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1.
Dermatol Pract Concept ; 14(3)2024 Jul 01.
Article in English | MEDLINE | ID: mdl-39122549

ABSTRACT

INTRODUCTION: Early detection of melanoma and optimal referral to the specialist starts in primary care. Medical education is usually deficient in training general physicians in early detection and risk management for most skin malignancies. A three-point dermoscopy checklist is used as a screening tool for differentiating malignant and benign pigmented lesions in non-expert clinicians using dermoscopy. OBJECTIVES: To evaluate the impact of brief medical training on the three-point dermoscopy algorithm in third-year medical students new to dermatology and to determine the levels of sensitivity and specificity to differentiate malignant and benign pigmented lesions. METHODS: Optional dermoscopy lecture for third-year medical students new to dermatology in the context of general medical semiology courses, with case discussion and evaluation of 50 dermoscopy cases (25 benign and 25 malignant). Students were asked to classify malignant versus benign pathology based on the three-point dermoscopy algorithm discussed. Sensitivity, specificity, and predictive values were calculated according to the students' responses. RESULTS: Sixty-five students provided 3250 responses. Malignant pathology was misclassified as benign in 154 responses, while benign pathology was misclassified as malignant in 668 responses. Sensitivity and specificity for differentiating malignant lesions were 89.70% and 61.99%, respectively. Moderate interobserver agreement was found (Kappa value = 0.50; [CI: 0.47-0.54]). CONCLUSION: When evaluating melanocytic lesions, the focus of primary healthcare and general medical education should emphasize the correct determination of malignant or benign pathology. Teaching the three-point dermoscopy rule to medical students new to dermatology yields satisfactory levels of sensitivity and specificity, comparable to general physicians.

2.
Prev Vet Med ; 230: 106264, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39003835

ABSTRACT

Identifying and restricting animal movements is a common approach used to mitigate the spread of diseases between premises in livestock systems. Therefore, it is essential to uncover between-premises movement dynamics, including shipment distances and network-based control strategies. Here, we analyzed three years of between-premises pig movements, which include 197,022 unique animal shipments, 3973 premises, and 391,625,374 pigs shipped across 20 U.S. states. We constructed unweighted, directed, temporal networks at 180-day intervals to calculate premises-to-premises movement distances, the size of connected components, network loyalty, and degree distributions, and, based on the out-going contact chains, identified network-based control actions. Our results show that the median distance between premises pig movements was 74.37 km, with median intrastate and interstate movements of 52.71 km and 328.76 km, respectively. On average, 2842 premises were connected via 6705 edges, resulting in a weak giant connected component that included 91 % of the premises. The premises-level network exhibited loyalty, with a median of 0.65 (IQR: 0.45 - 0.77). Results highlight the effectiveness of node targeting to reduce the risk of disease spread; we demonstrated that targeting 25 % of farms with the highest degree or betweenness limited spread to 1.23 % and 1.7 % of premises, respectively. While there is no complete shipment data for the entire U.S., our multi-state movement analysis demonstrated the value and the needs of such data for enhancing the design and implementation of proactive- disease control tactics.


Subject(s)
Animal Husbandry , Swine Diseases , Transportation , Animals , United States , Swine , Animal Husbandry/methods , Animal Husbandry/statistics & numerical data , Swine Diseases/epidemiology , Swine Diseases/prevention & control , Sus scrofa/physiology
3.
Eur J Immunol ; 54(5): e2250133, 2024 May.
Article in English | MEDLINE | ID: mdl-38571392

ABSTRACT

Live-attenuated yellow fever vaccine (YF17D) was developed in the 1930s as the first ever empirically derived human vaccine. Ninety years later, it is still a benchmark for vaccines made today. YF17D triggers a particularly broad and polyfunctional response engaging multiple arms of innate, humoral and cellular immunity. This unique immunogenicity translates into an extraordinary vaccine efficacy and outstanding longevity of protection, possibly by single-dose immunization. More recently, progress in molecular virology and synthetic biology allowed engineering of YF17D as a powerful vector and promising platform for the development of novel recombinant live vaccines, including two licensed vaccines against Japanese encephalitis and dengue, even in paediatric use. Likewise, numerous chimeric and transgenic preclinical candidates have been described. These include prophylactic vaccines against emerging viral infections (e.g. Lassa, Zika and SARS-CoV-2) and parasitic diseases (e.g. malaria), as well as therapeutic applications targeting persistent infections (e.g. HIV and chronic hepatitis), and cancer. Efforts to overcome historical safety concerns and manufacturing challenges are ongoing and pave the way for wider use of YF17D-based vaccines. In this review, we summarize recent insights regarding YF17D as vaccine platform, and how YF17D-based vaccines may complement as well as differentiate from other emerging modalities in response to unmet medical needs and for pandemic preparedness.


Subject(s)
Vaccines, Attenuated , Yellow Fever Vaccine , Yellow fever virus , Humans , Yellow Fever Vaccine/immunology , Yellow fever virus/immunology , Vaccines, Attenuated/immunology , Animals , Yellow Fever/prevention & control , Yellow Fever/immunology , Vaccination/methods
4.
J Cardiovasc Magn Reson ; 26(1): 100006, 2024.
Article in English | MEDLINE | ID: mdl-38215698

ABSTRACT

This position statement guides cardiovascular magnetic resonance (CMR) imaging program directors and learners on the key competencies required for Level II and III CMR practitioners, whether trainees come from a radiology or cardiology background. This document is built upon existing curricula and was created and vetted by an international panel of cardiologists and radiologists on behalf of the Society for Cardiovascular Magnetic Resonance (SCMR).


Subject(s)
Cardiology , Clinical Competence , Consensus , Curriculum , Education, Medical, Graduate , Magnetic Resonance Imaging , Humans , Education, Medical, Graduate/standards , Magnetic Resonance Imaging/standards , Cardiology/education , Cardiology/standards , Cardiovascular Diseases/diagnostic imaging , Cardiologists/education , Cardiologists/standards , Predictive Value of Tests , Radiologists/education , Radiologists/standards , Radiology/education , Radiology/standards , Societies, Medical/standards
5.
NPJ Vaccines ; 8(1): 99, 2023 Jul 11.
Article in English | MEDLINE | ID: mdl-37433816

ABSTRACT

Ebola virus (EBOV) and related filoviruses such as Sudan virus (SUDV) threaten global public health. Effective filovirus vaccines are available only for EBOV, yet restricted to emergency use considering a high reactogenicity and demanding logistics. Here we present YF-EBO, a live YF17D-vectored dual-target vaccine candidate expressing EBOV glycoprotein (GP) as protective antigen. Safety of YF-EBO in mice was further improved over that of parental YF17D vaccine. A single dose of YF-EBO was sufficient to induce high levels of EBOV GP-specific antibodies and cellular immune responses, that protected against lethal infection using EBOV GP-pseudotyped recombinant vesicular stomatitis virus (rVSV-EBOV) in interferon-deficient (Ifnar-/-) mice as surrogate challenge model. Concomitantly induced yellow fever virus (YFV)-specific immunity protected Ifnar-/- mice against intracranial YFV challenge. YF-EBO could thus help to simultaneously combat both EBOV and YFV epidemics. Finally, we demonstrate how to target other highly pathogenic filoviruses such as SUDV at the root of the 2022 outbreak in Uganda.

6.
Front Vet Sci ; 10: 1158306, 2023.
Article in English | MEDLINE | ID: mdl-37456959

ABSTRACT

Porcine reproductive and respiratory syndrome virus (PRRSV) remains widely distributed across the U.S. swine industry. Between-farm movements of animals and transportation vehicles, along with local transmission are the primary routes by which PRRSV is spread. Given the farm-to-farm proximity in high pig production areas, local transmission is an important pathway in the spread of PRRSV; however, there is limited understanding of the role local transmission plays in the dissemination of PRRSV, specifically, the distance at which there is increased risk for transmission from infected to susceptible farms. We used a spatial and spatiotemporal kernel density approach to estimate PRRSV relative risk and utilized a Bayesian spatiotemporal hierarchical model to assess the effects of environmental variables, between-farm movement data and on-farm biosecurity features on PRRSV outbreaks. The maximum spatial distance calculated through the kernel density approach was 15.3 km in 2018, 17.6 km in 2019, and 18 km in 2020. Spatiotemporal analysis revealed greater variability throughout the study period, with significant differences between the different farm types. We found that downstream farms (i.e., finisher and nursery farms) were located in areas of significant-high relative risk of PRRSV. Factors associated with PRRSV outbreaks were farms with higher number of access points to barns, higher numbers of outgoing movements of pigs, and higher number of days where temperatures were between 4°C and 10°C. Results obtained from this study may be used to guide the reinforcement of biosecurity and surveillance strategies to farms and areas within the distance threshold of PRRSV positive farms.

7.
Fish Shellfish Immunol ; 140: 108975, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37488040

ABSTRACT

The parr-smolt transformation in salmonids involves a critical period characterized by systemic changes associated with the fish's immune response. In this context, as a dietary ingredient in functional diets, microalgae offer an alternative due to their nutritional and bioactive compounds that could strengthen the immune status. This study evaluated the effect of a diet supplemented with Schizochytrium spp and Nannochloropsis gaditana on the expression of genes associated with the antibacterial response. Additionally, the study assessed the effect on the leukocyte population and erythrocyte maturity in Salmo salar blood. Fish were fed for 30 days with a microalgal mixture (1:1) at a 10% inclusion. Each diet was randomly assigned to a tank using a completely randomized design (CRD) with four replications. Each tank was stocked with 70 Atlantic salmon fingerlings with an initial mean weight of 78.87 ± 0.84. Transcription levels were quantified and analyzed by qRT-PCR from cell isolates and mucus tissue. Furthermore, cell count and identification of leukocytes and classification of cellular maturity of erythrocytes using a neural network with a multilayer perceptron (MLP) were performed. Our results showed a significant (p < 0.05) increase in fold change expression of C3 (2.54 ± 0.65) and NK-Lysine (6.84 ± 0.94) in erythrocytes of microalgae-supplemented fish. Moreover, a significant increase of 1.59 and 2.35 times in monocytes and immature erythrocytes, respectively, was observed in the same group of fish (p < 0.05). This study's results indicate that dual microalgae (Schizochytrium spp and N. gaditana) supplementation can increase innate humoral antibacterial components, particularly in erythrocyte tissue, and increase phagocytic cells and immature erythrocytes in S. salar blood.


Subject(s)
Microalgae , Salmo salar , Stramenopiles , Animals , Diet/veterinary , Immunity, Innate , Erythrocytes , Anti-Bacterial Agents , Animal Feed/analysis
8.
Clin Infect Dis ; 77(Suppl 1): S75-S81, 2023 07 05.
Article in English | MEDLINE | ID: mdl-37406045

ABSTRACT

BACKGROUND: Antimicrobial resistance is a global threat, heavily impacting low- and middle-income countries. This study estimated antimicrobial-resistant gram-negative bacteria (GNB) fecal colonization prevalence in hospitalized and community-dwelling adults in Chile before the coronavirus disease 2019 pandemic. METHODS: From December 2018 to May 2019, we enrolled hospitalized adults in 4 public hospitals and community dwellers from central Chile, who provided fecal specimens and epidemiological information. Samples were plated onto MacConkey agar with ciprofloxacin or ceftazidime added. All recovered morphotypes were identified and characterized according to the following phenotypes: fluoroquinolone-resistant (FQR), extended-spectrum cephalosporin-resistant (ESCR), carbapenem-resistant (CR), or multidrug-resistant (MDR; as per Centers for Disease Control and Prevention criteria) GNB. Categories were not mutually exclusive. RESULTS: A total of 775 hospitalized adults and 357 community dwellers were enrolled. Among hospitalized subjects, the prevalence of colonization with FQR, ESCR, CR, or MDR-GNB was 46.4% (95% confidence interval [CI], 42.9-50.0), 41.2% (95% CI, 37.7-44.6), 14.5% (95% CI, 12.0-16.9), and 26.3% (95% CI, 23.2-29.4). In the community, the prevalence of FQR, ESCR, CR, and MDR-GNB colonization was 39.5% (95% CI, 34.4-44.6), 28.9% (95% CI, 24.2-33.6), 5.6% (95% CI, 3.2-8.0), and 4.8% (95% CI, 2.6-7.0), respectively. CONCLUSIONS: A high burden of antimicrobial-resistant GNB colonization was observed in this sample of hospitalized and community-dwelling adults, suggesting that the community is a relevant source of antibiotic resistance. Efforts are needed to understand the relatedness between resistant strains circulating in the community and hospitals.


Subject(s)
Anti-Infective Agents , COVID-19 , Gram-Negative Bacterial Infections , Humans , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Bacteria , Carbapenems , Cephalosporins , Chile/epidemiology , Drug Resistance, Microbial , Drug Resistance, Multiple, Bacterial , Fluoroquinolones , Gram-Negative Bacteria , Gram-Negative Bacterial Infections/drug therapy , Hospitals , Risk Factors , Adult
9.
Rev. méd. Maule ; 38(1): 8-18, jun. 2023.
Article in Spanish | LILACS | ID: biblio-1562292

ABSTRACT

Migrants in Chile are a group of health users with particular needs, at least in mental health, they are faced with factors that can influence their psyche. Thus, the present work summarized the bibliography available in scientific search engines with the aim of summarizing them and associating them with mental symptoms. From it, it can be deduced that 9 factors can influence this group, among them, acculturation, poor access to health and mistreatment. The consequences of these are summarized in the generation of depressive and anxious symptoms, which are often not treated.


Subject(s)
Humans , Child , Adolescent , Adult , Stress, Psychological/psychology , Adaptation, Psychological , Emigrants and Immigrants/psychology , Acculturation , Mental Disorders/psychology , Socioeconomic Factors , Stress, Psychological/ethnology , Chile/ethnology , Surveys and Questionnaires , Mental Disorders/ethnology
10.
Cancer Imaging ; 23(1): 17, 2023 Feb 16.
Article in English | MEDLINE | ID: mdl-36793094

ABSTRACT

BACKGROUND: Although MRI is a radiation-free imaging modality, it has historically been limited in lung imaging due to inherent technical restrictions. The aim of this study is to explore the performance of lung MRI in detecting solid and subsolid pulmonary nodules using T1 gradient-echo (GRE) (VIBE, Volumetric interpolated breath-hold examination), ultrashort time echo (UTE) and T2 Fast Spin Echo (HASTE, Half fourier Single-shot Turbo spin-Echo). METHODS: Patients underwent a lung MRI in a 3 T scanner as part of a prospective research project. A baseline Chest CT was obtained as part of their standard of care. Nodules were identified and measured on the baseline CT and categorized according to their density (solid and subsolid) and size (> 4 mm/ ≤ 4 mm). Nodules seen on the baseline CT were classified as present or absent on the different MRI sequences by two thoracic radiologists independently. Interobserver agreement was determined using the simple Kappa coefficient. Paired differences were compared using nonparametric Mann-Whitney U tests. The McNemar test was used to evaluate paired differences in nodule detection between MRI sequences. RESULTS: Thirty-six patients were prospectively enrolled. One hundred forty-nine nodules (100 solid/49 subsolid) with mean size 10.8 mm (SD = 9.4) were included in the analysis. There was substantial interobserver agreement (k = 0.7, p = 0.05). Detection for all nodules, solid and subsolid nodules was respectively; UTE: 71.8%/71.0%/73.5%; VIBE: 61.6%/65%/55.1%; HASTE 72.4%/72.2%/72.7%. Detection rate was higher for nodules > 4 mm in all groups: UTE 90.2%/93.4%/85.4%, VIBE 78.4%/88.5%/63.4%, HASTE 89.4%/93.8%/83.8%. Detection of lesions ≤4 mm was low for all sequences. UTE and HASTE performed significantly better than VIBE for detection of all nodules and subsolid nodules (diff = 18.4 and 17.6%, p = < 0.01 and p = 0.03, respectively). There was no significant difference between UTE and HASTE. There were no significant differences amongst MRI sequences for solid nodules. CONCLUSIONS: Lung MRI shows adequate performance for the detection of solid and subsolid pulmonary nodules larger than 4 mm and can serve as a promising radiation-free alternative to CT.


Subject(s)
Lung Neoplasms , Lung , Humans , Prospective Studies , Lung/diagnostic imaging , Lung/pathology , Magnetic Resonance Imaging/methods , Tomography, X-Ray Computed/methods , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/pathology
11.
Nat Commun ; 13(1): 6644, 2022 11 04.
Article in English | MEDLINE | ID: mdl-36333374

ABSTRACT

Current COVID-19 vaccines are based on prototypic spike sequences from ancestral 2019 SARS-CoV-2 strains. However, the ongoing pandemic is fueled by variants of concern (VOC) escaping vaccine-mediated protection. Here we demonstrate how immunization in hamsters using prototypic spike expressed from yellow fever 17D (YF17D) as vector blocks ancestral virus (B lineage) and VOC Alpha (B.1.1.7) yet fails to fully protect from Beta (B.1.351). However, the same YF17D vectored vaccine candidate with an evolved antigen induced considerably improved neutralizing antibody responses against VOCs Beta, Gamma (P.1) and the recently predominant Omicron (B.1.1.529), while maintaining immunogenicity against ancestral virus and VOC Delta (B.1.617.2). Thus vaccinated animals resisted challenge by all VOCs, including vigorous high titre exposure to the most difficult to cover Beta, Delta and Omicron variants, eliminating detectable virus and markedly improving lung pathology. Finally, vaccinated hamsters did not transmit Delta variant to non-vaccinated cage mates. Overall, our data illustrate how current first-generation COVID-19 vaccines may need to be updated to maintain efficacy against emerging VOCs and their spread at community level.


Subject(s)
COVID-19 , Viral Vaccines , Yellow Fever Vaccine , Cricetinae , Animals , Humans , SARS-CoV-2/genetics , Viral Vaccines/genetics , COVID-19 Vaccines , COVID-19/prevention & control , Antibodies, Neutralizing , Antibodies, Viral , Spike Glycoprotein, Coronavirus/genetics
12.
EBioMedicine ; 83: 104240, 2022 Sep.
Article in English | MEDLINE | ID: mdl-36041265

ABSTRACT

BACKGROUND: The live-attenuated yellow fever vaccine YF17D holds great promise as alternative viral vector vaccine platform, showcased by our previously presented potent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine candidate YF-S0. Besides protection from SARS-CoV-2, YF-S0 also induced strong yellow fever virus (YFV)-specific immunity, suggestive for full dual activity. A vaccine concomitantly protecting from SARS-CoV-2 and YFV would be of great benefit for those living in YFV-endemic areas with limited access to current SARS-CoV-2 vaccines. However, for broader applicability, pre-existing vector immunity should not impact the potency of such YF17D-vectored vaccines. METHODS: The immunogenicity and efficacy of YF-S0 against YFV and SARS-CoV-2 in the presence of strong pre-existing YFV immunity were evaluated in mouse and hamster challenge models. FINDINGS: Here, we show that a single dose of YF-S0 is sufficient to induce strong humoral and cellular immunity against YFV as well as SARS-CoV-2 in mice and hamsters; resulting in full protection from vigorous YFV challenge in either model; in mice against lethal intracranial YF17D challenge, and in hamsters against viscerotropic infection and liver disease following challenge with highly pathogenic hamster-adapted YFV-Asibi strain. Importantly, strong pre-existing immunity against the YF17D vector did not interfere with subsequent YF-S0 vaccination in mice or hamsters; nor with protection conferred against SARS-CoV-2 strain B1.1.7 (Alpha variant) infection in hamsters. INTERPRETATION: Our findings warrant the development of YF-S0 as dual SARS-CoV-2 and YFV vaccine. Contrary to other viral vaccine platforms, use of YF17D does not suffer from pre-existing vector immunity. FUNDING: Stated in the acknowledgments.


Subject(s)
COVID-19 , Viral Vaccines , Yellow Fever Vaccine , Yellow Fever , Animals , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Cricetinae , Humans , Mice , SARS-CoV-2 , Viral Vaccines/genetics , Yellow Fever/prevention & control , Yellow fever virus/genetics
13.
Transbound Emerg Dis ; 69(5): e2757-e2768, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35694801

ABSTRACT

Most animal disease surveillance systems concentrate efforts in blocking transmission pathways and tracing back infected contacts while not considering the risk of transporting animals into areas with elevated disease risk. Here, we use a suite of spatial statistics and social network analysis to characterize animal movement among areas with an estimated distinct risk of disease circulation to ultimately enhance surveillance activities. Our model utilized equine infectious anemia virus (EIAV) outbreaks, between-farm horse movements, and spatial landscape data from 2015 through 2017. We related EIAV occurrence and the movement of horses between farms with climate variables that foster conditions for local disease propagation. We then constructed a spatially explicit model that allows the effect of the climate variables on EIAV occurrence to vary through space (i.e., non-stationary). Our results identified important areas in which in-going movements were more likely to result in EIAV infections and disease propagation. Municipalities were then classified as having high 56 (11.3%), medium 48 (9.66%), and low 393 (79.1%) spatial risk. The majority of the movements were between low-risk areas, altogether representing 68.68% of all animal movements. Meanwhile, 9.48% were within high-risk areas, and 6.20% were within medium-risk areas. Only 5.37% of the animals entering low-risk areas came from high-risk areas. On the other hand, 4.91% of the animals in the high-risk areas came from low- and medium-risk areas. Our results demonstrate that animal movements and spatial risk mapping could be used to make informed decisions before issuing animal movement permits, thus potentially reducing the chances of reintroducing infection into areas of low risk.


Subject(s)
Equine Infectious Anemia , Horse Diseases , Infectious Anemia Virus, Equine , Animals , Disease Outbreaks/prevention & control , Disease Outbreaks/veterinary , Equine Infectious Anemia/epidemiology , Farms , Horse Diseases/epidemiology , Horses , Social Network Analysis
14.
Article in English | MEDLINE | ID: mdl-35682199

ABSTRACT

(1) Background: a set of ergonomic parameters that are relevant for risk assessment methods for the prevention of occupational risks, such as REBA or NIOSH, have been measured by means of inertial sensors that allow capturing the movements of the human body. These methods base their assessment on a number of postural and dynamic parameters. In the case of police physical intervention techniques, trunk, legs, arms, forearms and wrists angles, joint contact force and sheer force at the L5-Pelvic junction, asymmetry (angle and factor), and muscle power are the more relevant parameters to be considered. (2) Method: The data have been collected by means of a motion capture suit equipped with 19 inertial sensors. The large amount of data and the 3-dimensional plots have been managed by a powerful software package specific for ergonomic analysis. The police physical intervention technique used was OTP. (3) Results: Five ergonomic parameters in a traditional police physical intervention technique have been analyzed. REBA scores and ergonomic metrics have been recorded and discussed with some prevention risk limits from the literature. (4) Conclusions: the usage of inertial sensors to capture the movements in OTPs provides a new and quite an efficient viewpoint for occupational risk research studies.


Subject(s)
Ergonomics , Police , Ergonomics/methods , Humans , Movement , National Institute for Occupational Safety and Health, U.S. , Torso , United States
15.
Microsc Res Tech ; 85(5): 1742-1756, 2022 May.
Article in English | MEDLINE | ID: mdl-34953102

ABSTRACT

Autofocus systems are essential in optical microscopy. These systems typically sweep the sample through the focal range and apply an algorithm to determine the contrast value of each image, where the highest value indicates the optimal focus position. As the optimal algorithm may vary according to the images' content, we evaluate the 15 most used algorithms in the field using 150 stacks of images from four different kinds of tissue. We use four measuring criteria and two types of analysis and propose a general methodology to apply to select the best fitting algorithm for any given application. In this paper, we present the results of this evaluation and a detailed discussion of different features: the threshold used for the algorithms, the criteria parameters, the analysis used, the bit depth of the images, their magnification, and the type of tissue, reaching the conclusion that some of these parameters are more relevant to the study than others, and the implementation of the proposed methodology can lead to a fast and reliable autofocus system capable of performing an analysis and selection of algorithms with no supervision required.


Subject(s)
Algorithms , Microscopy , Image Processing, Computer-Assisted/methods , Microscopy/methods
16.
Methods Mol Biol ; 2410: 177-192, 2022.
Article in English | MEDLINE | ID: mdl-34914047

ABSTRACT

The SARS-CoV-2 pandemic has impacted the health of humanity after the outbreak in Hubei, China in late December 2019. Ever since, it has taken unprecedented proportions and rapidity causing over a million fatal cases. Recently, a robust Syrian golden hamster model recapitulating COVID-19 was developed in search for effective therapeutics and vaccine candidates. However, overt clinical disease symptoms were largely absent despite high levels of virus replication and associated pathology in the respiratory tract. Therefore, we used micro-computed tomography (µCT) to longitudinally visualize lung pathology and to preclinically assess candidate vaccines. µCT proved to be crucial to quantify and noninvasively monitor disease progression, to evaluate candidate vaccine efficacy, and to improve screening efforts by allowing longitudinal data without harming live animals. Here, we give a comprehensive guide on how to use low-dose high-resolution µCT to follow-up SARS-CoV-2-induced disease and test the efficacy of COVID-19 vaccine candidates in hamsters. Our approach can likewise be applied for the preclinical assessment of antiviral and anti-inflammatory drug treatments in vivo.


Subject(s)
COVID-19 Vaccines , COVID-19 , Vaccine Efficacy , Animals , COVID-19/prevention & control , Cricetinae , X-Ray Microtomography
17.
Curr Probl Diagn Radiol ; 51(2): 225-234, 2022.
Article in English | MEDLINE | ID: mdl-33551194

ABSTRACT

Muscular dystrophies (MDs) are a group of inherited disorders caused by mutations that interfere with muscular structure, contraction, or relaxation. As the cardiac sarcomeric unit shares multiple proteins with the skeletal muscle unit, the heart is affected in several MDs, sometimes without apparent musculoskeletal involvement. Early detection of MD-related cardiomyopathy is crucial as timely initiation of cardioprotective therapy can slow adverse cardiac remodeling. Although transthoracic echocardiography is widely used for the evaluation of cardiac morphology and function, it has limitations in terms of reproducibility and image quality. The need for an optimal acoustic window may be particularly challenging to obtain in patients with MDs given their body habitus and position. Cardiac magnetic resonance (CMR) imaging has emerged as a useful tool in the evaluation of patients with MDs. Its superb tissue characterization capability through late gadolinium enhancement, T1 mapping, extracellular volume fraction quantification, and edema imaging detects early cardiac involvement, even when echocardiography and electrocardiogram are unremarkable. MDs that frequently present with cardiac involvement include Duchenne MD, Becker MD, Emery Dreifuss MD, Limb-Girdle MDs, and myotonic dystrophy. The purpose of this review article is to briefly describe the pathophysiology of these entities, discuss their clinical presentation and expected evolution, explain the role of CMR in the diagnosis and follow-up of these patients, and portray the different CMR findings present in MD patients.


Subject(s)
Contrast Media , Muscular Dystrophy, Duchenne , Gadolinium , Humans , Magnetic Resonance Imaging , Reproducibility of Results
18.
Emerg Microbes Infect ; 10(1): 2279-2290, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34792431

ABSTRACT

The live-attenuated yellow fever 17D (YF17D) vaccine is one of the most efficacious human vaccines and also employed as a vector for novel vaccines. However, in the lack of appropriate immunocompetent small animal models, mechanistic insight in YF17D-induced protective immunity remains limited. To better understand YF17D vaccination and to identify a suitable mouse model, we evaluated the immunogenicity and protective efficacy of YF17D in five complementary mouse models, i.e. wild-type (WT) BALB/c, C57BL/6, IFN-α/ß receptor (IFNAR-/-) deficient mice, and in WT mice in which type I IFN signalling was temporally ablated by an IFNAR blocking (MAR-1) antibody. Alike in IFNAR-/- mice, YF17D induced in either WT mice strong humoral immune responses dominated by IgG2a/c isotype (Th1 type) antibodies, yet only when IFNAR was blocked. Vigorous cellular immunity characterized by CD4+ T-cells producing IFN-γ and TNF-α were mounted in MAR-1 treated C57BL/6 and in IFNAR-/- mice. Surprisingly, vaccine-induced protection was largely mouse model dependent. Full protection against lethal intracranial challenge and a massive reduction of virus loads was conferred already by a minimal dose of 2 PFU YF17D in BALB/c and IFNAR-/- mice, but not in C57BL/6 mice. Correlation analysis of infection outcome with pre-challenge immunological markers indicates that YFV-specific IgG might suffice for protection, even in the absence of detectable levels of neutralizing antibodies. Finally, we propose that, in addition to IFNAR-/- mice, C57BL/6 mice with temporally blocked IFN-α/ß receptors represent a promising immunocompetent mouse model for the study of YF17D-induced immunity and evaluation of YF17D-derived vaccines.


Subject(s)
Yellow Fever Vaccine/administration & dosage , Yellow Fever Vaccine/immunology , Yellow Fever/prevention & control , Yellow fever virus/immunology , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Disease Models, Animal , Female , Humans , Immunity, Cellular , Immunity, Humoral , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , T-Lymphocytes/immunology , Vaccines, Attenuated/administration & dosage , Vaccines, Attenuated/genetics , Vaccines, Attenuated/immunology , Yellow Fever/immunology , Yellow Fever/virology , Yellow Fever Vaccine/genetics , Yellow fever virus/genetics
20.
EBioMedicine ; 68: 103403, 2021 Jun.
Article in English | MEDLINE | ID: mdl-34049240

ABSTRACT

BACKGROUND: Within one year after its emergence, more than 108 million people acquired SARS-CoV-2 and almost 2·4 million succumbed to COVID-19. New SARS-CoV-2 variants of concern (VoC) are emerging all over the world, with the threat of being more readily transmitted, being more virulent, or escaping naturally acquired and vaccine-induced immunity. At least three major prototypic VoC have been identified, i.e. the United Kingdom, UK (B.1.1.7), South African (B.1.351) and Brazilian (B.1.1.28.1) variants. These are replacing formerly dominant strains and sparking new COVID-19 epidemics. METHODS: We studied the effect of infection with prototypic VoC from both B.1.1.7 and B.1.351 variants in female Syrian golden hamsters to assess their relative infectivity and virulence in direct comparison to two basal SARS-CoV-2 strains isolated in early 2020. FINDINGS: A very efficient infection of the lower respiratory tract of hamsters by these VoC is observed. In line with clinical evidence from patients infected with these VoC, no major differences in disease outcome were observed as compared to the original strains as was quantified by (i) histological scoring, (ii) micro-computed tomography, and (iii) analysis of the expression profiles of selected antiviral and pro-inflammatory cytokine genes. Noteworthy however, in hamsters infected with VoC B.1.1.7, a particularly strong elevation of proinflammatory cytokines was detected. INTERPRETATION: We established relevant preclinical infection models that will be pivotal to assess the efficacy of current and future vaccine(s) (candidates) as well as therapeutics (small molecules and antibodies) against two important SARS-CoV-2 VoC. FUNDING: Stated in the acknowledgment.


Subject(s)
COVID-19/pathology , Cytokines/genetics , Respiratory System/virology , SARS-CoV-2/pathogenicity , Animals , COVID-19/diagnostic imaging , COVID-19/genetics , Disease Models, Animal , Evolution, Molecular , Female , Gene Expression Profiling , Gene Expression Regulation , Mesocricetus , Respiratory System/diagnostic imaging , Respiratory System/pathology , SARS-CoV-2/classification , SARS-CoV-2/immunology , Virulence , X-Ray Microtomography
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