Aberrant FOXP3 gene expression in eutopic and ectopic endometrium of infertile women with endometriosis

Background: Immunological theories suggest that changes in the immune system could prevent the ability to eliminate the endometrium of the pelvic cavity. In women with endometriosis is possible that changes in immunity mediated by T cells facilitate the implantation of endometrial fragments or cells in ectopic locations and recent studies have associated the FOXP3 gene with homeostasis of the immune system and the development of autoimmune diseases. We aimed to evaluate the expression of FOXP3 gene in both eutopic and ectopic endometrium of infertile women with endometriosis and controls.Methods: A case-control study was performed comprising 25 infertile women with endometriosis and 44 fertile women without endometriosis. FOXP3 and GAPDH expression was measured by mRNA using quantitative reverse transcription polymerase chain reaction (qRT-PCR) based on TaqMan methodology. The Mann-Whitney test was used to compare the values between the groups.Results: The results disclosed that mean expression of FOXP3 in eutopic endometrium of endometriosis group was significantly higher when compared to the control group (p=0,008), regardless the stage of the disease. Considering the samples of the ectopic endometrium, FOXP3 expression was also significantly higher in endometriosis group compared to the control group (p=0,004), regardless the stage of the disease.Conclusion: the results of this study point to an association between the expression of FOXP3 and the genesis/progression of endometriosis.Â

Chromosomal and molecular abnormalities in a group of Brazilian infertile men with severe oligozoospermia or non-obstructive azoospermia attending an infertility service

PURPOSE: To determine the frequency of genetic alterations in a population of Brazilian infertile men with severe oligozoospermia or non-obstructive azoospermia. MATERIALS AND METHODS: Retrospective study of a group of 143 infertile men with severe oligozoospermia or non-obstructive azoospermia from the Andrology Outpatient Clinic of the Human Reproduction Service at the ABC School of Medicine. Of these patients, 100 had severe oligozoospermia, and 43 non-obstructive azoospermia. All patients underwent a genetic study which included karyotype analysis and Y-microdeletion investigation. RESULTS: Genetic abnormalities were found in 18.8% of the studied patients. Chromosomal abnormalities were found in 6.2% of the patients, being more prevalent in the azoospermia group (11.6%) than in the oligozoospermia group (4%). Chromosomal variants were found in 8.3%, and Y-chromosome microdeletions in 4.2% of patients. CONCLUSION: The high frequency of genetic alterations (18.8%) in our series justified performing a genetic investigation in a population with idiopathic infertility, as results may help determine the prognosis, as well as the choice of an assisted reproduction technique. Moreover, a genetic investigation could minimize the risk of transmitting genetic abnormalities to future generations such as genetic male infertility, mental retardation, genital ambiguity and/or birth defects

Metabolic Insight into Glioma Heterogeneity: Mapping Whole Exome Sequencing to In Vivo Imaging with Stereotactic Localization and Deep Learning

Intratumoral heterogeneity (ITH) complicates the diagnosis and treatment of glioma, partly due to the diverse metabolic profiles driven by underlying genomic alterations. While multiparametric imaging enhances the characterization of ITH by capturing both spatial and functional variations, it falls short in directly assessing the metabolic activities that underpin these phenotypic differences. This gap stems from the challenge of integrating easily accessible, colocated pathology and detailed genomic data with metabolic insights. This study presents a multifaceted approach combining stereotactic biopsy with standard clinical open-craniotomy for sample collection, voxel-wise analysis of MR images, regression-based GAM, and whole-exome sequencing. This work aims to demonstrate the potential of machine learning algorithms to predict variations in cellular and molecular tumor characteristics. This retrospective study enrolled ten treatment-naïve patients with radiologically confirmed glioma. Each patient underwent a multiparametric MR scan (T1W, T1W-CE, T2W, T2W-FLAIR, DWI) prior to surgery. During standard craniotomy, at least 1 stereotactic biopsy was collected from each patient, with screenshots of the sample locations saved for spatial registration to pre-surgical MR data. Whole-exome sequencing was performed on flash-frozen tumor samples, prioritizing the signatures of five glioma-related genes: IDH1, TP53, EGFR, PIK3CA, and NF1. Regression was implemented with a GAM using a univariate shape function for each predictor. Standard receiver operating characteristic (ROC) analyses were used to evaluate detection, with AUC (area under curve) calculated for each gene target and MR contrast combination. Mean AUC for five gene targets and 31 MR contrast combinations was 0.75 ± 0.11; individual AUCs were as high as 0.96 for both IDH1 and TP53 with T2W-FLAIR and ADC, and 0.99 for EGFR with T2W and ADC. These results suggest the possibility of predicting exome-wide mutation events from noninvasive, in vivo imaging by combining stereotactic localization of glioma samples and a semi-parametric deep learning method. The genomic alterations identified, particularly in IDH1, TP53, EGFR, PIK3CA, and NF1, are known to play pivotal roles in metabolic pathways driving glioma heterogeneity. Our methodology, therefore, indirectly sheds light on the metabolic landscape of glioma through the lens of these critical genomic markers, suggesting a complex interplay between tumor genomics and metabolism. This approach holds potential for refining targeted therapy by better addressing the genomic heterogeneity of glioma tumors

Complex small supernumerary marker chromosome with a 15q/16p duplication: clinical implications

Abstract Background Complex small supernumerary marker chromosomes (sSMCs) consist of chromosomal material derived from more than one chromosome and have been implicated in reproductive problems such as recurrent pregnancy loss. They may also be associated with congenital abnormalities in the offspring of carriers. Due to its genomic architecture, chromosome 15 is frequently associated with rearrangements and the formation of sSMCs. Recently, several different CNVs have been described at 16p11.2, suggesting that this region is prone to rearrangements. Results We detected the concomitant occurrence of partial trisomy 15q and 16p, due to a complex sSMC, in a 6-year-old girl with clinical phenotypic. The karyotype was analyzed by G and C banding, NOR staining, FISH and SNP array and defined as 47,XX,+der(15)t(15;16)(q13;p13.2)mat. The array assay revealed an unexpected complex sSMC containing material from chromosomes 15 and 16, due to an inherited maternal translocation (passed along over several generations). The patient’s phenotype included microsomia, intellectual disability, speech delay, hearing impairment, dysphagia and other minor alterations. Discussion This is the first report on the concomitant occurrence of partial trisomy 15q and 16p. The wide range of phenotypes associated with complex sSMCs represents a challenge for genotype-phenotype correlation studies, accurate clinical assessment of patients and genetic counseling

Características clínico-epidemiológicas no carcinoma espinocelular de boca e orofaringe Clinic and epidemiologic characteristics in the with squamous cell carcinoma of the mouth and oropharynx

O câncer de boca e orofaringe é de comportamento agressivo e, no Brasil, a incidência é considerada uma das mais altas do mundo, sendo o mais comum da região de cabeça e pescoço. OBJETIVO: O objetivo deste trabalho é analisar os aspectos clínico-epidemiológicos dos pacientes e a evolução da doença. FORMA DE ESTUDO: Clínico retrospectivo. CASUÍSTICA E MÉTODO: Foram arrolados 43 casos de carcinoma espinocelular (CEC) de boca e 25 de orofaringe do Serviço de Cirurgia de Cabeça e Pescoço da Santa Casa de Misericórdia de Santos e do Hospital Ana Costa entre os anos de 1997 a 2000. Informações sobre idade, sexo, profissão, raça, hábitos de tabagismo e etilismo, uso de prótese dentária, origem do encaminhamento do paciente ao tratamento, localização da lesão, estadiamento clínico, grau de diferenciação histológica, tratamento, sobrevida e presença de segundo tumor primário foram analisados estatisticamente pelo Teste Exato de Fischer. RESULTADOS: Dos pacientes com CEC em boca, a relação de incidência masculino-feminino foi de 3,35:1, a idade variou de 46 a 91 anos (mediana de 62), 90,7% eram caucasianos, 81% foram referenciados por profissionais médicos, 76,8% eram tabagistas, 74% etilistas, 79% não utilizavam prótese dentária. O sítio mais acometido foi a língua (51,1%), 53% apresentaram-se nos estádios III e IV, 72,1% eram de grau histológico II, 53% foram tratados por cirurgia e 47% por cirurgia e radioterapia adjuvante e 9,3% apresentaram segundo tumor primário. Para a orofaringe, a relação masculino-feminino foi de 11,5:1, com idade entre 40 e 81 anos (mediana de 58), 92% eram caucasianos, 92% foram encaminhados por médicos, 84% eram tabagistas, 80% etilistas, 52% não utilizavam prótese, as tonsilas palatinas foram o sítio mais acometido (76%), 96% estavam em estádios III e IV, 84% eram de grau II, 80% foram tratados por cirurgia associada a radioterapia, 16% a cirurgia para resgate de falha após radioterapia e 4% a cirurgia exclusiva e 8% tiveram segundo primário. Não houve relação estatisticamente significativa entre o estadiamento e os hábitos de tabagismo, etilismo e uso de prótese. Tais hábitos, a faixa etária e o grau histológico não tiveram relação significativa com o sítio do tumor. Estavam vivos e livres de doença 69,7% dos pacientes com tumor de boca e 22% de orofaringe. CONCLUSÃO: O médico ou dentista que dá o atendimento inicial é fundamental no reconhecimento das lesões, para que se possa estabelecer o diagnóstico precoce.<br>Cancer of the oral cavity and oropharynx is aggressive. It is one of the commonest cancers in Brazil and may be considered as the commonest in the head and neck. AIM: The objective of this paper is to evaluate clinical and epidemiological factors and the outcome. STUDY DESIGN: Clinical retrospective. MATERIAL AND METHODS: In a descriptive retrospective study, the charts of 43 cases of oral and 25 of oropharyngeal squamous cell carcinoma (SCC) in the period 1997-2000 have been reviewed from the Departments of Head and Neck Surgery of Santa Casa de Misericórdia de Santos and Hospital Ana Costa. This was analyzed with emphasis on age, gender, profession, ethnic aspects, tobacco and alcohol use, dental prosthesis, referement origin, site of the lesion, clinical staging, histologic grade, treatment methods, survival and second cancer presence in the study group. The data were analysed by Exact Test of Fischer. RESULTS: In the oral cavity cancer patients, a male female ratio of 3.35:1 was observed, the median age was 62 years (ranging 46 to 91 years), 90.7% were Caucasian, 81% were referred from medical professionals, tobacco use was identified in 76.8%, alcohol intake in 74%, 79% were not dental prosthesis users, tongue was the commonest site identified (51.1%), 53% were staged as III and IV clinical stages, 72.1% were moderately differentiated SCC, combined modality of treatment (surgery and adjuvant radiation therapy) was employed in 47% and 9.3% presented a second primary tumor. For the oropharynx, the male female ratio was 11.5:1, the median age was 58 years (ranging 40 to 81 years), 92% were Caucasian, 92% were referred from medical professionals, exposure to tobacco and alcohol was respectively noted in 84% and 80%, 52% did not use dental prosthesis, the tonsils were the commonest site (76%), 96% were staged as III and IV, 84% had moderately differentiated SCC, 75% underwent combined treatment (surgery and adjuvant radiation therapy) and 8% presented a second tumor elsewhere. There was not significant relationship between the clinical staging and tobacco, alcohol and dental prosthesis exposure. These factors, the age and the histologic grade had no relationship with the tumor site. For the oral cavity, 69,7% were alive with no evidence of disease and for the oropharynx, 22% were under this condition. CONCLUSION: The professional who performs the first evaluation is important in recognizing the lesions in order to achieve early detection

Rickettsia in Synanthropic and Domestic Animals and Their Hosts from Two Areas of Low Endemicity for Brazilian Spotted Fever in the Eastern Region of Minas Gerais, Brazil

The aim of this study was to understand the current epidemiology of rickettsial diseases in two rickettsial-endemic regions in Brazil. In the municipalities of Pingo D'Agua and Santa Cruz do Escalvado, among serum samples obtained from horses and dogs, reactivity by immunofluorescent assay against spotted fever group rickettsiae was verified. In some serum samples from opossums (Didelphis aurita) captured in Santa Cruz do Escalvado, serologic response against rickettsiae was also verified. Polymerase chain reaction identified rickettsiae only in ticks and fleas obtained in Santa Cruz do Escalvado. Rickettsiae in samples had 100% sequence homology with Rickettsia felis. These results highlight the importance of marsupials in maintenance of the sylvatic cycle of rickettsial disease and potential integration with the domestic cycle. Our data also support the importance of horses and dogs as sentinels in monitoring circulation of rickettsiae in an urban area