Inflammation and Vascular disease: the role of C-reactive protein

Inflammation is an important component of active atherosclerotic disease. C-reactive protein (CRP)is a non-specific inflammatory marker that is increased in inflammatory conditions. Newer more sensitive assays (high sensitivity CRP) can detect the low levels of inflammation associated with vascular disease. CRP levels can give further risk assessment to individuals beyond predictions from traditional risk factors. This measurement is most useful in helping to discriminate risk in intermediate risk patients such as metabolic syndrome patients. Exercise and weight loss have been shown to significantly lower CRP levels. Lipid lowering therapies, especially with the statin class of medications, also lower CRP levels. A reduction in inflammation may be an important component of plaque stabilization and contribute to cardiovascular risk reduction.     

E6 and E7 variants of human papillomavirus‐16 and ‐52 in Japan,the Philippines,and Vietnam

Human papillomavirus (HPV) has several intragenotypic variants with different geographical and ethnic distributions. This study aimed to elucidate the distribution patterns of E6 and E7 (E6/E7) intragenotypic variants of HPV type 16 (HPV‐16), which is most common worldwide, and HPV‐52, which is common in Asian countries such as Japan, the Philippines, and Vietnam. In previous studies, genomic DNA samples extracted from cervical swabs were collected from female sex workers in these three countries and found to be positive for HPV‐16 or HPV‐52. Samples were amplified further for their E6/E7 genes using type‐specific primers and analyzed genetically. Seventy‐nine HPV‐16 E6/E7 genes were analyzed successfully and grouped into three lineages: European (Prototype), European (Asian), and African‐2. The prevalences of HPV‐16 European (Prototype)/European (Asian) lineages were 19.4%/80.6% (n = 31) in Japan, 75.0%/20.8% (n = 24) in the Philippines, and 0%/95.8% (n = 24) in Vietnam. The 109 HPV‐52 E6/E7 genes analyzed successfully were grouped into four lineages, A–D; the prevalences of lineages A/B/C/D were, respectively, 5.1%/92.3%/0%/2.6% in Japan (n = 39), 34.4%/62.5%/0%/3.1% in the Philippines (n = 32), and 15.8%/73.7%/7.9%/2.6% in Vietnam (n = 38). The distribution patterns of HPV‐16 and HPV‐52 lineages in these countries differed significantly (P < 0.000001 and P = 0.0048, respectively). There was no significant relationship between abnormal cervical cytology and either HPV‐16 E6/E7 lineages or specific amino acid mutations, such as E6 D25E, E6 L83V, and E7 N29S. Analysis of HPV‐16 and HPV‐52 E6/E7 genes can be a useful molecular‐epidemiological tool to distinguish geographical diffusion routes of these HPV types in Asia. J. Med. Virol. 85: 1069–1076, 2013. © 2013 Wiley Periodicals, Inc.     

Zoonotic coronavirus epidemics: Severe acute respiratory syndrome,Middle East respiratory syndrome,and coronavirus disease 2019

ObjectiveTo review the virology, immunology, epidemiology, clinical manifestations, and treatment of the following 3 major zoonotic coronavirus epidemics: severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and coronavirus disease 2019 (COVID-19).Data SourcesPublished literature obtained through PubMed database searches and reports from national and international public health agencies.Study SelectionsStudies relevant to the basic science, epidemiology, clinical characteristics, and treatment of SARS, MERS, and COVID-19, with a focus on patients with asthma, allergy, and primary immunodeficiency.ResultsAlthough SARS and MERS each caused less than a thousand deaths, COVID-19 has caused a worldwide pandemic with nearly 1 million deaths. Diagnosing COVID-19 relies on nucleic acid amplification tests, and infection has broad clinical manifestations that can affect almost every organ system. Asthma and atopy do not seem to predispose patients to COVID-19 infection, but their effects on COVID-19 clinical outcomes remain mixed and inconclusive. It is recommended that effective therapies, including inhaled corticosteroids and biologic therapy, be continued to maintain disease control. There are no reports of COVID-19 among patients with primary innate and T-cell deficiencies. The presentation of COVID-19 among patients with primary antibody deficiencies is variable, with some experiencing mild clinical courses, whereas others experiencing a fatal disease. The landscape of treatment for COVID-19 is rapidly evolving, with both antivirals and immunomodulators demonstrating efficacy.ConclusionFurther data are needed to better understand the role of asthma, allergy, and primary immunodeficiency on COVID-19 infection and outcomes.     

Recommendations for Responsible Development and Application of Neurotechnologies

Advancements in novel neurotechnologies, such as brain computer interfaces (BCI) and neuromodulatory devices such as deep brain stimulators (DBS), will have profound implications for society and human rights. While these technologies are improving the diagnosis and treatment of mental and neurological diseases, they can also alter individual agency and estrange those using neurotechnologies from their sense of self, challenging basic notions of what it means to be human. As an international coalition of interdisciplinary scholars and practitioners, we examine these challenges and make recommendations to mitigate negative consequences that could arise from the unregulated development or application of novel neurotechnologies. We explore potential ethical challenges in four key areas: identity and agency, privacy, bias, and enhancement. To address them, we propose (1) democratic and inclusive summits to establish globally-coordinated ethical and societal guidelines for neurotechnology development and application, (2) new measures, including “Neurorights,” for data privacy, security, and consent to empower neurotechnology users’ control over their data, (3) new methods of identifying and preventing bias, and (4) the adoption of public guidelines for safe and equitable distribution of neurotechnological devices.

     

Scoping Review on Search Queries and Social Media for Disease Surveillance: A Chronology of Innovation

Background

The threat of a global pandemic posed by outbreaks of influenza H5N1 (1997) and Severe Acute Respiratory Syndrome (SARS, 2002), both diseases of zoonotic origin, provoked interest in improving early warning systems and reinforced the need for combining data from different sources. It led to the use of search query data from search engines such as Google and Yahoo! as an indicator of when and where influenza was occurring. This methodology has subsequently been extended to other diseases and has led to experimentation with new types of social media for disease surveillance.

Objective

The objective of this scoping review was to formally assess the current state of knowledge regarding the use of search queries and social media for disease surveillance in order to inform future work on early detection and more effective mitigation of the effects of foodborne illness.

Methods

Structured scoping review methods were used to identify, characterize, and evaluate all published primary research, expert review, and commentary articles regarding the use of social media in surveillance of infectious diseases from 2002-2011.

Results

Thirty-two primary research articles and 19 reviews and case studies were identified as relevant. Most relevant citations were peer-reviewed journal articles (29/32, 91%) published in 2010-11 (28/32, 88%) and reported use of a Google program for surveillance of influenza. Only four primary research articles investigated social media in the context of foodborne disease or gastroenteritis. Most authors (21/32 articles, 66%) reported that social media-based surveillance had comparable performance when compared to an existing surveillance program. The most commonly reported strengths of social media surveillance programs included their effectiveness (21/32, 66%) and rapid detection of disease (21/32, 66%). The most commonly reported weaknesses were the potential for false positive (16/32, 50%) and false negative (11/32, 34%) results. Most authors (24/32, 75%) recommended that social media programs should primarily be used to support existing surveillance programs.

Conclusions

The use of search queries and social media for disease surveillance are relatively recent phenomena (first reported in 2006). Both the tools themselves and the methodologies for exploiting them are evolving over time. While their accuracy, speed, and cost compare favorably with existing surveillance systems, the primary challenge is to refine the data signal by reducing surrounding noise. Further developments in digital disease surveillance have the potential to improve sensitivity and specificity, passively through advances in machine learning and actively through engagement of users. Adoption, even as supporting systems for existing surveillance, will entail a high level of familiarity with the tools and collaboration across jurisdictions.     

A density functional theory study on silver and bis-silver complexes with lighter tetrylene: are silver and bis-silver carbenes candidates for SARS-CoV-2 inhibition? Insight from molecular docking simulation

Ribavirin and remdesivir have been preclinically reported as potential drugs for the treatment of SARS-CoV-2 infection, while light silver tetrylene complexes (NHE_Ph–AgCl and (NHE_Ph–AgCl)₂ with E = C, Si, and Ge) have gained significant interest due to their promising applicability on the cytological scale. Firstly, the structures and bonding states of silver–tetrylene complexes (NHE–Ag) and bis-silver–tetrylene complexes (NHE–Ag-bis) were investigated using density functional theory (DFT) at the BP86 level with the def2-SVP and def2-TZVPP basis sets. Secondly, the inhibitory capabilities of the carbene complexes (NHC–Ag and NHC–Ag-bis) and the two potential drugs (ribavirin and remdesivir) on human-protein ACE2 and SARS-CoV-2 protease PDB6LU7 were evaluated using molecular docking simulation. The carbene ligand NHC bonds in a head-on configuration with AgCl and (AgCl)₂, whereas, the other NHE (E = Si and Ge) tetrylene ligands bond in a side-on mode to the metal fragments. The bond dissociation energy (BDE) of the NHE–Ag bond in the complex families follows the order of NHC–Ag > NHSi–Ag > NHGe–Ag and NHSi–Ag-bis > NHGe–Ag-bis > NHC–Ag-bis. The natural bond orbital analysis implies that the [NHE_Ph→AgCl] and [(NHE_Ph)₂→(AgCl)₂] donations are derived mainly from the σ- and π-contributions of the ligands. The docking results indicate that both the ACE2 and PDB6LU7 proteins are strongly inhibited by silver–carbene NHC–Ag, bis-silver–carbene NHC–Ag-bis, ribavirin, and remdesivir with the docking score energy values varying from −17.5 to −16.5 kcal mol⁻¹ and −16.9 to −16.6 kcal mol⁻¹, respectively. The root-mean-square deviation values were recorded to be less than 2 Å in all the calculated systems. Thus, the present study suggests that silver–carbene NHC–Ag and bis-silver–carbene NHC–Ag-bis complexes are potential candidates to inhibit ACE2 and PDB6LU7, and thus potentially conducive to prevent infection caused by the SARS-CoV-2 virus.

Simultaneous inhibition of silver–carbene complexes to ACE2 and PDB6LU7 is conducive for the prevention of SARS-CoV-2 infection: a virtual prediction.     

Sensitivity of frequency-domain optical measurements to brain hemodynamics: simulations and human study of cerebral blood flow during hypercapnia

This study characterizes the sensitivity of noninvasive measurements of cerebral blood flow (CBF) by using frequency-domain near-infrared spectroscopy (FD-NIRS) and coherent hemodynamics spectroscopy (CHS). We considered six FD-NIRS methods: single-distance intensity and phase (SDI and SDϕ), single-slope intensity and phase (SSI and SSϕ), and dual-slope intensity and phase (DSI and DSϕ). Cerebrovascular reactivity (CVR) was obtained from the relative change in measured CBF during a step hypercapnic challenge. Greater measured values of CVR are assigned to a greater sensitivity to cerebral hemodynamics. In a first experiment with eight subjects, CVR_SDϕ was greater than CVR_SDI (p < 0.01), whereas CVR_DSI and CVR_DSϕ showed no significant difference (p > 0.5). In a second experiment with four subjects, a 5 mm scattering layer was added between the optical probe and the scalp tissue to increase the extracerebral layer thickness (L_ec), which caused CVR_DSϕ to become significantly greater than CVR_DSI (p < 0.05). CVR_SS measurements yielded similar results as CVR_DS measurements but with a greater variability, possibly resulting from instrumental artifacts in SS measurements. Theoretical simulations with two-layered media confirmed that, if the top (extracerebral) layer is more scattering than the bottom (brain) layer, the relative values of CVR_DSI and CVR_DSϕ depend on L_ec. Specifically, the sensitivity to the brain is greater for DSI than DSϕ for a thin extracerebral layer (L_ec < 13 mm), whereas it is greater for DSϕ than DSI for a thicker extracerebral layer.