Corrigendum to “The Possible Mechanistic Basis of Individual Susceptibility to Spike Protein Injury”

Cigarette smoking is the main risk factor for COPD (Chronic Obstructive Pulmonary Disease), yet only a subset of smokers develops COPD. Family members of patients with severe early-onset COPD have an increased risk to develop COPD and are therefore defined as “susceptible individuals”. Here we perform unbiased analyses of proteomic profiles to assess how “susceptible individuals” differ from age-matched “non-susceptible individuals” in response to cigarette smoking. Epithelial lining fluid (ELF) was collected at baseline and 24 hours after smoking 3 cigarettes in young individuals susceptible or non-susceptible to develop COPD and older subjects with established COPD. Controls at baseline were older healthy smoking and non-smoking individuals. Five samples per group were pooled and analysed by stable isotope labelling (iTRAQ) in duplicate. Six proteins were selected and validated by ELISA or immunohistochemistry. After smoking, 23 proteins increased or decreased in young susceptible individuals, 7 in young non-susceptible individuals, and 13 in COPD in the first experiment; 23 proteins increased or decreased in young susceptible individuals, 32 in young non-susceptible individuals, and 11 in COPD in the second experiment. SerpinB3 and Uteroglobin decreased after acute smoke exposure in young non-susceptible individuals exclusively, whereas Peroxiredoxin I, S100A9, S100A8, ALDH3A1 (Aldehyde dehydrogenase 3A1) decreased both in young susceptible and non-susceptible individuals, changes being significantly different between groups for Uteroglobin with iTRAQ and for Serpin B3 with iTRAQ and ELISA measures. Peroxiredoxin I, SerpinB3 and ALDH3A1 increased in COPD patients after smoking. We conclude that smoking induces a differential protein response in ELF of susceptible and non-susceptible young individuals, which differs from patients with established COPD. This is the first study applying unbiased proteomic profiling to unravel the underlying mechanisms that induce COPD. Our data suggest that SerpinB3 and Uteroglobin could be interesting proteins in understanding the processes leading to COPD.

Epidemic control is of great importance for human society. Adjusting interacting partners is an effective individualized control strategy. Intuitively, it is done either by shortening the interaction time between susceptible and infected individuals or by increasing the opportunities for contact between susceptible individuals. Here, we provide a comparative study on these two control strategies by establishing an epidemic model with nonuniform stochastic interactions. It seems that the two strategies should be similar, since shortening the interaction time between susceptible and infected individuals somehow increases the chances for contact between susceptible individuals. However, analytical results indicate that the effectiveness of the former strategy sensitively depends on the infectious intensity and the combinations of different interaction rates, whereas the latter one is quite robust and efficient. Simulations are shown to verify our analytical predictions. Our work may shed light on the strategic choice of disease control.

Neurally mediated syncope and Brugada syndrome (BS) share common pathophysiologic mechanisms related to autonomic nervous system modulations, and particularly with increased vagal tone. This study aimed to investigate the incidence of neurally mediated susceptibility in individuals with Brugada-type electrocardiogram (ECG) pattern. Eight asymptomatic male individuals (mean age 41.6 +/- 10.6 years) with spontaneous or procainamide-induced type 1 ECG pattern of BS and structurally normal hearts underwent a drug-free head-up tilt test. Twenty-five healthy male subjects (mean age 37.4 +/- 14.1 years) with normal ECG and without structural heart disease were included in the study, and served as comparative controls. A positive tilt test response was observed in three out of eight subjects with the Brugada-type ECG pattern (37%) and in three out of 25 controls (12%) (P = 0.018). This study demonstrates a high incidence of neurally mediated susceptibility in asymptomatic individuals with Brugada-type ECG pattern. Severe diagnostic and therapeutic dilemmas may rise from this coexistence. A positive tilt test in subjects with Brugada-type ECG displaying a history of syncope may mislead the physician to a false sense of security. Further studies are required to validate our findings and possibly evaluate the role of tilt test in risk stratification of patients with BS.

HIV-AIDS is a type of virus that attacks the human immune system so that the immune system becomes weak and susceptible to various diseases. The worst consequence of HIV-AIDS is death. HIV-AIDS is very easily spread through sexual contact between an infected individual and a susceptible individual. The risk of transmission for each subpopulation will be different, both the interaction between susceptible individuals vs. HIV-infected and the interaction between susceptible individuals vs. AIDS caused by the level of the virus in the patient's body. Therefore, in this study, a mathematical model of the spread of HIV-AIDS will be discussed by considering the effect of interactions on each subpopulation. The aim is to find out which interaction effect is dominant on the spread of HIV-AIDS. The method used is to construct a mathematical model of the spread of HIV-AIDS, determine the equilibrium point of the model, investigate the stability of equilibrium point, and interpret the simulation model by considering the effect of interactions on each subpopulation. From the constructed model, two equilibrium points are produced, namely the unstable HIV-AIDS-free equilibrium point and the stable endemic equilibrium point. This means that in the population there will always be individuals infected with HIV-AIDS. Based on the simulation results by considering the effect of interactions between subpopulations, it was found that there was a significant change in the number of individuals in the susceptible vs AIDS subpopulation compared to individuals in the susceptible vs HIV asymptomatic subpopulation and individuals in the susceptible vs HIV symptomatic subpopulation.

This paper considers a discrete-time opinion dynamics model in which each individual's susceptibility to being influenced by others is dependent on her current opinion. We first propose a general opinion dynamics model based on the DeGroot model, with a general function to describe the functional dependence of each individual's susceptibility to her own opinion, and characterize the set of all equilibria and stability of nontrivial equilibria. We then consider two classes of functions in which the individual's susceptibility depends on the polarity of her opinion (i.e., how extreme her opinion is), and provide motivating social examples. First, we consider stubborn positives, who have reduced susceptibility if their opinions are at one end of the interval and increased susceptibility if their opinions are at the opposite end. Second, we consider stubborn extremists, who are less susceptible when they hold opinions at either end of the opinion interval. For each susceptibility model, we establish limiting behavior for different initial conditions. Networks consisting of individuals with both types of susceptibility functions are also considered.

This paper investigates an optimal control strategy to mitigate the spread of HIV/AIDS by integrating media awareness campaigns and antiviral treatment efforts. A modified SI-type model is developed, dividing the population into five subgroups: unaware susceptible individuals, aware susceptible individuals, unaware infected individuals, aware infected individuals, and individuals undergoing treatment. Additionally, a separate compartment representing the level of media awareness is included to model the dynamics of awareness campaigns over time. Three control variables are introduced: the success of media awareness programs aimed at reducing contact between susceptible and infected individuals and encouraging infected individuals to seek and receive treatment; the effort to provide antiretroviral treatment; and the effort to strengthen the intensity of media awareness programs. The objective is to minimize the number of unaware susceptible and infected individuals while maximizing the number of individuals receiving treatment, and to reduce implementation costs. The model employs optimal control theory to identify the best combination of strategies by minimizing a cost functional. Numerical simulations explore seven control strategy combinations, ranging from single to multiple controls. The results indicate that combining all control variables yields the most significant reduction in unaware and infected individuals, a substantial increase in the number of individuals receiving treatment, and effective minimization of costs.

Susceptible-infectious-recovered models revisited: From the individual level to the population level

This paper examines the effect of pandemic vaccination on asset prices in a simple asset pricing model à la Lucas 1978. In this model, asset prices depend on susceptible individuals’ saving motives to insure against a reduction in labour income due to getting they get the virus. Hence distributing vaccine reduces precautionary saving motives and asset prices. This implies that reducing the income gap between susceptible and infected individuals, such as by cash handouts, eases the negative effect of vaccine supply on asset prices.

Effect of duck hepatitis A virus genotype 3 infection on glucose metabolism of Pekin ducklings and underlying mechanism.

Tuberculosis (TB) is a deadly infectious disease, which kills millions of people every year. The causative pathogen, Mycobacterium tuberculosis (MTB), is estimated to have infected up to a third of the world’s population; however, only approximately 10% of infected healthy individuals progress to active TB. Despite evidence for heritability, it is not currently possible to predict who may develop TB. To explore approaches to classify susceptibility to TB, we infected with MTB dendritic cells (DCs) from putatively resistant individuals diagnosed with latent TB, and from susceptible individuals that had recovered from active TB. We measured gene expression levels in infected and non-infected cells and found hundreds of differentially expressed genes between susceptible and resistant individuals in the non-infected cells. We further found that genetic polymorphisms nearby the differentially expressed genes between susceptible and resistant individuals are more likely to be associated with TB susceptibility in published GWAS data. Lastly, we trained a classifier based on the gene expression levels in the non-infected cells, and demonstrated reasonable performance on our data and an independent data set. Overall, our promising results from this small study suggest that training a classifier on a larger cohort may enable us to accurately predict TB susceptibility.

Glyphosate resistant Echinochloa colona is widespread in fallow systems of northern Australia from intensive glyphosate use. The inheritance of glyphosate resistance and the potential for gene transfer through pollen from resistant to susceptible individuals were investigated. A glyphosate resistant population A533.1, containing a mutation in EPSPS, was used as the resistant parent and Echi S as the susceptible parent. Gene flow via pollen between adjacent susceptible and resistant individuals was examined by treating progeny from the susceptible individuals at 240 g ha-1 glyphosate with 1.38% gene flow detected. Survivors were selfed and the progeny segregated 3:1 for survival to 240 g ha-1 glyphosate, consistent with single dominant gene inheritance. Hand crosses between resistant and susceptible individuals produced a single F1 seed which carried the mutation in EPSPS. The F2 generation from the hand cross had a response to glyphosate, intermediate between the two parents and similar to that expected for a single largely dominant gene. Sequencing the EPSPS cDNA detected at least two EPSPS genes expressed in E. colona, only one of which carried the mutation. Glyphosate resistance in this population of E. colona is inherited as a single largely dominant allele.

Infectious disease transmission is an inherently spatial process in which a host’s home location and their social mixing patterns are important, with the mixing of infectious individuals often different to that of susceptible individuals. Although incidence data for humans have traditionally been aggregated into low-resolution data sets, modern representative surveillance systems such as electronic hospital records generate high volume case data with precise home locations. Here, we use a gridded spatial transmission model of arbitrary resolution to investigate the theoretical relationship between population density, differential population movement and local variability in incidence. We show analytically that a uniform local attack rate is typically only possible for individual pixels in the grid if susceptible and infectious individuals move in the same way. Using a population in Guangdong, China, for which a robust quantitative description of movement is available (a travel kernel), and a natural history consistent with pandemic influenza; we show that local cumulative incidence is positively correlated with population density when susceptible individuals are more connected in space than infectious individuals. Conversely, under the less intuitively likely scenario, when infectious individuals are more connected, local cumulative incidence is negatively correlated with population density. The strength and direction of correlation changes sign for other kernel parameter values. We show that simulation models in which it is assumed implicitly that only infectious individuals move are assuming a slightly unusual specific correlation between population density and attack rate. However, we also show that this potential structural bias can be corrected by using the appropriate non-isotropic kernel that maps infectious-only code onto the isotropic dual-mobility kernel. These results describe a precise relationship between the spatio-social mixing of infectious and susceptible individuals and local variability in attack rates. More generally, these results suggest a genuine risk that mechanistic models of high-resolution attack rate data may reach spurious conclusions if the precise implications of spatial force-of-infection assumptions are not first fully characterized, prior to models being fit to data.

Diarrhea and edema disease in weaned piglets due to infection by Escherichia coli F18 is a leading cause of economic loss in the pig industry. Resistance to E. coli F18 depends on expression of receptors on intestinal epithelial cells, and individual immunity. This study was conducted in Sutai pig E. coli F18-resistant and -susceptible full sib-pair individuals, identified on the basis of resource populations and verification of adhesion assays. The molecular mechanism underlying E. coli F18 resistance was investigated through analysis of the expression of E. coli F18 receptor associated and innate immunity proteins, using proteomics and bioinformatics techniques. Two-dimensional electrophoresis analysis revealed a total of 20 differentially expressed proteins in E. coli F18-resistant and -susceptible groups (10 upregulated and 10 downregulated). A total of 16 differentially expressed proteins were identified by MALDI TOF/TOF mass spectral analysis. According to gene ontology and pathway analysis, differentially expressed proteins were mainly involved in cell adhesion, immune response and other biologically relevant functions. Network analysis of interactions between differentially expressed proteins indicated a likelihood of their involvement in E. coli F18 infection. The expression levels of several important proteins including actin beta (ACTB), vinculin (VCL), heat stress proteins (HSPs) and transferrin (TF) in E. coli F18-resistant and -susceptible individuals were verified by Western blotting, supporting the identification of ACTB, VCL, HSPs and TF as promising candidate proteins for association with E. coli F18 susceptibility.

There have been rapid and dramatic increases in the numbers of people on antiretroviral treatment in Africa [1]. These numbers should continue to grow substantially, if current treatment need is met and those progressing to later stages of infection are added into treatment programmes, especially if earlier initiation on treatment is adopted. Antiretroviral treatment itself may suppress HIV transmission rates by reducing viral load [2,3], but its preventive effect in populations will depend on its impact on sexual behaviour, with increases in risky behaviour potentially negating the benefits of reduced transmissibility and decreases in risky behaviour enhancing them. Indeed, a substantial part of the modelled impact of the ‘test and treat’ strategy promoted by the WHO was derived from an assumed change in risky behaviour [4]. The paper by Venkatesh et al.[5] published in this issue of AIDS suggests that initiation on treatment could lead to substantial reductions in risk behaviour in urban and rural populations in South Africa, which, if they can be replicated when treatment is initiated earlier and can be sustained for long periods after patients have regained their full health, would provide dramatic prevention benefits. These findings are very encouraging, especially because the comparison group comprised infected individuals who had previously received testing and counselling and could, therefore, already have adopted safer behaviour [6]. However, before we conclude that treatment will enhance HIV prevention efforts by reducing risk behaviour, we should consider, first, whether such a big effect in antiretroviral therapy (ART) patients is plausible – or is more likely to have resulted from methodological difficulties – and, second, what the influence of ART might be on the behaviour of susceptible and undiagnosed infected individuals. The study by Venkatesh et al.[5] has a prospective design (spanning periods up to and after ART initiation), a large representative sample (n = 6263 of whom 37% initiated treatment) with regular follow-ups, collected data on both sexes in both urban and rural areas, and applied rigorous statistical methods. As in some previous studies in sub-Saharan Africa [7,8], initiation on ART was associated with reductions in sexual activity, including reporting of unprotected sex and multiple sexual partnerships. However, the effect sizes in this study were particularly remarkable. The authors did not investigate the reasons for the reductions in risk behaviour in their setting and we wonder about the plausibility of such big effect sizes. Why would people who had been seriously ill (WHO stage 4 disease and/or CD4 cell count < 200 cells/μl.) and are now returned to good health become less sexually active and have fewer partners? Counselling and condoms were provided to newly diagnosed individuals as well as to those initiated on treatment; if disclosure to partners or fear of infecting others increased adoption of safer behaviours why would this be different for those who know they are infected, but are not yet treated? Methodological difficulties remain a concern: if interviewers were not blind to who was on treatment, interviewer bias could have affected the results. We are told that interviewers were trained to avoid social desirability bias, but this is very difficult to achieve especially when interviews are conducted in a clinical setting. It must be possible, therefore, that participants on ART felt a greater need to conceal risky behaviour. Concern over validity would be much assuaged by a good explanation for the behaviour change. In addition, trials showing the impact of expanded treatment on HIV incidence in populations would be welcome. In assessing the impact of ART on sexual transmission, it is important that we consider the right behaviours in the right people. The best indicator of risk is multiple partnerships, so it is notable that this was the indicator that changed the most amongst individuals initiated on ART in the South Africa study. Nevertheless, in assessing the prevention impact, it is important to consider the behaviour of those started on treatment in the context of the wider population. An increase in the fraction of the population that is HIV-positive owing to longer survival of those infected, other things being equal, might be expected to lead to an increase in exposure amongst susceptible individuals. More importantly, the effects of widespread availability of ART on behaviour will extend beyond those who are on treatment. In Western countries, studies have found evidence of behavioural disinhibition in susceptible and undiagnosed individuals in the presence of ART scale-up that resulted in the resurgence of epidemics [9]. The behaviour of these individuals will be as important, if not more so, than that of those on treatment in determining the future course of HIV epidemics within sub-Saharan Africa. The study by Venkatesh et al.[5] is a valuable contribution to our understanding of the impact of ART initiation on sexual behaviour of infected individuals and suggests that this impact could be large. However, more evidence through monitoring and evaluation is required before we can safely assume expanded treatment access is successfully reducing HIV incidence. Elucidating the reasons for changes in behaviour observed and establishing whether these changes extend to those with early treatment initiation and are sustained over time would be important contributions. Equally important, studies on the effects of increases in the availability of ART must be extended to encompass the effects on risk behaviour amongst undiagnosed and uninfected individuals. In the meantime, close integration of prevention activities within expanded care activities should continue [10].

Hepatitis B is an infectious disease that causes inflammation of the liver due to infection with the Hepatitis B virus. Hepatitis B is divided into two phases: the acute phase and the chronic phase. Hepatitis B virus (HBV) can be prevented through vaccination and treatment of susceptible and infected individuals. The spread of the virus can be modeled using mathematical modeling of epidemics. In this study, the model used consists of four classes, namely vulnerable individuals (S), acute individuals (A), chronic individuals (C), and recovered individuals (R). The purpose of this study is to explain the formation of the Hepatitis B disease epidemic model, analyze the stability of the model, perform simulations, and conduct parameter sensitivity analysis on the basic reproductive number. The result of this study is the construction of an epidemic model of the spread of hepatitis B disease in the form of a SACR model. This model takes into account the transmission that occurs not only through interactions between susceptible individuals and chronic individuals but also through the birth process, which occurs in chronic subpopulations because babies born can be chronically infected (vertical transmission from mother to baby). The model produces two equilibrium points, the disease-free equilibrium and the endemic equilibrium. Both points were analyzed for stability using the linearization method and were found to be asymptotically stable. Furthermore, the model simulation was carried out using the fourth-order Runge-Kutta method and sensitivity analysis of the basic reproduction number. From the results obtained, it can be concluded that the spread of hepatitis B disease can be minimized by reducing contact between susceptible and chronic individuals, increasing treatment of chronic individuals, and increasing the number of vaccinated individuals in susceptible populations.