Immunohistochemical Characterization of M1, M2, and M4 Macrophages in Leprosy Skin Lesions.

Mycobacterium leprae is the etiological agent of leprosy. Macrophages (Mφs) are key players involved in the pathogenesis of leprosy. In this study, immunohistochemical analysis was performed to examine the phenotype of Mφ subpopulations, namely M1, M2, and M4, in the skin lesions of patients diagnosed with leprosy. Based on the database of treatment-naïve patients treated between 2015 and 2019 at the Department of Dermatology of the University of the State of Pará, Belém, routine clinical screening samples were identified. The monolabeling protocol was used for M1 macrophages (iNOS, IL-6, TNF-α) and M2 macrophages (IL-10, IL-13, CD163, Arginase 1, TGF-ß, FGFb), and the double-labeling protocol was used for M4 macrophages (IL-6, MMP7, MRP8, TNF-α e CD68). To confirm the M4 macrophage lineage, double labeling of the monoclonal antibodies CD68 and MRP8 was also performed. Our results demonstrated a statistically significant difference for the M1 phenotype among the Virchowian (VV) (4.5 ± 1.3, p < 0.0001), Borderline (1.6 ± 0.4, p < 0.0001), and tuberculoid (TT) (12.5 ± 1.8, p < 0.0001) clinical forms of leprosy. Additionally, the M2 phenotype showed a statistically significant difference among the VV (12.5 ± 2.3, p < 0.0001), Borderline (1.3 ± 0.2, p < 0.0001), and TT (3.2 ± 0.7, p < 0.0001) forms. For the M4 phenotype, a statistically significant difference was observed in the VV (9.8 ± 1.7, p < 0.0001), Borderline (1.2 ± 0.2, p < 0.0001), and TT (2.6 ± 0.7, p < 0.0001) forms. A significant correlation was observed between the VV M1 and M4 (r = 0.8712; p = 0.0000) and between the VV M2 × TT M1 (r = 0.834; p = 0.0002) phenotypes. The M1 Mφs constituted the predominant Mφ subpopulation in the TT and Borderline forms of leprosy, whereas the M2 Mφs showed increased immunoexpression and M4 was the predominant Mφ phenotype in VV leprosy. These results confirm the relationship of the Mφ profile with chronic pathological processes of the inflammatory response in leprosy.

Comparative Analysis of Human Hepatic Lesions in Dengue, Yellow Fever, and Chikungunya: Revisiting Histopathological Changes in the Light of Modern Knowledge of Cell Pathology.

Arboviruses, such as yellow fever virus (YFV), dengue virus (DENV), and chikungunya virus (CHIKV), present wide global dissemination and a pathogenic profile developed in infected individuals, from non-specific clinical conditions to severe forms, characterised by the promotion of significant lesions in different organs of the harbourer, culminating in multiple organ dysfunction. An analytical cross-sectional study was carried out via the histopathological analysis of 70 samples of liver patients, collected between 2000 and 2017, with confirmed laboratory diagnoses, who died due to infection and complications due to yellow fever (YF), dengue fever (DF), and chikungunya fever (CF), to characterise, quantify, and compare the patterns of histopathological alterations in the liver between the samples. Of the histopathological findings in the human liver samples, there was a significant difference between the control and infection groups, with a predominance of alterations in the midzonal area of the three cases analysed. Hepatic involvement in cases of YF showed a greater intensity of histopathological changes. Among the alterations evaluated, cell swelling, microvesicular steatosis, and apoptosis were classified according to the degree of tissue damage from severe to very severe. Pathological abnormalities associated with YFV, DENV, and CHIKV infections showed a predominance of changes in the midzonal area. We also noted that, among the arboviruses studied, liver involvement in cases of YFV infection was more intense.

Different cell death mechanisms are involved in leprosy pathogenesis.

Leprosy is a chronic granulomatous disease that remains a serious public health problem in developing countries. According to the Madrid classification, leprosy presents in four clinical forms: two immunologically unstable forms (indeterminate and borderline) and two stable polar forms (tuberculoid and lepromatous). In leprosy, the relationship of cell death to clinical disease outcome remains unclear. Therefore, we investigated the extent of autophagy and different cell death mechanisms-such as apoptosis, necroptosis, and pyroptosis-in cutaneous lesions of patients with leprosy, as well as the role of these mechanisms in clinical disease progression. This cross-sectional analytical study included 30 patients with a confirmed diagnosis of leprosy, with 10 patients in each of the following groups: lepromatous (LL), tuberculoid (TT), and indeterminate (II) leprosy groups. For histopathological analysis, skin samples were subjected to haematoxylin-eosin staining and immunostaining for apoptotic and necroptotic markers. The results indicated that FasL expression was much higher in the LL form than in the TT and II forms. Similar results (higher expression in the LL form than in the TT and II forms) were observed for caspase 8, RIP1, and RIP3 expressions. MLKL, BAX, and caspase 3 expression levels were highest in the LL form, especially in globular foamy macrophages. Beclin-1 expression was highest in the TT form but was low in LL and II forms. Caspase 1 expression was highest in the LL form, followed by that in the TT and II forms. In conclusion, our study elucidates the role of different cell death mechanisms in the pathophysiology of various forms of leprosy and suggests measures that may be used to control the host response to infection and disease progression.

Computed tomography with 6-year follow-up demonstrates the evolution of HTLV-1 related lung injuries: A cohort study.

Previous observational studies have demonstrated the development of pulmonary impairments in human T-lymphotropic virus type 1 (HTLV-1) infected individuals. The main observed lesions due to chronic inflammation of viral infection in situ are bronchiectasis and lung-scarring injuries. This lung inflammation may be the causal agent of restrictive and obstructive lung diseases, primarily in tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP-HAM) patients. We conducted a prospective cohort study to compare spirometry and high-resolution computed tomography (HRCT) findings among 28 HTLV-1-carrier patients over the course of 6 years (2014-2019) (male/female: 7/21; mean age: 54.7 ± 9.5, range: 41-68 years). Chest HRCT exams revealed the development and evolution of lung lesions related to TSP-HAM: including centrilobular nodules, parenchymal bands, lung cysts, bronchiectasis, ground-glass opacity, mosaic attenuation, and pleural thickening. Spirometry exams showed maintenance of respiratory function, with few alterations in parameters suggestive of obstructive and restrictive disorders primarily in individuals with lung lesions and TSP-HAM. The findings of the present study indicate that pulmonary disease related to HTLV-1 is a progressive disease, with development of new lung lesions, mainly in individuals with TSP-HAM. To improve clinical management of these individuals, we recommend that individuals diagnosed with PET-MAH undergo pulmonary evaluation.

Decrease in naïve T cell production due to HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) development.

Human T-lymphocytic virus 1 (HTLV-1) is mainly associated with adult T-cell leukemia/lymphoma (ATLL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Patients with HAM/TSP exhibit significant changes in their immune response, and HTLV-1 infection can interfere in cytokine production and perhaps in T cell production. The aims of this study were to evaluate thymic function in HAM/TSP patients and HTLV-1 healthy carriers (HCs) and correlate it to age and interleukin 7 (IL-7) gene expression. Thymic function in 21 HAM/TSP patients and 12 HCs was evaluated by quantifying T cell receptor rearrangement excision circle (TREC) particles and IL-7 gene expression, both measured by quantitative polymerase chain reaction. HAM/TSP patients presented lower TREC particle counts (p = 0.0112) and lower IL-7 expression (p = 0.0102) than HCs. Both TREC particles and IL-7 gene expression were separately analyzed in two age groups: ≤ 59 years and ≥60 years, The ≤59-year-old HAM/TSP patients had a lower TREC count compared with the ≤59-year-old HCs (p = 0.0476). In conclusion, HAM/TSP development could interfere with thymic function because the results showed TREC particle reduction in HAM/TSP patients in relation to HCs, and it could be associated with a concomitant reduction in IL-7 expression.

Incomplete myelopathy and human T cell lymphotropic virus type-1 (HTLV-1).

This was a cross-sectional prospective study. We performed a multivariate statistical analysis of the neurological signs and symptoms of patients infected with human T cell lymphotropic virus type 1 (HTLV-1) in an attempt to separate them into distinct groups and identify clinical-neurological manifestations that could differentiate the various profiles. The study was performed in the city of Belém (state of Pará), located in the Amazon region of Brazil, from 2014 to 2016. We determined muscle strength and tone, reflexes, sensations, sphincter function, gait, and the Expanded Disability Status Scale score among individuals with HTLV-I. We then used exploratory statistical methods in an attempt to find different profiles and establish distinct groups. We analyzed 60 patients with HTLV-1. The filtering of the data, performed with mixed PCA, gave rise to a streamlined database with the most informative data and suggested the formation of three statistically distinct groups: asymptomatic carriers (AC), mono/oligosymptomatic (MOS), and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSPd), AC and MOS (p = 0.002), AC and HAM/TSPd (p < 0.001), and HAM/TSPd and MOS (p = 0.001). The subsequent cluster analysis confirmed the formation of three clusters. The classification and regression tree demonstrated that altered gait was the most important variable for the classification of an individual with HAM/TSPd and that, in the absence of this impairment, hyperreflexia characterized MOS. The present study was able to separate patients infected by HTLV-1 into three clinical groups (AC, HAM/TSPd, and MOS) and identify clinical manifestations that could differentiate the various patient groups.

High prevalence of sexual Chlamydia trachomatis infection in young women from Marajó Island, in the Brazilian Amazon.

BACKGROUND: Chlamydia trachomatis is the most prevalent bacterial sexually transmitted infection (STI) in the world. Approximately 80% of infected women are asymptomatic, although this infection can lead to serious complications in the female reproductive tract. Few data on Chlamydia infection are available in rural Amazonian communities. OBJECTIVES: To evaluate the prevalence of sexual C. trachomatis infection in women from Marajó Archipelago communities in the Amazon region of Brazil and to identify associated factors and genotypes. METHODS: We utilized amplification of the ompA gene by nested PCR. Positive samples were genotyped by sequencing. Study participants completed a questionnaire on social, epidemiological, and reproductive health variables. A Poisson regression was used to evaluate the degree of association of these variables with the infection. RESULTS: The sexual infection by C. trachomatis was observed in 4% (16/393) of the subjects, and was more often found in women aged ≤25 (14.3%; 95% CI = 2.83-35.47; p <0.001), and in women with a household income of less than one Brazilian monthly minimum wage (5.2%; 95% CI = 1.33-11.37; p = 0.014). The ompA gene was sequenced in 13 samples, revealing F genotypes (38.4%, n = 5), D (23%, n = 3), E (15.3%, n = 2), Ia (7.6%, N = 1), J (7.6%, n = 1) and B (7.6%, n = 1). CONCLUSIONS: We recorded a high prevalence of sexual infection by C. trachomatis in young and poor women from the interior of the Brazilian Amazon. This high prevalence and the frequencies of the main genotypes were similar to those found in major Brazilian urban centers. Our results reinforce the importance of the screening of this neglected infection, and the prevention of later sequelae in young women from rural and urban areas of Brazil.

Human papillomavirus infection and cervical cancer precursor lesions in women living by Amazon rivers: investigation of relations with markers of oxidative stress.

Objective To investigate the relation between oxidative stress markers, human papillomavirus infection and cervical cancer precursor lesions. Methods The study comprised women aged 14 to 60 years living in communities located by Amazon rivers in the state of Pará (Itaituba, Limoeiro do Ajuru and Bragança, 126, 68 and 43 women respectively). Papanicolau smears and polymerase chain reaction tests for human papillomavirus DNA detection were performed. Blood samples were collected to test malondialdehyde, total and oxidized glutathione levels. Results Malondialdehyde, total and oxidized glutathione concentrations did not differ significantly (p>0.05) between women with and without low-grade squamous intraepithelial lesions across communities. Malondialdehyde levels (8.02nmols/mL) were almost five times higher in human papillomavirus-positive compared to human papillomavirus-negative women (1.70nmols/mL) living in Itaituba (statistically significant difference; p<0.05). Malondialdehyde levels did not differ significantly (p>0.05) between human papillomavirus-positive and human papillomavirus-negative women living in remaining communities. Significant (p<0.05) differences in total glutathione levels between human papillomavirus-positive and human papillomavirus-negative women (8.20µg/mL and 1.47µg/mL, respectively) were limited to those living in Bragança. Conclusion Malondialdehyde and total glutathione levels were significantly associated with human papillomavirus infection. However, lack of similar associations with squamous lesions suggest oxidative stress alone does not explain correlations with cervical carcinogenesis. Other factors may therefore be involved.

Parvovirus B19 and in situ immune response in eczema and psoriasis skin lesions of patients from the Brazilian Amazon region.

Parvovirus B19 (PVB19) is a virus found in the skin that causes asymptomatic infections and can exist in the host for long periods to time. The virus induces a local inflammatory response and is associated with the development of arthritis and other autoimmunes diseases. Parvovirus B19 DNA was investigated by PCR in the skin of 20 patients with psoriasis and 20 patients with eczema. Additionally, immunohistochemistry was used to characterize the expression of cytokines in these lesions. The sociodemographic variables were similar in the two groups studied. Psoriasis vulgaris was the most common clinical type in men (50%) and women (80%) (p = 0.0106). Comorbidities were observed in most patients with psoriasis (75%), with an OR of 14 (p = 0.0068). Another important finding was the high prevalence (50%) of psychiatric disorders in patients with psoriasis (OR = 16, p = 0.0218). Only two patients (10%) with psoriasis were positive for PVB19. Comparison of cytokine expression showed the same cytokine profile in the two groups (p > 0.05). However, expression of TNF-α tended to be higher in psoriasis patients. There was no significant positivity for PVB19 in the two groups studied. Immunohistochemistry showed higher expression of TNF-α in psoriasis lesions compared to the eczema group.

Human papillomavirus infection and cervical cancer precursor lesions in women living by Amazon rivers: investigation of relations with markers of oxidative stress / Infecção por papilomavírus humano e lesões precursoras do câncer cervicouterino em Ribeirinhas da Amazônia: avaliação da relação com marcadores de estresse oxidativo

ABSTRACT Objective To investigate the relation between oxidative stress markers, human papillomavirus infection and cervical cancer precursor lesions. Methods The study comprised women aged 14 to 60 years living in communities located by Amazon rivers in the state of Pará (Itaituba, Limoeiro do Ajuru and Bragança, 126, 68 and 43 women respectively). Papanicolau smears and polymerase chain reaction tests for human papillomavirus DNA detection were performed. Blood samples were collected to test malondialdehyde, total and oxidized glutathione levels. Results Malondialdehyde, total and oxidized glutathione concentrations did not differ significantly (p>0.05) between women with and without low-grade squamous intraepithelial lesions across communities. Malondialdehyde levels (8.02nmols/mL) were almost five times higher in human papillomavirus-positive compared to human papillomavirus-negative women (1.70nmols/mL) living in Itaituba (statistically significant difference; p<0.05). Malondialdehyde levels did not differ significantly (p>0.05) between human papillomavirus-positive and human papillomavirus-negative women living in remaining communities. Significant (p<0.05) differences in total glutathione levels between human papillomavirus-positive and human papillomavirus-negative women (8.20μg/mL and 1.47μg/mL, respectively) were limited to those living in Bragança. Conclusion Malondialdehyde and total glutathione levels were significantly associated with human papillomavirus infection. However, lack of similar associations with squamous lesions suggest oxidative stress alone does not explain correlations with cervical carcinogenesis. Other factors may therefore be involved.

RESUMO Objetivo Avaliar a relação de marcadores de estresse oxidativo com a infecção pelo papilomavírus humano e as lesões precursoras do câncer cervical. Métodos Foram incluídas mulheres ribeirinhas da Amazônia (a saber: 126 do município de Itaituba, 68 de Limoeiro do Ajuru e 43 de Bragança), todas do Estado do Pará, de 14 a 60 anos. Foram realizados testes Papanicolau e de reação em cadeia de polimerase para a detecção de DNA do papilomavírus humano. Coleta de amostras de sangue foi realizada para a avaliação do malondialdeído e a determinação da glutationa total e oxidada. Resultados As concentrações oxidativas do malondialdeído e os teores de glutationa total e oxidada não apresentaram diferença significativa (p>0,05) nas mulheres com e sem lesão intraepitelial escamosa de baixo grau, em todas as comunidades pesquisadas. Mulheres com papilomavírus humano em Itaituba apresentaram níveis de malondialdeído (8,02nmols/mL) quase cinco vezes maior quando relacionadas àquelas sem o HPV (1,70nmols/mL), com diferença estatística significativa (p<0,05). As outras comunidades não mostraram diferença estatística significativa entre as concentrações de malondialdeído nas mulheres com e sem papilomavírus humano (p>0,05). Os teores de glutationa total mostraram diferença significativa (p<0,05) somente em Bragança naquelas com (8,20µg/mL) e sem a infecção pelo papilomavírus humano (1,47µg/mL). Conclusão Houve associação significativa da resposta oxidativa do malondialdeído e da glutationa total com a infecção pelo papilomavírus humano, porém não houve diferença quando associada à lesão escamosa, sugerindo que o estresse oxidativo isoladamente não explica a relação com a carcinogênese do colo uterino, que deve ser influenciada ainda por outros fatores.

Correction: CT Chest and pulmonary functional changes in patients with HTLV-associated myelopathy in the Eastern Brazilian Amazon.

[This corrects the article DOI: 10.1371/journal.pone.0186055.].

NFκB transcription factor (p65) immunohistochemistry in leprosy dermal microvasculature.

Leprosy caused by Mycobacterium leprae is characterized by a spectrum of clinical manifestations that are determined by the predominant immunological profile of the host. The recruitment of leukocytes to the sites of injury can influence the development of these profiles. Cell adhesion molecules such as ICAM-1, VCAM-1 and CD62E participate in this process and their expression is regulated by transcriptions factors such as NFκB. To correlate the expression of cell adhesion molecules and NFκB (p65) in leprosy lesions, 30 skin biopsies of patients with leprosy [16 with the tuberculoid (TT) or borderline tuberculoid (BT) forms and 14 with the lepromatous (LL) or borderline lepromatous (BL) forms] were analyzed by immunohistochemistry. A larger mean number of cells expressing VCAM-1 (BT/TT: 18.28 ± 1.4; BL/LL: 10.67 ± 1.2; p = 0.0002), ICAM-1 (BT/TT: 9.92 ± 1.1; BL/LL: 5.87 ± 1.0; p = 0.0084) and CD62E (BT/TT: 13.0 ± 1.5; BL/LL: 2.58 ± 0.3; p = 0.0001) were observed in BT and TT lesions. The mean number of cells expressing NFκB was similar in the two clinical forms (BT/TT: 2.21 ± 2.7; BL/LL: 2.35 ± 3.1;p = 0.9285). No significant correlation was observed between expression of the transcription factor and adhesion molecules analyzed. The synthesis of ICAM-1, VCAM-1 and CD62E depends on the activation of NFκB, which acts synergistically with other transcription factors. Adequate activation of intracellular signaling pathways results in the production of endothelial adhesion molecules, contributing to the recruitment of cells to the site of injury and thus eliciting an effective inflammatory response in the elimination of the bacillus.

CT Chest and pulmonary functional changes in patients with HTLV-associated myelopathy in the Eastern Brazilian Amazon.

The aim of this study was to compare computed tomography (CT) scans of chest and lung function among patients with Human T-Lymphotropic Virus Type 1 (HTLV) with and without HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). In this cross-sectional study performed between January 2013 and June 2016, we included 48 patients with HAM/TSP (19 women and 11 men) and without HAM/TSP (12 women and 6 men). We compared CT findings and lung functions of these groups. Patients who had HAM/TSP had abnormal CT findings (P = 0.000), including more frequent bronchiectasis (P = 0.049), parenchymal bands (P = 0.007), interlobular septal thickening (P = 0.035), and pleural thickening (P = 0.009). In addition, neither patients with HAM/TSP (9/30; 30%) nor the controls (0/18; 0%) had obstructive or restrictive lung disease (P = 0.009). HTLV diagnosis should be considered in all patients with abnormal CT findings in whom no other cause is apparent. It is important to remember that lung disease increases the rates of morbidity and mortality in developing countries.

Complete Genome Sequence of Porphyrobacter sp. Strain CACIAM 03H1, a Proteobacterium Obtained from a Nonaxenic Culture of Microcystis aeruginosa.

Here, we present a complete genome sequence and annotation of Porphyrobacter sp. strain CACIAM 03H1, which was obtained from a nonaxenic culture of Microcystis aeruginosa, a cyanobacterium isolated from an Amazonian freshwater environment.

Prevalence of Human Papillomavirus Infection and Cervical Cancer Screening among Riverside Women of the Brazilian Amazon / Prevalência da infecção pelo papilomavírus humano e rastreamento do câncer em mulheres ribeirinhas da Amazônia brasileira

Abstract Purpose The aim of this study was to evaluate the overall and type-specific prevalence of human papillomavirus (HPV) infection among females living in riverside communities in the state of Pará, in the Eastern Brazilian Amazon. These communities are inhabited by low-income people, and are accessible only by small boats. Cervical cytology and risk factors for HPV infection were also assessed. Methods Cervical samples from 353 women of selected communities were collected both for Papanicolau (Pap) test and HPV detection. Conventional polymerase chain reaction (PCR) and real-time PCR were used to assess the overall and type-specific prevalence of HPV-16 and HPV-18, the main oncogenic types worldwide. Epidemiological questionnaires were used for the assessment of the risk factors for HPV infection. Results The mean age of the participants was 37 years (standard deviation [SD] ± 13.7). Most were married or with a fixed sexual partner (79%), and had a low educational level (80%) and family monthly income (< U$ 250; 53%). Overall, HPV prevalence was 16.4% (n = 58), with 8 cases of HPV-16 (2.3%) and 5 of HPV-18 (1.4%). Almost 70% of the women surveyed had never undergone the Pap test. Abnormal cytology results were found in 27.5% (n = 97) of the samples, with higher rates of HPV infection according to the severity of the lesions (p = 0.026). Conclusions The infections by HPV-16 and HPV-18 were not predominant in our study, despite the high prevalence of overall HPV infection. Nevertheless, the oncogenic potential of these types and the low coverage of the Pap test among women from riverside communities demonstrate a potential risk for the development of cervical lesions and their progression to cervical cancer, since the access to these communities is difficult and, in most cases, these women do not have access to primary care and public health services.

Resumo Objetivo O objetivo deste estudo foi avaliar a prevalência global e tipo-específica da infecção pelo papilomavírus humano (HPV) entre mulheres que vivem em comunidades ribeirinhas do estado do Pará, Amazônia oriental, Brasil. Estas comunidades são habitadas por pessoas de baixa renda, e são acessíveis somente por meio de pequenos barcos. A citologia cervical e os fatores de risco para a infecção por HPV também foram avaliados. Métodos Amostras cervicais de 353 mulheres de comunidades selecionadas foram coletadas para a análise citológica e para a detecção do HPV. A prevalência global e tipoespecífica dos HPV-16 e HPV-18, principais tipos oncogênicos no mundo, foram avaliadas por meio de reação em cadeia de polimerase (PCR) convencional e PCR em tempo real. Os fatores de risco para a infecção por HPV foram avaliados a partir de questionários epidemiológicos. Resultados A idade média das participantes foi de 37 anos (desvio padrão [DP] ± 13,7). A maioria era casada ou tinha um parceiro sexual fixo (79%) e baixo nível de escolaridade (80%) e de renda familiar mensal (< U$ 250; 53%). A prevalência global do HPV foi de 16,4% (n = 58), com 8 casos de HPV-16 (2,3%) e 5 casos de HPV-18 (1,4%). Aproximadamente 70% das mulheres entrevistadas nunca tinha realizado o exame preventivo de Papanicolau. Os resultados citológicos anormais foram encontrados em 27,5% (n = 97) das amostras, com taxas mais altas da infecção por HPV de acordo com a severidade das lesões (p = 0,026). Conclusões As infecções por HPV-16 e HPV-18 não foram predominantes em nosso estudo, apesar da alta prevalência global da infecção por HPV. No entanto, o potencial oncogênico desses tipos e a baixa cobertura do exame de Papanicolau entre mulheres de comunidades ribeirinhas demonstram um risco potencial para o desenvolvimento de lesões cervicais e sua progressão para o câncer de colo do útero, uma vez que o acesso a essas comunidades é difícil e, na maioria dos casos, estas mulheres não têm acesso aos serviços de atenção primária e de saúde pública.

Prevalence of Human Papillomavirus Infection and Cervical Cancer Screening among Riverside Women of the Brazilian Amazon.

Purpose The aim of this study was to evaluate the overall and type-specific prevalence of human papillomavirus (HPV) infection among females living in riverside communities in the state of Pará, in the Eastern Brazilian Amazon. These communities are inhabited by low-income people, and are accessible only by small boats. Cervical cytology and risk factors for HPV infection were also assessed. Methods Cervical samples from 353 women of selected communities were collected both for Papanicolau (Pap) test and HPV detection. Conventional polymerase chain reaction (PCR) and real-time PCR were used to assess the overall and type-specific prevalence of HPV-16 and HPV-18, the main oncogenic types worldwide. Epidemiological questionnaires were used for the assessment of the risk factors for HPV infection. Results The mean age of the participants was 37 years (standard deviation [SD] ± 13.7). Most were married or with a fixed sexual partner (79%), and had a low educational level (80%) and family monthly income (< U$ 250; 53%). Overall, HPV prevalence was 16.4% (n = 58), with 8 cases of HPV-16 (2.3%) and 5 of HPV-18 (1.4%). Almost 70% of the women surveyed had never undergone the Pap test. Abnormal cytology results were found in 27.5% (n = 97) of the samples, with higher rates of HPV infection according to the severity of the lesions (p = 0.026). Conclusions The infections by HPV-16 and HPV-18 were not predominant in our study, despite the high prevalence of overall HPV infection. Nevertheless, the oncogenic potential of these types and the low coverage of the Pap test among women from riverside communities demonstrate a potential risk for the development of cervical lesions and their progression to cervical cancer, since the access to these communities is difficult and, in most cases, these women do not have access to primary care and public health services.

Objetivo O objetivo deste estudo foi avaliar a prevalência global e tipo-específica da infecção pelo papilomavírus humano (HPV) entre mulheres que vivem em comunidades ribeirinhas do estado do Pará, Amazônia oriental, Brasil. Estas comunidades são habitadas por pessoas de baixa renda, e são acessíveis somente por meio de pequenos barcos. A citologia cervical e os fatores de risco para a infecção por HPV também foram avaliados. Métodos Amostras cervicais de 353 mulheres de comunidades selecionadas foram coletadas para a análise citológica e para a detecção do HPV. A prevalência global e tipo-específica dos HPV-16 e HPV-18, principais tipos oncogênicos no mundo, foram avaliadas por meio de reação em cadeia de polimerase (PCR) convencional e PCR em tempo real. Os fatores de risco para a infecção por HPV foram avaliados a partir de questionários epidemiológicos. Resultados A idade média das participantes foi de 37 anos (desvio padrão [DP] ± 13,7). A maioria era casada ou tinha um parceiro sexual fixo (79%) e baixo nível de escolaridade (80%) e de renda familiar mensal (< U$ 250; 53%). A prevalência global do HPV foi de 16,4% (n = 58), com 8 casos de HPV-16 (2,3%) e 5 casos de HPV-18 (1,4%). Aproximadamente 70% das mulheres entrevistadas nunca tinha realizado o exame preventivo de Papanicolau. Os resultados citológicos anormais foram encontrados em 27,5% (n = 97) das amostras, com taxas mais altas da infecção por HPV de acordo com a severidade das lesões (p = 0,026). Conclusões As infecções por HPV-16 e HPV-18 não foram predominantes em nosso estudo, apesar da alta prevalência global da infecção por HPV. No entanto, o potencial oncogênico desses tipos e a baixa cobertura do exame de Papanicolau entre mulheres de comunidades ribeirinhas demonstram um risco potencial para o desenvolvimento de lesões cervicais e sua progressão para o câncer de colo do útero, uma vez que o acesso a essas comunidades é difícil e, na maioria dos casos, estas mulheres não têm acesso aos serviços de atenção primária e de saúde pública.

Hypomyopathic dermatomyositis associated with interstitial lung disease and good response to mycophenolate mofetil: case-based review.

Hypomyopathic dermatomyositis (HDM) is a rare form of dermatomyositis (DM). Interstitial lung disease (ILD) associated with clinically amyopathic DM (CADM-ILD) or hypomyopathic DM (HDM-ILD) is a rare condition with a more unfavorable prognosis than ILD associated with classic DM (CDM-ILD). There is no effective treatment for HDM-ILD. A 62-year-old woman with a 6-month history of chronic polyarthritis and myalgia presented skin lesions characteristic of DM (erythematous lesion on extensor surface of elbows, Gottron's papules, V-neck sign) with no clinical muscle impairment (global muscle strength: grade 5). Muscle enzymes (creatine kinase, lactic dehydrogenase, and aldolase) and electroneuromyography (ENMG) were normal. Computed tomography of the chest revealed ILD. Magnetic resonance imaging and muscle biopsy revealed subclinical muscle impairment. High doses of corticosteroids were used without success. As an alternative, 1500 mg/day of mycophenolate mofetil (MMF) was combined with low doses of prednisone, and the patient demonstrated a good clinical response after 3 months of this combination. Twenty-five months after initiating treatment, ILD remains in remission with the use of MMF and a low dose of prednisone. Therefore, MMF can be a good option for the treatment of HDM-ILD.

Endothelium adhesion molecules ICAM-1, ICAM-2, VCAM-1 and VLA-4 expression in leprosy.

Leprosy triggers a complex relationship between the pathogen and host immune response. Endothelium plays an important role in this immune response by directly influencing cell migration to infected tissues. The objective of this work is to investigate the possible role of endothelium in M. leprae infection, correlating the characteristics of endothelial markers with the expression pattern of cytokines. Thirty-six skin biopsy samples were cut into 5-µm thick sections and stained with hematoxylin-eosin and Ziehl-Neelsen for morphological analysis and then submitted to immunohistochemical analysis using monoclonal antibodies against ICAM-1, ICAM-2, VCAM-1, and VLA-4. Immunostaining for ICAM-1 showed a significantly larger number of stained endothelial cells in the tuberculoid leprosy (9.92 ± 1.11 cells/mm2) when compared to lepromatous samples (5.87 ± 1.01 cells/mm2) and ICAM-2 revealed no significant difference in the number of endothelial cells expressing this marker between the tuberculoid (13.21 ± 1.27 cells/mm2) and lepromatous leprosy (14.3 ± 1.02 cells/mm2). VCAM-1-immunostained showed 18.28 ± 1.46/mm2 cells in tuberculoid leprosy and 10.67 ± 1.25 cells/mm2 in the lepromatous leprosy. VLA-4 exhibited 22.46 ± 1.38 cells/mm2 in the tuberculoid leprosy 16.04 ± 1.56 cells/mm2 in the lepromatous leprosy. Samples with characteristics of the tuberculoid leprosy exhibited a larger number of cells stained with ICAM-1, VCAM-1 and VLA-4, demonstrating the importance of these molecules in the migration and selection of cells that reach the inflamed tissue.

Zika virus disrupts molecular fingerprinting of human neurospheres.

Zika virus (ZIKV) has been associated with microcephaly and other brain abnormalities; however, the molecular consequences of ZIKV to human brain development are still not fully understood. Here we describe alterations in human neurospheres derived from induced pluripotent stem (iPS) cells infected with the strain of Zika virus that is circulating in Brazil. Combining proteomics and mRNA transcriptional profiling, over 500 proteins and genes associated with the Brazilian ZIKV infection were found to be differentially expressed. These genes and proteins provide an interactome map, which indicates that ZIKV controls the expression of RNA processing bodies, miRNA biogenesis and splicing factors required for self-replication. It also suggests that impairments in the molecular pathways underpinning cell cycle and neuronal differentiation are caused by ZIKV. These results point to biological mechanisms implicated in brain malformations, which are important to further the understanding of ZIKV infection and can be exploited as therapeutic potential targets to mitigate it.

Clinical and epidemiological study of human papillomavirus infection in women with systemic lupus erythematosus in eastern brazilian amazon.

Cervical cancer, the second most common cancer affecting women in Northern Brazil, is strongly associated with human papillomavirus (HPV) infection. Diseases affecting the immune state of a patient, including autoimmune diseases like systemic lupus erythematosus (SLE), can lead to persistent HPV infection and cancer. We evaluated cervical HPV prevalence and the associated risk factors in 70 women with SLE in the city of Belém, located in Brazilian Amazon. HPV DNA was detected by PCR using primers MY9 and MY11. HPV subtypes were determined by real-time PCR, using specific probes. Overall, prevalence of cervical HPV in women with SLE was 22.8%. HPV prevalence was significantly higher in younger women (aged 18-25 years; 75%, p< 0.0001), in women who had not given birth (50%, p = 0.01), and in women with no prior pregnancy (57%, p = 0.003). Five women (7.1%) had Pap smears with a cytopathological outcome suggestive of HPV; four of these women were HPV-positive. No women with both, SLE and HPV, had a normal Pap smear. Of the women diagnosed with SLE in the last 1-5 years, 75% was HPV-positive (p = 0.04). The two most prevalent HPV subtypes were HPV 58 (37.5%) and HPV 31 (31.3%). These results are important for understanding HPV infection in women with SLE and are valuable tools for developing cervical cancer prevention strategies and health management policies.