On the fractional SIRD mathematical model and control for the transmission of COVID-19: The first and the second waves of the disease in Iran and Japan.

In this paper, a fractional-order SIRD mathematical model is presented with Caputo derivative for the transmission of COVID-19 between humans. We calculate the steady-states of the system and discuss their stability. We also discuss the existence and uniqueness of a non-negative solution for the system under study. Additionally, we obtain an approximate response by implementing the fractional Euler method. Next, we investigate the first and the second waves of the disease in Iran and Japan; then we give a prediction concerning the second wave of the disease. We display the numerical simulations for different derivative orders in order to evaluate the efficacy of the fractional concept on the system behaviors. We also calculate the optimal control of the system and display its numerical simulations.

SEIR epidemic model for COVID-19 transmission by Caputo derivative of fractional order.

We provide a SEIR epidemic model for the spread of COVID-19 using the Caputo fractional derivative. The feasibility region of the system and equilibrium points are calculated and the stability of the equilibrium points is investigated. We prove the existence of a unique solution for the model by using fixed point theory. Using the fractional Euler method, we get an approximate solution to the model. To predict the transmission of COVID-19 in Iran and in the world, we provide a numerical simulation based on real data.

A fractional differential equation model for the COVID-19 transmission by using the Caputo-Fabrizio derivative.

We present a fractional-order model for the COVID-19 transmission with Caputo-Fabrizio derivative. Using the homotopy analysis transform method (HATM), which combines the method of homotopy analysis and Laplace transform, we solve the problem and give approximate solution in convergent series. We prove the existence of a unique solution and the stability of the iteration approach by using fixed point theory. We also present numerical results to simulate virus transmission and compare the results with those of the Caputo derivative.

A mathematical model for COVID-19 transmission by using the Caputo fractional derivative.

We present a mathematical model for the transmission of COVID-19 by the Caputo fractional-order derivative. We calculate the equilibrium points and the reproduction number for the model and obtain the region of the feasibility of system. By fixed point theory, we prove the existence of a unique solution. Using the generalized Adams-Bashforth-Moulton method, we solve the system and obtain the approximate solutions. We present a numerical simulation for the transmission of COVID-19 in the world, and in this simulation, the reproduction number is obtained as R 0 = 1 : 610007996 , which shows that the epidemic continues.

HIV antiretroviral exposure in pregnancy induces detrimental placenta vascular changes that are rescued by progesterone supplementation.

Adverse birth outcomes are common in HIV-positive pregnant women receiving combination antiretroviral therapy (cART), especially when cART is initiated in early pregnancy. The mechanisms remain poorly understood. Using a mouse model we demonstrate that protease inhibitor based-cART exposure beginning on day 1 of pregnancy was associated with a pro-angiogenic/pro-branching shift in the placenta driven by lower Flt-1 levels and higher Gcm-1 expression. Micro-CT imaging revealed an increase in the number of arterioles in cART-treated placentas, which correlated with fetal growth restriction. Delaying initiation of cART, or supplementing cART-treated mice with progesterone, prevented the pro-angiogenic/pro-branching shift and the associated placenta vascular changes. In agreement with our mouse findings, we observed an increase in the number of terminal-villi capillaries in placentas from HIV-positive cART-exposed women compared to HIV-negative controls. Capillary number was inversely correlated to maternal progesterone levels. Our study provides evidence that cART exposure during pregnancy influences placenta vascular formation that may in turn contribute to fetal growth restriction. Our findings highlight the need for closer investigation of the placenta in HIV-positive pregnancies, particularly for pregnancies exposed to cART from conception, and suggest that progesterone supplementation could be investigated as a possible intervention to improve placenta function in HIV-positive pregnant women.

Low Prolactin and High 20-α-Hydroxysteroid Dehydrogenase Levels Contribute to Lower Progesterone Levels in HIV-Infected Pregnant Women Exposed to Protease Inhibitor-Based Combination Antiretroviral Therapy.

BACKGROUND: It has been reported that pregnant women receiving protease inhibitor (PI)-based combination antiretroviral therapy (cART) have lower levels of progesterone, which put them at risk of adverse birth outcomes, such as low birth weight. We sought to understand the mechanisms involved in this decline in progesterone level. METHODS: We assessed plasma levels of progesterone, prolactin, and lipids and placental expression of genes involved in progesterone metabolism in 42 human immunodeficiency virus (HIV)-infected and 31 HIV-uninfected pregnant women. In vitro studies and a mouse pregnancy model were used to delineate the effect of HIV from that of PI-based cART on progesterone metabolism. RESULTS: HIV-infected pregnant women receiving PI-based cART showed a reduction in plasma progesterone levels (P= .026) and an elevation in placental expression of the progesterone inactivating enzyme 20-α-hydroxysteroid dehydrogenase (20α-HSD; median, 2.5 arbitrary units [AU]; interquartile range [IQR], 1.00-4.10 AU), compared with controls (median, 0.89 AU; IQR, 0.66-1.26 AU;P= .002). Prolactin, a key regulator of 20α-HSD, was lower (P= .012) in HIV-infected pregnant women. We observed similar data in pregnant mice exposed to PI-based cART. In vitro inhibition of 20α-HSD activity in trophoblast cells reversed PI-based cART-induced decreases in progesterone levels. CONCLUSIONS: Our data suggest that the decrease in progesterone levels observed in HIV-infected pregnant women exposed to PI-based cART is caused, at least in part, by an increase in placental expression of 20α-HSD, which may be due to lower prolactin levels observed in these women.

HIV protease inhibitor use during pregnancy is associated with decreased progesterone levels, suggesting a potential mechanism contributing to fetal growth restriction.

BACKGROUND: Protease inhibitor (PI)-based combination antiretroviral therapy (cART) is administered during pregnancy to prevent perinatal human immunodeficiency virus (HIV) transmission. However, PI use has been associated with adverse birth outcomes, including preterm delivery and small-for-gestational-age (SGA) births. The mechanisms underlying these outcomes are unknown. We hypothesized that PIs contribute to these adverse events by altering progesterone levels. METHODS: PI effects on trophoblast progesterone production were assessed in vitro. A mouse pregnancy model was used to assess the impact of PI-based cART on pregnancy outcomes and progesterone levels in vivo. Progesterone levels were assessed in plasma specimens from 27 HIV-infected and 17 HIV-uninfected pregnant women. RESULTS: PIs (ritonavir, lopinavir, and atazanavir) but not nucleoside reverse transcriptase inhibitors (NRTIs) or nonnucleoside reverse transcriptase inhibitors reduced trophoblast progesterone production in vitro. In pregnant mice, PI-based cART but not dual-NRTI therapy was associated with significantly lower progesterone levels that directly correlated with fetal weight. Progesterone supplementation resulted in a significant improvement in fetal weight. We observed lower progesterone levels and smaller infants in HIV-infected women receiving PI-based cART, compared with the control group. In HIV-infected women, progesterone levels correlated significantly with birth weight percentile. CONCLUSIONS: Our data suggest that PI use in pregnancy may lead to lower progesterone levels that could contribute to adverse birth outcomes.

Some existence results on nonlinear fractional differential equations.

In this paper, by using fixed-point methods, we study the existence and uniqueness of a solution for the nonlinear fractional differential equation boundary-value problem D(α)u(t)=f(t,u(t)) with a Riemann-Liouville fractional derivative via the different boundary-value problems u(0)=u(T), and the three-point boundary condition u(0)=ß(1)u(η) and u(T)=ß(2)u(η), where T>0, t∈I=[0,T], 0<α<1, 0<η

Pharmacological inhibition of feline immunodeficiency virus (FIV).

Feline immunodeficiency virus (FIV) is a member of the retroviridae family of viruses and causes an acquired immunodeficiency syndrome (AIDS) in domestic and non-domestic cats worldwide. Genome organization of FIV and clinical characteristics of the disease caused by the virus are similar to those of human immunodeficiency virus (HIV). Both viruses infect T lymphocytes, monocytes and macrophages, and their replication cycle in infected cells is analogous. Due to marked similarity in genomic organization, virus structure, virus replication and disease pathogenesis of FIV and HIV, infection of cats with FIV is a useful tool to study and develop novel drugs and vaccines for HIV. Anti-retroviral drugs studied extensively in HIV infection have targeted different steps of the virus replication cycle: (1) inhibition of virus entry into susceptible cells at the level of attachment to host cell surface receptors and co-receptors; (2) inhibition of fusion of the virus membrane with the cell membrane; (3) blockade of reverse transcription of viral genomic RNA; (4) interruption of nuclear translocation and viral DNA integration into host genomes; (5) prevention of viral transcript processing and nuclear export; and (6) inhibition of virion assembly and maturation. Despite much success of anti-retroviral therapy slowing disease progression in people, similar therapy has not been thoroughly investigated in cats. In this article we review current pharmacological approaches and novel targets for anti-lentiviral therapy, and critically assess potentially suitable applications against FIV infection in cats.

Marek's disease virus influences the expression of genes associated with IFN-gamma-inducible MHC class II expression.

Chickens infected with Marek's disease virus (MDV) become lifelong carriers regardless of their susceptibility to clinical disease. Therefore various viral immune-evasive mechanisms must play a role in MDV-host interactions. MDV has previously been shown to influence the expression of major histocompatibility complex (MHC) class II molecules. However, little is known about the underlying mechanisms of this phenomenon. In the present study, we studied the effect of MDV infection on the expression of several genes associated with IFN-gamma-inducible MHC class II expression at 4, 7, 14, and 21 days post-infection (dpi). There was a significant (p

Characterization of host responses against a recombinant fowlpox virus-vectored vaccine expressing the hemagglutinin antigen of an avian influenza virus.

There currently are commercial fowlpox virus (FPV)-vectored vaccines for use in chickens, including TROVAC-AIV H5, which expresses the hemagglutinin (HA) antigen of an avian influenza virus and can confer immunity against avian influenza in chickens. Despite the use of recombinant FPV (rFPV) for vaccine delivery, very little is known about the immune responses generated by these viruses in chickens. The present study was designed to investigate host responses to rFPV in vivo and in vitro. In cultured cells infected with TROVAC-AIV H5, there was an early increase in the expression of type I interferons (IFN), Toll-like receptors 3 and 7 (TLR3 and TLR7, respectively), TRIF, and MyD88, which was followed by a decrease in the expression of these genes at later time points. There also was an increase in the expression of interleukin-1beta (IL-1beta), IL-8, and beta-defensin genes at early time points postinfection. In chickens immunized with TROVAC-AIV H5, there was higher expression of IFN-gamma and IL-10 at day 5 postvaccination in spleen of vaccinated birds than in that of control birds. We further investigated the ability of the vaccine to induce immune responses against the HA antigen and discovered that there was a cell-mediated response elicited in vaccinated chickens against this antigen. The findings of this study demonstrate that FPV-vectored vaccines can elicit a repertoire of responses marked by the early expression of TLRs, type I interferons, and proinflammatory cytokines, as well as cytokines associated with adaptive immune responses. This study provides a platform for designing future generations of rFPV-vectored vaccines.

The lactate dehydrogenase-elevating virus capsid protein is a nuclear-cytoplasmic protein.

Arteriviruses replicate in the cytoplasm and do not require the nucleus function for virus multiplication in vitro. However, nucleocapsid (N) protein of two arteriviruses, porcine reproductive respiratory syndrome virus and equine arteritis virus, has been observed to localize in the nucleus and nucleolus of virus-infected and N-gene-transfected cells in addition to their normal cytoplasmic distribution. In the present study, the N protein of lactate dehydrogenase-elevating virus (LDV) of mice was examined for nuclear localization. The subcellular localization of LDV-N was determined by tagging N with enhanced green fluorescence protein (EGFP) at the N- and C-terminus. Both N-EGFP and EGFP-N fusion proteins localized to the nucleus and nucleolus of gene-transfected cells. Labeled N also accumulated in the perinuclear region, the site of virus replication. The LDV-N sequence contains a putative 'pat4'-type nuclear localization signal (NLS) consisting of 38-KKKK. To determine its functional significance, a series of deletion constructs of N were generated and individually expressed in cells. The results showed that the 'pat4' NLS was essential for nuclear translocation. In addition, the LDV-N interacted with the importin-alpha and -beta proteins, suggesting that the LDV-N nuclear localization may occur via the importin-mediated nuclear transport pathway. These results provide further evidence for the nuclear localization of N as a common feature within the arteriviruses.