Electrocardiographic Findings Among Asymptomatic Adults With Haemophilia

Abstract Background: People with haemophilia (PwH) are living longer. Therefore, they can develop atherosclerotic cardiovascular disease (ASCVD). Electrocardiogram (ECG) alterations may be a sign of initial ASCVD before the occurrence of symptoms. Objective: To describe the prevalence of resting ECG alterations among PwH adults asymptomatic for ASCVD. Methods: PwH aged ≥ 30 years without previous ASCVD events were considered for the analysis. Resting ECG traces were analysed according to international reference values and the Brazilian Longitudinal Adult Health Study (ELSA-Brasil) results for asymptomatic Brazilian men. Based on the established normal values and using the QT index, we further described the altered ECGs as minor or major changes, according to the Minnesota Code. Differences between prevalences were evaluated by Pearson's χ2 test. Differences between medians were evaluated by the Mann-Whitney U test. A p-value < 0.05 was accepted as statistically significant. Results: A total of 64 PwH were included in the study. Median age was 44 years (interquartile range 35-52). Most patients had haemophilia A (81%) and 47% were severe. The prevalence of obesity, systemic arterial hypertension (SAH), diabetes mellitus (DM), and dyslipidaemia were 16%, 56%, 14%, and 72%, respectively. All the PwH had sinus rhythm, except for one, who had an implanted pacemaker due to idiopathic third-degree atrioventricular block. Altered ECGs were found in 25% and 30% of PwH, according to established criteria and ELSA-Brasil criteria, respectively. Major changes were found in eight (13%) PwH according to the Minnesota Code, including two ECGs with ischaemia-like wall inactivity. Conclusions: The prevalence of altered ECG varied from 25% to 30% among asymptomatic PwH.

Cardiovascular Risk Scores among Asymptomatic Adults with Haemophilia. / Escores de Risco Cardiovascular entre Adultos Assintomáticos com Hemofilia.

BACKGROUND: The mortality rate of Brazilian people with haemophilia (PwH) is decreasing, but the relative incidence of deaths associated with cardiovascular disease (CVD) is increasing. OBJECTIVES: We aimed to describe the CVD risk score of PwH according to Pooled Cohort Equations Risk (PCER) Calculator tool and its treatment recommendations. We also compared the PCER estimates with the respective Framingham Risk Score (FRS). METHODS: This cross-sectional study included male PwH ≥ 40 years treated at the Comprehensive Haemophilia Treatment Centre of Pernambuco (Recife/Brazil). PwH with a previous CVD event or a low-density lipid cholesterol ≥ 5.0 mmol/L were excluded. Interviews, medical file reviews, and blood tests were performed. The PCER tool was used to estimate the CVD risk and compare it with the respective FRS. A p-value < 0.05 was accepted as statistically significant. RESULTS: Thirty PwH were included. Median age was 51.5 [interquartile range-IQR; 46.0-59.5] years. The prevalence of obesity, systemic arterial hypertension, diabetes mellitus, hypertriglyceridaemia, hypercholesterolaemia, and hypoHDLaemia were 20%, 67%, 24%, 14%, 47%, and 23%, respectively. The median PCER score was 6.9% [IQR; 3.1-13.2], with 50% having a high risk (PCER ≥ 7.5%). Statin use was suggested for 54% of PwH. Blood pressure was poorly controlled in 47% of PwH. The agreement between PCER and FRS was 80% (κ = 0.60; p = 0.001). CONCLUSIONS: Half of the male people with haemophilia aged 40 years or older had a 10-year high risk of developing CVD with strong recommendations to improve control of dyslipidaemia and blood pressure.

FUNDAMENTO: A taxa de mortalidade de pessoas com hemofilia (PCH) no Brasil está diminuindo, mas a incidência relativa de mortes associadas a doenças cardiovasculares (DCV) tem aumentado. OBJETIVOS: Nosso objetivo foi descrever o escore de risco de DCV de PCHs de acordo com a ferramenta Pooled Cohort Equations Risk (PCER) Calculator e suas recomendações de tratamento. Além disso, foram comparadas as estimativas da PCER com o respectivo escore de risco de Framingham (FRS). MÉTODOS: Este estudo transversal incluiu PCHs do sexo masculino, com idade igual ou superior a 40 anos, tratados no Centro de Tratamento Integral de Hemofilia de Pernambuco (Recife/Brasil). PCHs com um evento cardiovascular prévio ou colesterol lipídico de baixa densidade ≥ 5,0 mmol/L foram excluídas. Entrevistas, revisões de prontuários médicos e exames de sangue foram realizados. A ferramenta PCER foi utilizada para estimar o risco de DCV e compará-lo com o respectivo FRS. Um valor de p < 0,05 foi aceito como estatisticamente significativo. RESULTADOS: Trinta PCHs foram incluídas. A idade mediana foi de 51,5 [intervalo interquartil-IIQ; 46,0-59,5] anos. A prevalência de obesidade, hipertensão arterial sistêmica, diabetes mellitus, hipertrigliceridemia, hipercolesterolemia e hipoHDLemia foi de 20%, 67%, 24%, 14%, 47% e 23%, respectivamente. O escore mediano da PCER foi de 6,9% [IIQ; 3,1-13,2], com 50% de alto risco (PCER ≥ 7,5%). O uso de estatina foi sugerido para 54% das PCHs. A pressão arterial estava mal controlada em 47% das PCHs. A concordância entre PCER e FRS foi de 80% (κ = 0,60; p = 0,001). CONCLUSÕES: Metade dos homens com hemofilia, com 40 anos de idade ou mais, teve um alto risco de desenvolver DCV em 10 anos, com fortes recomendações para melhorar o controle da dislipidemia e da pressão arterial.

Home visits in rural areas: demands in primary care.

INTRODUCTION: The rural population suffers from important limitations in accessing health care, often lacking a public policy approach to the health and sanitation conditions of their environment. In this sense, primary care emerges with the objective of offering comprehensive care to the population, applying some of its principles as territorialization, person-centered care, longitudinality, and resolution in health care. The goal is to offer the basic health needs of the population considering the determinants and conditions of health in each territory. METHODS: The present study is an experience report that aimed to raise the main health demands of the rural population in the areas of nursing, dentistry, and psychology of a village in the state of Minas Gerais through home visits carried out as part of primary care. RESULTS: Depression and psychological exhaustion were identified as the main psychological demands. Related to nursing, the difficulty of controlling chronic diseases was notable. Regarding dental care, the high prevalence of tooth loss was evident. In an attempt to minimize the limitations of access to health care, some strategies were created targeting the rural population. A radio program that aimed to disseminate basic health information in an accessible way was the main one. DISCUSSION: Therefore, the importance of home visits is evident, especially in rural areas, favoring educational health and preventive practices in primary care and considering the adoption of more effective care strategies for rural populations.

Escores de Risco Cardiovascular entre Adultos Assintomáticos com Hemofilia / Cardiovascular Risk Scores among Asymptomatic Adults with Haemophilia

Resumo Fundamento A taxa de mortalidade de pessoas com hemofilia (PCH) no Brasil está diminuindo, mas a incidência relativa de mortes associadas a doenças cardiovasculares (DCV) tem aumentado. Objetivos Nosso objetivo foi descrever o escore de risco de DCV de PCHs de acordo com a ferramenta Pooled Cohort Equations Risk (PCER) Calculator e suas recomendações de tratamento. Além disso, foram comparadas as estimativas da PCER com o respectivo escore de risco de Framingham (FRS). Métodos Este estudo transversal incluiu PCHs do sexo masculino, com idade igual ou superior a 40 anos, tratados no Centro de Tratamento Integral de Hemofilia de Pernambuco (Recife/Brasil). PCHs com um evento cardiovascular prévio ou colesterol lipídico de baixa densidade ≥ 5,0 mmol/L foram excluídas. Entrevistas, revisões de prontuários médicos e exames de sangue foram realizados. A ferramenta PCER foi utilizada para estimar o risco de DCV e compará-lo com o respectivo FRS. Um valor de p < 0,05 foi aceito como estatisticamente significativo. Resultados Trinta PCHs foram incluídas. A idade mediana foi de 51,5 [intervalo interquartil-IIQ; 46,0-59,5] anos. A prevalência de obesidade, hipertensão arterial sistêmica, diabetes mellitus, hipertrigliceridemia, hipercolesterolemia e hipoHDLemia foi de 20%, 67%, 24%, 14%, 47% e 23%, respectivamente. O escore mediano da PCER foi de 6,9% [IIQ; 3,1-13,2], com 50% de alto risco (PCER ≥ 7,5%). O uso de estatina foi sugerido para 54% das PCHs. A pressão arterial estava mal controlada em 47% das PCHs. A concordância entre PCER e FRS foi de 80% (κ = 0,60; p = 0,001). Conclusões Metade dos homens com hemofilia, com 40 anos de idade ou mais, teve um alto risco de desenvolver DCV em 10 anos, com fortes recomendações para melhorar o controle da dislipidemia e da pressão arterial.

Abstract Background The mortality rate of Brazilian people with haemophilia (PwH) is decreasing, but the relative incidence of deaths associated with cardiovascular disease (CVD) is increasing. Objectives We aimed to describe the CVD risk score of PwH according to Pooled Cohort Equations Risk (PCER) Calculator tool and its treatment recommendations. We also compared the PCER estimates with the respective Framingham Risk Score (FRS). Methods This cross-sectional study included male PwH ≥ 40 years treated at the Comprehensive Haemophilia Treatment Centre of Pernambuco (Recife/Brazil). PwH with a previous CVD event or a low-density lipid cholesterol ≥ 5.0 mmol/L were excluded. Interviews, medical file reviews, and blood tests were performed. The PCER tool was used to estimate the CVD risk and compare it with the respective FRS. A p-value < 0.05 was accepted as statistically significant. Results Thirty PwH were included. Median age was 51.5 [interquartile range-IQR; 46.0-59.5] years. The prevalence of obesity, systemic arterial hypertension, diabetes mellitus, hypertriglyceridaemia, hypercholesterolaemia, and hypoHDLaemia were 20%, 67%, 24%, 14%, 47%, and 23%, respectively. The median PCER score was 6.9% [IQR; 3.1-13.2], with 50% having a high risk (PCER ≥ 7.5%). Statin use was suggested for 54% of PwH. Blood pressure was poorly controlled in 47% of PwH. The agreement between PCER and FRS was 80% (κ = 0.60; p = 0.001). Conclusions Half of the male people with haemophilia aged 40 years or older had a 10-year high risk of developing CVD with strong recommendations to improve control of dyslipidaemia and blood pressure.

Percepção dos enfermeiros sobre a transição do cuidado na alta hospitalar / Nurses' perception about the transition of care at hospital discharge

Existe uma clara lacuna na transição entre Atenção Hospitalar (AH) e Atenção Primária à Saúde (APS). A efetividade da Transição do Cuidado (TC) depende de uma excelente capacidade de comunicação entre profissionais e serviços, sendo a alta hospitalar um momento crítico. O objetivo deste estudo foi investigar as percepções dos enfermeiros da Atenção Hospitalar (AH) e Atenção Primária em Saúde (APS) sobre aspectos da alta hospitalar Trata-se de um estudo transversal e quantitativo realizado com dados de enfermeiros atuantes na AH e na APS no estado de Santa Catarina. Os dados foram coletados entre dezembro de 2020 e janeiro de 2021, por meio de formulário eletrônico. Foi realizada análise descritiva e inferencial. Para comparação entre grupos utilizou-se teste de qui-quadrado de Pearson. Há algumas sobre posições nas percepções dos enfermeiros da AH e APS sobre a temática, sendo que consideram importante o acompanhamento do paciente após a alta hospitalar (54; 91,5%), entende que existe pouca e fraca comunicação entre serviços de saúde (52; 88%). Ainda, são realizadas orientações verbalmente para pacientes e familiares no momento da alta (32; 54,2%), pouca informação é compreendida pelos pacientes (47; 79,7%) e o plano de alta não é individualizado (30; 50,8%), na maioria dos casos. A comunicação é uma grande fragilidade na alta hospitalar, que se expressa nesse estudo, pela percepção dos enfermeiros de uma comunicação fraca entre AH e APS, pela fragilidade do plano de alta e orientações realizadas verbalmente. A melhoria do processo de transição do cuidado, especialmente a alta hospitalar, permite uma assistência à saúde mais integrada, segura e centrada no paciente. O investimento em estratégias que aprimorem esse processo é essencial para a qualidade do cuidado.

There is a clear gap in the transition between Hospital Care (HC) and Primary Health Care (PHC). The effectiveness of the Care Transition (TC) depends on an excellent communication ability between professionals and services, with hospital discharge being a critical moment. The objective of this study was to investigate the perceptions of HC and PHC nurses on aspects of hospital discharge. This is a cross-sectional and quantitative study carried out with data from nurses working in HC and PHC in the state of Santa Catarina. Data was collected between December 2020 and January 2021, using an electronic form. Descriptive and inferential analysis were performed. Pearson's chi-square test was used for comparison between groups. There are some overlapping positions in the perceptions of HC and PHC nurses on the subject, considering that patient follow-up after hospital discharge is important (54; 91.5%), they understand that there is little and weak communication between health services (52; 88%). Also, verbal guidelines are given to patients and family members at discharge (32; 54.2%), little information is understood by patients (47; 79.7%) and the discharge plan is not individualized (30; 50.8%), in most cases. Communication is a major weakness in hospital discharge, which is expressed in this study, by the nurses' perception of poor communication between HC and PHC, by the fragility of the discharge plan and verbally given guidelines. Improving the care transition process, especially hospital discharge, allows for more integrated, safe and patient-centered healthcare. Investment in strategies that improve this process is essential for the quality of care.

Clinical characteristics and evolution of 71 neonates born to mothers with COVID-19 at a tertiary center in Brazil.

INTRODUCTION: Limited data are available on pregnant women with COVID-19 and their neonates. OBJECTIVE: This study aimed to describe clinical characteristics and evolution from birth to discharge of a retrospective cohort of 71 neonates, with one set of twins, born to women with COVID-19 diagnosed at the end of pregnancy. The authors included all newborns admitted into a neonatal unit of a tertiary hospital in Brazil, between March 2020 and March 2021, whose unvaccinated mothers had COVID-19 symptoms and RT-PCR (Real-Time Polymerase Chain Reaction) for SARS-CoV-2 positive within fourteen days prior to delivery. Newborns to mothers with COVID-19 symptoms and negative tests for SARS-CoV-2 were excluded. RESULTS: The main route of birth delivery was cesarean, corresponding to 60 pregnant women (84.5%). The foremost indications for cesarean were pregnant with critical disease (24.6%) and acute fetal distress (20.3%). The mean birth weight was 2452 g (865‒3870 g) and the mean gestational age was 345/7 weeks (25‒40 weeks). There were 45 premature newborns (63.3%), of which 21 newborns (29.5%) were less than 32 weeks of gestational age. RT-PCR for SARS-CoV-2 on oropharyngeal swabs was positive in 2 newborns (2.8%) and negative in the other 69 newborns (97.2%). Most newborns (51.4%) needed respiratory support. Therapeutic interventions during hospitalization were inotropic drugs (9.9%), antibiotics (22.8%), parenteral nutrition (26.8%), and phototherapy (46.5%). CONCLUSION: Maternal COVID-19 diagnosticated close to delivery has an impact on the first days of neonatal life.

Transcriptomics and network analysis highlight potential pathways in the pathogenesis of pterygium.

Pterygium is a common ocular surface condition frequently associated with irritative symptoms. The precise identity of its critical triggers as well as the hierarchical relationship between all the elements involved in the pathogenesis of this disease are not yet elucidated. Meta-analysis of gene expression studies represents a novel strategy capable of identifying key pathogenic mediators and therapeutic targets in complex diseases. Samples from nine patients were collected during surgery after photo documentation and clinical characterization of pterygia. Gene expression experiments were performed using Human Clariom D Assay gene chip. Differential gene expression analysis between active and atrophic pterygia was performed using limma package after adjusting variables by age. In addition, a meta-analysis was performed including recent gene expression studies available at the Gene Expression Omnibus public repository. Two databases including samples from adults with pterygium and controls fulfilled our inclusion criteria. Meta-analysis was performed using the Rank Production algorithm of the RankProd package. Gene set analysis was performed using ClueGO and the transcription factor regulatory network prediction was performed using appropriate bioinformatics tools. Finally, miRNA-mRNA regulatory network was reconstructed using up-regulated genes identified in the gene set analysis from the meta-analysis and their interacting miRNAs from the Brazilian cohort expression data. The meta-analysis identified 154 up-regulated and 58 down-regulated genes. A gene set analysis with the top up-regulated genes evidenced an overrepresentation of pathways associated with remodeling of extracellular matrix. Other pathways represented in the network included formation of cornified envelopes and unsaturated fatty acid metabolic processes. The miRNA-mRNA target prediction network, also reconstructed based on the set of up-regulated genes presented in the gene ontology and biological pathways network, showed that 17 target genes were negatively correlated with their interacting miRNAs from the Brazilian cohort expression data. Once again, the main identified cluster involved extracellular matrix remodeling mechanisms, while the second cluster involved formation of cornified envelope, establishment of skin barrier and unsaturated fatty acid metabolic process. Differential expression comparing active pterygium with atrophic pterygium using data generated from the Brazilian cohort identified differentially expressed genes between the two forms of presentation of this condition. Our results reveal differentially expressed genes not only in pterygium, but also in active pterygium when compared to the atrophic ones. New insights in relation to pterygium's pathophysiology are suggested.

Clinical characteristics and evolution of 71 neonates born to mothers with COVID-19 at a tertiary center in Brazil

Abstract Introduction Limited data are available on pregnant women with COVID-19 and their neonates. Objective This study aimed to describe clinical characteristics and evolution from birth to discharge of a retrospective cohort of 71 neonates, with one set of twins, born to women with COVID-19 diagnosed at the end of pregnancy. The authors included all newborns admitted into a neonatal unit of a tertiary hospital in Brazil, between March 2020 and March 2021, whose unvaccinated mothers had COVID-19 symptoms and RT-PCR (Real-Time Polymerase Chain Reaction) for SARS-CoV-2 positive within fourteen days prior to delivery. Newborns to mothers with COVID-19 symptoms and negative tests for SARS-CoV-2 were excluded. Results The main route of birth delivery was cesarean, corresponding to 60 pregnant women (84.5%). The foremost indications for cesarean were pregnant with critical disease (24.6%) and acute fetal distress (20.3%). The mean birth weight was 2452 g (865‒3870 g) and the mean gestational age was 345/7weeks (25‒40 weeks). There were 45 premature newborns (63.3%), of which 21 newborns (29.5%) were less than 32 weeks of gestational age. RT-PCR for SARS-CoV-2 on oropharyngeal swabs was positive in 2 newborns (2.8%) and negative in the other 69 newborns (97.2%). Most newborns (51.4%) needed respiratory support. Therapeutic interventions during hospitalization were inotropic drugs (9.9%), antibiotics (22.8%), parenteral nutrition (26.8%), and phototherapy (46.5%). Conclusion Maternal COVID-19 diagnosticated close to delivery has an impact on the first days of neonatal life.

Spatial and Temporal Distribution of Rodents during the Epizootic and Enzootic Periods of Plague, with a Focus on Exu, Northeastern Brazil.

The plague caused by the Yersinia pestis bacterium is primarily a flea-transmitted zoonosis of rodents that can also be conveyed to humans and other mammals. In this work, we analyzed the spatial and temporal distribution of rodent populations during epizootic and enzootic periods of the plague in the municipality of Exu, northeastern Brazil. The geospatial analyses showed that all the rodent species appeared through the whole territory of the municipality, with different occurrence hotspots for the different species. Important fluctuations in the rodent populations were observed, with a reduction in the wild rodent fauna following the end of a plague epizootic period, mostly represented by Necromys lasiurus and an increase in the commensal species Rattus rattus. A higher abundance of rats might lead to an increased exposure of human populations, favoring spillovers of plague and other rodent-borne diseases. Our analysis highlights the role of wild rodent species as amplifier hosts and of commensal rats (R. rattus) as preserver hosts in the enzootic period of a specific transmission infection area.

West Nile Virus in the State of Ceará, Northeast Brazil.

In June 2019, a horse with neurological disorder was diagnosed with West Nile virus (WNV) in Boa Viagem, a municipality in the state of Ceará, northeast Brazil. A multi-institutional task force coordinated by the Brazilian Ministry of Health was deployed to the area for case investigation. A total of 513 biological samples from 78 humans, 157 domestic animals and 278 free-ranging wild birds, as well as 853 adult mosquitoes of 22 species were tested for WNV by highly specific serological and/or molecular tests. No active circulation of WNV was detected in vertebrates or mosquitoes by molecular methods. Previous exposure to WNV was confirmed by seroconversion in domestic birds and by the detection of specific neutralizing antibodies in 44% (11/25) of equids, 20.9% (14/67) of domestic birds, 4.7% (13/278) of free-ranging wild birds, 2.6% (2/78) of humans, and 1.5% (1/65) of small ruminants. Results indicate that not only equines but also humans and different species of domestic animals and wild birds were locally exposed to WNV. The detection of neutralizing antibodies for WNV in free-ranging individuals of abundant passerine species suggests that birds commonly found in the region may have been involved as amplifying hosts in local transmission cycles of WNV.

Cardiovascular risk factors among adult patients with haemophilia.

Since the introduction of episodic and prophylactic treatments with safer factor concentrates, the life expectancy of people with haemophilia (PwH) has improved considerably. Ageing-related diseases such as cardiovascular disease (CVD) have also become more prevalent in PwH. This cross-sectional study aimed to evaluate CVD risk factors and estimate 10-year risk for CVD events among PwH. Male patients ≥ 30 years were interviewed and examined. Blood tests were performed at the local laboratory. Eighty-two patients were included, of whom 83% had haemophilia A and half had severe disease. Median age at study entry was 43.0 years (interquartile range [IQR], 36.0-51.3). Prevalence of obesity, systemic arterial hypertension (SAH) and diabetes mellitus were 16%, 60% and 16%, respectively. Hypertriglyceridaemia, hypercholesterolaemia and low HDL blood levels were present in 18%, 41% and 30% of patients, respectively. Metabolic syndrome was found in 37%. The Framingham Risk Score showed that 39% of PwH had a high risk of developing cardiovascular events in the following 10 years. We conclude that, in this cohort, PwH have a higher prevalence of SAH when compared with Brazilian men without haemophilia and about two-fifths have a high risk of developing a CVD event in the following 10 years.

Tear proteomic profile in three distinct ocular surface diseases: keratoconus, pterygium, and dry eye related to graft-versus-host disease.

BACKGROUND: Diseases of the anterior segment of the eye may present different mechanisms, intensity of symptoms, and impact on the patients' quality of life and vision. The tear film is in direct contact with the ocular surface and cornea and can be easily accessed for sample collection, figuring as a promising source of potential biomarkers for diagnosis and treatment control. This study aimed to evaluate tear proteomic profile in 3 distinct ocular diseases: keratoconus (corneal ectasia), severe dry eye related to graft-versus-host-disease (tear film dysfunction and ocular inflammatory condition) and pterygium (conjunctival fibrovascular degenerative disease). METHODS: Tear samples were collected from patients of each condition and a control group. By using mass spectrometric analysis combined with statistics and bioinformatics tools, a detailed comparison of protein profile was performed. RESULTS: After Student's t-test analyses comparing each condition to the control group, we found the following number of differentially expressed proteins: 7 in keratoconus group, 29 in pterygium group, and 79 in GVHD group. Following multivariate analyses, we also report potential candidates as biomarkers for each disease. CONCLUSIONS: We demonstrated herein that mass spectrometry-based proteomics was able to indicate proteins that differentiate three distinct ocular conditions, which is a promising tool for the diagnosis of ocular diseases.

Mechanisms and biomarker candidates in pterygium development / Mecanismos e candidatos a biomarcadores no desenvolvimento do pterígio

ABSTRACT Pterygium pathogenesis has been mainly asso ciated with UV light exposure; however, this association remains quite controversial. The complete mechanism of pterygium also remains to be clarified. Factors such as inflammation, viral infection, oxidative stress, DNA methylation, inflammatory mediators, extracellular matrix modulators, apoptotic and oncogenic proteins, loss of heterozygosity, microsatellite instability, lymphangiogenesis, epithelial-mesenchymal cell transition, and alterations in cholesterol metabolism have been identified as causes. Several studies aimed to clarify the molecular mechanisms underlying the growth and proliferation of pterygium. Understanding its molecular basis provides new potential therapeutic targets for its prevention and treatment. A comprehensive search of the databases, namely, MedLine, EMBASE, and LILACS, was conducted with the following key words: pterygium, epidemiology, pathogenesis, biomarkers, and review. This review describes the epidemiology, clinical presentation, and current investigation of biological mediators involved in pterygium development.

RESUMO A patogênese do pterígio tem sido relacionada, prin cipalmente, à exposição à luz ultravioleta, mas esta asso ciação permanece bastante controversa. O mecanismo completo do pte rígio também permanece por esclarecer. Fatores como inflamação, infecção viral, estresse oxidativo, metilação do DNA, mediadores inflamatórios, moduladores de matriz extracelular, proteínas apoptóticas e oncogênicas, perda de heterozigose, instabilidade de microssatélites, linfangiogênese, transição celular epitelial-mesenquimal e alterações no metabolismo do colesterol tem sido identificados como causas. Diversos estudos visam esclarecer os mecanismos moleculares subjacentes ao crescimento e proliferação do pterígio. Entender sua base mo lecular fornece novos alvos terapêuticos potenciais para sua prevenção e tratamento. Uma busca abrangente nas bases de dados, a saber, MedLine, EMBASE e LILACS, foi realizada com as seguintes palavras-chave: pterígio; epidemiologia; patogênese; biomarcadores e revisão. Esta revisão descreve a epidemiologia, apresentação clínica e a atual investigação de mediadores biológicos envolvidos no desenvolvimento do pterígio.

Mechanisms and biomarker candidates in pterygium development.

Pterygium pathogenesis has been mainly asso ciated with UV light exposure; however, this association remains quite controversial. The complete mechanism of pterygium also remains to be clarified. Factors such as inflammation, viral infection, oxidative stress, DNA methylation, inflammatory mediators, extracellular matrix modulators, apoptotic and oncogenic proteins, loss of heterozygosity, microsatellite instability, lymphangiogenesis, epithelial-mesenchymal cell transition, and alterations in cholesterol metabolism have been identified as causes. Several studies aimed to clarify the molecular mechanisms underlying the growth and proliferation of pterygium. Understanding its molecular basis provides new potential therapeutic targets for its prevention and treatment. A comprehensive search of the databases, namely, MedLine, EMBASE, and LILACS, was conducted with the following key words: pterygium, epidemiology, pathogenesis, biomarkers, and review. This review describes the epidemiology, clinical presentation, and current investigation of biological mediators involved in pterygium development.

FIPLIQ: an alternative solution for gynecological and oral cytology / FIPLIQ: uma solução alternativa para exames citológicos ginecológicos e bucais

ABSTRACT Introduction: Liquid-based solution for cytology has been developed to improve Pap test. Some liquid media are commercially available, however, due to the high cost there are difficulties in implementing it in the public health programs of many countries. Objectives: To study the suitability of alternative liquid media for the collection and preservation of samples for cytologic examinations, comparing the results with the conventional Papanicolaou methodology. Material and methods: In this study, 127 different compositions of alternative liquid-based solutions were tested with samples from 10 volunteers for oral cytology and 20 samples from volunteers for cervical cytology. Formaldehyde-isopropanol-phosphate (FIPLIQ) was used to preserve cervical samples prepared and analyzed on the same day and 3, 7, and 15 days after collection, compared with Pap smear. Evaluations on quality and adequacy of cell types, microorganisms or their cytopathic effects, reactive, degenerative and dysplastic cell alterations were performed. Results: Samples processed with FIPLIQ showed results similar to those of conventional Pap smear when analyzing staining cytoplasm with indistinct cytoplasm borders, chromatin structure, presence or absence of different types of cell and microorganisms, reparative process, preneoplastic, and neoplastic cell changes; the samples were stored for up to 15 days after collection. Conclusion: Preliminary results suggest that FIPLIQ is suitable for the preparation and preservation of cytology specimens for up to 15 days.

RESUMEN Introducción: La citología en medio líquido fue desarrollada para mejorar la prueba de Papanicolaou. Algunos medios líquidos son comercialmente disponibles; no obstante, debido al costo elevado, hay dificultades para su implementación en programas de salud pública en muchos países. Objetivos: Estudiar la adecuación de medios líquidos alternativos para recolecta y la preservación de muestras para exámenes citológicos, comparando los resultados con la metodología convencional de Papanicolaou. Material y métodos: En este estudio, 127 diferentes composiciones de soluciones alternativas de medios líquidos fueron testadas con muestras de 10 voluntarios para citología oral y 20 muestras de voluntarias para citología cervical. El fosfato de formaldehído- isopropanol (FIPLIQ) fue usado para preservación de muestras cervicales preparadas y analizadas en el mismo día, y tres, siete y 15 días después de la recolecta, en comparación con la citología convencional. Se hicieron evaluaciones de calidad y adecuación de los tipos celulares, microorganismos o sus efectos citopáticos, cambios celulares reactivos, degenerativos y displásicos. Resultados: Las muestras procesadas con FIPLIQ presentaron resultados similares a los de la prueba convencional de Papanicolaou cuando analizados color y bordes citoplasmáticos mal definidos, estructura de cromatina, presencia o ausencia de diferentes tipos de células y microorganismos, proceso reparativo, pre-neoplásico y alteraciones celulares neoplásicas; las muestras se conservaron hasta 15 días después de la recolección. Conclusión: Los resultados preliminares sugieren que el FIPLIQ es adecuado para preparación y preservación de especímenes citológicos hasta 15 días.

RESUMO Introdução: A citologia em meio líquido foi desenvolvida para melhorar o teste de Papanicolaou. Alguns meios líquidos são comercialmente disponíveis, no entanto, devido ao alto custo, há dificuldades para sua implementação em programas de saúde pública em muitos países. Objetivos: Estudar a adequabilidade de meios líquidos alternativos para a coleta e a preservação de amostras para exames citológicos, comparando os resultados com a metodologia convencional de Papanicolaou. Material e métodos: Neste estudo, 127 diferentes composições de soluções alternativas de meios líquidos foram testadas com amostras de 10 voluntários para citologia oral e 20 amostras de voluntárias para citologia cervical. O fosfato de formaldeído-isopropanol (FIPLIQ) foi utilizado para preservar amostras cervicais preparadas e analisadas no mesmo dia e três, sete e 15 dias após coleta, em comparação com a citologia convencional. Avaliações de qualidade e adequação dos tipos celulares, de microrganismos ou seus efeitos citopáticos, de alterações celulares reativas, degenerativas e displásicas foram realizadas. Resultados: As amostras processadas com FIPLIQ apresentaram resultados semelhantes aos do teste convencional de Papanicolaou quando analisados coloração e apagamento de bordas citoplasmáticas, estrutura de cromatina, presença ou ausência de diferentes tipos de células e microrganismos, processo reparativo, pré-neoplásico e alterações celulares neoplásicas; as amostras foram conservadas por até 15 dias após a coleta. TOPICO Conclusão: Os resultados preliminares sugerem que o FIPLIQ é adequado para a preparação e a preservação de espécimes citológicos por até 15 dias.

Impact of pterygium on the ocular surface and meibomian glands.

PURPOSE: To analyze how ocular surface parameters correlate to presence of pterygium and investigate the possible impact of pterygia on tear film findings and meibomian glands findings. METHODS: We investigated objective parameters of the ocular surface such as conjunctival hyperemia, tear film stability and volume, meibomian gland dysfunction, dry eye disease, corneal topography comparing healthy individuals and correlating with the pterygium clinical presentation. RESULTS: A total of 83 patients were included. Corneal astigmatism induction was 2.65 ± 2.52 D (0.4-11.8). The impact of pterygium on the ocular surface parameters compared to matched controls was seen in: conjunctival hyperemia (control 1.55±0.39/pterygium 2.14±0.69; p = 0.0001), tear meniscus height (control 0.24±0.05 mm/pterygium 0.36±0.14mm; p 0.0002), meiboscore lower eyelid (control 0.29±0.64/pterygium 1.38±0.95; p 0.0001) and meiboscore upper eyelid (control 0.53±0.62/pterygium 0.98±0.75; p = 0.0083). We found a high number of pterygium patients (88%) presented meibomian gland alterations. Interestingly, meibomian gland loss was coincident to the localization of the pterygium in 54% of the upper and 77% lower lids. CONCLUSION: Pterygium greatly impacts on ocular surface by inducing direct alterations in the pattern of meibomian glands besides corneal irregularities, conjunctival hyperemia and lacrimal film alterations, inducing significant symptoms and potential signs of dysfunction.

Genome-wide identification, characterisation and expression profiling of the ubiquitin-proteasome genes in Biomphalaria glabrata.

BACKGROUND: Biomphalaria glabrata is the major species used for the study of schistosomiasis-related parasite-host relationships, and understanding its gene regulation may aid in this endeavor. The ubiquitin-proteasome system (UPS) performs post-translational regulation in order to maintain cellular protein homeostasis and is related to several mechanisms, including immune responses. OBJECTIVE: The aims of this work were to identify and characterise the putative genes and proteins involved in UPS using bioinformatic tools and also their expression on different tissues of B. glabrata. METHODS: The putative genes and proteins of UPS in B. glabrata were predicted using BLASTp and as queries reference proteins from model organism. We characterised these putative proteins using PFAM and CDD software describing the conserved domains and active sites. The phylogenetic analysis was performed using ClustalX2 and MEGA5.2. Expression evaluation was performed from 12 snail tissues using RPKM. FINDINGS: 119 sequences involved in the UPS in B. glabrata were identified, which 86 have been related to the ubiquitination pathway and 33 to proteasome. In addition, the conserved domains found were associated with the ubiquitin family, UQ_con, HECT, U-box and proteasome. The main active sites were lysine and cysteine residues. Lysines are responsible and the starting point for the formation of polyubiquitin chains, while the cysteine residues of the enzymes are responsible for binding to ubiquitin. The phylogenetic analysis showed an organised distribution between the organisms and the clades of the sequences, corresponding to the tree of life of the animals, for all groups of sequences analysed. The ubiquitin sequence was the only one with a high expression profile found in all libraries, inferring its wide range of performance. MAIN CONCLUSIONS: Our results show the presence, conservation and expression profile of the UPS in this mollusk, providing a basis and new knowledge for other studies involving this system. Due to the importance of the UPS and B. glabrata, this work may influence the search for new methodologies for the control of schistosomiasis.

Avaliação da efetividade de tratamentos conservadores para disfunções temporomandibulares miogênicas: revisão integrativa da literatura / Evaluation of the effectiveness of conservative treatments for miogenic temporomandibular dysfunctions: integrating review of the literature

Objetivo: revisão integrativa sobre os principais métodos de tratamento conservador para disfunção temporomandibular, sendo eles: placa oclusal, aconselhamento e farmacoterapia. Materiais e método: a busca foi feita nas bases de dados PubMed, SciELO, Lilacs e Google Acadêmico, utilizando os seguintes descritores: "counseling and temporomandibular joint"; "counseling and facial pain"; "counseling and temporomandibular joint dysfunction syndrome"; "counseling and temporomandibular joint and drug therapy"; e "counseling and drug therapy and facial pain". Resultados: no total, foram encontrados 314 estudos nesta pesquisa, porém, somente 8 foram incluídos no estudo. Esses comprovam a eficácia desses métodos de tratamento, fazendo com que o paciente obtenha diminuição da sintomatologia dolorosa, melhora das funções mastigatórias, além de proporcionar um alívio na tensão muscular, devido ao relaxamento das estruturas relacionadas. A placa oclusal tende a diminuir as forças oclusais aplicadas, redistribuindo a carga mastigatória sobre as superfícies oclusais. Alguns fármacos (anti-inflamatórios, antidepressivos e relaxantes musculares) são capazes de minimizar a sintomatologia dolorosa, proporcionando uma melhora na qualidade do sono e a redução de episódios de dor intensa. Por sua vez, o aconselhamento orienta os pacientes para que possam evitar atitudes que piorem sua doença, educando-os e conscientizando-os sobre seus hábitos parafuncionais, além de reduzir os fatores causadores de sintomatologia dolorosa. Conclusão: conseguimos observar que esses tratamentos apresentam índices de sucesso relevantes, quando se referem à diminuição dos sintomas, especialmente o aconselhamento, que ainda é uma terapia conservadora pouco explorada. Faz-se necessária a realização de mais estudos neste campo, para que sejam obtidos resultados cada vez mais concretos e conclusivos. (AU)

Objective: integrative review on the main methods of conservative treatment for Temporomandibular Dysfunction, being occlusal plaque, counseling and pharmacotherapy. Materials and method: the search was done in the databases PubMed, SciELO, Lilacs and Google Scholar using the descriptors: "counseling" and "temporomandibular joint", "counseling" and "facial pain", "counseling" and "temporomandibular joint dysfunction syndrome", "counseling" and "temporomandibular joint" and "drug therapy" and "counseling" and "drug therapy" and "facial pain". Results: in total were found 314 studies in this work, but only 8 were included. These tests prove the efficacy of these treatment methods, causing to the patient a decrease in painful symptoms, an increase in masticatory functions, and also providing a relief in muscle tension due to the relaxation of related structures. The occlusal plaque tends to decrease the forces applied in the occlusion, preventing the muscles from exerting excessive force. Some drugs (anti-inflammatories, antidepressants and muscle relaxants) are able to minimize the painful symptomatology, providing an improvement in the quality of sleep and reduction of episodes of intense pain. In turn, counseling guides patients to avoid attitudes that worsen their illness, educating them and making them aware of their parafunctional habits, as well as reducing the factors that cause painful symptoms. Conclusion: we could observe that these treatments present relevant success indexes when it refers to the decrease of the symptoms, especially the counseling, which is still a little explored conservative therapy. It is still necessary to carry out further studies in this field in order to obtain increasingly concrete and conclusive results. (AU)

Is it possible to teach Geriatric Medicine in a stimulating way? Measuring the effect of active learning activities in Brazilian medical students.

OBJECTIVE: To describe the experience of a Brazilian medical school in implementing different active methods to teach Geriatric Medicine, reporting the students' opinions and satisfaction with the classes and comparing pre- and postcourse measurements of knowledge, attitudes and skills. METHODS: A total of 166 third-year medical students received different active theoretical-practical activities for teaching Geriatric Medicine and their knowledge, attitudes, clinical skills and satisfaction were investigated. RESULTS: All activities had good acceptance among students ranging from 8.54 in the activity "Walking aids" to 9.81 in the activity "Nursing Home visit" (ranging 0-10). After the course, students had better attitudes towards older persons (r = 0.55-0.81, P < 0.001), better knowledge (r = 0.84, P < 0.001), greater empathy (r = 0.51, P < 0.001) and better clinical skills (r = 0.86, P < 0.001). Finally, the course was evaluated positively by the students. CONCLUSION: New active Geriatric Medicine learning activities resulted in improvement in medical students knowledge, attitudes and skills.

Synthesis of novel pyrazoline derivatives and the evaluation of death mechanisms involved in their antileukemic activity.

Malignant neoplasms are one of the leading causes of death worldwide and hematologic malignancies, including acute leukemia (AL) is one of the most relevant cancer types. Current available chemotherapeutics are associated with high morbidity and mortality rates, therefore, the search for new molecules with antitumor activity, specific and selective for neoplastic cells, became a great challenge for researchers in the oncology field. As pyrazolines stand out in the literature for their great variety of biological activities, the aim of this study was to synthesize and evaluate the antileukemic activity of five new pyrazoline derivatives. All pyrazolines showed adequate physicochemical properties for a good oral bioavailability. The two unpublished and most effective pyrazoline derivatives have been selected for further experiments. These compounds are highly selective for leukemic cells when compared to non-neoplastic cells and did not cause lysis on human red blood cells. Additionally, selected pyrazolines induced cell cycle arrest at G0/G1 phase and decreased cell proliferation marker KI67. Apoptotic cell death induced by selected pyrazolines was confirmed by morphological analysis, assessment of phosphatidylserine residue exposure and DNA fragmentation. Several factors indicate that both intrinsic and extrinsic apoptosis occurred. These were: increased FasR expression; the predominance of Bax in relation to Bcl-2; the loss of mitochondrial membrane potential; AIF release; decreased expression of survivin (an antiapoptotic protein); and the activation of caspase-3. The selected pyrazolines were also found to be cytotoxic against neoplastic cells collected from the peripheral blood and bone marrow of patients with different subtypes of acute leukemia.