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1.
Front Microbiol ; 15: 1324243, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38725689

RESUMO

Introduction: Lumpy skin disease (LSD) is a highly contagious vector-borne viral disease of cattle. LSD has emerged in Bangladesh in 2019, causing significant economic losses due to its high morbidity and mortality. This research was designed to isolate, identify, and assess the immunogenicity of LSD virus (LSDV) using nodular tissue samples obtained from affected cattle during the 2019-20 outbreak across nine districts of Bangladesh. Methods: To determine the presence of LSDV in nodular tissues, we initially used iiPCR and PCR, followed by histopathological examination. 151 were positive via iiPCR and PCR among the 180 collected samples. The PCR positive 151 samples were then inoculated into 10-day-old embryonated chicken eggs via the CAM route to isolate LSDV, confirmed through PCR. Subsequently, partial sequencing and phylogenetic analysis of the P32 gene were performed to determine the origin of the circulating LSDV strain. The immunogenicity of selected LSDV strains was assessed through an ELISA test. Results: The PCR results revealed a distinct positive band at 192 bp in both the nodular tissue samples and the LSDV isolated from chicken embryo inoculations. Microscopic analysis of the nodular lesions revealed thickening of the epidermis, ballooning degeneration of keratinocytes, and proliferation of follicular epithelia. Additionally, mononuclear infiltration was observed at the demarcation line between infected and healthy tissue, with necrosis of muscular tissues beneath the epidermis. The LSDV isolate from Bangladesh exhibited a close genetic relationship with LSDV strains isolated from neighboring and other regional countries including India, Myanmar, and Mongolia. This observation strongly suggests the possibility of a transboundary spread of the LSD outbreak in Bangladesh during 2019-2020. The results of the immunogenicity test showed that the serum antibody titer remained at a protective level for up to 18 months following secondary immunization with inactivated LSDV antigen. This finding suggests that the inactivated LSDV antigen could be a potential vaccine candidate to protect cattle in Bangladesh against LSDV. Conclusion: In conclusion, our research successfully isolated, identified, and characterized LSDV in cattle nodular tissues from the 2019-20 outbreak in Bangladesh. Furthermore, it provided insights into the probable origin of the circulating strain and investigated a potential vaccine candidate to protect cattle in the region from LSDV.

2.
ACS Mater Lett ; 6(5): 1906-1912, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38726044

RESUMO

Single crystal X-ray diffraction (SCXRD) is arguably the most definitive method for molecular structure determination, but it is often challenged by compounds that are liquids or oils at room temperature or do not form crystals adequate for analysis. Our laboratory previously reported a simple, cost-effective, single-step crystallization method based on guanidinium organosulfonate (GS) hydrogen bonded frameworks for structure determination of a wide range of encapsulated guest molecules, including assignment of the absolute configuration of chiral centers. Herein, we expand on those results and report a head-to-head comparison of the GS method with adamantoid "molecular chaperones", which have been reported to be useful hosts for structure determination. Inclusion compounds limited to only two GS hosts are characterized by low R1 values and Flack parameters, infrequent disorder of the host and guest, and manageable disorder when it does exist. The structures of some target molecules that were not included or resolved using the adamantoid chaperones were successfully included and resolved by the GS hosts, and vice versa. Of the 32 guests attempted by the GS method, 31 inclusion compounds afforded successful guest structure solutions, a 97% success rate. The GS hosts and adamantoid chaperones are complementary with respect to guest inclusion, arguing that both should be employed in the arsenal of methods for structure determination. Furthermore, the low cost of organosulfonate host components promises an accessible route to molecular structure determination for a wide range of users.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38733609

RESUMO

The management of diabetes mellitus and its resultant end organ dysfunction represents a major challenge to global health-care systems. Diabetic cardiac and kidney disease commonly co-occur and are significant contributors to the morbidity and mortality of patients with diabetes, carrying a poor prognosis. The tight link of these parallel end organ manifestations suggests a deeper common underlying pathology. Here, we outline the mechanistic link between diabetic cardiac and kidney disease, providing evidence for the role of endothelial dysfunction in both processes and the potential for cellular therapy to correct these disorders. Specifically, we review the preclinical and clinical evidence for endothelial progenitor cell therapy in cardiac, kidney, and cardio-renal disease applications. Finally, we outline novel approaches to endothelial progenitor cell therapy through cell enhancement and the use of extracellular vesicles, discussing published and future work.

4.
Cytometry A ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38722042

RESUMO

To achieve high-sensitivity cell measurements (<1 in 105 cells) by flow cytometry (FCM), the minimum number of acquired cells must be considered and conventional immunophenotyping protocols fall short of these numbers. The bulk lysis (BL) assay is a standardized erythrocyte lysing approach that allows the analysis of the millions of cells required for high-sensitivity measurable residual disease (MRD) detection. However, this approach has been associated with significant cell loss, along with potential over or underestimates of rare cells when using this method. The aim of this study was to evaluate bulk lysis protocols and compare them with minimal sample perturbation (MSP) protocols, which are reported to better preserve the native cellular state and avoid significant cell loss due to washing steps. To achieve this purpose, we first generated an MRD model by spiking fresh peripheral blood with K562 cells, stably expressing EGFP, at known percentages of EGFP positive cells to leukocytes. Samples were then prepared with BL and MSP protocols and analyzed using FCM. For all percentages of K562 cells established and evaluated, a significant decrease of this population was detected in BL samples compared with MSP samples, even at low K562 cell percentages. Significant decreases for non-necrotic cells were also observed in BL samples relative to MSP samples. In conclusion, the evaluation of the potential effects of BL protocols in obtaining the final count is of great interest, especially for over- or under-estimation of target cells, as in the case of measurable residual disease. Since conventional flow cytometry or minimal sample perturbation assays fall short in obtaining the minimum numbers required to reach high sensitivity measurements, significant efforts may be needed to improve bulk lysis solution reagents.

5.
Infect Dis Poverty ; 13(1): 28, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38610035

RESUMO

BACKGROUND: Despite the increasing focus on strengthening One Health capacity building on global level, challenges remain in devising and implementing real-world interventions particularly in the Asia-Pacific region. Recognizing these gaps, the One Health Action Commission (OHAC) was established as an academic community for One Health action with an emphasis on research agenda setting to identify actions for highest impact. MAIN TEXT: This viewpoint describes the agenda of, and motivation for, the recently formed OHAC. Recognizing the urgent need for evidence to support the formulation of necessary action plans, OHAC advocates the adoption of both bottom-up and top-down approaches to identify the current gaps in combating zoonoses, antimicrobial resistance, addressing food safety, and to enhance capacity building for context-sensitive One Health implementation. CONCLUSIONS: By promoting broader engagement and connection of multidisciplinary stakeholders, OHAC envisions a collaborative global platform for the generation of innovative One Health knowledge, distilled practical experience and actionable policy advice, guided by strong ethical principles of One Health.


Assuntos
Saúde Única , Animais , Ásia , Fortalecimento Institucional , Políticas , Zoonoses/prevenção & controle
6.
Cryst Growth Des ; 24(8): 3483-3490, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38659662

RESUMO

During the past three decades, the ability of guanidinium arenesulfonate host frameworks to encapsulate a wide range of guests has been amply demonstrated, with more than 700 inclusion compounds realized. Herein, we report crystalline inclusion compounds based on a new aliphatic host, guanidinium cyclohexanemonosulfonate, which surprisingly exhibits four heretofore unobserved architectures, as described by the projection topologies of the organosulfonate residues above and below hydrogen-bonded guanidinium sulfonate sheets. The inclusion compounds adopt a layer motif of guanidinium sulfonate sheets interleaved with guest molecules, resembling a mille-feuille pastry. The aliphatic character of this remarkably simple host, combined with access to greater architectural diversity and adaptability, enables the host framework to accommodate a wide range of guests and promises to expand the utility of guanidinium organosulfonate hosts.

7.
Nat Neurosci ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38600167

RESUMO

In neurons, RNA granules are transported along the axon for local translation away from the soma. Recent studies indicate that some of this transport involves hitchhiking of RNA granules on lysosome-related vesicles. In the present study, we leveraged the ability to prevent transport of these vesicles into the axon by knockout of the lysosome-kinesin adaptor BLOC-one-related complex (BORC) to identify a subset of axonal mRNAs that depend on lysosome-related vesicles for transport. We found that BORC knockout causes depletion of a large group of axonal mRNAs mainly encoding ribosomal and mitochondrial/oxidative phosphorylation proteins. This depletion results in mitochondrial defects and eventually leads to axonal degeneration in human induced pluripotent stem cell (iPSC)-derived and mouse neurons. Pathway analyses of the depleted mRNAs revealed a mechanistic connection of BORC deficiency with common neurodegenerative disorders. These results demonstrate that mRNA transport on lysosome-related vesicles is critical for the maintenance of axonal homeostasis and that its failure causes axonal degeneration.

9.
Chem Mater ; 36(5): 2432-2440, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38495899

RESUMO

Many long-lasting insecticidal bed nets for protection against disease vectors consist of poly(ethylene) fibers in which insecticide is incorporated during manufacture. Insecticide molecules diffuse from within the supersaturated polymers to surfaces where they become bioavailable to insects and often crystallize, a process known as blooming. Recent studies revealed that contact insecticides can be highly polymorphic. Moreover, insecticidal activity is polymorph-dependent, with forms having a higher crystal free energy yielding faster insect knockdown and mortality. Consequently, the crystallographic characterization of insecticide crystals that form on fibers is critical to understanding net function and improving net performance. Structural characterization of insecticide crystals on bed net fiber surfaces, let alone their polymorphs, has been elusive owing to the minute size of the crystals, however. Using the highly polymorphous compound ROY (5-methyl-2-[(2-nitrophenyl)-amino]thiophene-3-carbonitrile) as a proxy for insecticide crystallization, we investigated blooming and crystal formation on the surface of extruded poly(ethylene) fibers containing ROY. The blooming rates, tracked from the time of extrusion, were determined by UV-vis spectroscopy after successive washes. Six crystalline polymorphs (of the 13 known) were observed on poly(ethylene) fiber surfaces, and they were identified and characterized by Raman microscopy, scanning electron microscopy, and 3D electron diffraction. These observations reveal that the crystallization and phase behavior of polymorphs forming on poly(ethylene) fibers is complex and dynamic. The characterization of blooming and microcrystals underscores the importance of bed net crystallography for the optimization of bed net performance.

10.
Int J Cardiol Heart Vasc ; 51: 101384, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38496257

RESUMO

Background: CT coronary angiography (CTCA) is a guideline-endorsed assessment for patients with stable angina and suspected coronary disease. Although associated with excellent negative predictive value in ruling out obstructive coronary disease, there are limitations in the ability of CTCA to predict hemodynamically significant coronary disease. The CAPTivAte study aims to assess the utility of Aggregated Plaque Burden (APB) in predicting ischemia based on Fractional Flow Reserve (FFR). Methods: In this retrospective study, patients who had a CTCA and invasive FFR of the LAD were included. The entire length of the LAD was analyzed using semi-automated software which characterized total plaque burden and plaque morphological subtype (including Low Attenuation Plaque (LAP), Non-calcific plaque (NCP) and Calcific Plaque (CP). Aggregated Plaque Burden (APB) was calculated. Univariate and multivariate analysis were performed to assess the association between these CT-derived parameters and invasive FFR. Results: There were 145 patients included in this study. 84.8 % of patients were referred with stable angina. There was a significant linear association between APB and FFR in both univariate and multivariate analysis (Adjusted R-squared = 0.0469; p = 0.035). Mean Agatston scores are higher in FFR positive vessels compared to FFR negative vessels (371.6 (±443.8) vs 251.9 (±283.5, p = 0.0493). Conclusion: CTCA-derived APB is a reliable predictor of ischemia assessed using invasive FFR and may aid clinicians in rationalizing invasive vs non-invasive management strategies. Vessel-specific Agatston scores are significantly higher in FFR-positive vessels than in FFR-negative vessels. Associations between HU-derived plaque subtype and invasive FFR were inconclusive in this study.

12.
Animals (Basel) ; 14(5)2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38473189

RESUMO

Jumps racing is a form of Thoroughbred horse racing that involves hurdles and steeples and typically longer distances, and heavier weights compared with flat racing, which does not incorporate obstacles. In Australia, jumps racing is carried out only in Victoria, one of eight states and territories. The continuation of jumps racing is contentious due to the higher risk of fatalities, falls and injuries for horses, compared with flat racing. While measures have been introduced by the industry to improve the safety of riders and horses, the rates of fatalities, falls and injuries in horses participating in jumps races have not been collectively reported in Australia since the 2012 to 2014 race seasons. Although information on individual horse fatalities, falls and injuries is published by Racing Victoria in Stewards' Reports, the data are not aggregated, and so cannot readily be used to assess trends or evaluate the efficacy of safety measures introduced by the industry. The aim of this study was to determine the fatality, fall and injury rates for horses participating in hurdle and steeplechase races in Victoria in the 2022 and 2023 Thoroughbred horse jumps racing seasons compared with horses participating in flat races at the same race meets. Data on horse fatalities, falls and injuries were extracted from the published Racing Victoria race results and Stewards' Reports for the jumps races (n = 150) and corresponding flat races (n = 157) held at the 38 jumps race meets in Victoria in 2022 and 2023. Overall, horse fatalities, falls and injuries occurred at higher rates in jumps races compared with flat races during the study period. The rate of horse fatalities in jumps races was 3.3 per 1000 starts, with no fatalities in flat races. The rate of horse falls in hurdle races was 24 per 1000 starts and 41.6 per 1000 starts in steeplechase races, comparable with rates previously reported in the 2012 to 2014 seasons. There were no falls in flat races. Horse injuries occurred at a rate of 68.9 per 1000 starts in jumps races compared with 18.8 per 1000 starts in flat races. In hurdle and steeplechase races, veterinary clearance being required following horse injury was 5.4 times (OR 5.4, 95% CI 2.8-10.2) and 7.2 times (OR 7.2, 95% CI 3.3-15.6) more likely, respectively, compared with flat races. The risk of trauma was 4 times more likely in hurdle and steeplechase races (OR 4.8, 95% CI 1.7-13.3 and OR 4.1, 95% CI 1.2-13.4, respectively) and the risk of lameness was increased by 2.5 times in hurdles (OR 2.5, 95% CI 1.2-5.2) and 5.1 times in steeplechase races (OR 5.1, 95% CI 2.3-11.5), compared with flat races. These findings support concerns about the welfare of horses involved in jumps racing and of the need for further safety measures to reduce these risks.

13.
Int J Pharm Pract ; 32(3): 251-255, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38466920

RESUMO

OBJECTIVES: The objective of this project was to obtain students' perception of an educational companion video designed to increase the understanding of a national medicines information resource. METHODS: An instructional video was developed to guide students in utilizing the online version of the Australian Medicines Handbook (AMH). All students enrolled in the Bachelor of Pharmacy program during 2021 were given access to this video. A cross-sectional electronic survey was administered to evaluate the video's effectiveness and its impact on students' confidence. The survey results were analysed using both descriptive and inferential statistics, in addition to qualitative analysis to identify common themes. Ethics approval was obtained prior to conducting the study. KEY FINDINGS: Most students (78%; n = 72/92) reported that watching the video increased their understanding. The most growth in confidence was seen by students in their first or second year of study. Fifty-four percent (n = 48/89) of students was very likely or extremely likely to recommend the video to others, and 37% (n = 33/89) of students were somewhat likely. Students found the instructional video to be useful and expressed a desire for similar content to be integrated into other facets of teaching. The audio-visual mode of delivery was regarded as effective for this context. Constructive feedback included suggestions of incorporating more advanced educational features such as how to interpret comparative medication charts and interaction checkers. CONCLUSIONS: The 'How to use the AMH' video is a good introductory resource for undergraduate Australian healthcare students. Our results indicate that this video would be best suited to complement the teaching of students early on in their studies.


Assuntos
Educação em Farmácia , Estudantes de Farmácia , Humanos , Estudantes de Farmácia/psicologia , Estudos Transversais , Austrália , Educação em Farmácia/métodos , Feminino , Masculino , Inquéritos e Questionários , Gravação em Vídeo , Adulto Jovem , Adulto
14.
Chemistry ; 30(27): e202400501, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38433109

RESUMO

The ability of an octanuclear cubic coordination cage to catalyse a nucleophilic aromatic substitution reaction on a cavity-bound guest was studied with 2,4-dinitrofluorobenzene (DNFB) as the guest/substrate. It was found that DNFB undergoes a catalysed reaction with hydroxide ions within the cavity of the cubic cage (in aqueous buffer solution, pH 8.6). The rate enhancement of kcat/kuncat was determined to be 22, with cavity binding of the guest being required for catalysis to occur. The product, 2,4-dinitrophenolate (DNP), remained bound within the cavity due to electrostatic stabilisation and exerts two apparently contradictory effects: it initially auto-catalyses the reaction when present at low concentrations, but at higher concentrations inhibits catalysis when a pair of DNP guests block the cavity. When encapsulated, the UV/Vis absorption spectrum of DNP is red-shifted when compared to the spectrum of free DNP in aqueous solution. Further investigations using other aromatic guests determined that a similar red-shift on cavity binding also occurred for 4-nitrophenolate (4NP) at pH 8.6. The red-shift was used to determine the stoichiometry of guest binding of DNP and 4NP within the cage cavity, which was confirmed by structural analysis with X-ray crystallography; and was also used to perform catalytic kinetic studies in the solution-state.

15.
bioRxiv ; 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38352495

RESUMO

Gracia-Diaz and colleagues analysed high-density DNA microarray and whole genome sequencing (WGS) data from the KOLF2.1J 'reference' human induced pluripotent stem cell (hiPSC) line1, and report the presence of five high-confidence heterozygous copy number variants (CNVs) at least 100kbp in length2. Since three of these CNVs span coding genes, some of which have been associated with neurodevelopmental disease, the authors raise the concern that these CNVs may compromise the utility of KOLF2.1J for neurological disease modelling. We appreciate their thorough analysis and thoughtful interpretation, and agree that potential users of this line should be made aware of all cases where KOLF2.1J differs from the reference genome. However, we believe that the benefits from the widespread use of KOLF2.1J outweigh the potential risks that might arise from the identified CNVs.

16.
bioRxiv ; 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38313254

RESUMO

Nuclear depletion and cytoplasmic aggregation of the RNA-binding protein TDP-43 is the hallmark of ALS, occurring in over 97% of cases. A key consequence of TDP-43 nuclear loss is the de-repression of cryptic exons. Whilst TDP-43 regulated cryptic splicing is increasingly well catalogued, cryptic alternative polyadenylation (APA) events, which define the 3' end of last exons, have been largely overlooked, especially when not associated with novel upstream splice junctions. We developed a novel bioinformatic approach to reliably identify distinct APA event types: alternative last exons (ALE), 3'UTR extensions (3'Ext) and intronic polyadenylation (IPA) events. We identified novel neuronal cryptic APA sites induced by TDP-43 loss of function by systematically applying our pipeline to a compendium of publicly available and in house datasets. We find that TDP-43 binding sites and target motifs are enriched at these cryptic events and that TDP-43 can have both repressive and enhancing action on APA. Importantly, all categories of cryptic APA can also be identified in ALS and FTD post mortem brain regions with TDP-43 proteinopathy underlining their potential disease relevance. RNA-seq and Ribo-seq analyses indicate that distinct cryptic APA categories have different downstream effects on transcript and translation. Intriguingly, cryptic 3'Exts occur in multiple transcription factors, such as ELK1, SIX3, and TLX1, and lead to an increase in wild-type protein levels and function. Finally, we show that an increase in RNA stability leading to a higher cytoplasmic localisation underlies these observations. In summary, we demonstrate that TDP-43 nuclear depletion induces a novel category of cryptic RNA processing events and we expand the palette of TDP-43 loss consequences by showing this can also lead to an increase in normal protein translation.

17.
J Immunol Methods ; 527: 113649, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38395105

RESUMO

While the single-platform flow cytometric CD34+ cell counting method is the preferred choice to predict the yield of mobilized peripheral blood stem cells, most flow cytometers lack the ability of hematology counter analyzers to perform volumetric counting. However, one of the problems using reference microbeads is the vanishing counting bead phenomenon. This phenomenon results in a drop in microbeads concentration and reduces the total and relative number of beads in calibration procedures. In the last years, flow cytometers including a volumetric system to quantify cells have been developed and may represent a promising alternative to enumerate CD34+ cells avoiding the use of beads. In this study we have used a direct true volumetric counting of CD34+ cells under continuous flow pump to overcome potential drawbacks with impact in rare cell analysis. To confirm this hypothesis, we have compared the results of CD34+ cell enumeration using non-volumetric vs. volumetric systems with FC500 (Beckman Coulter) and Attune NxT (ThermoFisher) flow cytometers, respectively, in mobilized peripheral blood samples. No statistically significant differences were observed between measurements of CD34+ cells using beads, when the FC500 and Attune NxT absolute counting values were compared, or when CD34+ counts were compared on the Attune NxT, either using or not using beads. Linear regressions to study the relationship between volumetric and non-volumetric CD34+ counts confirmed the accuracy of each method. Bland-Altman test showed agreement between both methods. Our data showed that CD34+ cell enumeration using a volumetric system is comparable with current counting systems. This method represents an alternative with the advantage of the simplification of sample preparation and the reduction of the analysis subjectivity.


Assuntos
Citometria de Fluxo , Citometria de Fluxo/métodos , Contagem de Células , Modelos Lineares , Antígenos CD34 , Microesferas
18.
Zoonoses Public Health ; 71(3): 314-323, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38362732

RESUMO

AIMS: Outbreaks of avian influenza in poultry farms are currently increasing in frequency, with devastating consequences for animal welfare, farmers and supply chains. Some studies have documented the direct spread of the avian influenza virus between farms. Prevention of spread between farms relies on biosecurity surveillance and control measures. However, the evolution of an outbreak on a farm might vary depending on the virus strain and poultry species involved; this would have important implications for surveillance systems, epidemiological investigations and control measures. METHODS AND RESULTS: In this study, we utilized existing parameter estimates from the literature to evaluate the predicted course of an epidemic in a standard poultry flock with 10,000 birds. We used a stochastic SEIR simulation model to simulate outbreaks in different species and with different virus subtypes. The simulations predicted large differences in the duration and severity of outbreaks, depending on the virus subtypes. For both turkeys and chickens, outbreaks with HPAI were of shorter duration than outbreaks with LPAI. In outbreaks involving the infection of chickens with different virus subtypes, the shortest epidemic involved H7N7 and HPAIV H5N1 (median duration of 9 and 17 days, respectively) and the longest involved H5N2 (median duration of 68 days). The most severe outbreaks (number of chickens infected) were predicted for H5N1, H7N1 and H7N3 virus subtypes, and the least severe for H5N2 and H7N7, in which outbreaks for the latter subtype were predicted to develop most slowly. CONCLUSIONS: These simulation results suggest that surveillance of certain subtypes of avian influenza virus, in chicken flocks in particular, needs to be sensitive and timely if infection is to be detected with sufficient time to implement control measures. The variability in the predictions highlights that avian influenza outbreaks are different in severity, speed and duration, so surveillance and disease response need to be nuanced and fit the specific context of poultry species and virus subtypes.


Assuntos
Virus da Influenza A Subtipo H5N1 , Vírus da Influenza A Subtipo H5N2 , Vírus da Influenza A Subtipo H7N1 , Vírus da Influenza A Subtipo H7N7 , Influenza Aviária , Doenças das Aves Domésticas , Animais , Aves Domésticas , Vírus da Influenza A Subtipo H7N3 , Galinhas , Surtos de Doenças/veterinária , Doenças das Aves Domésticas/epidemiologia
19.
Nat Commun ; 15(1): 1722, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38409240

RESUMO

Crimean-Congo hemorrhagic fever virus (CCHFV) is a WHO priority pathogen. Antibody-based medical countermeasures offer an important strategy to mitigate severe disease caused by CCHFV. Most efforts have focused on targeting the viral glycoproteins. However, glycoproteins are poorly conserved among viral strains. The CCHFV nucleocapsid protein (NP) is highly conserved between CCHFV strains. Here, we investigate the protective efficacy of a CCHFV monoclonal antibody targeting the NP. We find that an anti-NP monoclonal antibody (mAb-9D5) protected female mice against lethal CCHFV infection or resulted in a significant delay in mean time-to-death in mice that succumbed to disease compared to isotype control animals. Antibody protection is independent of Fc-receptor functionality and complement activity. The antibody bound NP from several CCHFV strains and exhibited robust cross-protection against the heterologous CCHFV strain Afg09-2990. Our work demonstrates that the NP is a viable target for antibody-based therapeutics, providing another direction for developing immunotherapeutics against CCHFV.


Assuntos
Vírus da Febre Hemorrágica da Crimeia-Congo , Febre Hemorrágica da Crimeia , Feminino , Animais , Camundongos , Vírus da Febre Hemorrágica da Crimeia-Congo/metabolismo , Proteínas do Nucleocapsídeo/metabolismo , Anticorpos Monoclonais , Febre Hemorrágica da Crimeia/prevenção & controle , Glicoproteínas/metabolismo , Anticorpos Antivirais
20.
JMIR Public Health Surveill ; 10: e44349, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38412011

RESUMO

BACKGROUND: COVID-19 screening is an effective nonpharmaceutical intervention for identifying infected individuals and interrupting viral transmission. However, questions have been raised regarding its effectiveness in controlling the spread of novel variants and its high socioeconomic costs. Therefore, the optimization of COVID-19 screening strategies has attracted great attention. OBJECTIVE: This review aims to summarize the evidence and provide a reference basis for the optimization of screening strategies for the prevention and control of COVID-19. METHODS: We applied a methodological framework for scoping reviews and the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) checklist. We conducted a scoping review of the present publications on the optimization of COVID-19 screening strategies. We searched the PubMed, Web of Science, and Elsevier ScienceDirect databases for publications up to December 31, 2022. English publications related to screening and testing strategies for COVID-19 were included. A data-charting form, jointly developed by 2 reviewers, was used for data extraction according to the optimization directions of the screening strategies. RESULTS: A total of 2770 unique publications were retrieved from the database search, and 95 abstracts were retained for full-text review. There were 62 studies included in the final review. We summarized the results in 4 major aspects: the screening population (people at various risk conditions such as different regions and occupations; 12/62, 19%), the timing of screening (when the target population is tested before travel or during an outbreak; 12/62, 19%), the frequency of screening (appropriate frequencies for outbreak prevention, outbreak response, or community transmission control; 6/62, 10%), and the screening and detection procedure (the choice of individual or pooled detection and optimization of the pooling approach; 35/62, 56%). CONCLUSIONS: This review reveals gaps in the optimization of COVID-19 screening strategies and suggests that a number of factors such as prevalence, screening accuracy, effective allocation of resources, and feasibility of strategies should be carefully considered in the development of future screening strategies.


Assuntos
COVID-19 , Humanos , COVID-19/diagnóstico , COVID-19/epidemiologia , Bases de Dados Factuais , Surtos de Doenças , Viagem
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