number of centroblasts present in 300 lymphoid cells and in 10 HPF in TP Papanicolaou-stained slides was evaluated. The percentage of CD10-positive small cells was calculated with FC results. Statistical analysis was performed with the Jonckheer-Terpstra nonparametric trend test and the Wilcoxon rank sum test. RESULTS: The statistical analysis demonstrated a significant upward trend in the number of centroblasts as the grades increased. Also, all 3 methods had statistically significant results to distinguish different grades of FL, except when FC was used to distinguish Grade 2 from Grade 3 FL. CONCLUSIONS: Counting centroblasts, either in 300 lymphoid cells or per 10 HPF in TP slides, represented a statistically significant method to separate different grades of FL in FNA samples. Analysis of cell size by FC was not as reliable to distinguish different grades of FL, especially Grade 2 from 3.

Assessment of RET/PTC oncogene activation in thyroid nodules utilizing laser microdissection followed by nested RT-PCR.

Single palpable nodules of the thyroid gland are common in clinical practice; the majority of such lesions are benign. However, noninvasive thyroid nodules that exhibit borderline morphological signs of papillary cancer represent a diagnostic challenge. Rearrangements of the RET oncogene have been proposed as a marker for papillary thyroid cancer. In this chapter, methods for the analysis of the RET oncogene in laser microdissected papillary thyroid cancer tissue are described.