RESUMO

Malignant pleural mesothelioma (MPM) is a rare and aggressive neoplasm of the pleural tissue that lines the lungs and is mainly associated with long latency from asbestos exposure. This tumor has no effective therapeutic opportunities nowadays and has a very low five-year survival rate. In this sense, identifying molecular events that trigger the development and progression of this tumor is highly important to establish new and potentially effective treatments. We conducted a meta-analysis of genome-wide expression studies publicly available at the Gene Expression Omnibus (GEO) and ArrayExpress databases. The differentially expressed genes (DEGs) were identified, and we performed functional enrichment analysis and protein-protein interaction networks (PPINs) to gain insight into the biological mechanisms underlying these genes. Additionally, we constructed survival prediction models for selected DEGs and predicted the minimum drug inhibition concentration of anticancer drugs for MPM. In total, 115 MPM tumor transcriptomes and 26 pleural tissue controls were analyzed. We identified 1046 upregulated DEGs in the MPM samples. Cellular signaling categories in tumor samples were associated with the TNF, PI3K-Akt, and AMPK pathways. The inflammatory response, regulation of cell migration, and regulation of angiogenesis were overrepresented biological processes. Expression of SOX17 and TACC1 were associated with reduced survival rates. This meta-analysis identified a list of DEGs in MPM tumors, cancer-related signaling pathways, and biological processes that were overrepresented in MPM samples. Some therapeutic targets to treat MPM are suggested, and the prognostic potential of key genes is shown.

Assuntos

Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurais , Humanos , Mesotelioma/genética , Mesotelioma/metabolismo , Fosfatidilinositol 3-Quinases , Neoplasias Pleurais/genética , Neoplasias Pleurais/metabolismo , Neoplasias Pulmonares/patologia

RESUMO

Background: Intraocular pressure (IOP) peaks are key factors on the onset and progression of glaucoma. The water drinking test (WDT) detects IOP fluctuations and estimates the maximum IOP. Objective: To assess the IOP variations during the WDT in patients diagnosed or suspected of glaucoma treated at an ophthalmology clinic. Methods: This is an observational, descriptive, and retrospective study, using clinical records of patients whom underwent the WDT between January 2017 and August 2019. Results: The study included 300 eyes. The WDT was positive in 23.3% of the eyes. Basal IOP at 15, 30, and 45 min, as well as the maximum pressure, presented a similar mean, median, and mode, as well as a varying coefficient without much variability. The negative test group had a maximum IOP of 18.9 mmHg, compared with 20.3 mmHg in the positive test group. Conclusion: In a Colombian cohort of patients with diagnosed or suspected glaucoma whom underwent a WDT, 23.3% had positive result. 90% of the tests were positive at the 30-min interval. This test is a complementary tool in the follow-up of patients with glaucoma.

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Introducción: Los picos de presión intraocular son factores importantes para la aparición y progresión del glaucoma. La prueba de sobrecarga hídrica permite detectar fluctuaciones de presión intraocular y estimar la presión máxima. Objetivo: Evaluar las variaciones en la presión intraocular durante la prueba de sobrecarga hídrica en pacientes de una clínica oftalmológica. Métodos: Estudio observacional, descriptivo, retrospectivo de revisión de historias clínicas de pacientes sometidos a la prueba de sobrecarga hídrica entre enero de 2017 y agosto de 2019. Resultados: Se incluyeron 300 ojos. La prueba de sobrecarga hídrica fue positiva en el 23,3% de los ojos. La presión intraocular basal, a los 15, 30 y 45 min, al igual que la presión máxima, tuvieron una media, mediana y moda similares, con un coeficiente de variación sin mucha variabilidad. El grupo con resultados negativos tuvo una presión intraocular máxima de 18,9 mmHg comparado con 20,3 mmHg del grupo con resultados positivos. Conclusión: En una cohorte colombiana de pacientes con diagnóstico o sospecha de glaucoma quienes se les realizó la prueba de sobrecarga hídrica, el 23,3% tuvo resultados positivos. El 90% de las pruebas fueron positivas en el intervalo de 30 min. Esta prueba es una herramienta complementaria en el seguimiento de pacientes con glaucoma.

Assuntos

Humanos , Colômbia

RESUMO

Trypanosomatid infections are an important public health threat affecting many low-income countries across the tropics, particularly in the Americas. Trypanosomatids can infect many vertebrate, invertebrate, and plant species and play an important role as human pathogens. Among these clinically relevant pathogens are species from the genera Leishmania and Trypanosoma. Mixed trypanosomatid infections remain a largely unexplored phenomenon. Herein, we describe the application of an amplicon-based next-generation sequencing (NGS) assay to detect and identify trypanosomatid species in mammalian reservoirs, human patients, and sand fly vectors throughout regions of Leishmania endemicity. Sixty-five samples from different departments of Colombia, including two samples from Venezuela, were analyzed: 49 samples from cutaneous leishmaniasis (CL) patients, 8 from sand flies, 2 from domestic reservoirs (Canis familiaris), and 6 from wild reservoirs (Phyllostomus hastatus). DNA from each sample served to identify the presence of trypanosomatids through conventional PCR using heat shock protein 70 (HSP70) gene as the target. PCR products underwent sequencing by Sanger sequencing and NGS, and trypanosomatid species were identified by using BLASTn against a reference database built from trypanosomatid-derived HSP70 sequences. The alpha and beta diversity indexes of amplicon sequence variants were calculated for each group. The results revealed the presence of mixed infections with more than two Leishmania species in 34% of CL samples analyzed. Trypanosoma cruzi was identified in samples from wild reservoirs, as well as in sand fly vectors. Coinfection events with three different Leishmania species were identified in domestic reservoirs. These findings depose the traditional paradigm of leishmaniasis as being a single-species-driven infection and redraw the choreography of host-pathogen interaction in the context of multiparasitism. Further research is needed to decipher how coinfections may influence disease progression. This knowledge is key to developing an integrated approach for diagnosis and treatment. IMPORTANCE Traditionally, there has been a frequent, yet incorrect assumption that phlebotomine vectors, animal reservoirs, and human hosts are susceptible to Leishmania infection by a single parasite species. However, current evidence supports that these new vector-parasite-reservoir associations lend vectors and reservoirs greater permissiveness to certain Leishmania species, thus promoting the appearance of coinfection events, particularly in disease-endemic regions. The present study describes the application of an amplicon-based next-generation sequencing (NGS) assay to detect and identify trypanosomatid species in mammalian reservoirs, human patients, and sand fly vectors from regions of endemicity for leishmaniasis. This changes our understanding of the clinical course of leishmaniasis in areas of endemicity.

Assuntos

Sequenciamento de Nucleotídeos em Larga Escala , Leishmania/genética , Leishmania/isolamento & purificação , Trypanosoma/genética , Trypanosoma/isolamento & purificação , Animais , Cães , Proteínas de Choque Térmico HSP70/genética , Humanos , Indanos , Leishmania/classificação , Leishmaniose Cutânea/parasitologia , Masculino , Mamíferos/parasitologia , Phlebotomus , Filogenia , Reação em Cadeia da Polimerase , Psychodidae/parasitologia , Análise de Sequência , Trypanosoma/classificação , Venezuela

RESUMO

Purpose: The keratoconus end-points assessment questionnaire (KEPAQ) is a disease-specific scale designed to evaluate the quality of life in keratoconus patients and provides the measurement of both functional and emotional compromise in keratoconus. It was previously developed, tested, and validated and now we want to evaluate the test-retest reliability of the KEPAQ, in an effort to contribute evidence on its internal consistency and capability of measuring clinical state with minimal inference of random chance. Methods: This is a prospective analytical study, designed to evaluate the test-retest reliability of the KEPAQ through the repeated application of the questionnaire to a group of clinically stable individuals. A number of patients with a confirmed diagnosis of keratoconus underwent double application of the KEPAQ, seven days apart. Mean KEPAQ score was obtained through Rasch analysis, while test-retest reliability was evaluated through Spearman rank-order correlation and intraclass correlation coefficient. Rasch analysis was performed in JMetrik version 4.1.1 (Psychomeasurement Systems LLC; Charlottesville, VA, USA) in a MacBook Air computer running macOS Catalina version 10.15.2 (Apple Inc.; Cupertino, CA, USA). Results: A total of 100 patients were included. For KEPAQ-E, Spearman correlation was R = 0.963 while ICC was 0.981 (95% confidence interval 0.972-0.987). For KEPAQ-F, Spearman correlation was R = 0.921 while ICC was 0.952 (95% confidence interval 0.929-0.968). Conclusion: The KEPAQ is a robust, well-developed, extremely reliable scale which can be confidently used for clinical and research endeavors.

Assuntos

Ceratocone , Qualidade de Vida , Humanos , Ceratocone/diagnóstico , Ceratocone/epidemiologia , Estudos Prospectivos , Reprodutibilidade dos Testes , Inquéritos e Questionários

RESUMO

This study aimed to analyse the patterns of diversity, blood sources and Leishmania species of phlebotomines in a focus of cutaneous leishmaniasis in Arboledas, Eastern Colombia. In total, 1729 phlebotomines were captured in two localities (62.3% Siravita and 37.7% Cinera) and five environments of Norte de Santander. We identified 18 species of phlebotomines: Pintomyia ovallesi (29.8%), Psychodopygus davisi (20.3%), Pi. spinicrassa (18.5%) and Lutzomyia gomezi (15.8%) showed the highest abundance. Species diversities were compared between Cinera (15.00) and Siravita (20.00) and among five microenvironments: forest remnants (19.49), coffee plantations (12.5), grassland (12.99), cane plantations (11.66) and citrus plantations (12.22). Leishmania DNA was detected in 5.8% (80/1380) of females, corresponding mainly to Pi. ovallesi (22/80; 27.2%), Lu. gomezi (17/80; 21.3%) and Pi. spinicrassa (11/80; 13.8%). Leishmania species were 63.1% L. braziliensis, 18.5% L. panamensis, 13.2% L. infantum and 6.1% L. amazonensis. The most frequent feeding sources were Homo sapiens (50%), Bos taurus (13.8%) and Canis lupus familiaris (10.3%). This focus of cutaneous leishmaniasis has a high diversity of Leishmania-carrying phlebotomines that feed on domestic animals. The transmission of leishmaniasis to human hosts was mainly associated with Lu. gomezi, Pi. ovallesi and L. braziliensis.

RESUMO

[This corrects the article DOI: 10.1098/rsos.200266.].