Pace of Coreceptor Tropism Switch in HIV-1-Infected Individuals after Recent Infection.

HIV-1 entry into target cells influences several aspects of HIV-1 pathogenesis, including viral tropism, HIV-1 transmission and disease progression, and response to entry inhibitors. The evolution from CCR5- to CXCR4-using strains in a given human host is still unpredictable. Here we analyzed timing and predictors for coreceptor evolution among recently HIV-1-infected individuals. Proviral DNA was longitudinally evaluated in 66 individuals using Geno2pheno[coreceptor] Demographics, viral load, CD4+ and CD8+ T cell counts, CCR5Δ32 polymorphisms, GB virus C (GBV-C) coinfection, and HLA profiles were also evaluated. Ultradeep sequencing was performed on initial samples from 11 selected individuals. A tropism switch from CCR5- to CXCR4-using strains was identified in 9/49 (18.4%) individuals. Only a low baseline false-positive rate (FPR) was found to be a significant tropism switch predictor. No minor CXCR4-using variants were identified in initial samples of 4 of 5 R5/non-R5 switchers. Logistic regression analysis showed that patients with an FPR of >40.6% at baseline presented a stable FPR over time whereas lower FPRs tend to progressively decay, leading to emergence of CXCR4-using strains, with a mean evolution time of 27.29 months (range, 8.90 to 64.62). An FPR threshold above 40.6% determined by logistic regression analysis may make it unnecessary to further determine tropism for prediction of disease progression related to emergence of X4 strains or use of CCR5 antagonists. The detection of variants with intermediate FPRs and progressive FPR decay over time not only strengthens the power of Geno2pheno in predicting HIV tropism but also indirectly confirms a continuous evolution from earlier R5 variants toward CXCR4-using strains.IMPORTANCE The introduction of CCR5 antagonists in the antiretroviral arsenal has sparked interest in coreceptors utilized by HIV-1. Despite concentrated efforts, viral and human host features predicting tropism switch are still poorly understood. Limited longitudinal data are available to assess the influence that these factors have on predicting tropism switch and disease progression. The present study describes longitudinal tropism evolution in a group of recently HIV-infected individuals to determine the prevalence and potential correlates of tropism switch. We demonstrated here that a low baseline FPR determined by the Geno2pheno[coreceptor] algorithm can predict tropism evolution from CCR5 to CXCR4 coreceptor use.

Fractional epidemic model of coronavirus disease with vaccination and crowding effects.

Most of the countries in the world are affected by the coronavirus epidemic that put people in danger, with many infected cases and deaths. The crowding factor plays a significant role in the transmission of coronavirus disease. On the other hand, the vaccines of the covid-19 played a decisive role in the control of coronavirus infection. In this paper, a fractional order epidemic model (SIVR) of coronavirus disease is proposed by considering the effects of crowding and vaccination because the transmission of this infection is highly influenced by these two factors. The nonlinear incidence rate with the inclusion of these effects is a better approach to understand and analyse the dynamics of the model. The positivity and boundedness of the fractional order model is ensured by applying some standard results of Mittag Leffler function and Laplace transformation. The equilibrium points are described analytically. The existence and uniqueness of the non-integer order model is also confirmed by using results of the fixed-point theory. Stability analysis is carried out for the system at both the steady states by using Jacobian matrix theory, Routh-Hurwitz criterion and Volterra-type Lyapunov functions. Basic reproductive number is calculated by using next generation matrix. It is verified that disease-free equilibrium is locally asymptotically stable if R 0 < 1 and endemic equilibrium is locally asymptotically stable if R 0 > 1 . Moreover, the disease-free equilibrium is globally asymptotically stable if R 0 < 1 and endemic equilibrium is globally asymptotically stable if R 0 > 1 . The non-standard finite difference (NSFD) scheme is developed to approximate the solutions of the system. The simulated graphs are presented to show the key features of the NSFD approach. It is proved that non-standard finite difference approach preserves the positivity and boundedness properties of model. The simulated graphs show that the implementation of control strategies reduced the infected population and increase the recovered population. The impact of fractional order parameter α is described by the graphical templates. The future trends of the virus transmission are predicted under some control measures. The current work will be a value addition in the literature. The article is closed by some useful concluding remarks.

Insight into the Physical Properties of Fluoro-Perovskites Compounds of Tl-Based TlMF3 (M = Au, Ga) Compounds Studied for Energy Generation Utilizing the TB-MBJ Potential Approximation Approach.

Fluoro-perovskites compounds based on the Tl element TlMF3 (M = Au, Ga) were examined computationally, and their different aspects, studied utilizing TB-mBJ potential approximations, can be used for the generation of energy because of their ever-increasing power conversion efficiency. Birch Murnaghan's graph and tolerance factor show that these composites are structurally cubic and stable. The optimum volume of the compounds corresponding to the optimum energies and the optimized lattice constants were computed. The algorithm IRelast was used to predict the elastic information, and these results demonstrated that the presented compounds are stable mechanically and show anisotropic and ductile properties. TlAuF3 and TlGaF3 have an indirect band energy gap at (M-X) positions, with a forbidden energy gap of -0.55 eV for TlAuF3 and 0.46 eV for TlGaF3. The compounds show a metallic nature due to a small indirect band gap. Different component states corresponding to the upper and lower bands of the Fermi energy level are influenced by the total density in the different states and the density in various directions (TDOS & PDOS). These composites exhibit strong absorption, conductivity, and reflective coefficients at higher energy series together with a low refractive index, given by an inquiry into optical properties. The applications of these composites are thought to be good for conduction purposes in industries due to the indirect band gap. For the first time, computational analysis of these novel compounds offers a thorough understanding of their many characteristics.

On the stability of the diffusive and non-diffusive predator-prey system with consuming resources and disease in prey species.

This research deals with formulating a multi-species eco-epidemiological mathematical model when the interacting species compete for the same food sources and the prey species have some infection. It is assumed that infection does not spread vertically. Infectious diseases severely affect the population dynamics of prey and predator. One of the most important factors in population dynamics is the movement of species in the habitat in search of resources or protection. The ecological influences of diffusion on the population density of both species are studied. The study also deals with the analysis of the effects of diffusion on the fixed points of the proposed model. The fixed points of the model are sorted out. The Lyapunov function is constructed for the proposed model. The fixed points of the proposed model are analyzed through the use of the Lyapunov stability criterion. It is proved that coexisting fixed points remain stable under the effects of self-diffusion, whereas, in the case of cross-diffusion, Turing instability exists conditionally. Moreover, a two-stage explicit numerical scheme is constructed, and the stability of the said scheme is found by using von Neumann stability analysis. Simulations are performed by using the constructed scheme to discuss the model's phase portraits and time-series solution. Many scenarios are discussed to display the present study's significance. The impacts of the transmission parameter 𝛾 and food resource f on the population density of species are presented in plots. It is verified that the availability of common food resources greatly influences the dynamics of such models. It is shown that all three classes, i.e., the predator, susceptible prey and infected prey, can coexist in the habitat, and this coexistence has a stable nature. Hence, in the realistic scenarios of predator-prey ecology, the results of the study show the importance of food availability for the interacting species.

A new explicit numerical scheme for enhancement of heat transfer in Sakiadis flow of micro polar fluid using electric field.

This article suggests a fourth-order numerical approach for solving ordinary differential equations (ODEs) that are both linear and nonlinear. The suggested scheme is an explicit predictor-corrector scheme. For linear ODE, the proposed numerical scheme's stability area is discovered. The proposed strategy yields the same stability region as the traditional fourth-order Runge-Kutta method. In addition, partial differential equations (PDEs) are used to develop the mathematical model for the flow of non-Newtonian micro-polar fluid over the sheet and heat and mass transit using electric field effects. These PDEs are further transformed into dimensionless boundary value problems. Boundary value problems are resolved using the proposed shooting-based scheme. The findings show that increasing values of ion kinetic work and Joule heating parameters cause the temperature profile to climb. The results produced by the suggested strategy are compared to those discovered through earlier studies. The results of this study could serve as a starting point for future fluid-flow investigations in a secure industrial environment.

Development of Explicit Schemes for Diffusive SEAIR COVID-19 Epidemic Spreading Model: An Application to Computational Biology.

In this contribution, a first-order time scheme is proposed for finding solutions to partial differential equations (PDEs). A mathematical model of the COVID-19 epidemic is modified where the recovery rate of exposed individuals is also considered. The linear stability of the equilibrium states for the modified COVID-19 model is given by finding its Jacobian and applying Routh-Hurwitz criteria on characteristic polynomial. The proposed scheme provides the first-order accuracy in time and second-order accuracy in space. The stability of the proposed scheme is given using the von Neumann stability criterion for standard parabolic PDEs. The consistency for the proposed scheme is also given by expanding the involved terms in it using the Taylor series. The scheme can be used to obtain the condition of getting a positive solution. The stability region of the scheme can be enlarged by choosing suitable values of the contained parameter. Finally, a comparison of the proposed scheme is made with the existing non-standard finite difference method. The results indicate that the non-standard classical technique is incapable of preserving the unique characteristics of the model's epidemiologically significant solutions, whereas the proposed approaches are capable of doing so. A computational code for the proposed discrete model scheme may be made available to readers upon request for convenience.

An explicit unconditionally stable scheme: application to diffusive Covid-19 epidemic model.

An explicit unconditionally stable scheme is proposed for solving time-dependent partial differential equations. The application of the proposed scheme is given to solve the COVID-19 epidemic model. This scheme is first-order accurate in time and second-order accurate in space and provides the conditions to get a positive solution for the considered type of epidemic model. Furthermore, the scheme's stability for the general type of parabolic equation with source term is proved by employing von Neumann stability analysis. Furthermore, the consistency of the scheme is verified for the category of susceptible individuals. In addition to this, the convergence of the proposed scheme is discussed for the considered mathematical model.

Design of nonstandard computational method for stochastic susceptible-infected-treated-recovered dynamics of coronavirus model.

The current effort is devoted to investigating and exploring the stochastic nonlinear mathematical pandemic model to describe the dynamics of the novel coronavirus. The model adopts the form of a nonlinear stochastic susceptible-infected-treated-recovered system, and we investigate the stochastic reproduction dynamics, both analytically and numerically. We applied different standard and nonstandard computational numerical methods for the solution of the stochastic system. The design of a nonstandard computation method for the stochastic system is innovative. Unfortunately, standard computation numerical methods are time-dependent and violate the structure properties of models, such as positivity, boundedness, and dynamical consistency of the stochastic system. To that end, convergence analysis of nonstandard computational methods and simulation with a comparison of standard computational methods are presented.

Nicotinamide activates latent HIV-1 ex vivo in ART suppressed individuals, revealing higher potency than the association of two methyltransferase inhibitors, chaetocin and BIX01294.

BACKGROUND: Latent HIV-1 is a major hurdle in obtaining HIV-1 sustained virological remission (SVR). Here we explored histone deacetylation inhibition property of nicotinamide (NAM; n=17) for the first time in comparison to a combination of methyltransferase inhibitors (MTIs; Chaetocin and BIX01294; n=25) to reactivate latent HIV ex vivo in CD8-depleted PBMCs from antiretroviral treated aviremic individuals. RESULTS: NAM reactivated HIV-1 from 13/17 (76.4%) samples compared to 20/25 (80.0%) using MTIs with mean viral load (VLs) of 4.32 and 3.22 log10 RNA copies/mL, respectively (p=0.004). Mean purging time after NAM and MTIs stimulation was 5.1 and 6.75 days, respectively (p=0.73). Viral purging in autologous cultures exhibited blunted HIV recovery with fluctuating VLs followed by a complete viral extinction when expanded in allogenic system. Electron microscopy from five supernatants revealed anomalous viral particles, with lack of complete viral genomes when characterized by ultradeep sequencing through metagenomics approach (n=4). CONCLUSION: NAM alone was more potent HIV-1 activator than combination of MTIs, with potential of clinical use.

Competitive analysis for stochastic influenza model with constant vaccination strategy.

This manuscript discusses a competitive analysis of stochastic influenza model with constant vaccination strategy. The stochastic influenza model is comparatively more pragmatic versus the deterministic influenza model. The effect of influenza generation number holds in the stochastic model. If the value of this number is less than one, this situation will help us to control the disease in a population. A greater than one value of this threshold number shows the persistence of disease to become endemic. The proposed structure for the stochastic influenza model as stochastic non-standard finite difference scheme conserve all vital characteristics like positivity, boundedness and dynamical consistency defined by Mickens.

Thalidomide is Associated With Increased T Cell Activation and Inflammation in Antiretroviral-naive HIV-infected Individuals in a Randomised Clinical Trial of Efficacy and Safety.

TRIAL DESIGN: Open-label, randomised, controlled, pilot proof-of-concept clinical trial. METHODS: Participants: Antiretroviral naïve adult males with CD4 count ≥350cells/mm3. INTERVENTIONS: Patients were randomised to receive thalidomide 200mg QD for 3weeks (Thalidomide group) or not (Control group) and followed for 48weeks. OBJECTIVE: We hypothesized that short-term Thalidomide use would reduce HIV related inflammation and HIV replication among antiretroviral naïve HIV infected individuals. OUTCOME: Viral loads, CD4/CD8 counts, ultra-sensitive C-reactive protein (US-CRP), cell activation markers, and plasma lipopolysaccharide (LPS) were analyzed. Randomisation: Unrestricted randomisation. Blinding: No blinding was used. RESULTS: Numbers randomised: Thirty recruited individuals were randomised to Thalidomide (16 patients) or Control (14 patients) groups. Recruitment: Patients were recruited from April 2011 to January 2013. OUTCOME: Viral loads remained stable in both groups. During thalidomide treatment, a decrease in CD4/CD8 ratio (p=0.04), a decrease in CD4 count (p=0.04), an increase in cell activation calculated by the percentage of CD38 +/HLA-DR+ CD8 cells (p<0.05) and an increase in US-CRP (p<0.01) were observed in the Thalidomide group, with all parameters returning to baseline levels after thalidomide interruption. We confirmed that thalidomide increased HIV replication in vitro of 6 of 7 samples from long-term antiretroviral suppressed individuals. HARMS: No class 3/4 adverse events occurred. CONCLUSIONS: Short-term use of thalidomide led to an intense transient increase in T cell activation and inflammation, with a decrease in the CD4+ cell count without changes to the CD8+ cell count. We confirmed that thalidomide acts in vitro as a latency reversal agent and speculate that the in vivo results obtained were due to an increase in HIV replication.

High prevalence and incidence of HIV-1 in a counseling and testing center in the city of Itajaí, Brazil.

Itajaí is a port city in southern Brazil with one of the highest incidence and mortality rates from AIDS in the country. The prevalence and incidence of HIV infection were investigated in 1085 of 3196 new HIV-1 infection cases evaluated in the counseling and testing center of Itajaí from January 2002 to August 2008. Recent infections were assessed using the BED™, and pol region sequencing was performed in 76 samples. The prevalence ranged from 3.08% to 6.17% among women and from 10.26% to 17.36% among men. A total of 17% of infections were classified as recent, with annual incidence varying from 1.6% to 4.8 per 100 patient/year among women and from 2.05% to 8.5 per 100 patient/year among men. Pol sequences were obtained from 38 randomly recent infections selected individuals: 71% were infected by subtype C, 24% B, 2% D, and 2% F1. Among 38 subjects with established infection, 76% were subtype C, and 24% B. Transmitted drug resistance was detected in 18.4% of recent infection subjects (7.8% to nucleoside analog reverse-transcriptase inhibitors, 5.2% to non-nucleoside reverse-transcriptase inhibitors, and 5.2% protease inhibitors) and 5.2% of subjects with established infection had nucleoside analog reverse-transcriptase inhibitors resistance. The high prevalence and incidence of HIV infection in this region is unprecedented in studies involving cases evaluated in the counseling and testing centers in Brazil.

Nicotinamide activates latent HIV-1 ex vivo in ART suppressed individuals, revealing higher potency than the association of two methyltransferase inhibitors, chaetocin and BIX01294

ABSTRACT Background: Latent HIV-1 is a major hurdle in obtaining HIV-1 sustained virological remission (SVR). Here we explored histone deacetylation inhibition property of nicotinamide (NAM; n = 17) for the first time in comparison to a combination of methyltransferase inhibitors (MTIs; Chaetocin and BIX01294; n = 25) to reactivate latent HIV ex vivo in CD8-depleted PBMCs from antiretroviral treated aviremic individuals. Results: NAM reactivated HIV-1 from 13/17 (76.4%) samples compared to 20/25 (80.0%) using MTIs with mean viral load (VLs) of 4.32 and 3.22 log10 RNA copies/mL, respectively (p = 0.004). Mean purging time after NAM and MTIs stimulation was 5.1 and 6.75 days, respectively (p = 0.73). Viral purging in autologous cultures exhibited blunted HIV recovery with fluctuating VLs followed by a complete viral extinction when expanded in allogenic system. Electron microscopy from five supernatants revealed anomalous viral particles, with lack of complete viral genomes when characterized by ultradeep sequencing through metagenomics approach (n = 4). Conclusion: NAM alone was more potent HIV-1 activator than combination of MTIs, with potential of clinical use.

Short communication: HIV type 1 tropism determination in a novel dried blood spot membrane and the use of a mixture of outer nested polymerase chain reaction primers.

Genotropism was determined in 608 Brazilian samples collected in dried blood spots using Polyethersulfone collection cards. Patients were infected by subtype B (88.8%), F (5.6%), C (3.3%), A (1.8%), and G (0.5%). All patients were exposed to three classes of antiretrovirals, and 59.8% of the samples harbored R5 viruses, 35% non-R5-tropic viruses, and 5.1% harbored mixtures of R5 and non-R5-tropic viruses, with non-R5 more prevalent among clade B-infected patients as compared to non-B (42.8% versus 19.1%; p<0.0003). A strategy using a mixture of outer nested polymerase chain reaction (PCR) primers reduced the number of negative PCR results from 39% to 19%.

Mutations in the gene phospholipase C, delta-1 (PLCD1) underlying hereditary leukonychia.

Hereditary leukonychia or porcelain nails is a nail dystrophy characterized by whitening of the nail plates in all nails of the hands and feet. It may exhibit an autosomal recessive or autosomal dominant pattern of inheritance. Mutations in the gene PLCD1 have been reported to underlie hereditary leukonychia. In the present study, two Pakistani families with autosomal recessive hereditary leukonychia were investigated. Affected members of the families exhibited characteristic features of hereditary leukonychia with involvement of nails on both the hands and feet. Genotyping using microsatellite markers linked the families to the gene PLCD1 on chromosome 3p22.2. Sequence analysis of the gene detected one novel (p.Ser740ArgfsX19) and one previously reported mutation (p.Arg437X). This study expands spectrum of the mutations in the gene PLCD1 causing hereditary leukonychia.

High prevalence and incidence of HIV-1 in a counseling and testing center in the city of Itajaí, Brazil

ABSTRACT Itajaí is a port city in southern Brazil with one of the highest incidence and mortality rates from AIDS in the country. The prevalence and incidence of HIV infection were investigated in 1085 of 3196 new HIV-1 infection cases evaluated in the counseling and testing center of Itajaí from January 2002 to August 2008. Recent infections were assessed using the BED(tm), and polregion sequencing was performed in 76 samples. The prevalence ranged from 3.08% to 6.17% among women and from 10.26% to 17.36% among men. A total of 17% of infections were classified as recent, with annual incidence varying from 1.6% to 4.8 per 100 patient/year among women and from 2.05% to 8.5 per 100 patient/year among men. Pol sequences were obtained from 38 randomly recent infections selected individuals: 71% were infected by subtype C, 24% B, 2% D, and 2% F1. Among 38 subjects with established infection, 76% were subtype C, and 24% B. Transmitted drug resistance was detected in 18.4% of recent infection subjects (7.8% to nucleoside analog reverse-transcriptase inhibitors, 5.2% to non-nucleoside reverse-transcriptase inhibitors, and 5.2% protease inhibitors) and 5.2% of subjects with established infection had nucleoside analog reverse-transcriptase inhibitors resistance. The high prevalence and incidence of HIV infection in this region is unprecedented in studies involving cases evaluated in the counseling and testing centers in Brazil.