The ongoing coronavirus disease 2019 (COVID-19) pandemic has highlighted the need to better understand virus-host interactions. We developed a network-based method that expands the severe acute ...respiratory syndrome coronavirus-2 (SARS-CoV-2)-host protein interaction network and identifies host targets that modulate viral infection. To disrupt the SARS-CoV-2 interactome, we systematically probed for potent compounds that selectively target the identified host proteins with high expression in cells relevant to COVID-19. We experimentally tested seven chemical inhibitors of the identified host proteins for modulation of SARS-CoV-2 infection in human cells that express ACE2 and TMPRSS2. Inhibition of the epigenetic regulators bromodomain-containing protein 4 (BRD4) and histone deacetylase 2 (HDAC2), along with ubiquitin-specific peptidase (USP10), enhanced SARS-CoV-2 infection. Such proviral effect was observed upon treatment with compounds JQ1, vorinostat, romidepsin and spautin-1, when measured by cytopathic effect and validated by viral RNA assays, suggesting that the host proteins HDAC2, BRD4 and USP10 have antiviral functions. We observed marked differences in antiviral effects across cell lines, which may have consequences for identification of selective modulators of viral infection or potential antiviral therapeutics. While network-based approaches enable systematic identification of host targets and selective compounds that may modulate the SARS-CoV-2 interactome, further developments are warranted to increase their accuracy and cell-context specificity.
Autoantibodies that bind self-antigens are a hallmark of autoimmune diseases, but can also be present in healthy individuals. Clinical assays that detect and titer antigen-specific autoantibodies are ...an important component of the diagnosis and monitoring of autoimmune diseases. Autoantibodies may contribute to disease pathogenesis via effector functions that are dictated by both the antigen-binding site and constant domain.
In this review, we discuss features of antibodies, in addition to antigen-binding specificity, which determine effector function. These features include class, subclass, allotype, and glycosylation. We discuss emerging data indicating that analysis of these antibody features may be informative for diagnosis and monitoring of autoimmune diseases. We also consider methodologies to interrogate these features and consider how they could be implemented in the clinical laboratory.
Future autoantibody assays may incorporate assessment of additional antibody features that contribute to autoimmune disease pathogenesis and provide added clinical value.
Background: Laboratory research and a growing number of epidemiologic studies have provided evidence for a reduced risk of
breast cancer associated with dietary intake of certain classes of ...flavonoids. However, the effects of flavonoids on survival
are not known. In a population-based cohort of breast cancer patients, we investigated whether dietary flavonoid intake before
diagnosis is associated with subsequent survival.
Methods: Women ages 25 to 98 years who were newly diagnosed with a first primary invasive breast cancer between August 1,
1996, and July 31, 1997, and participated in a population-based, case-control study ( n = 1,210) were followed for vital status through December 31, 2002. At the case-control interview conducted shortly after
diagnosis, respondents completed a FFQ that assessed dietary intake in the previous 12 months. All-cause mortality ( n = 173 deaths) and breast cancer–specific mortality ( n = 113 deaths) were determined through the National Death Index.
Results: Reduced hazard ratios age- and energy-adjusted hazard ratio (95% confidence interval) for all-cause mortality were
observed among premenopausal and postmenopausal women for the highest quintile of intake, compared with the lowest, for flavones
0.63 (0.41-0.96), isoflavones 0.52 (0.33-0.82), and anthocyanidins 0.64 (0.42-0.98). No significant trends in risk were
observed. Results were similar for breast cancer–specific mortality only.
Conclusion: Mortality may be reduced in association with high levels of dietary flavones and isoflavones among postmenopausal
U.S. breast cancer patients. Larger studies are needed to confirm our findings. (Cancer Epidemiol Biomarkers Prev 2007;16(11):2285–92)
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load on admission was associated with a significantly increased 30-day mortality (odds ratio OR, 4.20; 95% CI, 1.62–10.86), ...and anti-SARS-CoV-2 nucleocapisid IgG seropositivity on admission trended toward a reduced 30-day mortality (OR, 0.43; 95% CI, 0.15–1.26). Reporting of quantitative SARS-CoV-2 viral load and serologic assays may offer prognostic clinical information.
A study of 181 individuals from a single community hospital found SARS-CoV-2 viral load on admission was associated with a significantly increased 30-day mortality (OR 4.20 95% CI: 1.62-10.86), and anti-SARS-CoV-2 IgG seropositivity on admission trended toward a reduced 30-day mortality (OR 0.43 95% CI: 0.15-1.26).
The 2019 classification criteria for systemic lupus erythematosus (SLE) includes an initial criterion requiring the presence of an antinuclear antibody (ANA), positive at a titer of at least 1:80 on ...HEp-2 cells, or equivalent. However, results of ANA tests performed on HEp-2 cells vary when tested in different laboratories. Calibration of ANA assays by achieving a common specificity in healthy control populations offers the possibility of achieving harmonization via population interrogation, but the expected specificity in a healthy control population is not known.
The studies used to determine the use of ANAs performed by immunofluorescence microscopy on HEp-2 cells as the entry criterion for classification of SLE were reanalyzed by a meta-analysis to determine the expected frequency of positive ANAs in healthy control populations at serum dilutions of 1:40 and 1:80.
Our meta-analysis demonstrated that the expected specificity in a healthy control population of ANA performed using serum diluted 1:80 is 91.3% (CI 86.1-94.7%). The expected specificity of ANA performed at 1:40 serum dilution is 79.2% (CI 72.3-84.8%).
One approach to achieving harmonization of ANA assays from different laboratories with each other and with expected performance would involve adjusting assays so that about 10% of a healthy control population has a positive ANA when tested at 1:80 dilution, and about 20% of the healthy control population has a positive ANA when tested at 1:40 dilution. This pragmatic approach to calibration and harmonization adjustment via population interrogation offers an opportunity for individual laboratories to be aligned with each other and with ANA performance expected for consistent categorization of patients with SLE.
Flavonoids are found in a variety of foods and have anticarcinogenic properties in experimental models. Few epidemiologic studies have examined whether flavonoid intake is associated with breast ...cancer in humans. In this study, the authors investigated whether dietary flavonoid intake was associated with reduced risk of breast cancer in a population-based sample of US women. They conducted a case-control study among women who resided in Nassau and Suffolk counties on Long Island, New York. Cases and controls were interviewed about known and suspected risk factors and asked to complete a food frequency questionnaire regarding their average intake in the prior 12 months. A total of 1,434 breast cancer cases and 1,440 controls provided adequate responses. A decrease in breast cancer risk was associated with flavonoid intake; the decrease was most pronounced among postmenopausal women for flavonols (odds ratio (OR) = 0.54, 95% confidence interval (CI): 0.40, 0.73), flavones (OR = 0.61, 95% CI: 0.45, 0.83), flavan-3-ols (OR = 0.74, 95% CI: 0.55, 0.99), and lignans (OR = 0.69, 95% CI: 0.51, 0.94). The authors conclude that intake of flavonols, flavones, flavan-3-ols, and lignans is associated with reduced risk of incident postmenopausal breast cancer among Long Island women. These results suggest that US women can consume sufficient levels of flavonoids to benefit from their potential chemopreventive effects.
Abstract Objectives This article described parents' experience and identifies outcomes important to parents following their child's critical illness. Methods Semistructured interviews with 22 female ...and 4 male parents representing 26 critically ill children with predominately neurologic and respiratory diagnoses. Most children were younger than 5 years at discharge with a median (interquartile range) of 2 (2.0–3.0) years from discharge to interview. Results Many children returned home with life-altering physical and cognitive disabilities requiring months to years of rehabilitation. Parents remembered feeling unprepared and facing an intense, chaotic time when the child first returned home. They described how they suddenly had to center their daily activities around the child's needs amidst competing needs of siblings and partners, and in some cases, the medicalization of the home. They recounted negotiating adjustments almost daily with insurance agencies, medical doctors and therapists, employers, the child, and other family members to keep the family functioning. In the long term, families developed a new norm, choosing to focus on what the child could still do rather than what they could not. Even if the child returned to baseline, parents remembered the adjustments made to keep the child alive and the family functioning. Conclusion Heightened awareness of family experiences after pediatric critical illness will allow health care providers to improve family preparedness for the transition from hospital to home.
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