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1.
J Orthop Case Rep ; 14(7): 93-97, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39035394

ABSTRACT

Introduction: Securing stable internal fixation for fractures in osteoporotic intra-articular distal femur proves to be a demanding task due to thin cortices, a wide medullary canal, diminished bone stock, and fracture comminution. No singular therapeutic approach has successfully tackled all facets of this injury. Consequently, we now introduce a pioneering fixation method in our report, aiming to offer a holistic solution to the intricate challenges associated with this scenario. Case Report: A 60-year-old female presented with an intra-articular distal femur fracture, and underwent a combination fixation of distal femur plate and intramedullary interlocking nailing. The patient was rehabilitated with active knee range of motion on post-operative day 7 and has now attained full knee range of motion. Conclusion: The utilization of anatomical plates with locking mechanisms, in tandem with intramedullary interlocking nailing, holds promise for the secure stabilization and fixation of osteoporotic distal femur fractures, potentially leading to an expedited recovery process.

2.
J Public Health Manag Pract ; 30: S162-S166, 2024.
Article in English | MEDLINE | ID: mdl-39041752

ABSTRACT

In New York City (NYC), hypertension and high cholesterol disproportionately affect residents with low household income and people of color. The NYC Health Department employed practice facilitation (PF) to help nonphysician staff assume added roles aligned with team-based care. The objective was to improve blood pressure (BP) and cholesterol management in 132 small primary care practices serving mostly patients of color. We categorized practices into higher or lower levels of integrated PF, defined as physicians and nonphysician staff collectively participating in PF. Higher integrated PF was associated with improvements in BP (rate ratio [RR] = 1.09, P-value < .05) and cholesterol management (RR = 1.12, P-value < .01). Nonphysician staff in higher integrated PF practices reported skills enhancement and improved teamwork. Involving nonphysician staff in PF-mediated quality improvement efforts can be an effective strategy to improve health outcomes in small clinical practices serving communities with a higher burden of chronic disease and disproportionately impacted by poverty and structural racism.


Subject(s)
Quality Improvement , Humans , New York City , Primary Health Care/standards , Hypertension/therapy , Male
3.
J Orthop Case Rep ; 14(3): 78-82, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38560300

ABSTRACT

Introduction: The femoral neck system (FNS) represents an emerging fixation system designed for the management of femoral neck fractures. This innovative system combines the mechanical benefits of compression and anti-rotation properties in internal fixation. Biomechanical studies have demonstrated the superior axial and rotational stability of the FNS implant when compared to traditional cannulated screws and dynamic hip screw. Despite these promising mechanical advantages, there is currently a limited body of literature addressing the factors contributing to FNS failure. A thorough assessment of the safety and outcomes associated with this novel implant is essential. Case Report: In this context, we present three cases wherein FNS failure occurred, aiming to elucidate the potential causes behind these failures, and had to undergo either an implant removal or bipolar hemiarthroplasty. Conclusion: While considering the femoral neck system as the implant of choice, we should consider the age, injury to surgery time, and the location of the fracture line. However, we cannot conclusively ascertain whether age contributes independently to the risk of failure.

4.
ACS Appl Mater Interfaces ; 15(48): 55885-55894, 2023 Dec 06.
Article in English | MEDLINE | ID: mdl-37991323

ABSTRACT

Atomically dispersed cerium catalysts on an inert, crystalline MgO powder support were prepared by using both Ce(III) and Ce(IV) precursors. The materials were used as catalysts for CO oxidation in a once-through flow reactor and characterized by atomic-resolution scanning transmission electron microscopy, X-ray absorption near-edge structure spectroscopy, X-ray photoelectron spectroscopy, and temperature-programmed reduction, among other techniques, before and after catalysis. The most active catalysts, formed from the precursor incorporating Ce(III), displayed performance similar to that reported for bulk ceria under comparable conditions. The catalyst provided stable time-on-stream performance for as long as it was kept on-stream, 2 days, increasing slightly in activity as the atomically dispersed cerium ions were transformed into ceria nanodomains represented as CeOx and having increased reducibility on the MgO support. The results suggest how highly dispersed supported ceria catalysts with low cerium loadings can be prepared and may pave the way for improved efficiencies of cerium utilization in oxidation catalysis.

5.
JACS Au ; 3(3): 785-800, 2023 Mar 27.
Article in English | MEDLINE | ID: mdl-37006774

ABSTRACT

The removal of tar and CO2 in syngas from biomass gasification is crucial for the upgrading and utilization of syngas. CO2 reforming of tar (CRT) is a potential solution which simultaneously converts the undesirable tar and CO2 to syngas. In this study, a hybrid dielectric barrier discharge (DBD) plasma-catalytic system was developed for the CO2 reforming of toluene, a model tar compound, at a low temperature (∼200 °C) and ambient pressure. Periclase-phase (Mg, Al)O x nanosheet-supported NiFe alloy catalysts with various Ni/Fe ratios were synthesized from ultrathin Ni-Fe-Mg-Al hydrotalcite precursors and employed in the plasma-catalytic CRT reaction. The result demonstrated that the plasma-catalytic system is promising in promoting the low-temperature CRT reaction by generating synergy between DBD plasma and the catalyst. Among the various catalysts, Ni4Fe1-R exhibited superior activity and stability because of its highest specific surface area, which not only provided sufficient active sites for the adsorption of reactants and intermediates but also enhanced the electric field in the plasma. Furthermore, the stronger lattice distortion of Ni4Fe1-R provided more isolated O2- for CO2 adsorption, and having the most intensive interaction between Ni and Fe in Ni4Fe1-R restrained the catalyst deactivation induced by the segregation of Fe from the alloy to form FeO x . Finally, in situ Fourier transform infrared spectroscopy combined with comprehensive catalyst characterization was used to elucidate the reaction mechanism of the plasma-catalytic CRT reaction and gain new insights into the plasma-catalyst interfacial effect.

6.
Small ; 19(26): e2207272, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36942900

ABSTRACT

Atomically dispersed metal catalysts offer the advantages of efficient metal utilization and high selectivities for reactions of technological importance. Such catalysts have been suggested to be strong candidates for dry reforming of methane (DRM), offering prospects of high selectivity for synthesis gas without coke formation, which requires ensembles of metal sites and is a challenge to overcome in DRM catalysis. However, investigations of the structures of isolated metal sites on metal oxide supports under DRM conditions are lacking, and the catalytically active sites remain undetermined. Data characterizing the DRM reaction-driven structural evolution of a cerium oxide-supported catalyst, initially incorporating atomically dispersed platinum, and the corresponding changes in catalyst performance are reported. X-ray absorption and infrared spectra show that the reduction and agglomeration of isolated cationic platinum atoms to form small platinum clusters/nanoparticles are necessary for DRM activity. Density functional theory calculations of the energy barriers for methane dissociation on atomically dispersed platinum and on platinum clusters support these observations. The results emphasize the need for in-operando experiments to assess the active sites in such catalysts. The inferences about the catalytically active species are suggested to pertain to a broad class of catalytic conversions involving the rate-limiting dissociation of light alkanes.

7.
J Med Chem ; 66(5): 3411-3430, 2023 03 09.
Article in English | MEDLINE | ID: mdl-36823782

ABSTRACT

The unique bisubunit structure of Leishmania donovani topoisomerase 1B (LdTop1) is a potential drug target in the parasites unlike the monomeric Top1 from its human host counterpart. Here, we report the design, synthesis, and validation of a chimeric pyrido[2',1':2,3]imidazo[4,5-c]quinoline derivative (C17) as a novel antileishmanial agent that poisons topoisomerase 1-DNA covalent complexes (LdTop1cc) inside the parasites and inhibits Top1 religation activity both in the drug sensitive and antimony-resistant L. donovani clinical isolates. Importantly, the human Top1 is not sensitive to C17. Further, C17 overcomes the chemical instability of camptothecin (CPT) by generating persistent LdTop1cc-induced DNA breaks inside the parasites even after 12 h of drug removal. Intraperitoneal administration of C17 results in marked reduction of the Leishmania amastigotes from the infected spleen and liver of BALB/c mice. C17 confers a host protective immune-response up-regulating the Th1 cytokines facilitating parasite clearance which can be exploited for treating drug-resistant leishmaniasis.


Subject(s)
Antiprotozoal Agents , Leishmania donovani , Leishmaniasis, Visceral , Leishmaniasis , Poisons , Quinolines , Animals , Mice , Humans , Leishmaniasis, Visceral/drug therapy , Leishmaniasis, Visceral/parasitology , Antimony/pharmacology , Antimony/therapeutic use , Poisons/therapeutic use , Antiprotozoal Agents/pharmacology , Antiprotozoal Agents/therapeutic use , Leishmaniasis/drug therapy , DNA/chemistry , Quinolines/pharmacology , Quinolines/therapeutic use , Mice, Inbred BALB C
8.
Front Cell Infect Microbiol ; 13: 1001973, 2023.
Article in English | MEDLINE | ID: mdl-36814446

ABSTRACT

Leishmania is an intracellular, zoonotic, kinetoplastid eukaryote with more than 1.2 million cases all over the world. The leishmanial chromosomes are divided into polymorphic chromosomal ends, conserved central domains, and antigen-encoding genes found in telomere-proximal regions. The genome flexibility of chromosomal ends of the leishmanial parasite is known to cause drug resistance and intracellular survival through the evasion of host defense mechanisms. Therefore, in this review, we discuss the plasticity of Leishmania genome organization which is the primary cause of drug resistance and parasite survival. Moreover, we have not only elucidated the causes of such genome plasticity which includes aneuploidy, epigenetic factors, copy number variation (CNV), and post-translation modification (PTM) but also highlighted their impact on drug resistance and parasite survival.


Subject(s)
Leishmania donovani , Parasites , Animals , Leishmania donovani/genetics , DNA Copy Number Variations , Drug Resistance , Perception
9.
STAR Protoc ; 4(1): 102004, 2023 03 17.
Article in English | MEDLINE | ID: mdl-36638018

ABSTRACT

Isolation of extraordinarily long-length super-enhancers (SEs) using typical chromatin immune precipitation (ChIP) techniques can lead to DNA breakage due to uncontrolled cross-linking. We present a redefined ChIP technique for SE purification. After controlled paraformaldehyde-based cross-linking, glycine was used to quench the cross-linker followed by mild sonication. The sonication produced ideal fragment length of long-length SE chromatin. Presently, miR146a-5p SE of macrophages was pulled using BRD4 protein. Our protocol can reproducibly simplify the SE element isolation issues, in a quality-controlled manner. For complete details on the use and execution of this protocol, please refer to Das et al. (2021).1.


Subject(s)
Nuclear Proteins , Transcription Factors , Nuclear Proteins/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Chromatin/genetics , Macrophages/metabolism , Enhancer Elements, Genetic , Immunoprecipitation
10.
J Am Chem Soc ; 145(5): 2911-2929, 2023 Feb 08.
Article in English | MEDLINE | ID: mdl-36715296

ABSTRACT

Catalysts for hydroformylation of ethene were prepared by grafting Rh into nests of ≡SiOZn-OH or ≡SiOCo-OH species prepared in dealuminated BEA zeolite. X-ray absorption spectra and infrared spectra of adsorbed CO were used to characterize the dispersion of Rh. The Rh dispersion was found to increase markedly with increasing M/Rh (M = Zn or Co) ratio; further increases in Rh dispersion occurred upon use for ethene hydroformylation catalysis. The turnover frequency for ethene hydroformylation measured for a fixed set of reaction conditions increased with the fraction of atomically dispersed Rh. The ethene hydroformylation activity is 15.5-fold higher for M = Co than for M = Zn, whereas the propanal selectivity is slightly greater for the latter catalyst. The activity of the Co-containing catalyst exceeds that of all previously reported Rh-containing bimetallic catalysts. The rates of ethene hydroformylation and ethene hydrogenation exhibit positive reaction orders in ethene and hydrogen but negative orders in carbon monoxide. In situ IR spectroscopy and the kinetics of the catalytic reactions suggest that ethene hydroformylation is mainly catalyzed by atomically dispersed Rh that is influenced by Rh-M interactions, whereas ethene hydrogenation is mainly catalyzed by Rh nanoclusters. In situ IR spectroscopy also indicates that the ethene hydroformylation is rate limited by formation of propionyl groups and by their hydrogenation, a conclusion supported by the measured H/D kinetic isotope effect. This study presents a novel method for creating highly active Rh-containing bimetallic sites for ethene hydroformylation and provides new insights into the mechanism and kinetics of this process.

11.
Front Cell Infect Microbiol ; 12: 914477, 2022.
Article in English | MEDLINE | ID: mdl-35846748

ABSTRACT

Canine visceral leishmaniasis (CVL) due to Leishmania infantum infection is a zoonotic disease prevalent in the areas of South America and the Mediterranean. Infected dogs as reservoirs can contribute to disease transmission and can be a scourge to public health. Therefore, early diagnosis of infected dogs may play a pivotal role in circumscribing disease progression. Invasive tissue aspiration and insufficient serological methods impair a single assay for prompt CVL diagnosis. In the present study, we aimed to evaluate the potential of Leishmania donovani isolated membrane protein, LAg, for the diagnosis of CVL through immunological assays. Initially, enzyme-linked immunosorbent assay was done with Brazilian dog sera to evaluate the performance of LAg in diagnosing CVL and found sensitivity and specificity of 92.50% and 95%, respectively. The study further confirmed the diagnostic efficacy of LAg in a dipstick format. The dipstick test of canine sera from three centers in Brazil and one center in Italy collectively showed sensitivity values in the range of 53.33% to 100% in recognizing symptomatic dogs and specificity values between 75% and 100% to rule out healthy dogs. Moreover, a rapid immunochromatographic test was developed and optimized using LAg. This test was able to identify 94.73% of CVL of Brazilian origin with specificity of 97.29%. The current results highlight the reactive potential of the L. donovani antigen, LAg, for L. infantum CVL diagnosis and support our previous findings, which suggest the utility of LAg for the diagnosis of both L. donovani and L. infantum human VL in a variety of endemic regions. LAg as a diagnostic candidate may be employed to identify comprehensive CVL cases in epidemiological areas.


Subject(s)
Dog Diseases , Leishmania donovani , Leishmania infantum , Leishmaniasis, Visceral , Animals , Antibodies, Protozoan , Antigens, Protozoan , Brazil/epidemiology , Dog Diseases/diagnosis , Dog Diseases/epidemiology , Dogs , Enzyme-Linked Immunosorbent Assay/methods , Enzyme-Linked Immunosorbent Assay/veterinary , Humans , Leishmaniasis, Visceral/diagnosis , Leishmaniasis, Visceral/veterinary , Sensitivity and Specificity
12.
Virulence ; 13(1): 903-935, 2022 12.
Article in English | MEDLINE | ID: mdl-35531875

ABSTRACT

Leishmaniasis is a group of disease caused by the intracellular protozoan parasite of the genus Leishmania. Infection by different species of Leishmania results in various host immune responses, which usually lead to parasite clearance and may also contribute to pathogenesis and, hence, increasing the complexity of the disease. Interestingly, the parasite tends to reside within the unfriendly environment of the macrophages and has evolved various survival strategies to evade or modulate host immune defense. This can be attributed to the array of virulence factors of the vicious parasite, which target important host functioning and machineries. This review encompasses a holistic overview of leishmanial virulence factors, their role in assisting parasite-mediated evasion of host defense weaponries, and modulating epigenetic landscapes of host immune regulatory genes. Furthermore, the review also discusses the diagnostic potential of various leishmanial virulence factors and the advent of immunomodulators as futuristic antileishmanial drug therapy.


Subject(s)
Leishmania , Leishmaniasis , Host-Parasite Interactions , Humans , Leishmania/genetics , Leishmaniasis/drug therapy , Leishmaniasis/parasitology , Virulence , Virulence Factors/genetics
13.
Pathogens ; 11(2)2022 Jan 20.
Article in English | MEDLINE | ID: mdl-35215064

ABSTRACT

Visceral leishmaniasis (VL) is one of the major global health concerns due to its association with morbidity and mortality. All available diagnostic tools have been, until now, unable to provide a very specific and cost-effective mode of detection for VL globally. Therefore, the design of robust, specific, and commercially translatable diagnostic tests is urgently required. Currently, we are attempting to identify and explore the diagnostic potential of a novel parasite antigen. Repressor of differentiation kinase 2 (RDK2), a serine/threonine kinase, has a versatile role in parasite life cycle progression. However, its role as a diagnostic candidate for VL has not been investigated. Herein, we cloned and over-expressed LdRDK2 and studied the recombinant RDK2 for the diagnosis of human VL using serum and urine samples. In silico analysis predicted that RDK2 is conserved among Leishmania species with the least conservation in humans. RDK2 developed immune-reactive bands with antibodies present in VL patients' sera, and it demonstrated no cross-reactivity with sera from healthy controls and other diseases. Additionally, RDK2 antigen demonstrated a significant reactivity with IgG antibodies of VL patients' sera, with 78% sensitivity and 86.67% specificity as compared to healthy controls and other diseases. Furthermore, we evaluated its utility for non-invasive diagnosis of VL using patients' urine samples and found 93.8% sensitivity and 85.7% specificity. RDK2 was found to have better sensitivity and treatment response in patients' urine compared to serum samples, indicating its role as a promising point of care (POC) antigen. In a nutshell, we explored the role of RDK2 as a potential diagnostic marker for VL in both invasive and non-invasive modes as well as its utility as a promising POC antigen for treatment response cases.

14.
ACS Appl Mater Interfaces ; 14(4): 5363-5375, 2022 Feb 02.
Article in English | MEDLINE | ID: mdl-35072474

ABSTRACT

Plasma-catalytic direct nonoxidative coupling of methane (NCM) into C2 hydrocarbons was investigated over ceria-supported atomically dispersed Pt (Pt/CeO2-SAC) and nanoparticle Pt (Pt/CeO2-NP) catalysts in dielectric barrier discharge (DBD) plasma. Nonthermal plasma facilitated C-H bond dissociation in CH4 at low temperatures (<150 °C) and atmospheric pressure. The presence of Pt/CeO2 catalysts in plasma further enhanced CH4 conversion and C2 hydrocarbon selectivity by enabling the conversion of vibrationally excited methane species with high internal energy on active Pt sites. Noticeably, the Pt/CeO2-SAC catalyst displayed a more remarkable performance, with a CH4 conversion of 39% and a C2 selectivity of 54% at 54 W. The enhanced CH4 conversion was attributed to abundant coordinatively unsaturated Pt sites in Pt/CeO2-SAC, which were more active for C-H bond scission. Meanwhile, isolated Pt atoms in Pt/CeO2-SAC promoted C2 hydrocarbon formation by hindering the unselective formation of coke from deep dehydrogenation of CHx• intermediates and higher hydrocarbons from oligomerization reactions.

15.
Contemp Econ Policy ; 2022 Nov 12.
Article in English | MEDLINE | ID: mdl-36718418

ABSTRACT

This paper examines the potential persistent effects (scarring) of the COVID-19 pandemic on the economy and the channels through which they may occur. Our findings from a broad set of historical recessions confirm that recessions are associated with persistent output losses and that the greatest scarring has occurred following financial crises. The amount of scarring following pandemic and epidemic recessions in the sample is in between that of typical recessions and financial crises. Results on the channels show that the productivity channel is important, as all types of recessions have been followed by persistent losses to total factor productivity.

16.
Clin Epidemiol Glob Health ; 12: 100835, 2021.
Article in English | MEDLINE | ID: mdl-34368502

ABSTRACT

The science about the usage of face masks by the common public to avert COVID-19 transmission is proceeding swiftly. A primary route of transmission of COVID-19 is probably through small respiratory droplets, and it is transmissible from asymptomatic and pre-symptomatic individuals. According to the World Health Organization, wearing a mask in public can help reduce the transmission of the COVID-19 virus. Different categories and types of masks and their usage are reviewed in this work. In a nutshell, this review work elucidates the aspects of utilizing the various face masks along with all possibilities to fight against the ongoing pandemic of COVID-19.

17.
FASEB J ; 35(9): e21755, 2021 09.
Article in English | MEDLINE | ID: mdl-34383962

ABSTRACT

Visceral leishmaniasis (VL) is a debilitating human pathogenesis in which the body's immune functions are severely compromised. Various subsets of T cells, including Th17 cells are important regulators of immune responses observed in various pathologies. The role of Th17 cells and its correlation with immuno-regulatory cytokines are however not well understood in human VL. Herein we studied how IL-17 is associated with the progression of Leishmania donovani infection using murine model of VL. We found induction of a strong IL-17 response at the early phase of infection which progressively reduced to basal level during chronic VL. The mechanistic study of this behavior was found to be linked with the role of regulatory T cells (CD4+ CD25+ T cells) that suppresses the proliferation of the Th17 cell population. Moreover, TGF-ß and IL-35 derived from CD4+ CD25+ T cells are the key mediators for the downregulation of IL-17 during chronic VL. Thus, this study points to an antagonistic effect of Tregs and Th17 cells that can be used for designing better therapeutic and preventive strategies against leishmaniasis.


Subject(s)
Interleukins/immunology , Leishmaniasis, Visceral/immunology , Th17 Cells/immunology , Transforming Growth Factor beta/immunology , Animals , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/parasitology , Cells, Cultured , Interleukin-2 Receptor alpha Subunit/immunology , Leishmania donovani/parasitology , Leishmaniasis, Visceral/parasitology , Mice , Mice, Inbred BALB C , Th17 Cells/parasitology
18.
PLoS Pathog ; 17(2): e1009343, 2021 02.
Article in English | MEDLINE | ID: mdl-33630975

ABSTRACT

The outcome of Leishmania donovani infection depends upon the dynamic interchanges between M1 and M2 macrophages. Information of the involvement of microRNAs (miRNAs) and epigenetic modifiers in regulating macrophage plasticity during L. donovani infection is still elusive. Differential expression analysis of polarization-regulating miRNAs, revealed significant enrichment of miR146a-5p during Leishmania donovani infection. A sustained enrichment of miR146a-5p was observed in both infected bone marrow derived macrophages (BMDMs) and BALB/c mice organs. We found involvement of miR146a-5p in phagocytosis and survivability of parasites. Moreover, miR146a-5pgot enriched in interleukin 4- stimulated BMDMs, indicating its possible involvement in M2 polarization. Upon transfecting BMDMs with miRVANA anti-146a oligos, M2 markers (CCR7, YM-1, FIZZ-1, arginase-1, IL10 and IL4) and transcription factors (p-STAT6 and c/EBPß) got depleted with concomitant augmentation of M1-polarizing transcription factors (p-STAT1, AP1 and IRF-1), miR146a target genes (TRAF6 and IRAK1), M1 cytokines (IL12 and TNFα), iNOS, nitric oxide, and nuclear translocation of phospho p-65 subunit. Neutralization of intracellular mature miR146a-5p pool in infected BALB/c mice lower organ parasite burden and expressions of M2 markers and IL10 with enrichment of M1 markers like iNOS and IL12. Additionally, we explored the novel role of super enhancer (SE), a cis-acting regulatory component, to enrich miR146a-5p expression during infection. Enhanced expression and nuclear retention of SE components like BET bromodomain 4 (BRD4) and p300 were found in infected BMDMs. Upon silencing BRD4, expressions of miR146a-5p and M2 markers were down regulated and TRAF6, IRAK1 and iNOS levels increased. STRING V.11 based predication and immune precipitation confirmed the strong interaction amongst BRD4, p300 and RNA pol II (RpbI). Chromatin immune precipitation studies suggested the recruitment of BRD4 at the enhancer loci of miR146a-5p gene during infection. Altogether, our findings revealed a novel role of BRD4/p300-depdendent super-enhancer in regulating miR146a expression during L. donovani infection which in turn mediates M2 polarization and immune-suppression.


Subject(s)
Enhancer Elements, Genetic , Leishmania donovani/physiology , Leishmaniasis/immunology , Macrophages/immunology , MicroRNAs/genetics , Phagocytosis , Animals , Interleukin-1 Receptor-Associated Kinases/genetics , Interleukin-1 Receptor-Associated Kinases/metabolism , Leishmaniasis/genetics , Leishmaniasis/metabolism , Leishmaniasis/parasitology , Macrophages/metabolism , Mice , Mice, Inbred BALB C , Nitric Oxide Synthase Type II/genetics , Nitric Oxide Synthase Type II/metabolism , STAT6 Transcription Factor/genetics , STAT6 Transcription Factor/metabolism
19.
medRxiv ; 2021 Mar 05.
Article in English | MEDLINE | ID: mdl-33330881

ABSTRACT

Understanding the impact of non-pharmaceutical interventions as well as accounting for the unascertained cases remain critical challenges for epidemiological models for understanding the transmission dynamics of COVID-19 spread. In this paper, we propose a new epidemiological model (eSEIRD) that extends the widely used epidemiological models such as extended Susceptible-Infected-Removed model (eSIR) and SAPHIRE (initially developed and used for analyzing data from Wuhan). We fit these models to the daily ascertained infected (and removed) cases from March 15, 2020 to Dec 31, 2020 in South Africa that reported the largest number of confirmed COVID-19 cases and deaths from the WHO African region. Using the eSEIRD model, the COVID-19 transmission dynamics in South Africa was characterized by the estimated basic reproduction number (R 0) starting at 3.22 (95%CrI: [3.19, 3.23]) then dropping below 2 following a mandatory lockdown implementation and subsequently increasing to 3.27 (95%CrI: [3.27, 3.27]) by the end of 2020. The initial decrease of effective reproduction number followed by an increase suggest the effectiveness of early interventions and the combined effect of relaxing strict interventions and emergence of a new coronavirus variant in South Africa. The low estimated ascertainment rate was found to vary from 1.65% to 9.17% across models and time periods. The overall infection fatality ratio (IFR) was estimated as 0.06% (95%CrI: [0.04%, 0.22%]) accounting for unascertained cases and deaths while the reported case fatality ratio was 2.88% (95% CrI: [2.45%, 6.01%]). The models predict that from December 31, 2020, to April 1, 2021, the predicted cumulative number of infected would reach roughly 70% of total population in South Africa. Besides providing insights on the COVID-19 dynamics in South Africa, we develop powerful forecasting tools that enable estimation of ascertainment rates and IFR while quantifying the effect of intervention measures on COVID-19 spread.

20.
Parasit Vectors ; 13(1): 272, 2020 May 30.
Article in English | MEDLINE | ID: mdl-32473634

ABSTRACT

BACKGROUND: Visceral leishmaniasis (VL), is a parasitic disease that causes serious medical consequences if treatment is delayed. Despite a decline in the number of VL cases in the Indian subcontinent, the commencement of the disease in newer areas continues to be a major concern. Although serological diagnosis mainly by immunochromatographic tests has been found to be effective, a test of cure in different phases of treatment is still desired. Even though a good prophylactic response has been obtained in murine models by a number of vaccine candidates, few have been proposed for human use. METHODS: In this study, nine antigenic components (31, 34, 36, 45, 51, 63, 72, 91 and 97 kDa) of Leishmania promastigote membrane antigens (LAg), were electroeluted and evaluated through ELISA to diagnose and distinguish active VL from one month cured and six months post-treatment patients. Further, to investigate the immunogenicity of electroeluted proteins, human PBMCs of cured VL patients were stimulated with 31, 34, 51, 63, 72 and 91 kDa proteins. RESULTS: We found that 34 and 51 kDa proteins show 100% sensitivity and specificity with healthy controls and other diseases. After six months post-treatment, antibodies to 72 and 91 kDa antigens show a significant decline to almost normal levels. This suggests that 34 and 51 kDa proteins are efficient in diagnosis, whereas 72 and 91 kDa proteins may be used to monitor treatment outcome. In another assay, 51 and 63 kDa proteins demonstrated maximum ability to upregulate IFN-γ and IL-12 with minimum induction of IL-10 and TGF-ß. The results indicating that 51 and 63 kDa proteins could be strong candidates for human immunization against VL. In contrast, 34 and 91 kDa proteins demonstrated a reverse profile and may not be a good vaccine candidate. CONCLUSIONS: The preliminary data obtained in this study proposes the potential of some of the antigens in Leishmania diagnosis and for test of cure. Additionally, some antigens demonstrated good immunoprophylactic cytokine production through T cell-mediated immune response, suggesting future vaccine candidates for VL. However, further studies are necessary to explore these antigens in diagnosis and to access the long-term immune response.


Subject(s)
Antigens, Protozoan/immunology , Leishmaniasis Vaccines/immunology , Leishmaniasis, Visceral/diagnosis , Leishmaniasis, Visceral/prevention & control , Leukocytes, Mononuclear/immunology , Protozoan Proteins/immunology , Cytokines/immunology , Humans , Immunogenicity, Vaccine , Leishmaniasis, Visceral/immunology
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