Cardiac manifestations of PRKAG2 mutation.

BACKGROUND:The Protein Kinase AMP-Activated Non-Catalytic Subunit Gamma 2 (PRKAG2) cardiac syndrome is characterized by glycogen accumulation in the cardiac tissue. The disease presents clinically with hypertrophic cardiomyopathy (HCM), and it is often associated with conduction abnormalities. CASE PRESENTATION:A 23 year-old female with history of Wolff-Parkinson-White (WPW) and HCM presented for evaluation after an episode of Non-ST Elevation Myocardial Infarction (NSTEMI). The patient was found to have severe coronary bridging on angiography and underwent an unroofing of the left anterior descending artery (LAD). Due to the constellation of symptoms, the patient underwent genetic testing and a cardiac muscle biopsy. Genetic testing was significant for an Arg302Gln mutation in the PRKAG2 gene. Cardiac tissue biopsy revealed significant myocyte hypertrophy and large vacuoles with glycogen stores. CONCLUSION:The pathologic and genetics findings of our patient are consistent with PRKAG2 syndrome. Patients presenting with conduction abnormalities and suspected HCM should be considered for genetic testing to identify possible underlying genetic etiologies

Hypertrophic and Fibrotic Human PKD Hearts are Associated with Macrophage Infiltration and Abnormal TGF-β1 Signaling

Autosomal dominant polycystic kidney disease (PKD) is a hereditary kidney disorder which can affect cardiovascular system. Cardiac hypertrophy and cardiomyopathy in PKD have been reported by echocardiography analyses, but histopathology analyses of human PKD hearts have never been examined. The current studies evaluated human heart tissues from five subjects without PKD (non-PKD) and five subjects with PKD. Our histopathology data of human PKD hearts showed an increased extracellular matrix associated with cardiac hypertrophy and fibrosis. Hypertrophy- and fibrosis-associated pathways involving abnormal cardiac structure were next analyzed. We found that human PKD myocardium was infiltrated by inflammatory macrophage M1 and M2; expression of transforming growth factor (TGF-β1) and its receptor were upregulated with overexpression of pSmad3 and β-catenin. Because patients with PKD have an abnormal kidney function that could potentially affect heart structure, we used a heart-specific PKD mouse model to validate that cardiac hypertrophy and fibrosis were independent from polycystic kidney. In summary, our data show that hearts from human PKD were characterized by hypertrophy, interstitial fibrosis, perivascular fibrosis, and conduction system fibrosis with upregulated TGF-β1 and its receptor. We suggest that such structural abnormalities may predispose to systolic and diastolic cardiac dysfunction in the PKD myocardium

HIV and COVID-19: two pandemics with significant (but different) central nervous system complications

Human immunodeficiency virus (HIV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cause significant neurologic disease. Central nervous system (CNS) involvement of HIV has been extensively studied, with well-documented invasion of HIV into the brain in the initial stage of infection, while the acute effects of SARS-CoV-2 in the brain are unclear. Neuropathologic features of active HIV infection in the brain are well characterized whereas neuropathologic findings in acute COVID-19 are largely non-specific. On the other hand, neuropathologic substrates of chronic dysfunction in both infections, as HIV-associated neurocognitive disorders (HAND) and post-COVID conditions (PCC)/long COVID are unknown. Thus far, neuropathologic studies on patients with HAND in the era of combined antiretroviral therapy have been inconclusive, and autopsy studies on patients diagnosed with PCC have yet to be published. Further longitudinal, multidisciplinary studies on patients with HAND and PCC and neuropathologic studies in comparison to controls are warranted to help elucidate the mechanisms of CNS dysfunction in both conditions

Demographic, social cognitive and social ecological predictors of intention and participation in screening for colorectal cancer

Extent: 10p.Background: Previous research points to differences between predictors of intention to screen for colorectal cancer (CRC) and screening behavior, and suggests social ecological factors may influence screening behavior. The aim of this study was to compare the social cognitive and social ecological predictors of intention to screen with predictors of participation. Methods: People aged 50 to 74 years recruited from the electoral roll completed a baseline survey (n = 376) and were subsequently invited to complete an immunochemical faecal occult blood test (iFOBT). Results: Multivariate analyses revealed five predictors of intention to screen and two predictors of participation. Perceived barriers to CRC screening and perceived benefits of CRC screening were the only predictor of both outcomes. There was little support for social ecological factors, but measurement problems may have impacted this finding. Conclusions: This study has confirmed that the predictors of intention to screen for CRC and screening behaviour, although overlapping, are not the same. Research should focus predominantly on those factors shown to predict participation. Perceptions about the barriers to screening and benefits of screening are key predictors of participation, and provide a focus for intervention programs.Tess A Gregory, Carlene Wilson, Amy Duncan, Deborah Turnbull, Stephen R Cole and Graeme Youn

Effect of a Brief Video Intervention on Incident Infection among Patients Attending Sexually Transmitted Disease Clinics

In a controlled trial at three urban STD clinics, Lee Warner and colleagues find that showing an educational video in waiting rooms reduced new infections by approximately 10%

Capillary Proliferation in Systemic-Sclerosis-Related Pulmonary Fibrosis: Association with Pulmonary Hypertension

We sought to determine if any histopathologic component of the pulmonary microcirculation can distinguish systemic sclerosis (SSc)-related pulmonary fibrosis (PF) with and without pulmonary hypertension (PH)

The Digital Fish Library: Using MRI to Digitize, Database, and Document the Morphological Diversity of Fish

Museum fish collections possess a wealth of anatomical and morphological data that are essential for documenting and understanding biodiversity. Obtaining access to specimens for research, however, is not always practical and frequently conflicts with the need to maintain the physical integrity of specimens and the collection as a whole. Non-invasive three-dimensional (3D) digital imaging therefore serves a critical role in facilitating the digitization of these specimens for anatomical and morphological analysis as well as facilitating an efficient method for online storage and sharing of this imaging data. Here we describe the development of the Digital Fish Library (DFL, http://www.digitalfishlibrary.org), an online digital archive of high-resolution, high-contrast, magnetic resonance imaging (MRI) scans of the soft tissue anatomy of an array of fishes preserved in the Marine Vertebrate Collection of Scripps Institution of Oceanography. We have imaged and uploaded MRI data for over 300 marine and freshwater species, developed a data archival and retrieval system with a web-based image analysis and visualization tool, and integrated these into the public DFL website to disseminate data and associated metadata freely over the web. We show that MRI is a rapid and powerful method for accurately depicting the in-situ soft-tissue anatomy of preserved fishes in sufficient detail for large-scale comparative digital morphology. However these 3D volumetric data require a sophisticated computational and archival infrastructure in order to be broadly accessible to researchers and educators

Cardiac manifestations of PRKAG2 mutation.

BACKGROUND:The Protein Kinase AMP-Activated Non-Catalytic Subunit Gamma 2 (PRKAG2) cardiac syndrome is characterized by glycogen accumulation in the cardiac tissue. The disease presents clinically with hypertrophic cardiomyopathy (HCM), and it is often associated with conduction abnormalities. CASE PRESENTATION:A 23 year-old female with history of Wolff-Parkinson-White (WPW) and HCM presented for evaluation after an episode of Non-ST Elevation Myocardial Infarction (NSTEMI). The patient was found to have severe coronary bridging on angiography and underwent an unroofing of the left anterior descending artery (LAD). Due to the constellation of symptoms, the patient underwent genetic testing and a cardiac muscle biopsy. Genetic testing was significant for an Arg302Gln mutation in the PRKAG2 gene. Cardiac tissue biopsy revealed significant myocyte hypertrophy and large vacuoles with glycogen stores. CONCLUSION:The pathologic and genetics findings of our patient are consistent with PRKAG2 syndrome. Patients presenting with conduction abnormalities and suspected HCM should be considered for genetic testing to identify possible underlying genetic etiologies

Coronary atherosclerotic lesions in human immunodeficiency virus-infected patients: a histopathologic study

BACKGROUND: Studies suggest human immunodeficiency virus-positive (HIV+) patients have an increased risk of coronary artery disease (CAD), yet little is known about the histopathology, severity, or distribution of lesions. METHODS: The coronary arteries of 66 deceased AIDS patients and 19 HIV controls (age or=75% of at least one artery. Compared to controls, HIV+ patients had three times greater odds of stenosis >or=75%, controlling for age and sex (one-sided P=.03). Older age and male sex were also risk factors (one-sided P<.001). HIV seropositivity was associated with increased plaque lipid content (one-sided P=.02) and calcification (one-sided P=.08). Duration of HIV infection, antiretroviral therapy, and immune status did not predict severe disease in multivariate analyses. Previously unreported patterns of dystrophic calcification were observed in HIV+ patients and older controls. CONCLUSIONS: Young to middle-aged patients dying from advanced AIDS have atherosclerotic CAD that may result in luminal narrowing, heavy calcification, and high plaque lipid content. The pattern of disease, location of lesions, and plaque composition are typical of atherosclerosis in HIV-negative patients. No relationship between antiretroviral therapies and atherosclerosis was seen in this small study of heavily treated patients