Modeling the dynamics of COVID-19 in the presence of Delta and Omicron variants with vaccination and non-pharmaceutical interventions.

Since its inception in December 2019, many safe and effective vaccines have been invented and approved for use against COVID-19 along with various non-pharmaceutical interventions. But the emergence of numerous SARS-CoV-2 variants has put the effectiveness of these vaccines, and other intervention measures under threat. So it is important to understand the dynamics of COVID-19 in the presence of its variants of concern (VOC) in controlling the spread of the disease. To address these situations and to find a way out of this problem, a new mathematical model consisting of a system of non-linear differential equations considering the original COVID-19 strain with its two variants of concern (Delta and Omicron) has been proposed and formulated in this paper. We then analyzed the proposed model to study the transmission dynamics of this multi-strain model and to investigate the consequences of the emergence of multiple new SARS-CoV-2 variants which are more transmissible than the previous ones. The control reproduction number, an important threshold parameter, is then calculated using the next-generation matrix method. Further, we presented the discussion about the stability of the model equilibrium. It is shown that the disease-free equilibrium (DFE) of the model is locally asymptotic stable when the control reproduction is less than unity. It is also shown that the model has a unique endemic equilibrium (EEP) which is locally asymptotic stable when the control reproduction number is greater than unity. Using the Center Manifold theory it is shown that the model also exhibits the backward bifurcation phenomenon when the control reproduction number is less than unity. Again without considering the re-infection of the recovered individuals, it is proved that the disease-free equilibrium is globally asymptotically stable when the reproduction threshold is less than unity. Finally, numerical simulations are performed to verify the analytic results and to show the impact of multiple new SARS-CoV-2 variants in the population which are more contagious than the previous variants. Global uncertainty and sensitivity analysis has been done to identify which parameters have a greater impact on disease dynamics and control disease transmission. Numerical simulation suggests that the emergence of new variants of concern increases COVID-19 infection and related deaths. It also reveals that a combination of non-pharmaceutical interventions with vaccination programs of new more effective vaccines should be continued to control the disease outbreak. This study also suggests that more doses of vaccine should provide to combat new and deadly variants like Delta and Omicron.

A proteomic study to unveil lead toxicity-induced memory impairments invoked by synaptic dysregulation.

Lead (Pb2+), a ubiquitously present heavy metal toxin, has various detrimental effects on memory and cognition. However, the molecular processes affected by Pb2+ causing structural and functional anomalies are still unclear. To explore this, we employed behavioral and proteomic approaches using rat pups exposed to lead acetate through maternal lactation from postnatal day 0 (P0) until weaning. Behavioral results from three-month-old rats clearly emphasized the early life Pb2+ exposure induced impairments in spatial cognition. Further, proteomic analysis of synaptosomal fractions revealed differential alteration of 289 proteins, which shows functional significance in elucidating Pb2+ induced physiological changes. Focusing on the association of Small Ubiquitin-like MOdifier (SUMO), a post-translational modification, with Pb2+ induced cognitive abnormalities, we identified 45 key SUMO target proteins. The significant downregulation of SUMO target proteins such as metabotropic glutamate receptor 3 (GRM3), glutamate receptor isoforms 2 and 3 (GRIA 2 and GRIA3) and flotilin-1 (FLOT1) indicates SUMOylation at the synapses could contribute to and drive Pb2+ induced physiological imbalance. These findings identify SUMOylation as a vital protein modifier with potential roles in hippocampal memory consolidation and regulation of cognition. Data availbility: The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD034212".

Effect of awareness, quarantine and vaccination as control strategies on COVID-19 with Co-morbidity and Re-infection.

In this paper, a deterministic compartmental model is presented to assess the impact of vaccination and non-pharmaceutical interventions (social distance, awareness, face mask, and quarantine) on the transmission dynamics of COVID-19 with co-morbidity and re-infection. An expression for the basic reproduction number is then derived for this model. Theoretical analysis shows that the model exhibits backward bifurcation phenomenon when the basic reproduction number is less than unity. But for the case of no re-infection, the model has a globally asymptotically stable disease-free equilibrium (DFE) when the basic reproduction number is less than unity. Furthermore, it is shown that in the case of no re-infection, a unique endemic equilibrium point (EEP) of the model exists which is globally asymptotically stable whenever the reproduction number is greater than unity. From the global sensitivity and uncertainty analysis, we have identified mask coverage, mask efficacy, vaccine coverage, vaccine efficacy, and contact rate as the most influential parameters influencing the spread of COVID-19. Numerical simulation results show that the use of effective vaccines with proper implementation of non-pharmaceutical interventions could lead to the elimination of COVID-19 from the community. Numerical simulations also suggest that the control strategy that ensures a continuous and effective mass vaccination program is the most cost-effective control strategy. The study also shows that in the presence of any co-morbidity and with the occurrence of re-infection, the disease burden may increase.

Comparison of Different Doses of Dexmedetomidine as Adjuvant for Infraumbilical Surgery in Patients Receiving Bupivacaine Spinal Anesthesia: A Randomized Controlled Trial.

BACKGROUND: Infraumbilical surgery today is done preferentially under subarachnoid block. The relatively short duration of analgesia is a limiting factor which is overcome by adding an adjuvant to intrathecal bupivacaine. We aimed to determine optimum dose of intrathecal dexmedetomidine as adjuvant to 0.5% hyperbaric bupivacaine in infraumbilical surgery. METHODS: A parallel group, double blind, randomized controlled trial was done with 105 adult patients posted for infraumbilical surgery under subarachnoid block. All subjects received 3.0 mL (15.0 mg) of 0.5% hyperbaric bupivacaine. Groups D5.0, D7.5, and D10.0 (n = 35 each) received additionally 5.0, 7.5, and 10.0 mcg intrathecal dexmedetomidine as adjuvant. The onset time of sensory block, its peak level and time to this level, maximum motor block and time to it, total duration of analgesia (time to first rescue), and vital parameters were recorded at intervals. Postoperative analgesia was assessed by visual analog scale score at 15 and 30 minutes, then every 30 minutes until 2 hours and then every hour until 6 hours. Treatment emergent adverse events (bradycardia, hypotension, and sedation) were documented. RESULTS: Maximum sensory level achieved was higher in Group D10.0 than in the other two groups. There was significant and dose-dependent shortening of the mean time to peak sensory block (3.9, 3.3, and 2.9 min; P ＜ 0.001) and peak motor block (5.6, 5.3, and 4.8 min; P ＜ 0.001), and prolongation of postoperative analgesia duration (206.9, 220.8, and 244.0 min; P ＜ 0.001) with escalating doses (5.0, 7.5, and 10.0 mcg, respectively) of dexmedetomidine. Hemodynamic effects and adverse events were comparable in the three groups. CONCLUSIONS: Intrathecal dexmedetomidine (10.0 mcg), as adjuvant to 0.5% hyperbaric bupivacaine (15.0 mg), facilitates rapid onset sensory and motor block and prolongs duration of postoperative analgesia in spinal anesthesia without significant adverse effects. Although absolute differences are modest, the results are better compared to 5.0 and 7.5 mcg doses.

Dynamics of novel COVID-19 in the presence of Co-morbidity.

A novel coronavirus (COVID-19) has emerged as a global serious public health issue from December 2019. People having a weak immune system are more susceptible to coronavirus infection. It is a double challenge for people of any age with certain underlying medical conditions including cardiovascular disease, diabetes, high blood pressure and cancer etc. Co-morbidity increases the probability of COVID-19 complication. In this paper a deterministic compartmental model is formulated to understand the transmission dynamics of COVID-19. Rigorous mathematical analysis of the model shows that it exhibits backward bifurcation phenomenon when the basic reproduction number is less than unity. For the case of no re-infection it is shown that having the reproduction number less than one is necessary and sufficient for the effective control of COVID-19, that is, the disease free equilibrium is globally asymptotically stable when the reproduction threshold is less than unity. Furthermore, in the absence of reinfection, a unique endemic equilibrium of the model exists which is globally asymptotically stable whenever the reproduction number is greater than unity. Numerical simulations of the model, using data relevant to COVID-19 transmission dynamics, show that the use of efficacious face masks publicly could lead to the elimination of COVID-19 up to a satisfactory level. The study also shows that in the presence of co-morbidity, the disease increases significantly.

Global survey-based assessment of lifestyle changes during the COVID-19 pandemic.

Along with the major impact on public health, the COVID-19 outbreak has caused unprecedented concerns ranging from sudden loss of employment to mental stress and anxiety. We implemented a survey-based data collection platform to characterize how the COVID-19 pandemic has affected the socio-economic, physical and mental health conditions of individuals. We focused on three broad areas, namely, changes in social interaction during home confinement, economic impact and their health status. We identified a substantial increase in virtual interaction among individuals, which might be a way to alleviate the sudden unprecedented mental health burden, exacerbated by general awareness about viral infections or other manifestations associated with them. The majority of participants (85%) lived with one or more companions and unemployment issues did not affect 91% of the total survey takers, which was one of the crucial consequences of the pandemic. Nevertheless, measures such as an increased frequency of technology-aided distant social interaction, focus on physical fitness and leisure activities were adopted as coping mechanisms during this period of home isolation. Collectively, these metrics provide a succinct and informative summary of the socio-economic and health impact of the COVID-19 pandemic on the individuals. Findings from our study reflect that continuous surveillance of the psychological consequences for outbreaks should become routine as part of preparedness efforts worldwide. Given the limitations of analyzing the large number of variables, we have made the raw data publicly available on the OMF ME/CFS Data Center server to facilitate further analyses (https://igenomed.stanford.edu/dataset/survey-study-on-lifestyle-changes-during-covid-19-pandemic).

Core-shell magnetoelectric nanorobot - A remotely controlled probe for targeted cell manipulation.

We have developed a remotely controlled dynamic process of manipulating targeted biological live cells using fabricated core-shell nanocomposites, which comprises of single crystalline ferromagnetic cores (CoFe2O4) coated with crystalline ferroelectric thin film shells (BaTiO3). We demonstrate them as a unique family of inorganic magnetoelectric nanorobots (MENRs), controlled remotely by applied a.c. or d.c. magnetic fields, to perform cell targeting, permeation, and transport. Under a.c. magnetic field excitation (50 Oe, 60 Hz), the MENR acts as a localized electric periodic pulse generator and can permeate a series of misaligned cells, while aligning them to an equipotential mono-array by inducing inter-cellular signaling. Under a.c. magnetic field (40 Oe, 30 Hz) excitation, MENRs can be dynamically driven to a targeted cell, avoiding untargeted cells in the path, irrespective of cell density. D.C. magnetic field (-50 Oe) excitation causes the MENRs to act as thrust generator and exerts motion in a group of cells.