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Vaccination is one of the most effective and most controlled interventions in the occurrence of infectious diseases, and it is essential to analyze vaccination coverage and homogeneity between municipalities. The National Immunization Program (PNI), together with the Epidemiological Surveillance System in Brazil, seek to generate an impact on the control, elimination and even eradication of preventable diseases, immunizing the general population, especially children. This study aims to analyze vaccination coverage and homogeneity in the Midwest of Brazil and to relate to the incidence of immunopreventable diseases in children under five years of age. This is an ecological study, based on data from the Information System of the National Immunization Program (SI-PNI), for the period 2018-2022, analyzing the indicators of vaccination coverage, homogeneity and the incidence of immunopreventable diseases in children under five years of age.

Objetivo: A doença renal crônica terminal (DRCT) ocasiona um grande impacto na qualidade de vida do indivíduo portador. Neste contexto, a espiritualidade e religiosidade são vistos como recursos que possam ajudar estas pessoas a lidarem com a sua enfermidade. Portanto, este trabalho parte da seguinte questão norteadora: “Como a espiritualidade e a religiosidade influencia na vida das pessoas em tratamento hemodialítico?”. O objetivo foi identificar evidências sobre como a espiritualidade e religiosidade pode influenciar a vida do paciente renal crônico terminal em hemodiálise. Método: Constitui de uma revisão da literatura do tipo integrativa, realizada por pares, nas seguintes bases: PubMed, Web of Science, CINAHL, Science Direct, BVS, em fevereiro de 2022, foram adotados como critérios de inclusão artigos primários e excluídos artigos secundários, seguindo as recomendações do método. Resultado: Foram identificados 994 registros, e 987 estudos irrelevantes para a revisão, duplicatas, editoriais e resumos de congresso foram descartados, restando sete artigos. Após a leitura na integra cinco artigos foram selecionados para a revisão. Conclusão: Os benefícios da espiritualidade e religiosidade no enfrentamento das diversidades encontradas pelo renal crônico em hemodiálise durante o seu tratamento, mostraram se presentes neste estudo, no entanto ressaltou a necessidade de agregar novos conhecimentos sobre a temática no aperfeiçoamento da assistência do indivíduo. Objective: End-stage chronic kidney disease (ESRD) has a major impact on the quality of life of the individual with it. In this context, spirituality and religiosity are seen as resources that can help these people to deal with their illness. Therefore, this work starts from the following guiding question: “How do spirituality and religiosity influence the lives of people undergoing hemodialysis treatment? The objective was to identify evidence on how spirituality and religiosity can influence the life of end-stage renal patients on hemodialysis. Method: It consists of an integrative literature review, carried out by peers, in the following bases: PubMed, Web of Science, CINAHL, Science Direct, BVS, in February 2022, primary articles were adopted as inclusion criteria and secondary articles were excluded , following the method recommendations. Result: 994 records were identified, and 987 studies irrelevant to the review, duplicates, editorials and congress abstracts were discarded, leaving seven articles. After reading in full, five articles were selected for review. Conclusion: The benefits of spirituality and religiosity in coping with the diversities encountered by chronic renal patients on hemodialysis during their treatment were present in this study, however, it highlighted the need to add new knowledge on the subject in order to improve the care of the individual. Objetivo: La enfermedad renal crónica (ERT) terminal tiene un gran impacto en la calidad de vida del individual que la padece. En este contexto, la espiritualidad y la religiosidad son vistas como recursos que pueden ayudar a estas personas a enfrentar su enfermedad. Por lo tanto, este trabajo parte de la siguiente pregunta orientadora: “¿Cómo influyen la espiritualidad y la religiosidad en la vida de las personas en tratamiento de hemodiálisis? El objetivo fue identificar evidencias sobre cómo la espiritualidad y la religiosidad pueden influir en la vida de los pacientes renales terminales en hemodiálisis. Método: Consiste en una revisión integrativa de la literatura, realizada por pares, en las siguientes bases: PubMed, Web of Science, CINAHL, Science Direct, BVS, en febrero de 2022, se adoptaron como criterios de inclusión los artículos primarios y se excluyeron los artículos secundarios. siguiendo las recomendaciones del método. Resultado: se identificaron 994 registros y se descartaron 987 estudios irrelevantes para la revisión, duplicados, editoriales y resúmenes de congresos, quedando siete artículos. Después de la lectura completa, se seleccionaron cinco artículos para su revisión. Conclusión: Los beneficios de la espiritualidad y la religiosidad en el enfrentamiento de las diversidades encontradas por los pacientes renales crónicos en hemodiálisis durante su tratamiento estuvieron presentes en este estudio, sin embargo, se destacó la necesidad de agregar nuevos conocimientos sobre el tema para mejorar la atención de los pacientes. individual.

Acral lentiginous melanoma (ALM) is a rare subtype of melanoma with aggressive behavior. IMPDH enzyme, involved in de novo GTP biosynthesis, has been reported to assemble into large filamentary structures called rods/rings (RR) or cytoophidium (cellular snakes). RR assembly induces a hyperactive state in IMPDH, usually to supply a high demand for GTP nucleotides, such as in highly proliferative cells. We investigate whether aggressive melanoma tumor cells present IMPDH-based RR structures. Forty-five ALM paraffin-embedded tissue samples and 59 melanocytic nevi were probed with anti-IMPDH2 antibody. Both the rod- and ring-shaped RR could be observed, with higher frequency in ALM. ROC curve analyzing the proportions of RR-positive cells in ALM versus nevi yielded a 0.88 AUC. Using the cutoff of 5.5% RR-positive cells, there was a sensitivity of 80% and specificity of 85% for ALM diagnosis. In ALM, 36 (80%) showed RR frequency above the cutoff, being classified as RR-positive, compared with only 9 (15%) of the nevi (p .001). Histopathology showed that 71% of the RR-positive specimens presented Breslow thickness 4.0mm, compared with only 29% in the RR-low/negative (p = .039). We propose that screening for RR structures in biopsy specimens may be a valuable tool helping differentiate ALM from nevi and accessing tumor malignancy.

Recently, cytoophidium, a nonmembrane-bound intracellular polymeric structure, has been shown to exist in various organisms, including tumor tissues, but its function and mechanism have not yet been examined. Examination of cytoophidia-assembled gene inosine monophosphate dehydrogenase (IMPDH) and cytidine triphosphate synthetase (CTPS) mRNA levels showed that only IMPDH1 levels were significantly higher in the clear cell renal cell carcinoma (ccRCC). IMPDH1 was positively correlated with the metastasis-related gene Y-box binding protein 1 (YB-1) and served as an independent prognostic factor in ccRCC. Kaplan-Meier analysis indicated that patients with tumors that expressed high IMPDH1 levels had a shorter overall survival (OS) and disease-free survival (DFS). Furthermore, detection of cytoophidia by immunofluorescence staining in ccRCC tissues showed that IMPDH1-assembled cytoophidia are positively associated with tumor metastasis. Mechanistically, IMPDH1 and YB-1 formed an autoregulatory positive feedback loop: IMPDH1 maintained YB-1 protein stabilization; YB-1 induced IMPDH1 expression by binding to the IMPDH1 promoter motif. Functionally, IMPDH1-assembled cytoophidia physically interacted with YB-1 and translocated YB-1 into the cell nucleus, thus correlating with ccRCC metastasis. Our findings provide the first solid theoretical rationale for targeting the IMPDH1/YB-1 axis to improve metastatic renal cancer treatment.

PATIENTS AND METHODS Samples of acral lentiginous melanomas (ALMs) were obtained from the Department of Pathology at Escola Paulista de Medicina-Universidade Federal de Sao Paulo (UNIFESP), Sao Paulo, Brazil. Demographic, clinical, and follow-up data were obtained from the charts of Hospital Sao Paulo. From 2 tissue microarrays containing 60 nevi and quadruplicate samples of ≥1.0-mm of 49 ALM, sections were stained to evaluate SCF, KIT, BRAF, CYCLIND1, MYC, and PTEN immunohistochemical protein expression. RESULTS Nevi and ALM from 2006 to 2010 were reviewed and collected. All specimens were in the vertical growth phase, and histopathological parameters indicated that tumors were at an advanced stage at diagnosis. Average tumor thickness was 6.95 mm, 63% were ulcerated, average mitotic index was 5 mitotic cells per mm, and 43% were at Clark's level V. Compared with nevi, the χ test showed that ALM significantly correlated with SCF protein expression (P = 0.001) and expression heterogeneity (P < 0.000). Similar findings were observed for KIT (P = 0.005, P = 0.003, respectively), MYC (P < 0.000, P < 0.000), and PTEN (P = 0.005, P < 0.000). Malignancy did not correlate with BRAF and CYCLIN D1 expression (P = 0.053 and P = 0.259, respectively), but it did significantly correlate with their heterogeneous expression (P < 0.000, P = 0.024, respectively). Combined protein expression had an odds ratio of greater malignancy when BRAF and MYC were positive and/or heterogeneously expressed (OR of 78 and 95, respectively). DISCUSSION AND CONCLUSION We show that marker protein expression, when combined with heterogeneous expression as shown by immunohistochemistry, is a powerful indicator of malignancy in ALMs, especially, when protein pairs are combined.

Melanoma is an aggressive skin malignancy, and the acral lentiginous melanoma (ALM) subtype affects non-sun-exposed sites such as the volar surface of the hands and feet and the subungual region and is most common in Asians, Hispanics, and Afro-descendants. The presence of different clones within the same tumor seems to influence the aggressiveness of tumors. Patients with mutations in the KIT gene have shown a good response to tyrosine kinase inhibitor therapy. We tested the hypothesis of intratumor heterogeneity through analysis of KIT gene mutations in ALM and determined the correlation between KIT mutations and demographic, clinical, and histopathological variables. Twenty-five ALM samples were examined. We selected up to four different regions per tumor for sequencing by the Sanger method for analysis of KIT gene exon 11 and exon 13 mutations. Advanced lesions were predominant, and the main histopathological characteristics of lesions were Breslow index >4.0 mm (17/25, 68%), Clark level IV/V (21/25, 84%), ulceration (16/25, 64%), and >3 mitoses/mm (8/25, 32%). KIT gene mutations were detected in 11/25 cases (44%), and all these 11 cases displayed intratumor heterogeneity, that is, at least 2 tumor regions had different mutational profiles. The predicted effect of most mutations detected was detrimental to protein function. No significant correlations between histopathological variables and either KIT mutations or intratumor heterogeneity were observed. The hypothesis of intratumor heterogeneity of KIT gene mutations in acral lentiginous melanoma was supported.

The choice of appropriate therapeutic strategies may be influenced by intratumor heterogeneity and makes cancer treatment considerably more challenging. We aimed to evaluate the heterogeneity of BRAF exon 15 mutations in different areas of acral lentiginous melanoma (ALM). The entire exon 15 was sequenced in 4 different areas of paraffin-embedded samples from 26 patients with ALM. A total of 26 of 49 cases of ≥1 mm in depth of ALM identified by clinical, anatomical, and pathological data fulfilled the inclusion and exclusion criteria for this study. Tumors had a mean Breslow depth of 7.2 mm and an average mitotic index of 3 mitosis/mm. Mutations distinct from the common V600E and V600K were detected in 31%, and intratumor heterogeneity was observed in 31% of samples. Interestingly, 63.5% of all mutations had been previously associated with cancer. Most (62.5%) of the missense BRAF exon 15 mutations found in the ALM samples examined here were deemed "detrimental" for protein function according to at least 2 functional prediction programs, and 3 mutations (37.5%) were predicted to be "neutral," with no effect on protein function. BRAF exon 15 mutations were detected frequently in ALM and displayed heterogeneity, a finding to be further investigated.

Diante do alto índice de violência LGBTfóbica no Brasil, o presente artigo discorre acerca das consequências da LGBTfobia na saúde mental de pessoas Lésbicas, Gays, Bissexuais, Travestis e Transexuais (LGBTs). Objetivou-se compreender as consequências da LGBTfobia na saúde mental das pessoas LGBTs, assim como descrever as principais formas de discriminação sofridas. Para alcançar esses objetivos, realizou-se uma pesquisa qualitativa com entrevistas semiestruturadas, utilizando o sistema “bola de neve” para acessar as(os) entrevistadas(os). As entrevistas foram realizadas com 19 pessoas LGBTs com idade igual ou superior a 18 anos, sendo elas: 3 homens cisgêneros gays, 3 mulheres cisgêneros lésbicas, 3 homens cisgêneros bissexuais, 3 mulheres cisgêneros bissexuais, 2 homens transexuais, 3 mulheres transexuais e 2 mulheres travestis. Os dados foram analisados através da análise de conteúdo. Verificou-se que a discriminação vivenciada pelas pessoas LGBTs ocorre no ambiente familiar, trabalho, relações amorosas e no contexto escolar. Também foi observado que o discurso religioso corrobora com esses comportamentos LGBTfóbicos, utilizando da “homofobia religiosa” para desqualificar as diversidades sexuais e de gênero. Por conseguinte, a pesquisa concluiu que a grande maioria das pessoas vítimas de LGBTfobia está sujeita à ocorrência de efeitos prejudiciais à saúde mental e averiguou que as redes de apoio possuem um papel importante no sentido de fornecer suporte emocional. Constatou-se, também, que famílias protetivas e acolhedoras contribuem significativamente para o enfrentamento da LGBTfobia cotidiana e são capazes de reduzir a ocorrência de sofrimento psíquico e mental nas pessoas atingidas.

Malaria is a major global health problem, affecting mainly tropical and subtropical areas. In Brazil, in most cases, it was caused by Plasmodium vivax and Plasmodium falciparum, respectively. Malaria can lead to severe complications like severe anemia, placental malaria, cerebral malaria and others. When associated with lung, severe malaria can cause Acute Respiratory Distress Syndrome (ARDS). The main problems of this syndrome are the presence of inflammatory infiltrate, hemorrhages and edema. It is not known what starts the development of malaria associated ARDS, but it could be related to adhesion molecules expressed by the parasite on the surface of the erythrocyte membrane, or with the inflammatory responses of the host. However, latest researches show new mechanisms involving neutrophils are the key to the establishment of this syndrome.

The use of molecular biology in combination with morphological analysis is increasing because of the treatments by target therapies. However, to improve the methods for obtaining DNA for molecular analyses from formalin-fixed, paraffin-embedded (FFPE) tissue is a challenge. The aim of this study was to evaluate the DNA extracted from FFPE tissue blocks (non-tumoral liver, spleen, and brain), obtained from autopsy, 8–24 h post mortem , using three methods of DNA extraction. PCR of the β-actin (136pb) and human amelogenin (AMEL 212–218 bp/106–112 bp) genes, as well as short tandem repeat (STR) (100–400 bp fragments), reported in forensic scientific analysis, was performed to evaluate the effectiveness of the methods of DNA extraction. We used 28 archived (1 and 5 years) and 12 recent autopsy cases. The commercial kit showed reproducible and consistent results in the PCR amplification of the β-actin and AMEL genes and in analysis by STR used in forensic analysis. This is the first report using non-tumoral samples from FFPE autopsy tissues, comparing the three most common methods of DNA extraction and using the STR previously described in forensics. Our study has clarified the challenges for pathologists in applying the molecular biology approach in combination with methods suited for morphology, which must be improved. The data provided here should be used in other molecular studies in FFPE samples.

Em 30 pacientes com pênfigo foliáceo, a freqüência da estrongiloidíase foi de 40,0%, através de três exames de Baermann-Moraes. No "Hospital do Pênfigo", em Uberaba, as freqüências da estrongiloidíase nos funcionários (n = 14) e escolares (n = 47) da Escola-creche, anexa, também foram altas, respectivamente 35,7% e 23,4%. Em 7 (58,3 %) das 12 amostras do solo, do jardim/pátio do "Hospital", foram observadas formas de vida livre do Strongyloides stercoralis. O fator ambiental e a predisposição dos pacientes foram associados à alta transmissão da estrongiloidíase.In 30 patients with foliaceous pemphigus the frequency of strongyloidiasis was 40%, by three Baermann- Moraes examination. In the "Hospital do Penfigo", for patients with pemphigus of Uberaba, the frequencies of strongyloidiasis in the employees (n = 14) and students (n=47), of the annexed nursery, also were high, respectively 35.7 % and 23.4%. In 7(58.3) of 12 samples from the soil of the hospital courtyard were found free-life forms of Strongyloides. The environmental factor and the susceptibility of the pacients were associated with the high transmission of the strongyloidiasis.

Development and standardization of reliable methods for detection of Mycobacterium tuberculosis in clinical samples is an important goal in laboratories throughout the world. In this work, lung and spleen fragments from a patient who died with the diagnosis of miliary tuberculosis were used to evaluate the influence of the type of fixative as well as the fixation and paraffin inclusion protocols on PCR performance in paraffin embedded specimens. Tissue fragments were fixed for four h to 48 h, using either 10% non-buffered or 10% buffered formalin, and embedded in pure paraffin or paraffin mixed with bee wax. Specimens were submitted to PCR for amplification of the human beta-actin gene and separately for amplification of the insertion sequence IS6110, specific from the M. tuberculosis complex. Amplification of the beta-actin gene was positive in all samples. No amplicons were generated by PCR-IS6110 when lung tissue fragments were fixed using 10% non-buffered formalin and were embedded in paraffin containing bee wax. In conclusion, combined inhibitory factors interfere in the detection of M. tuberculosis in stored material. It is important to control these inhibitory factors in order to implement molecular diagnosis in pathology laboratories. O desenvolvimento e a padronização de métodos confiáveis para a detecção de Mycobacterium tuberculosis em amostras clínicas é um objetivo importante nos laboratórios de todo o mundo. Neste trabalho, fragmentos de pulmão e baço de paciente que morreu com o diagnóstico de tuberculose miliar foram usados para avaliar a influência do tipo de fixador e dos protocolos de fixação e inclusão em parafina na performance da PCR. Fragmentos de tecido foram fixados por quatro h a 48 h, usando formalina não tamponada a 10% ou formalina tamponada a 10% e incluídos em parafina pura ou misturada a cera de abelha. As amostras foram submetidas a PCR para amplificação do gene da beta-actina humana e, separadamente, para amplificação da sequência de inserção IS6110, específica do complexo M. tuberculosis. O resultado da amplificação do gene da beta-actina foi positivo em todas as amostras. Não foram gerados amplicons na PCR-IS6110 em amostras de tecido pulmonar fixadas usando formalina não tamponada a 10% e incluídas em parafina com cera de abelha. Em conclusão, fatores inibitórios combinados interferiram na detecção de M. tuberculosis em material de arquivo. É importante controlar estes fatores inibitórios para poder implementar o diagnóstico molecular em laboratórios de patologia.

e20092 Background: Cutaneous melanoma (CM) is the skin malignancy with the highest potential of mortality. The MAPK pathway is constitutively activated in the majority of melanomas and it is the ma...

A instabilidade cromossômica e a aneuploidia são características associadas às células malignas. Sabe-se que essas alterações podem ser resultantes de erros em eventos durante a mitose. Com o objetivo de gerar uma população com ganho de ploidia, utilizamos dois inibidores de fases distintas da mitose. Resultando no aumento da frequência celular em G2/M, ou seja, células com 4 vezes o número de cromossomos (4C) e de células com DNA acima de 4, hipertetraploide. Quantificamos a quantidade de núcleos e demonstramos que o tratamento, especificamente, levou a uma NCI, e não a multinucleação. Ambas linhagens celulares submetidas ao tratamento apresentaram alterações morfológicas, como protrusões de membrana, indicando alterações no citoesquelto. Nas análises de mRNA e da expressão proteica, observamos alterações na regulação da actina, coincidindo com a elevação dos mRNAs de YAP/TAZ, efetores co-transcricionais da via Hippo, regulada por alterações no citoesqueleto de actina. Desde modo, propomos, que o tratamento utilizado é um método eficiente para o estudo de células aneuploides e da NCI, que o citoesqueleto de actina é modulado por esse fenótipo e requer YAP/TAZ, provavelmente para manter a sobrevivência e favorecer a proliferação celular observada após o tratamento. Chromosomal instability and aneuploidy are characteristics associated with malignant cells. It is known that these changes may be due to errors in events during mitosis. In order to generate a population with gain of ploidy, we used two inhibitors of distinct phases of mitosis. Resulting in increasing cell frequency in G2/M, cells with 4 times the number of chromosomes (4C) and cells with DNA above 4, hypertetraploid. We quantified the number of nuclei and demonstrated that the treatment specifically led to NCI, not multinucleation. Both cell lines submitted to treatment presented morphological alterations, such as membrane protrusions, indicating changes in the cytoskeleton. In the analysis of mRNA and protein expression, we observed alterations in actin regulation, coinciding with the elevation of YAP / TAZ mRNAs, co-transcriptional effectors of the Hippo signaling pathway, regulated by changes in the actin cytoskeleton. We propose, that the treatment used is an efficient method for the study of aneuploid cells as well NCI. Also, the actin cytoskeleton is modulated by that phenotype which requires high YAP / TAZ, probably to maintain cell survival and promote cell proliferation observed.