Global analysis of an age-structured tuberculosis model with an application to Jiangsu, China.

Diagnostic delay for TB infected individuals and the lack of TB vaccines for adults are the main challenges to achieve the goals of WHO by 2050. In order to evaluate the impacts of diagnostic delay and vaccination for adults on prevalence of TB, we propose an age-structured model with latent age and infection age, and we incorporate Mycobacterium TB in the environment and vaccination into the model. Diagnostic delay is indicated by the age of infection before receiving treatment. The threshold dynamics are established in terms of the basic reproduction number R 0 . When R 0 < 1 , the disease-free equilibrium is globally asymptotically stable, which means that TB epidemic will die out; When R 0 = 1 , the disease-free equilibrium is globally attractive; there exists a unique endemic equilibrium and the endemic equilibrium is globally attractive when R 0 > 1 . We estimate that the basic reproduction number R 0 = 0.5320 (95% CI (0.3060, 0.7556)) in Jiangsu Province, which means that TB epidemic will die out. However, we find that the annual number of new TB cases by 2050 is 1,151 (95%CI: (138, 8,014)), which means that it is challenging to achieve the goal of WHO by 2050. To this end, we evaluate the possibility of achieving the goals of WHO if we start vaccinating adults and reduce diagnostic delay in 2025. Our results demonstrate that when the diagnostic delay is reduced from longer than four months to four months, or 20% adults are vaccinated, the goal of WHO in 2050 can be achieved, and 73,137 (95%CI: (23,906, 234,086)) and 54,828 (95%CI: (15,811, 206,468)) individuals will be prevented from being infected from 2025 to 2050, respectively. The modeling approaches and simulation results used in this work can help policymakers design control measures to reduce the prevalence of TB.

Vaccine hesitancy promotes emergence of new SARS-CoV-2 variants.

The successive emergence of SARS-CoV-2 mutations has led to an unprecedented increase in COVID-19 incidence worldwide. Currently, vaccination is considered to be the best available solution to control the ongoing COVID-19 pandemic. However, public opposition to vaccination persists in many countries, which can lead to increased COVID-19 caseloads and hence greater opportunities for vaccine-evasive mutant strains to arise. To determine the extent that public opinion regarding vaccination can induce or hamper the emergence of new variants, we develop a model that couples a compartmental disease transmission framework featuring two strains of SARS-CoV-2 with game theoretical dynamics on whether or not to vaccinate. We combine semi-stochastic and deterministic simulations to explore the effect of mutation probability, perceived cost of receiving vaccines, and perceived risks of infection on the emergence and spread of mutant SARS-CoV-2 strains. We find that decreasing the perceived costs of being vaccinated and increasing the perceived risks of infection (that is, decreasing vaccine hesitation) will decrease the possibility of vaccine-resistant mutant strains becoming established by about fourfold for intermediate mutation rates. Conversely, we find increasing vaccine hesitation to cause both higher probability of mutant strains emerging and more wild-type cases after the mutant strain has appeared. We also find that once a new variant has emerged, perceived risk of being infected by the original variant plays a much larger role than perceptions of the new variant in determining future outbreak characteristics. Furthermore, we find that rapid vaccination under non-pharmaceutical interventions is a highly effective strategy for preventing new variant emergence, due to interaction effects between non-pharmaceutical interventions and public support for vaccination. Our findings indicate that policies that combine combating vaccine-related misinformation with non-pharmaceutical interventions (such as reducing social contact) will be the most effective for avoiding the establishment of harmful new variants.

Infectivity versus fatality of SARS-CoV-2 mutations and influenza.

OBJECTIVES: Because of the spread of the Omicron variant, many countries have experienced COVID-19 case numbers unseen since the start of the pandemic. We aimed to compare the epidemiological characteristics of Omicron with previous variants and different strains of influenza to provide context for public health responses. METHODS: We developed transmission models for SARS-CoV-2 variants and influenza, in which transmission, death, and vaccination rates were taken to be time-varying. We fit our model based on publicly available data in South Africa, the United States, and Canada. We used this model to evaluate the relative transmissibility and mortality of Omicron compared with previous variants and influenza. RESULTS: We found that Omicron is more transmissible and less fatal than both seasonal and 2009 H1N1 influenza and the Delta variant; these characteristics make Omicron epidemiologically more similar to influenza than it is to Delta. We estimate that as of February 7, 2022, booster doses have prevented 4.29×107 and 1.14×106 Omicron infections in the United States and Canada, respectively. CONCLUSION: Our findings indicate that the high infectivity of Omicron will keep COVID-19 endemic, similar to influenza. However, because of Omicron's lower fatality rate, our work suggests that human populations living with SARS-CoV-2 are most likely.

Evaluating Strategies For Tuberculosis to Achieve the Goals of WHO in China: A Seasonal Age-Structured Model Study.

Although great progress has been made in the prevention and mitigation of TB in the past 20 years, China is still the third largest contributor to the global burden of new TB cases, accounting for 833,000 new cases in 2019. Improved mitigation strategies, such as vaccines, diagnostics, and treatment, are needed to meet goals of WHO. Given the huge variability in the prevalence of TB across age-groups in China, the vaccination, diagnostic techniques, and treatment for different age-groups may have different effects. Moreover, the statistics data of TB cases show significant seasonal fluctuations in China. In view of the above facts, we propose a non-autonomous differential equation model with age structure and seasonal transmission rate. We derive the basic reproduction number, [Formula: see text], and prove that the unique disease-free periodic solution, [Formula: see text] is globally asymptotically stable when [Formula: see text], while the disease is uniformly persistent and at least one positive periodic solution exists when [Formula: see text]. We estimate that the basic reproduction number [Formula: see text] ([Formula: see text]), which means that TB is uniformly persistent. Our results demonstrate that vaccinating susceptible individuals whose ages are over 65 and between 20 and 24 is much more effective in reducing the prevalence of TB, and each of the improved vaccination strategy, diagnostic strategy, and treatment strategy leads to substantial reductions in the prevalence of TB per 100,000 individuals compared with current approaches, and the combination of the three strategies is more effective. Scenario A (i.e., coverage rate [Formula: see text], diagnosis rate [Formula: see text], relapse rate [Formula: see text]) is the best and can reduce the prevalence of TB per 100,000 individuals by [Formula: see text] and [Formula: see text] in 2035 and 2050, respectively. Although the improved strategies will significantly reduce the incidence rate of TB, it is challenging to achieve the goal of WHO in 2050. Our findings can provide guidance for public health authorities in projecting effective mitigation strategies of TB.

Evaluating the impacts of non-pharmaceutical interventions on the transmission dynamics of COVID-19 in Canada based on mobile network.

The COVID-19 outbreak has caused two waves and spread to more than 90% of Canada's provinces since it was first reported more than a year ago. During the COVID-19 epidemic, Canadian provinces have implemented many Non-Pharmaceutical Interventions (NPIs). However, the spread of the COVID-19 epidemic continues due to the complex dynamics of human mobility. We develop a meta-population network model to study the transmission dynamics of COVID-19. The model takes into account the heterogeneity of mitigation strategies in different provinces of Canada, such as the timing of implementing NPIs, the human mobility in retail and recreation, grocery and pharmacy, parks, transit stations, workplaces, and residences due to work and recreation. To determine which activity is most closely related to the dynamics of COVID-19, we use the cross-correlation analysis to find that the positive correlation is the highest between the mobility data of parks and the weekly number of confirmed COVID-19 from February 15 to December 13, 2020. The average effective reproduction numbers in nine Canadian provinces are all greater than one during the time period, and NPIs have little impact on the dynamics of COVID-19 epidemics in Ontario and Saskatchewan. After November 20, 2020, the average infection probability in Alberta became the highest since the start of the COVID-19 epidemic in Canada. We also observe that human activities around residences do not contribute much to the spread of the COVID-19 epidemic. The simulation results indicate that social distancing and constricting human mobility is effective in mitigating COVID-19 transmission in Canada. Our findings can provide guidance for public health authorities in projecting the effectiveness of future NPIs.

Evaluating the impact of the travel ban within mainland China on the epidemic of the COVID-19.

OBJECTIVES: The ongoing COVID-19 pandemic expanded its geographic distribution through the movement of humans and caused subsequent local outbreaks. Hence, it is essential to investigate how human mobility and travel ban affect the transmission and spatial spread while minimizing the impact on social activities and national economics. METHODS: We developed a mobility network model for spatial epidemics, explicitly taking into account time-varying inter-province and inner-province population flows, spatial heterogeneity in terms of disease transmission, as well as the impact of media reports. The model is applied to study the epidemic of the dynamic network of 30 provinces of mainland China. The model was calibrated using the publicly available incidence and movement data. RESULTS: We estimated that the second outbreak occurred approximately on February 24, 2020, and the cumulative number of cases as of March 15, 2020, increased by 290.1% (95% CI: (255.3%, 324.9%)) without a travel ban in mainland China (excluding Hubei and Tibet). We found that intra-province travel contributes more to the increase of cumulative number of cases than inter-province travel. CONCLUSION: Our quantitative and qualitative research results suggest that the strict travel ban has successfully prevented a severe secondary outbreak in mainland China, which provides solutions for many countries and regions experiencing secondary outbreaks of COVID-19.

Modelling the effects of media coverage and quarantine on the COVID-19 infections in the UK.

A new COVID-19 epidemic model with media coverage and quarantine is constructed. The model allows for the susceptibles to the unconscious and conscious susceptible compartment. First, mathematical analyses establish that the global dynamics of the spread of the COVID-19 infectious disease are completely determined by the basic reproduction number R0. If R0 ≤ 1, then the disease free equilibrium is globally asymptotically stable. If R0 > 1, the endemic equilibrium is globally asymptotically stable. Second, the unknown parameters of model are estimated by the MCMC algorithm on the basis of the total confirmed new cases from February 1, 2020 to March 23, 2020 in the UK. We also estimate that the basic reproduction number is R0 = 4.2816(95%CI: (3.8882, 4.6750)). Without the most restrictive measures, we forecast that the COVID-19 epidemic will peak on June 2 (95%CI: (May 23, June 13)) (Figure 3a) and the number of infected individuals is more than 70% of UK population. In order to determine the key parameters of the model, sensitivity analysis are also explored. Finally, our results show reducing contact is effective against the spread of the disease. We suggest that the stringent containment strategies should be adopted in the UK.

A data-driven network model for the emerging COVID-19 epidemics in Wuhan, Toronto and Italy.

The ongoing Coronavirus Disease 2019 (COVID-19) pandemic threatens the health of humans and causes great economic losses. Predictive modeling and forecasting the epidemic trends are essential for developing countermeasures to mitigate this pandemic. We develop a network model, where each node represents an individual and the edges represent contacts between individuals where the infection can spread. The individuals are classified based on the number of contacts they have each day (their node degrees) and their infection status. The transmission network model was respectively fitted to the reported data for the COVID-19 epidemic in Wuhan (China), Toronto (Canada), and the Italian Republic using a Markov Chain Monte Carlo (MCMC) optimization algorithm. Our model fits all three regions well with narrow confidence intervals and could be adapted to simulate other megacities or regions. The model projections on the role of containment strategies can help inform public health authorities to plan control measures.

Modeling the Effects of Meteorological Factors and Unreported Cases on Seasonal Influenza Outbreaks in Gansu Province, China.

Influenza usually breaks out seasonally in temperate regions, especially in winter, infection rates and mortality rates of influenza increase significantly, which means that dry air and cold temperatures accelerate the spread of influenza viruses. However, the meteorological factors that lead to seasonal influenza outbreaks and how these meteorological factors play a decisive role in influenza transmission remain unclear. During the epidemic of infectious diseases, the neglect of unreported cases leads to an underestimation of infection rates and basic reproduction number. In this paper, we propose a new non-autonomous periodic differential equation model with meteorological factors including unreported cases. First, the basic reproduction number is obtained and the global asymptotic stability of the disease-free periodic solution is proved. Furthermore, the existence of periodic solutions and the uniformly persistence of the model are demonstrated. Second, the best-fit parameter values in our model are identified by the MCMC algorithm on the basis of the influenza data in Gansu province, China. We also estimate that the basic reproduction number is 1.2288 (95% CI:(1.2287, 1.2289)). Then, to determine the key parameters of the model, uncertainty and sensitivity analysis are explored. Finally, our results show that influenza is more likely to spread in low temperature, low humidity and low precipitation environments. Temperature is a more important factor than relative humidity and precipitation during the influenza epidemic. In addition, our results also show that there are far more unreported cases than reported cases.

Intermittent Administration of Parathyroid Hormone Enhances Odonto/Osteogenic Differentiation of Stem Cells from the Apical Papilla via JNK and P38 MAPK Pathways.

OBJECTIVE: Parathyroid hormone (PTH) is considered to be essential during the tooth development. Stem cells from the apical papilla (SCAPs) are responsible for dentine formation. However, the interaction between PTH and SCAPs remains unclear. This study was aimed at investigating the effects of PTH on odonto/osteogenic differentiation capacity of SCAPs and elucidating the underlying molecular mechanisms. Materials and Methods. Here, SCAPs were isolated and identified in vitro. Effects of PTH on the proliferation of SCAPs were determined by Cell Counting Kit-8 (CCK-8), flow cytometry (FCM), and EdU. Alkaline phosphatase (ALP) activity, alizarin red staining, Western blot, and RT-PCR were carried out to detect the odonto/osteogenic differentiation of PTH-treated SCAPs as well as the participation of the MAPK signaling pathway. RESULTS: An ALP activity assay determined that 10-8 mol/L PTH was the optimal concentration for the induction of SCAPs with no significant influence on the proliferation of SCAPs as indicated by CCK-8, FCM, and EdU. The expression of odonto/osteogenic markers was significantly upregulated in mRNA levels and protein levels. Moreover, intermittent treatment of PTH also increased phosphorylation of JNK and P38, and the differentiation was suppressed following the inhibition of JNK and P38 MAPK pathways. CONCLUSION: PTH can regulate the odonto/osteogenic differentiation of SCAPs via JNK and P38 MAPK pathways.

Parathyroid hormone enhances the osteo/odontogenic differentiation of dental pulp stem cells via ERK and P38 MAPK pathways.

OBJECTIVE: Parathyroid hormone (PTH) is a main systemic mediator of calcium and phosphate homeostasis in the bone. Dental pulp stem cells (DPSCs) have been extensively studied in the regeneration of bone and tooth tissues. This paper aims to uncover the influences of PTH on the proliferative ability and osteo/odontogenic differentiation of DPSCs, as well as the underlying mechanisms. MATERIALS AND METHODS: The optimal concentration of PTH on DPSCs was determined by alkaline phosphatase (ALP) activity assay, ALP staining and western blot analysis. Proliferative ability and cell cycle distribution of DPSCs were analyzed by Cell counting kit-8, 5-ethynyl-20-deoxyuridine assay, and flow cytometry. Osteo/odontogenic capacity of DPSCs was evaluated and finally, the involvement of mitogen-activated protein kinase (MAPK) pathway was assessed. RESULTS: Purified DPSCs were obtained by enzymatic digestion, which presented a typical fibroblast-like morphology. 10-9 mol/L PTH was concerned as the optimal concentration for DPSCs induction. 10-9 mol/L PTH treatment did not change the proliferative rate of DPSCs (p > .05). Relative expressions of DSPP/DSPP, RUNX2/RUNX2, OSX/OSX, and ALP/ALP were upregulated in PTH-treated DPSCs relative to control group. Particularly, their mRNA/protein levels at Day 7 were markedly higher relative to those at Day 3 (p < .05 or p < .01). Mineralized nodules were formed after PTH induction, and calcium content increased by cetylpyridinium chloride quantitative analysis. Mechanistically, the protein levels of p-ERK and p-P38 significantly increased after PTH treatment, and the inhibitors targeting MAPK were identified that weakened the effects of PTH on the committed differentiation of DPSCs. CONCLUSIONS: PTH enhances the osteo/odontogenic differentiation capacity of DPSCs via ERK and P38 signaling pathways.

Modelling and analysis of an alcoholism model with treatment and effect of Twitter.

A new alcoholism model with treatment and effect of Twitter is introduced. The stability of all equilibria which is determined by the basic reproductive number ro is obtained. The occurrence of backward and forward bifurcation for a certain defined range of ro are established by the center manifold theory. Numerical results and sensitivity analysis on several parameters are conducted. Our results show that Twitter may be a good indicator of alcoholism model and affect the emergence and spread of drinking behavior.

Surface Hydrophilicity and Antifungal Properties of TiO2 Films Coated on a Co-Cr Substrate.

The purpose of this study was to deposit a thin layer of TiO2 on a Co-Cr substrate, serving as a deactivation film protecting the metallic fitting surface. The crystalline structure and surface morphology of the film were characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM). A scratch tester was used to examine the adhesion strength between the TiO2 film and the Co-Cr substrate. The water contact angles and antifungal efficacy against C. albicans of the TiO2-deposited Co-Cr samples were investigated and further compared with those of uncoated Co-Cr substrates. The results indicated that a pure anatase microstructure and dense and smooth surface texture as well as strong binding to the underlying metallic surface were obtained. The originally hydrophobic Co-Cr alloy surface turned hydrophilic after TiO2 film coating. Most importantly, the TiO2-coated surface showed a superior antifungal capability under UV-irradiation compared to those without TiO2 coating. This work contains meaningful results for the development of a new metallic framework coating with improved hydrophilicity and antifungal properties.

Effects of canonical NF-κB signaling pathway on the proliferation and odonto/osteogenic differentiation of human stem cells from apical papilla.

BACKGROUND INFORMATION: NF-κB signaling pathway plays a complicated role in the biological functions of mesenchymal stem cells. However, the effects of NF-κB pathway on the odonto/osteogenic differentiation of stem cells from apical papilla (SCAPs) remain unclear. The present study was designed to evaluate the effects of canonical NF-κB pathway on the osteo/odontogenic capacity of SCAPs in vitro. RESULTS: Western blot results demonstrated that NF-κB pathway in SCAPs was successfully activated by TNF-α or blocked by BMS-345541. NF-κB pathway-activated SCAPs presented a higher proliferation activity compared with control groups, as indicated by dimethyl-thiazol-diphenyl tetrazolium bromide assay (MTT) and flow cytometry assay (FCM). Wound scratch assay revealed that NF-κB pathway-activated SCAPs presented an improved migration capacity, enhanced alkaline phosphatase (ALP) activity, and upregulated mineralization capacity of SCAPs, as compared with control groups. Meanwhile, the odonto/osteogenic markers (ALP/ALP, RUNX2/RUNX2, OSX/OSX, OCN/OCN, OPN/OPN, BSP/BSP, DSPP/DSP, and DMP-1/DMP-1) in NF-κB pathway-activated SCAPs were also significantly upregulated as compared with control groups at both protein and mRNA levels. However, NF-κB pathway-inhibited SCAPs exhibited a lower proliferation/migration capacity, and decreased odonto/osteogenic ability in comparison with control groups. CONCLUSION: Our findings suggest that classical NF-κB pathway plays a paramount role in the proliferation and committed differentiation of SCAPs.

[Effect of estrogen deficiency on the proliferation and osteogenic differentiation potential of mandibular bone marrow stromal cells].

OBJECTIVE: To determine the effects of estrogen deficiency on the proliferation and osteogenic differentiation of mandibular bone marrow stromal cells (mBMSC). METHODS: Ten 8-week-old female SD rats were randomly divided into two groups, ovariectomized group (OVX, n = 5) and sham-operation group (n = 5). All rats were anesthetized and both ovaries of OVX-rats were gently removed. Sham-operation rats were treated with the same incisions to expose the ovaries but without any hurt to them. One month after the operation, the mandibular bones were gently separated and mBMSC were isolated. Methyl thiazolyl tetrazolium (MTT) assay, alkaline phosphotase (ALP) activity, alizarin red staining, real-time reverse transcription (RT)-PCR and Western blotting were respectively used to examine the proliferative activity and osteogenic potential of mBMSC. RESULTS: MTT results showed that OVX-mBMSC exhibited the decreased proliferative activity as compared with Sham-mBMSC. ALP activity of OVX-mBMSC [(0.710±0.011) Sigma unit/protein] was lower than that of Sham-mBMSC [(1.512±0.021) Sigma unit/protein] (P < 0.01). Alizarin red staining showed that OVX-mBMSC formed less calcified nodules than Sham-mBMSC. Ca(2+) concentration analysis showed Ca(2+) of OVX-mBMSC [(0.433±0.045) µg/g] was less than Sham-mBMSC [(1.453±0.131) µg/g] (P < 0.01). Real-time RT-PCR and Western blotting results showed that the expression of osteogenic markers (Alp, Runx2/RUNX2, Osx/OSX, Ocn/OCN) in OVX-mBMSC was significantly inhibited as compared with Sham-mBMSC (P < 0.05). CONCLUSIONS: Estrogen deficiency significantly inhibits the proliferation and osteogenic capacity of mBMSC.