Composite endpoints in COVID-19 randomized controlled trials: a systematic review.

BACKGROUND/AIMS: This study aimed to determine the prevalence of ordinal, binary, and numerical composite endpoints among coronavirus disease 2019 trials and the potential bias attributable to their use. METHODS: We systematically reviewed the Cochrane COVID-19 Study Register to assess the prevalence, characteristics, and bias associated with using composite endpoints in coronavirus disease 2019 randomized clinical trials. We compared the effect measure (relative risk) of composite outcomes and that of its most critical component (i.e. death) by estimating the Bias Attributable to Composite Outcomes index [ln(relative risk for the composite outcome)/ln(relative risk for death)]. RESULTS: Composite endpoints accounted for 152 out of 417 primary endpoints in coronavirus disease 2019 randomized trials, being more frequent among studies published in high-impact journals. Ordinal endpoints were the most common (54% of all composites), followed by binary or time-to-event (34%), numerical (11%), and hierarchical (1%). Composites predominated among trials enrolling patients with severe disease when compared to trials with a mild or moderate case mix (odds ratio = 1.72). Adaptations of the seven-point World Health Organization scale occurred in 40% of the ordinal primary endpoints, which frequently underwent dichotomization for the statistical analyses. Mortality accounted for a median of 24% (interquartile range: 6%-48%) of all events when included in the composite. The median point estimate of the Bias Attributable to Composite Outcomes index was 0.3 (interquartile range: -0.1 to 0.7), being significantly lower than 1 in 5 of 24 comparisons. DISCUSSION: Composite endpoints were used in a significant proportion of coronavirus disease 2019 trials, especially those involving severely ill patients. This is likely due to the higher anticipated rates of competing events, such as death, in such studies. Ordinal composites were common but often not fully appreciated, reducing the potential gains in information and statistical efficiency. For studies with binary composites, death was the most frequent component, and, unexpectedly, composite outcome estimates were often closer to the null when compared to those for mortality death. Numerical composites were less common, and only two trials used hierarchical endpoints. These newer approaches may offer advantages over traditional binary and ordinal composites; however, their potential benefits warrant further scrutiny. CONCLUSION: Composite endpoints accounted for more than a third of coronavirus disease 2019 trials' primary endpoints; their use was more common among studies that included patients with severe disease and their point effect estimates tended to underestimate those for mortality.

The Effects of Collagen Peptides as a Dietary Supplement on Muscle Damage Recovery and Fatigue Responses: An Integrative Review.

BACKGROUND/OBJECTIVES: The oral administration of hydrolyzed collagen peptides is a scientifically validated intervention for enhancing skeletal muscle health and performance. This integrative review consolidates the evidence supporting the use of low molecular weight collagen peptides (2000-3500 daltons) for their superior bioavailability and absorption. Our objective was to review the effects of collagen peptide or hydrolyzed collagen supplementation on muscle damage, recovery, and construction related to physical exercise. METHODS: A bibliographic search was conducted in major English-language databases, including PubMed/Medline, using terms like "Peptides Collagen and Damage" and "collagen peptides AND Soreness Muscle". This review followed PRISMA guidelines, with bias risk assessed via the PEDro scale. The inclusion criteria were (a) randomized clinical trials, (b) randomized studies in humans with a control or placebo group, (c) studies assessing muscle damage or delayed onset muscle soreness via physiological markers or strength performance tests, and (d) studies using hydrolyzed collagen or collagen peptides. RESULTS: Initially, 752 articles were identified. After applying the inclusion and exclusion criteria, including duplicate removal, eight articles with 286 participants were included. Of these, 130 participants received collagen peptide supplementation, while 171 received a placebo or control. CONCLUSION: This integrative review supports the potential of collagen peptide supplementation to mitigate muscle stress from acute strenuous resistance training. However, due to the methodological heterogeneity among the studies, further clinical trials are needed to clarify the mechanisms underlying muscle improvement with collagen supplementation.

Four years of the COVID-19 pandemic: how does Brazil deal with the impacts? A DOHaD perspective.

Over the last few years, during the pandemic, the Brazilian population has suffered several problems, ranging from health to socioeconomic impacts. When we consider Brazilian science, there has been an undeniable scientific delay generated by the pandemic, especially in areas that are not related to the coronavirus. In this context, with the aim of fostering collaboration among researchers in the field of Developmental Origins of Health and Diseases (DOHaD) and enhancing the potential for implementing public health strategies to prevent noncommunicable chronic diseases, the Brazilian Association of Developmental Origins of Health and Diseases (DOHaD Brazil) was established in 2020. In this narrative, we explore the effects of the COVID-19 pandemic in Brazil, focusing on its impacts on scientific research conducted in universities. Additionally, we underscore the significance of the DOHaD Brazil Association, particularly from the perspective of young researchers engaged in DOHaD research in Brazil.

Mpox, sexually transmitted infections and combination prevention: insights from a major cohort in Rio de Janeiro, Brazil.

OBJECTIVE: To evaluate the prevalence and characteristics of concurrent bacterial sexually transmitted infections (bSTIs) among individuals with mpox. DESIGN: Prospective cohort study of participants aged 18 years or older with confirmed mpox conducted in Rio de Janeiro, Brazil. This cross-sectional analysis includes only participants who underwent bSTI testing at baseline between June 2022 and January 2024. METHODS: Participants were offered testing for chlamydia/gonorrhea (NAAT, anorectal swabs) and syphilis (active diagnosis if VDRL ≥ 1/8). Baseline prevalence of bSTIs was calculated, and participant characteristics were described based on concomitant bSTI diagnosis (yes/no). Chi-squared/Fisher's tests were used for qualitative variables, and the Wilcoxon rank-sum test for quantitative variables. RESULTS: Out of 634 enrolled participants, 538 (84.9%) were tested for STIs and included in this analysis, mostly cisgender men, aged 30-39 years with postsecondary education. Overall prevalence of concomitant bSTI was 37.3%, mainly syphilis, followed by chlamydia and gonorrhea. Half of the participants were living with HIV, and one third was on HIV pre-exposure prophylaxis. Concomitant bSTI diagnosis at the time of mpox assessment was associated with being aged 30-39 years, self-identifying as cisgender men, having HIV-positive status, reporting proctitis symptoms and reporting any STI in the past 12 months. CONCLUSIONS: Our data reveals a notable prevalence of concomitant bSTIs among participants with confirmed mpox at a prominent infectious diseases' referral center in Rio de Janeiro, Brazil. These findings underscore the importance of integrating mpox into the differential diagnosis of anogenital manifestations and the promotion of combination prevention strategies within sexual healthcare services.

Exploring the Resurgence of a Neglected Disease: Lessons From the 2023-2024 Mpox Outbreak in Rio de Janeiro, Brazil.

Following the 2022 global mpox outbreak, diagnoses decreased worldwide, even in settings with limited vaccine access. In 2023-2024, a new outbreak emerged in Rio de Janeiro, Brazil, highlighting the importance of continuous surveillance, preventive measures such as vaccination in vulnerable populations, and treatment options, emphasizing equitable global health technology distribution.

Complete phylogeny of Micrathena spiders suggests multiple dispersal events among Neotropical rainforests, islands and landmasses, and indicates that Andean orogeny promotes speciation.

The Neotropical region is the most diverse on the planet, largely owing to its mosaic of tropical rainforests. Multiple tectonic and climatic processes have been hypothesized to contribute to generating this diversity, including Andean orogeny, the closure of the Isthmus of Panama, the GAARlandia land bridge and historical connections among currently isolated forests. Micrathena spiders are diverse and widespread in the region, and thus a complete phylogeny of this genus allows the testing of hypotheses at multiple scales. We estimated a complete, dated phylogeny using morphological data for 117 Micrathena species and molecular data of up to five genes for a subset of 79 species. Employing event-based approaches and biogeographic stochastic mapping while considering phylogenetic uncertainty, we estimated ancestral distributions, the timing and direction of dispersal events and diversification rates among areas. The phylogeny is generally robust, with uncertainty in the position of some of the species lacking sequences. Micrathena started diversifying around 25 Ma. Andean cloud forests show the highest in-situ speciation, while the Amazon is the major dispersal source for adjacent areas. The Dry Diagonal generated few species and is a sink of diversity. Species exchange between Central and South America involved approximately 23 dispersal events and started ~20 Ma, which is consistent with a Miocene age for the Isthmus of Panama closure. We inferred four dispersal events from Central America to the Antilles in the last 20 Myr, indicating the spiders did not reach the islands through the GAARlandia land bridge. We identified important species exchange routes among the Amazon, Andean cloud forests and Atlantic forests during the Plio-Pleistocene. Sampling all species of the genus was fundamental to the conclusions above, especially in identifying the Andean forests as the area that generated the majority of species. This highlights the importance of complete taxonomic sampling in biogeographic studies.

Driving pressure, as opposed to tidal volume based on predicted body weight, is associated with mortality: results from a prospective cohort of COVID-19 acute respiratory distress syndrome patients.

OBJECTIVE: To evaluate the association between driving pressure and tidal volume based on predicted body weight and mortality in a cohort of patients with acute respiratory distress syndrome caused by COVID-19. METHODS: This was a prospective, observational study that included patients with acute respiratory distress syndrome due to COVID-19 admitted to two intensive care units. We performed multivariable analyses to determine whether driving pressure and tidal volume/kg predicted body weight on the first day of mechanical ventilation, as independent variables, are associated with hospital mortality. RESULTS: We included 231 patients. The mean age was 64 (53 - 74) years, and the mean Simplified Acute and Physiology Score 3 score was 45 (39 - 54). The hospital mortality rate was 51.9%. Driving pressure was independently associated with hospital mortality (odds ratio 1.21, 95%CI 1.04 - 1.41 for each cm H2O increase in driving pressure, p = 0.01). Based on a double stratification analysis, we found that for the same level of tidal volume/kg predicted body weight, the risk of hospital death increased with increasing driving pressure. However, changes in tidal volume/kg predicted body weight were not associated with mortality when they did not lead to an increase in driving pressure. CONCLUSION: In patients with acute respiratory distress syndrome caused by COVID-19, exposure to higher driving pressure, as opposed to higher tidal volume/kg predicted body weight, is associated with greater mortality. These results suggest that driving pressure might be a primary target for lung-protective mechanical ventilation in these patients.

Driving pressure, as opposed to tidal volume based on predicted body weight, is associated with mortality: results from a prospective cohort of COVID-19 acute respiratory distress syndrome patients / Driving pressure, em oposição ao volume corrente ajustado para o peso corporal predito, associa-se com a mortalidade: resultados de uma coorte prospectiva de pacientes com síndrome do desconforto respiratório agudo por COVID-19

ABSTRACT Objective: To evaluate the association between driving pressure and tidal volume based on predicted body weight and mortality in a cohort of patients with acute respiratory distress syndrome caused by COVID-19. Methods: This was a prospective, observational study that included patients with acute respiratory distress syndrome due to COVID-19 admitted to two intensive care units. We performed multivariable analyses to determine whether driving pressure and tidal volume/kg predicted body weight on the first day of mechanical ventilation, as independent variables, are associated with hospital mortality. Results: We included 231 patients. The mean age was 64 (53 - 74) years, and the mean Simplified Acute and Physiology Score 3 score was 45 (39 - 54). The hospital mortality rate was 51.9%. Driving pressure was independently associated with hospital mortality (odds ratio 1.21, 95%CI 1.04 - 1.41 for each cm H2O increase in driving pressure, p = 0.01). Based on a double stratification analysis, we found that for the same level of tidal volume/kg predicted body weight, the risk of hospital death increased with increasing driving pressure. However, changes in tidal volume/kg predicted body weight were not associated with mortality when they did not lead to an increase in driving pressure. Conclusion: In patients with acute respiratory distress syndrome caused by COVID-19, exposure to higher driving pressure, as opposed to higher tidal volume/kg predicted body weight, is associated with greater mortality. These results suggest that driving pressure might be a primary target for lung-protective mechanical ventilation in these patients.

RESUMO Objetivo: Avaliar a associação entre driving pressure e volume corrente ajustado pelo peso predito com a mortalidade em uma coorte de pacientes com síndrome do desconforto respiratório agudo por COVID-19. Métodos: Estudo prospectivo e observacional que incluiu pacientes com síndrome do desconforto respiratório agudo por COVID-19 admitidos em duas unidades de terapia intensiva. Foi realizada análise multivariada para determinar se a driving pressure e o volume corrente/kg de peso predito, aferidos no primeiro dia de ventilação mecânica, associavam-se de forma independente com a mortalidade hospitalar. Resultados: Foram incluídos 231 pacientes. A mediana de idade foi de 64 (53 - 74) anos, e a mediana do Simplified Acute and Physiology Score 3 foi de 45 (39 - 54). A mortalidade hospitalar foi de 51,9%. A driving pressure se associou de forma independente com a mortalidade hospitalar (razão de chance de 1,21; IC95% de 1,04 - 1,41 para cada cm H2O de aumento da driving pressure, p = 0,01). Com base na análise de dupla estratificação, encontrou-se que, para o mesmo nível de volume corrente/kg de peso predito, o risco de mortalidade hospitalar aumentava com o incremento da driving pressure. No entanto, mudanças no volume corrente/kg de peso predito não se associaram com a mortalidade quando não resultavam em aumento da driving pressure. Conclusão: Em pacientes com síndrome do desconforto respiratório agudo por COVID-19, exposição a maior driving pressure, ao contrário da exposição a maior volume corrente/kg de peso predito, associou-se com maior mortalidade hospitalar. Os resultados sugerem que a driving pressure poderia ser o alvo primário para a condução da ventilação mecânica protetora nesses pacientes.

Mpox severity and associated hospitalizations among people with HIV and related immunosuppression in Brazil.

OBJECTIVES: This study aimed to analyze characteristics of mpox hospitalization in a Brazilian cohort, further exploring the impact of HIV on mpox-related outcomes and hospitalization. DESIGN: We conducted a descriptive analysis, comparing characteristics of individuals diagnosed with mpox according to hospitalization and HIV status, and described the mpox cases among those living with HIV. METHODS: This was a single-center, prospective cohort study conducted at a major infectious diseases referral center in Rio de Janeiro, Brazil, that enrolled participants older than 18 years of age diagnosed with mpox. Information was collected on standardized forms, including data on sociodemographic, behavioral, clinical and laboratory characteristics. For comparisons, we used chi-squared, Fisher's exact and the Moods median tests whenever appropriate. RESULTS: From June to December, 2022, we enrolled 418 individuals diagnosed with mpox, of whom 52% were people with HIV (PWH). PWH presented more frequently with fever, anogenital lesions and proctitis. The overall hospitalization rate was 10.5% ( n  = 43), especially for pain control. Among hospitalized participants, PWH had more proctitis and required invasive support. Mpox severity was related to poor HIV continuum of care outcomes and low CD4 + cell counts. All deaths ( n  = 2) occurred in PWH with CD4 + less than 50 cells/µl. CONCLUSION: HIV-related immunosuppression likely impacts mpox clinical outcomes. This is of special concern in settings of poor adherence and late presentation to care related to socioeconomic inequalities, such as Brazil. The HIV continuum of care must be taken into account when responding to the mpox outbreak.

Práticas de fim de vida: análise bioética dos projetos do Poder Legislativo brasileiro, 1981-2020 / End-of-life practices: a bioethical analysis of Brazilian Legislative projects, 1981-2020

Resumo Eutanásia voluntária ativa (EVA) e suicídio assistido (SA) são práticas de fim de vida que, embora permeadas de tabus e controvérsias, visam minimizar o sofrimento das pessoas com doenças incuráveis, preservando sua dignidade humana diante da morte. Neste artigo, objetivamos investigar a situação jurídico-normativa dessas práticas no Brasil, por meio de uma pesquisa documental qualitativa que buscou dados do período de 1981 a 2020 nos sites do Poder Legislativo Federal. Com base na proposta hermenêutica dialética, discutimos o percurso das decisões políticas sobre EVA, SA (e suas relações com a ortotanásia e cuidados paliativos) e os efeitos práticos de suas construções valorativas e morais para a autodeterminação das pessoas tanto no processo de morte quanto na sociedade.

Abstract Voluntary active euthanasia (VAE) and assisted suicide (AS) constitute end-of-life practices that aim to minimize the suffering of people with incurable diseases, preserving their human dignity in the face of death. However, taboos and controversies still surround them. This study aims to investigate the legal-normative status of these practices in Brazil via a qualitative documentary research with data from the Federal Legislative Power websites from 1981 and 2020. The dialectical hermeneutic proposal of this study discusses the path of political decisions on VAE, AS (and their relations with orthothanasia and palliative care), and the practical effects of their values and moral constructions on people's self-determination in the dying process and in society.

Assessing the In Vitro Potential of Glatiramer Acetate (Copaxone®) as a Chemotherapeutic Candidate for the Treatment of Cryptococcus neoformans Infection.

Cryptococcosis is a systemic mycosis affecting immunosuppressed individuals, caused by various Cryptococcus species. The current treatment utilizes a combination of antifungal drugs, but issues such as nephrotoxicity, restricted or limited availability in certain countries, and resistance limit their effectiveness. Repurposing approved drugs presents a viable strategy for developing new antifungal options. This study investigates the potential of glatiramer acetate (Copaxone®) as a chemotherapy candidate for Cryptococcus neoformans infection. Various techniques are employed to evaluate the effects of glatiramer acetate on the fungus, including microdilution, XTT analysis, electron and light microscopy, and physicochemical measurements. The results demonstrate that glatiramer acetate exhibits antifungal properties, with an IC50 of 0.470 mg/mL and a minimum inhibitory concentration (MIC) of 2.5 mg/mL. Furthermore, it promotes enhanced cell aggregation, facilitates biofilm formation, and increases the secretion of fungal polysaccharides. These findings indicate that glatiramer acetate not only shows an antifungal effect but also modulates the key virulence factor-the polysaccharide capsule. In summary, repurposing glatiramer acetate as a potential chemotherapy option offers new prospects for combating C. neoformans infection. It addresses the limitations associated with current antifungal therapies by providing an alternative treatment approach.

Brain Spectroscopy Analysis in Retired Soccer Players With Chronic Exposure to Mild Traumatic Brain Injuries.

Soccer players are at risk of suffering cranial injuries in the short and long term. There is growing concern that this may lead to traumatic brain injury in soccer players. Magnetic resonance spectroscopy (MRS) is an analytical method that enables the measurement of changes in brain metabolites that usually occur before significant structural changes. This study aimed to use MRS to compare variations in brain metabolite levels between retired soccer players and a control group. Twenty retired professional soccer players and 22 controls underwent magnetic resonance imaging, including MRS sequences and Mini-Mental State Examination (MMSE). Metabolite analysis was conducted based on absolute concentration and relative ratios. N-acetyl-aspartate, choline, glutamate, glutamine, and myoinositol were the metabolites of interest for the statistical analysis. Retired soccer players had an average age of 57.8 years, whereas the control group had an average age of 63.2 years. Median cognitive evaluation score, assessed using the MMSE, was 28 [26-29] for athletes and 29 [28-30] for controls (p = 0.01). Uni- and multi-variate analyses of the absolute concentration of metabolites (mM) between former athletes and controls did not yield any statistically significant results. Comparison of metabolites to creatine ratio concentrations did not yield any statistically significant results. There were no changes in concentrations of brain metabolites that indicated brain metabolic changes in retired soccer players compared with controls.

Adaptação e evidências de validade da Child-Adolescent Perfectionism Scale no Português Brasileiro / Adaptation and validity evidence of the Child-Adolescent Perfectionism Scale to Brazilian Portuguese / Adaptación y evidencia de validez de Child-Adolescent Perfectionism Scale al Portugués Brasileño

This study presents the Brazilian version of the Child-Adolescent Perfectionism Scale (CAPS), one of the most widely used instruments for assessing perfectionism in young people. The objective of this study was to present the adaptation and evidence of validity for the CAPS in Brazilian Portuguese. The study was conducted on 599 adolescents (Mean age = 15.46 SD = 1.15), 66% girls. We investigated CAPS's internal structure, measurement properties according to age and sex, and its relationship with other questionnaires. We found a good fit for a two-factor structure for the CAPS controlling for an acquiescent responding style. We found evidence of invariance across participants' sex and lack of bias (using a MIMIC approach) due to participant age. The CAPS scores were associated with personality traits and a measure of mental health. The CAPS can be used as a questionnaire to assess perfectionism in Brazilian adolescents.

O presente estudo apresenta a versão brasileira da Child-Adolescent Perfectionism Scale (Caps), um dos instrumentos mais utilizados para avaliação do perfeccionismo em adolescentes. O objetivo do presente estudo foi apresentar a adaptação e evidências de validade da Caps para o português brasileiro. O estudo foi realizado com uma amostra de 599 adolescentes (média de idade = 15,46 DP = 1,15), 66% meninas. Foi investigada a estrutura interna da Caps, e a relação da medida com idade e sexo, bem como sua associação com outros questionários. Foi encontrado um ajuste aceitável para uma estrutura de dois fatores para a Caps, controlando o estilo de resposta aquiescente. Foi encontrada evidência de invariância de medida entre o sexo dos participantes e ausência de viés (usando uma abordagem MIMIC) devido à idade dos participantes. Houve associação dos escores da Caps com traços de personalidade e uma medida de saúde mental. A Caps pode ser usada como um questionário para avaliar o perfeccionismo em adolescentes brasileiros

Este estudio presenta la versión brasileña de la Child-Adolescent Perfectionism Scale (CAPS), uno de los instrumentos más utilizados para la evaluación del perfeccionismo en jóvenes. El objetivo de este estudio fue presentar la adaptación y las pruebas de validez del CAPS en el portugués de Brasil. El estudio se realizó sobre una muestra de 599 adolescentes (Edad media = 15,46 DE = 1,15), 66% niñas. Se investigó la estruc-tura interna del CAPS, las propiedades de medida según edad y sexo, y su relación con otros cuestionarios. Encontramos un buen ajuste para una estructura de dos factores para el CAPS controlador el estilo de respuesta aquiescente. Encontramos evidencia de invariancia entre el sexo de los participantes y falta de sesgo (usando un enfoque MIMIC) debido a la edad de los participantes. Hubo una asociación de las pun-tuaciones CAPS con rasgos de personalidad y una medida de salud mental. El CAPS podría ser utilizado como cuestionario para evaluar el perfeccionismo en adolescentes brasileños

ONLAY VERSUS SUBLAY TECHNIQUES FOR INCISIONAL HERNIA REPAIR: 30-DAY POSTOPERATIVE OUTCOMES.

BACKGROUND: The development of an incisional hernia is a common complication following laparotomy. It also has an important economic impact on healthcare systems and social security budget. The mesh reinforcement of the abdominal wall was an important advancement to increase the success of the repairs and reduce its long-term recurrence. The two most common locations for mesh placement in ventral hernia repairs include the premuscular (onlay technique) and retromuscular planes (sublay technique). However, until now, there is no consensus in the literature about the ideal location of the mesh. AIM: The aim of this study was to compare the two most common incisional hernia repair techniques (onlay and sublay) with regard to the complication rate within the first 30 days of postoperative care. METHOD: This study analyzes 115 patients who underwent either onlay or sublay incisional hernia repairs and evaluates the 30-day postoperative surgical site occurrences and hernia recurrence for each technique. RESULTS: We found no difference in the results between the groups, except in seroma formation, which was higher in patients submitted to the sublay technique, probably due to the lower rate of drain placement in this group. CONCLUSION: Both techniques of mesh placement seem to be adequate in the repair of incisional hernias, with no major difference in surgical site occurrences.

Telemedicine in the National Immunization Program (Brazil): A promising tool.

The coronavirus disease 2019 pandemic abruptly changed the dynamics of basic health care, with the consequent need for adjustments in essential services. The objective of this study was to evaluate the acceptance and impact of telemedicine at a Reference Center for Special Immunobiologicals (CRIE). Methods: Patients aged 18 years or older who had a medical referral to CRIE and agreed to have a telemedicine consultation were included. After the medical appointments, participants answered a satisfaction survey. Results: From April 2021 to February 2022, 702 telemedicine consultation were conducted. Over 3,380 vaccines were prescribed via telemedicine. Of all the participants who answered the satisfaction questionnaire, 99.8% stated that they would recommend the service to other people. Conclusions: Telemedicine proved to be promising tool for healthcare at CRIE and had good acceptance by users, potentially improving access and extending the reach of the National Immunization Program.

Optical coherence tomography in neurodegenerative disorders.

BACKGROUND: Structural imaging of the brain is the most widely used diagnostic tool for investigating neurodegenerative diseases. More advanced structural imaging techniques have been applied to early or prodromic phases, but they are expensive and not widely available. Therefore, it is highly desirable to search for noninvasive, easily accessible, low-cost clinical biomarkers suitable for large-scale population screening, in order to focus on making diagnoses at the earliest stages of the disease. In this scenario, imaging studies focusing on the structures of the retina have increasingly been used for evaluating neurodegenerative diseases. The retina shares embryological, histological, biochemical, microvascular and neurotransmitter similarities with the cerebral cortex, thus making it a uniquely promising biomarker for neurodegenerative diseases. Optical coherence tomography is a modern noninvasive imaging technique that provides high-resolution two-dimensional cross-sectional images and quantitative reproducible three-dimensional volumetric measurements of the optic nerve head and retina. This technology is widely used in ophthalmology practice for diagnosing and following up several eye diseases, such as glaucoma, diabetic retinopathy and age-related macular degeneration. Its clinical impact on neurodegenerative diseases has raised enormous interest over recent years, as several clinical studies have demonstrated that these diseases give rise to reduced thickness of the inner retinal nerve fiber layer, mainly composed of retinal ganglion cells and their axons. In this review, we aimed to address the clinical utility of optical coherence tomography for diagnosing and evaluating different neurodegenerative diseases, to show the potential of this noninvasive and easily accessible method.

Omega-3 production by fish oil hydrolysis using a lipase from Burkholderia gladioli BRM58833 immobilized and stabilized by post-immobilization techniques.

Immobilization of lipase from Burkholderia gladioli BRM58833 on octyl sepharose (OCT) resulted in catalysts with higher activity and stability. Following, strategies were studied to further stabilize and secure the enzyme to the support using functionalized polymers, like polyethylenimine (PEI) and aldehyde-dextran (DEXa), to cover the catalyst with layers at different combinations. Alternatively, the construction of a bifunctional layer was studied using methoxypolyethylene glycol amine (NH 2 -PEG) and glycine. The catalyst OCT-PEI-DEXa was the most thermostable, with a 263.8-fold increase in stability when compared to the control condition. When evaluated under alkaline conditions, OCT-DEXa-PEG 10 /Gly was the most stable, reaching stability 70.1 times greater than the control condition. Proportionally, the stabilization obtained for B. gladioli BRM58833 lipase was superior to that obtained for the commercial B. cepacia lipase. Preliminary results in the hydrolysis of fish oil demonstrated the potential of the coating technique with bifunctional polymers, resulting in a stable catalyst with greater catalytic capacity for the production of omega-3 PUFAs. According to the results obtained, it is possible to modulate B. gladioli BRM58833 lipase properties like stability and catalytic activity for enrichment of omega-3 fatty acids.

Optical coherence tomography in neurodegenerative disorders / Tomografia de coerência óptica em doenças neurodegenerativas

ABSTRACT Structural imaging of the brain is the most widely used diagnostic tool for investigating neurodegenerative diseases. More advanced structural imaging techniques have been applied to early or prodromic phases, but they are expensive and not widely available. Therefore, it is highly desirable to search for noninvasive, easily accessible, low-cost clinical biomarkers suitable for large-scale population screening, in order to focus on making diagnoses at the earliest stages of the disease. In this scenario, imaging studies focusing on the structures of the retina have increasingly been used for evaluating neurodegenerative diseases. The retina shares embryological, histological, biochemical, microvascular and neurotransmitter similarities with the cerebral cortex, thus making it a uniquely promising biomarker for neurodegenerative diseases. Optical coherence tomography is a modern noninvasive imaging technique that provides high-resolution two-dimensional cross-sectional images and quantitative reproducible three-dimensional volumetric measurements of the optic nerve head and retina. This technology is widely used in ophthalmology practice for diagnosing and following up several eye diseases, such as glaucoma, diabetic retinopathy and age-related macular degeneration. Its clinical impact on neurodegenerative diseases has raised enormous interest over recent years, as several clinical studies have demonstrated that these diseases give rise to reduced thickness of the inner retinal nerve fiber layer, mainly composed of retinal ganglion cells and their axons. In this review, we aimed to address the clinical utility of optical coherence tomography for diagnosing and evaluating different neurodegenerative diseases, to show the potential of this noninvasive and easily accessible method.

RESUMO A avaliação estrutural do cérebro, feita por meio dos exames de neuroimagem, é a forma mais utilizada de ferramenta diagnóstica e de acompanhamento das doenças neurodegenerativas. Técnicas de imagem mais sofisticadas podem ser necessárias especialmente nas fases mais precoces, antes mesmo do surgimento de quaisquer sintomas, porém costumam ser caras e pouco acessíveis. Sendo assim, é de fundamental importância a busca de biomarcadores não invasivos, de fácil acesso e baixo custo, que possam ser utilizados para rastreio populacional e diagnóstico mais precoce. Nesse cenário, o número de estudos com ênfase em técnicas de imagem para avaliação estrutural da retina em pacientes com doenças neurodegenerativas tem aumentado nos últimos anos. A retina apresenta similaridade embriológica, histológica, bioquímica, microvascular e neurotransmissora com o córtex cerebral, tornando-se assim um biomarcador único e promissor nas doenças neurodegenerativas. A tomografia de coerência óptica é uma moderna técnica de imagem não invasiva que gera imagens seccionais bidimensionais de alta resolução e medidas volumétricas tridimensionais reprodutivas do disco óptico e da mácula. Essa tecnologia é amplamente utilizada na prática oftalmológica para o diagnóstico e o seguimento de diversas doenças oculares, como glaucoma, retinopatia diabética e degeneração macular relacionada à idade. A redução da espessura da camada de fibras nervosas da retina e das camadas de células ganglionares em pacientes com doenças neurodegenerativas foi demonstrada em diversos estudos clínicos nos últimos anos. Nesta revisão, abordamos as principais aplicações clínicas da tomografia de coerência óptica nas doenças neurodegenerativas e discutimos o seu papel como potencial biomarcador nessas afecções.

Evidence of positive selection on six spider developmental genes.

Spiders constitute more than 49,000 described species distributed all over the world, and all ecological environments. Their order, Araneae, is defined by a set of characteristics with no parallel among their arachnid counterparts (e.g., spinnerets, silk glands, chelicerae that inoculate venom, among others). Changes in developmental pathways often underlie the evolution of morphological synapomorphies, and as such spiders are a promising model to study the role of developmental genes in the origin of evolutionary novelties. With that in mind, we investigated changes in the evolutionary regime of a set of six developmental genes, using spiders as our model. The genes were mainly chosen for their roles in spinneret ontogeny, yet they are pleiotropic, and it is likely that the origins of other unique morphological phenotypes are also linked to changes in their sequences. Our results indicate no great differences in the selective pressures on those genes when comparing spiders to other arachnids, but a few site-specific positive selection evidence were found in the Araneae lineage. These findings lead us to new insights on spider evolution that are to be further tested.