An Unexpected Association in a Patient with Heart Failure Presenting a Surgical Challenge

Bicuspid aortic valve (BAV) is the most common form of congenital heart disease and frequently leads to premature valvular dysfunction. BAV is associated with aortic wall abnormalities and a high prevalence of ascending aorta dilatation and coarctation of the aorta (CoA). Consequently, in patients with BAV a careful assessment of the valve, and also of the aortic root and the ascending aorta, should be performed. The most feared complication is aortic dissection, however, the actual incidence of this complication is low. We report the case of a 58-year-old man who presented with New York Heart Association class III heart failure. The work-up revealed BAV with severe stenosis and severe compromise of left ventricle systolic function. In addition, CoA in the isthmus region, and type B dissection of the aorta were diagnosed.info:eu-repo/semantics/publishedVersio

Dynamin-related protein 1 at the crossroads of cancer

Mitochondrial dynamics are known to have an important role in so-called age-related diseases, including cancer. Mitochondria is an organelle involved in many key cellular functions and responds to physiologic or stress stimuli by adapting its structure and function. Perhaps the most important structural changes involve mitochondrial dynamics (fission and fusion), which occur in normal cells as well as in cells under dysregulation, such as cancer cells. Dynamin-related protein 1 (DRP1), a member of the dynamin family of guanosine triphosphatases (GTPases), is the key component of mitochondrial fission machinery. Dynamin-related protein 1 is associated with different cell processes such as apoptosis, mitochondrial biogenesis, mitophagy, metabolism, and cell proliferation, differentiation, and transformation. The role of DRP1 in tumorigenesis may seem to be paradoxical, since mitochondrial fission is a key mediator of two very different processes, cellular apoptosis and cell mitosis. Dynamin-related protein 1 has been associated with the development of distinct human cancers, including changes in mitochondrial energetics and cellular metabolism, cell proliferation, and stem cell maintenance, invasion, and promotion of metastases. However, the underlying mechanism for this association is still being explored. Herein, we review the published knowledge on the role of DRP1 in cancer, exploring its interaction with different biological processes in the tumorigenesis context.Acknowledgments: The authors would like to acknowledge all the members of the Cancer Signalling and Metabolism research group at IPATIMUP/i3S for their input on different topics of the manuscript. This work was supported by Portuguese funds through FCT—Fundação para a Ciência e a Tecnologia—in the framework of project UID/BIM/04293/2013. It was also financed by FEDER—Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020—Operational Program for Competitiveness and Internationalization (POCI), Portugal 2020, and by Portuguese funds through FCT—Fundação para a Ciência e Tecnologia/Ministério da Ciência, Tecnologia e Inovação in the framework of the projects “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274). Further funding was obtained from the project “Advancing cancer research: from basic knowledgment to application” NORTE-01-0145-FEDER-000029: “Projetos Estruturados de I & D & I”, funded by Norte 2020—Programa Operacional Regional do Norte

Pregnancy Outcomes in Women with Pre-Existing Diabetes

OBJETIVO: Avaliar as alterações epidemiológicas, de perfil clínico e de prognóstico obstétrico em pacientes portadoras de diabetes mellitus pré-gestacional. MÉTODOS: Estudo retrospetivo (coorte) de todas as gestações simples, com diagnóstico de diabetes prévio que foram seguidas num centro com apoio perinatal diferenciado entre 2004 e 2011 (n=194). Analisaram-se tendências relacionadas com dados demográficos e variáveis clínicas maternas, dados de indicadores de cuidados pre-concepcionais e durante a gravidez, e de controle metabólico. Dados do parto como a idade gestacional(IG) do parto, via do parto e peso do neonato foram variáveis também estudadas. RESULTADOS: A frequência global de diabetes prévia, durante o período estudado, foi de 4,4 por mil, não se verificando variações significativas durante o período de estudo. Os casos de diabetes tipo 2 permaneceram constantes. Em 67% dos casos o parto foi de termo(máximo de 80% em 2010–2011), registrou-se uma redução significativa dos partos por cesárea eletiva (p=0,03) e na incidência de neonatos considerados grandes para a IG (p=0,04) ao longo dos anos em estudo. Apesar dos bons resultados relacionados com o controle metabólico ao longo da vigilância da gravidez não foi registrada nenhuma melhora ao longo do tempo. Da mesma forma a proporção de gestantes diabéticas com avaliação pre-concepcional permaneceu pouco animadora. CONCLUSÕES: O seguimento de gestantes portadoras de diabetes mellitus em unidades multidisciplinares parece permitir um ajuste metabólico tão precoce quanto possível, de forma a conseguir melhorar o prognóstico obstétrico. A melhora nos cuidados pré-concepcionais continua sendo um desafio

La ecografía del páncreas canino

This study describes the ultrasonographic techniques currently used in the evaluation of the canine pancreas. Ultrasonography was the first method to enable direct visualization of the pancreas in humans and it has been subsequently applied to animals. Currently, it is the method of choice for pancreatic evaluation and is essential as a diagnostic tool in the detection of abnormalities, especially tumors. Innovative equipment technology has led to the emergence of techniques complementary to B-mode ultrasound; such as Doppler, elastography, and contrast-enhanced ultrasonography, which have enabled more accurate diagnosis. Doppler provides information on vascular architecture and the hemodynamic aspect of blood vessels in multiple organs. ARFI elastography provides detailed images of the alterations detected by conventional examination (qualitative method) and assists in differentiating between benign and malignant processes (quantitative method). Microbubble contrast agents determine parameters related to homogeneous and heterogeneous filling of organs with microbubbles, mainly nodular areas, thus defining high and low intensity patterns.Este estudio describe las técnicas ecográficas frecuentemente utilizadas para evaluar el pancreas del perro. La ecografía fue el primer método que permitió la visualización directa del páncreas en seres humanos y que luego se aplicó en animales. Es actualmente el método de elección para la evaluación del páncreas y es esencial como herramienta diagnóstica en la detección de anomalías, especialmente tumores. La tecnología innovadora de los equipos, llevó a la aparición de técnicas complementarias al modo B, tales como Doppler, elastografía, ecografía de contraste, que han permitido realizar diagnósticos más precisos. El Doppler proporciona información sobre la arquitectura vascular y aspectos hemodinámicos de los vasos sanguíneos en múltiples órganos. La elastografía ARFI ofrece imágenes detalladas de las alteraciones detectadas en exámenes convencionales (método cualitativo) y ayuda a diferenciar entre procesos benignos y malignos (método cuantitativo). Los agentes de contraste con microburbujas permiten determinar parámetros relacionados con el llenado homogéneo o heterogéneo de los órganos, principalmente áreas nodulares, definiendo, por tanto, patrones de alta o baja intensidad

Optic neuritis in an adult patient with chickenpox

Central nervous system involvement in a patient with primary infection with Varicella zoster virus is rare, especially in the immunocompetent adult. In particular, isolated optic neuritis has been described in a small number of cases. The authors present a case of optic neuritis in an immunocompetent patient. A 28-year-old woman presented to the emergency room with a history of headaches during the previous week, without visual symptoms. The examination was unremarkable, except for a rash suggestive of chickenpox and hyperemic and edematous optic disc, bilaterally. Visual acuity and neurological examination were normal. Two days later, she complained of pain on eye movement and decreased visual acuity, which was 20/32 in her right eye and 20/60 in her left eye. Four days after admission, her visual acuity started to improve, and two months later, she had 20/20 visual acuity in both eyes. To our knowledge, this is the first reported case of an immunocompetent adult in which a Varicella zoster virus associated optic neuritis presented with fundoscopic changes before decreased visual acuity. This suggests that this condition may be underdiagnosed in asymptomatic patients

Ceramide synthase TLCD3B is a novel gene associated with human recessive retinal dystrophy

PURPOSE: Previous studies suggest that ceramide is a proapoptotic lipid as high levels of ceramides can lead to apoptosis of neuronal cells, including photoreceptors. However, no pathogenic variant in ceramide synthases has been identified in human patients and knockout of various ceramide synthases in mice has not led to photoreceptor degeneration. METHODS: Exome sequencing was used to identify candidate disease genes in patients with vision loss as confirmed by standard evaluation methods, including electroretinography (ERG) and optical coherence tomography. The vision loss phenotype in mice was evaluated by ERG and histological analyses. RESULTS: Here we have identified four patients with cone-rod dystrophy or maculopathy from three families carrying pathogenic variants in TLCD3B. Consistent with the phenotype observed in patients, the Tlcd3bKO/KO mice exhibited a significant reduction of the cone photoreceptor light responses, thinning of the outer nuclear layer, and loss of cone photoreceptors across the retina. CONCLUSION: Our results provide a link between loss-of-function variants in a ceramide synthase gene and human retinal dystrophy. Establishment of the Tlcd3b knockout murine model, an in vivo photoreceptor cell degeneration model due to loss of a ceramide synthase, will provide a unique opportunity in probing the role of ceramide in survival and function of photoreceptor cells

HIV-1-Transmitted Drug Resistance and Transmission Clusters in Newly Diagnosed Patients in Portugal Between 2014 and 2019

Objective: To describe and analyze transmitted drug resistance (TDR) between 2014 and 2019 in newly infected patients with HIV-1 in Portugal and to characterize its transmission networks. Methods: Clinical, socioepidemiological, and risk behavior data were collected from 820 newly diagnosed patients in Portugal between September 2014 and December 2019. The sequences obtained from drug resistance testing were used for subtyping, TDR determination, and transmission cluster (TC) analyses. Results: In Portugal, the overall prevalence of TDR between 2014 and 2019 was 11.0%. TDR presented a decreasing trend from 16.7% in 2014 to 9.2% in 2016 (p for-trend = 0.114). Multivariate analysis indicated that TDR was significantly associated with transmission route (MSM presented a lower probability of presenting TDR when compared to heterosexual contact) and with subtype (subtype C presented significantly more TDR when compared to subtype B). TC analysis corroborated that the heterosexual risk group presented a higher proportion of TDR in TCs when compared to MSMs. Among subtype A1, TDR reached 16.6% in heterosexuals, followed by 14.2% in patients infected with subtype B and 9.4% in patients infected with subtype G. Conclusion: Our molecular epidemiology approach indicates that the HIV-1 epidemic in Portugal is changing among risk group populations, with heterosexuals showing increasing levels of HIV-1 transmission and TDR. Prevention measures for this subpopulation should be reinforced.info:eu-repo/semantics/publishedVersio

Frequency of CDH1 germline mutations in gastric carcinoma coming from high- and low-risk areas: metanalysis and systematic review of the literature

<p>Abstract</p> <p>Background</p> <p>The frequency of E-cadherin germline mutations in countries with different incidence rates for gastric carcinoma has not been well established. The goal of this study was to assess the worldwide frequency of <it>CDH1 </it>germline mutations in gastric cancers coming from low- and high-risk areas.</p> <p>Methods</p> <p>English articles using MEDLINE access (from 1998 to 2011). Search terms included <it>CDH1</it>, E-cadherin, germline mutation, gastric cancer, hereditary, familial and diffuse histotype.</p> <p>The study included all E-cadherin germline mutations identified in gastric cancer patients; somatic mutations and germline mutations reported in other tumors were excluded.</p> <p>The method of this study was scheduled in accordance with the "PRISMA statement for reporting systematic reviews and meta-analyses". Countries were classified as low- or middle/high risk-areas for gastric carcinoma incidence. Statistical analysis was performed to correlate the <it>CDH1 </it>mutation frequency with gastric cancer incidence areas.</p> <p>Results</p> <p>A total of 122 E-cadherin germline mutations have been identified; the majority (87.5%) occurred in gastric cancers coming from low-risk areas. In high-risk areas, we identified 16 mutations in which missense mutations were predominant. (68.8%). We verified a significant association between the mutation frequency and the gastric cancer risk area (<it>p </it>< 0.001: overall identified mutations in low- vs. middle/high-risk areas).</p> <p>Conclusions</p> <p>E-cadherin genetic screenings performed in low-risk areas for gastric cancer identified a higher frequency of <it>CDH1 </it>germline mutations. This data could open new approaches in the gastric cancer prevention test; before proposing a proband candidate for the <it>CDH1 </it>genetic screening, geographic variability, alongside the family history should be considered.</p

Dinosaurs reveal the geographical signature of an evolutionary radiation

Dinosaurs dominated terrestrial ecosystems across the globe for over 100 million years and provide a classic example of an evolutionary radiation. However, little is known about how these animals radiated geographically to become globally distributed. Here, we use a biogeographical model to reconstruct the dinosaurs’ ancestral locations, revealing the spatial mechanisms that underpinned this 170-million-year-long radiation. We find that dinosaurs spread rapidly initially, followed by a significant continuous and gradual reduction in their speed of movement towards the Cretaceous/Tertiary boundary (66 million years ago). This suggests that the predominant mode of dinosaur speciation changed through time with speciation originally largely driven by geographical isolation—when dinosaurs speciated more, they moved further. This was gradually replaced by increasing levels of sympatric speciation (species taking advantage of ecological opportunities within their existing environment) as terrestrial space became a limiting factor. Our results uncover the geographical signature of an evolutionary radiation