1,161 research outputs found

    SARS-CoV-2 infection is associated with anti-desmoglein 2 autoantibody detection

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    Post-acute cardiac sequelae, following SARS-CoV-2 infection, are well recognized as complications of COVID-19. We have previously shown the persistence of autoantibodies against antigens in skin, muscle, and heart in individuals following severe COVID-19; the most common staining on skin tissue displayed an inter-cellular cement pattern consistent with antibodies against desmosomal proteins. Desmosomes play a critical role in maintaining the structural integrity of tissues. For this reason, we analyzed desmosomal protein levels and the presence of anti-desmoglein (DSG) 1, 2, and 3 antibodies in acute and convalescent sera from patients with COVID-19 of differing clinical severity. We find increased levels of DSG2 protein in sera from acute COVID-19 patients. Furthermore, we find that DSG2 autoantibody levels are increased significantly in convalescent sera following severe COVID-19 but not in hospitalized patients recovering from influenza infection or healthy controls. Levels of autoantibody in sera from patients with severe COVID-19 were comparable to levels in patients with non-COVID-19-associated cardiac disease, potentially identifying DSG2 autoantibodies as a novel biomarker for cardiac damage. To determine if there was any association between severe COVID-19 and DSG2, we stained post-mortem cardiac tissue from patients who died from COVID-19 infection. This confirmed DSG2 protein within the intercalated discs and disruption of the intercalated disc between cardiomyocytes in patients who died from COVID-19. Our results reveal the potential for DSG2 protein and autoimmunity to DSG2 to contribute to unexpected pathologies associated with COVID-19 infection

    Ultrafast nonlocal control of spontaneous emission

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    Solid-state cavity quantum electrodynamics systems will form scalable nodes of future quantum networks, allowing the storage, processing and retrieval of quantum bits, where a real-time control of the radiative interaction in the cavity is required to achieve high efficiency. We demonstrate here the dynamic molding of the vacuum field in a coupled-cavity system to achieve the ultrafast nonlocal modulation of spontaneous emission of quantum dots in photonic crystal cavities, on a timescale of ~200 ps, much faster than their natural radiative lifetimes. This opens the way to the ultrafast control of semiconductor-based cavity quantum electrodynamics systems for application in quantum interfaces and to a new class of ultrafast lasers based on nano-photonic cavities.Comment: 15 pages, 4 figure

    The Social and Political Dimensions of the Ebola Response: Global Inequality, Climate Change, and Infectious Disease

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    The 2014 Ebola crisis has highlighted public-health vulnerabilities in Liberia, Sierra Leone, and Guinea – countries ravaged by extreme poverty, deforestation and mining-related disruption of livelihoods and ecosystems, and bloody civil wars in the cases of Liberia and Sierra Leone. Ebola’s emergence and impact are grounded in the legacy of colonialism and its creation of enduring inequalities within African nations and globally, via neoliberalism and the Washington Consensus. Recent experiences with new and emerging diseases such as SARS and various strains of HN influenzas have demonstrated the effectiveness of a coordinated local and global public health and education-oriented response to contain epidemics. To what extent is international assistance to fight Ebola strengthening local public health and medical capacity in a sustainable way, so that other emerging disease threats, which are accelerating with climate change, may be met successfully? This chapter considers the wide-ranging socio-political, medical, legal and environmental factors that have contributed to the rapid spread of Ebola, with particular emphasis on the politics of the global and public health response and the role of gender, social inequality, colonialism and racism as they relate to the mobilization and establishment of the public health infrastructure required to combat Ebola and other emerging diseases in times of climate change

    Abdominal functional electrical stimulation to improve respiratory function after spinal cord injury: a systematic review and meta-analysis

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    Objectives: Abdominal functional electrical stimulation (abdominal FES) is the application of a train of electrical pulses to the abdominal muscles, causing them to contract. Abdominal FES has been used as a neuroprosthesis to acutely augment respiratory function and as a rehabilitation tool to achieve a chronic increase in respiratory function after abdominal FES training, primarily focusing on patients with spinal cord injury (SCI). This study aimed to review the evidence surrounding the use of abdominal FES to improve respiratory function in both an acute and chronic manner after SCI. Settings: A systematic search was performed on PubMed, with studies included if they applied abdominal FES to improve respiratory function in patients with SCI. Methods: Fourteen studies met the inclusion criteria (10 acute and 4 chronic). Low participant numbers and heterogeneity across studies reduced the power of the meta-analysis. Despite this, abdominal FES was found to cause a significant acute improvement in cough peak flow, whereas forced exhaled volume in 1 s approached significance. A significant chronic increase in unassisted vital capacity, forced vital capacity and peak expiratory flow was found after abdominal FES training compared with baseline. Conclusions: This systematic review suggests that abdominal FES is an effective technique for improving respiratory function in both an acute and chronic manner after SCI. However, further randomised controlled trials, with larger participant numbers and standardised protocols, are needed to fully establish the clinical efficacy of this technique

    Percentile reference values for anthropometric body composition indices in European children from the IDEFICS study

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    INTRODUCTION: To characterise the nutritional status in children with obesity or wasting conditions, European anthropometric reference values for body composition measures beyond the body mass index (BMI) are needed. Differentiated assessment of body composition in children has long been hampered by the lack of appropriate references. OBJECTIVES: The aim of our study is to provide percentiles for body composition indices in normal weight European children, based on the IDEFICS cohort (Identification and prevention of Dietary-and lifestyle-induced health Effects in Children and infantS). METHODS: Overall 18 745 2.0-10.9-year-old children from eight countries participated in the study. Children classified as overweight/obese or underweight according to IOTF (N = 5915) were excluded from the analysis. Anthropometric measurements (BMI (N = 12 830); triceps, subscapular, fat mass and fat mass index (N = 11 845-11 901); biceps, suprailiac skinfolds, sum of skinfolds calculated from skinfold thicknesses (N = 8129-8205), neck circumference (N = 12 241); waist circumference and waist-to-height ratio (N = 12 381)) were analysed stratified by sex and smoothed 1st, 3rd, 10th, 25th, 50th, 75th, 90th, 97th and 99th percentile curves were calculated using GAMLSS. RESULTS: Percentile values of the most important anthropometric measures related to the degree of adiposity are depicted for European girls and boys. Age-and sex-specific differences were investigated for all measures. As an example, the 50th and 99th percentile values of waist circumference ranged from 50.7-59.2 cm and from 51.3-58.7 cm in 4.5-to < 5.0-year-old girls and boys, respectively, to 60.6-74.5 cm in girls and to 59.9-76.7 cm in boys at the age of 10.5-10.9 years. CONCLUSION: The presented percentile curves may aid a differentiated assessment of total and abdominal adiposity in European children

    Radiation Retinopathy: Case report and review

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    BACKGROUND: Ocular damage from radiation treatment is a well established phenomenon. Many factors are now known to influence the incidence of radiation retinopathy, including total dosage and daily fraction size. Patients who are diabetic, hypertensive or received previous chemotherapy are more susceptible to radiation retinopathy. CASE PRESENTATION: A 55 year old male was referred from the oncology department with epiphora. His medical history included Type 2 Insulin treated Diabetes Mellitus and hypertension. One year prior to presentation he had undergone a total rhinectomy with a 4 week course of post-operative radiotherapy for an aggressive sqaumous cell carcinoma of the nose. On examination the visual acuity was noted to be 6/36 left eye and 6/9 right eye. Posterior segment examination revealed marked retinal ischaemia present in the posterior pole and macular region of both eyes. The appearance was not thought to be typical of diabetic changes, radiation retinopathy being the more likely diagnosis especially in view of his history. Over the next four months the vision in both eyes rapidly deteriorated to 3/60 left eye and 1/60 right eye. Bilateral pan retinal photocoagulation was thought to be appropriate treatment at this point. CONCLUSION: This case highlights the importance for ophthalmologists and oncologists to be aware of the close relationship between diabetes and radiation treatment and the profound rapid impact this combination of factors may have on visual function. Radiation is being used with increasing frequency for ocular and orbital disease, because of this more cases of radiation retinopathy may become prevalent. Factors which may potentiate radiation retinopathy should be well known including, increased radiation dosage, increased fraction size, concomitant systemic vascular disease and use of chemotherapy. Counselling should be offered in all cases at risk of visual loss. As no effective treatment currently exists to restore visual function, monitoring of visual acuity in all cases and early referral to the ophthalmologist as appropriate is warranted

    Krüppel-like Factor 4 Regulates Intestinal Epithelial Cell Morphology and Polarity

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    Krüppel-like factor 4 (KLF4) is a zinc finger transcription factor that plays a vital role in regulating cell lineage differentiation during development and maintaining epithelial homeostasis in the intestine. In normal intestine, KLF4 is predominantly expressed in the differentiated epithelial cells. It has been identified as a tumor suppressor in colorectal cancer. KLF4 knockout mice demonstrated a decrease in number of goblet cells in the colon, and conditional ablation of KLF4 from the intestinal epithelium led to altered epithelial homeostasis. However, the role of KLF4 in differentiated intestinal cells and colon cancer cells, as well as the mechanism by which it regulates homeostasis and represses tumorigenesis in the intestine is not well understood. In our study, KLF4 was partially depleted in the differentiated intestinal epithelial cells by a tamoxifen-inducible Cre recombinase. We found a significant increase in the number of goblet cells in the KLF4-deleted small intestine, suggesting that KLF4 is not only required for goblet cell differentiation, but also required for maintaining goblet cell numbers through its function in inhibiting cell proliferation. The number and position of Paneth cells also changed. This is consistent with the KLF4 knockout study using villin-Cre [1]. Through immunohistochemistry (IHC) staining and statistical analysis, we found that a stem cell and/or tuft cell marker, DCAMKL1, and a proliferation marker, Ki67, are affected by KLF4 depletion, while an enteroendocrine cell marker, neurotensin (NT), was not affected. In addition, we found KLF4 depletion altered the morphology and polarity of the intestinal epithelial cells. Using a three-dimensional (3D) intestinal epithelial cyst formation assay, we found that KLF4 is essential for cell polarity and crypt-cyst formation in human colon cancer cells. These findings suggest that, as a tumor suppressor in colorectal cancer, KLF4 affects intestinal epithelial cell morphology by regulating proliferation, differentiation and polarity of the cells

    Assessing newborn body composition using principal components analysis: differences in the determinants of fat and skeletal size

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    BACKGROUND: Birth weight is a composite of skeletal size and soft tissue. These components are likely to have different growth patterns. The aim of this paper is to investigate the association between established determinants of birth weight and these separate components. METHODS: Weight, length, crown-rump, knee-heel, head circumference, arm circumference, and skinfold thicknesses were measured at birth in 699 healthy, term, UK babies recruited as part of the Exeter Family Study of Childhood Health. Corresponding measurements were taken on both parents. Principal components analysis with varimax rotation was used to reduce these measurements to two independent components each for mother, father and baby: one highly correlated with measures of fat, the other with skeletal size. RESULTS: Gestational age was significantly related to skeletal size, in both boys and girls (r = 0.41 and 0.52), but not fat. Skeletal size at birth was also associated with parental skeletal size (maternal: r = 0.24 (boys), r = 0.39 (girls) ; paternal: r = 0.16 (boys), r = 0.25 (girls)), and maternal smoking (0.4 SD reduction in boys, 0.6 SD reduction in girls). Fat was associated with parity (first borns smaller by 0.45 SD in boys; 0.31 SD in girls), maternal glucose (r = 0.18 (boys); r = 0.27 (girls)) and maternal fat (r = 0.16 (boys); r = 0.36 (girls)). CONCLUSION: Principal components analysis with varimax rotation provides a useful method for reducing birth weight to two more meaningful components: skeletal size and fat. These components have different associations with known determinants of birth weight, suggesting fat and skeletal size may have different regulatory mechanisms, which would be important to consider when studying the associations of birth weight with later adult disease
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