Human T-lymphotropic virus 1 (HTLV-1) is associated with the development of several pathologies and chronic infection in humans. The inefficiency of the available treatments and the challenge in ...developing a protective vaccine highlight the need to produce effective immunotherapeutic tools. The HTLV-1 basic leucine zipper (bZIP) factor (HBZ) plays an important role in the HTLV-1 persistence, conferring a survival advantage to infected cells by reducing the HTLV-1 proteins expression, allowing infected cells to evade immune surveillance, and enhancing cell proliferation leading to increased proviral load.
We have generated a recombinant Modified Virus Vaccinia Ankara (MVA-HBZ) and a plasmid DNA (pcDNA3.1(+)-HBZ) expressing a multiepitope protein based on peptides of HBZ to study the immunogenic potential of this viral-derived protein in BALB/c mice model. Mice were immunized in a prime-boost heterologous protocol and their splenocytes (T CD4
and T CD8
) were immunophenotyped by flow cytometry and the humoral response was evaluated by ELISA using HBZ protein produced in prokaryotic vector as antigen.
T CD4
and T CD8
lymphocytes cells stimulated by HBZ-peptides (HBZ
and HBZ
) showed polyfunctional double positive responses for TNF-α/IFN-γ, and TNF-α/IL-2. Moreover, T CD8
cells presented a tendency in the activation of effector memory cells producing granzyme B (CD44
/CD62L
), and the activation of Cytotoxic T Lymphocytes (CTLs) and cytotoxic responses in immunized mice were inferred through the production of granzyme B by effector memory T cells and the expression of CD107a by CD8
T cells. The overall data is consistent with a directive and effector recall response, which may be able to operate actively in the elimination of HTLV-1-infected cells and, consequently, in the reduction of the proviral load. Sera from immunized mice, differently from those of control animals, showed IgG-anti-HBZ production by ELISA.
Our results highlight the potential of the HBZ multiepitope protein expressed from plasmid DNA and a poxviral vector as candidates for therapeutic vaccine.
Fast, precise, and low-cost diagnostic testing to identify persons infected with SARS–CoV-2 virus is pivotal to control the global pandemic of COVID-19 that began in late 2019. The gold standard ...method of diagnostic recommended is the RT-qPCR test. However, this method is not universally available, and is time-consuming and requires specialized personnel, as well as sophisticated laboratories. Currently, machine learning is a useful predictive tool for biomedical applications, being able to classify data from diverse nature. Relying on the artificial intelligence learning process, spectroscopic data from nasopharyngeal swab and tracheal aspirate samples can be used to leverage characteristic patterns and nuances in healthy and infected body fluids, which allows to identify infection regardless of symptoms or any other clinical or laboratorial tests. Hence, when new measurements are performed on samples of unknown status and the corresponding data is submitted to such an algorithm, it will be possible to predict whether the source individual is infected or not. This work presents a new methodology for rapid and precise label-free diagnosing of SARS-CoV-2 infection in clinical samples, which combines spectroscopic data acquisition and analysis via artificial intelligence algorithms. Our results show an accuracy of 85% for detection of SARS-CoV-2 in nasopharyngeal swab samples collected from asymptomatic patients or with mild symptoms, as well as an accuracy of 97% in tracheal aspirate samples collected from critically ill COVID-19 patients under mechanical ventilation. Moreover, the acquisition and processing of the information is fast, simple, and cheaper than traditional approaches, suggesting this methodology as a promising tool for biomedical diagnosis vis-à-vis the emerging and re-emerging viral SARS-CoV-2 variant threats in the future.
The incidence of anal cancer has increased over the past 25 years, and HIV/HPV coinfection is the most important risk factor for anal squamous cell carcinoma. In this study, we demonstrated that the ...evaluation of systemic and compartmentalized anal mucosa immune response is relevant to differentiating HIV(+) patients at risk of anal intraepithelial neoplasia (AIN).
A systems biology approach was used to integrate different immunological parameters from anal mucosal tissue and peripheral blood assessed by phenotypic and intracytoplasmic analysis of lymphocytes and dendritic cell subsets.
Our data demonstrated that anal mucosal mononuclear cells from AIN(+)HIV(+) patients showed a robust capacity in producing proinflammatory/regulatory cytokines, mainly mTNF-α > IL-4 > IL-10 > IL-6 = IL-17A. Mucosal TNF-α/IFN-γ/IL-17A are selective high-grade squamous intraepithelial lesion (HSIL)-related biomarkers. Higher levels of circulating CD11cCD123cells and CD1a cells along with elevated levels of IFN-γCD4 T cells are major features associated with HSIL in AIN(+)HIV(+) patients. Regardless of the presence of AIN, HIV(+) patients presented a complex biomarker network, rich in negative connections. Among those patients, however, HSIL+ patients displayed stronger positive links between peripheral blood and anal mucosa environments, exemplified by the subnet of IL-17A/TNF-α/CD4IFN-γ/CD11cCD123 cells.
The significant association between HSIL and the levels of TNF-α/IL-17A/IFN-γ along with the different subsets of DCs present in the anal mucosa milieu should be studied in more detail as a way to identify and categorize HIV(+) patients vis à vis the high risk of anal cancer outcome.
A data set corresponding to an integrated luminosity of 9 fb(-1) of proton-proton collisions collected by the LHCb experiment has been analysed to search for D-(s)(()*())+ ((D) over bar)(*)0 decays. ...The decays are fully or partially reconstructed, where one or two (8) missing neutral pions or photons from the decay of an excited charm meson are allowed. Upper limits for the branching fractions, normalised to B+ decays to final states with similar topologies, are obtained for sixteen B-c(+) decay modes. For the decay B-c(+) -> D-s(+)(D) over bar (0), an excess with a significance of 3.4 standard deviations is found.
Observation of new excited $${B} ^0_{s} $$ states Aiola, S.; Albero, A. Alfonso; Artamonov, A. ...
The European physical journal. C, Particles and fields,
07/2021, Letnik:
81, Številka:
7
Journal Article
Recenzirano
Odprti dostop
Abstract
A structure is observed in the
$${B} ^{\pm }{K} ^{\mp }$$
B
±
K
∓
mass spectrum in a sample of proton–proton collisions at centre-of-mass energies of 7, 8, and 13 TeV, collected with the ...LHCb detector and corresponding to a total integrated luminosity of 9
$$\,\text {fb} ^{-1}$$
fb
-
1
. The structure is interpreted as the result of overlapping excited
$${B} ^0_{s} $$
B
s
0
states. With high significance, a two-peak hypothesis provides a better description of the data than a single resonance. Under this hypothesis the masses and widths of the two states, assuming they decay directly to
$${B} ^{\pm }{K} ^{\mp }$$
B
±
K
∓
, are determined to be
$$\begin{aligned} m_1&= 6063.5 \pm 1.2 \text { (stat)} \pm 0.8\text { (syst)}\,\text {Me}\text {V}, \\ \Gamma _1&= 26 \pm 4 \text { (stat)} \pm 4\text { (syst)}\,\text {Me}\text {V}, \\ m_2&= 6114 \pm 3 \text { (stat)} \pm 5\text { (syst)}\,\text {Me}\text {V}, \\ \Gamma _2&= 66 \pm 18 \text { (stat)} \pm 21\text { (syst)}\,\text {Me}\text {V}. \end{aligned}$$
m
1
=
6063.5
±
1.2
(stat)
±
0.8
(syst)
Me
,
Γ
1
=
26
±
4
(stat)
±
4
(syst)
Me
,
m
2
=
6114
±
3
(stat)
±
5
(syst)
Me
,
Γ
2
=
66
±
18
(stat)
±
21
(syst)
Me
.
Alternative values assuming a decay through
$${B} ^{*\pm }{K} ^{\mp }$$
B
∗
±
K
∓
, with a missing photon from the
$$B^{*\pm } \rightarrow B^{\pm }\gamma $$
B
∗
±
→
B
±
γ
decay, which are shifted by approximately 45
$$\,\text {Me}$$
Me
V, are also determined. The possibility of a single state decaying in both channels is also considered. The ratio of the total production cross-section times branching fraction of the new states relative to the previously observed
$$B_{s2}^{*0}$$
B
s
2
∗
0
state is determined to be
$$0.87 \pm 0.15 \text { (stat)} \pm 0.19 \text { (syst)}$$
0.87
±
0.15
(stat)
±
0.19
(syst)
.
Summary
Cutaneous leishmaniasis (CL) treatment is based on therapy with Glucantime®, yet, there are few laboratory methods to monitor its success. In this study, ex vivo and in vitro evaluations of ...peripheral blood monocytes were performed in a longitudinal study to characterize the impact of Glucantime® on overall phenotypic/functional features of these cells from CL patients to identify predictive biomarkers for post‐therapeutic monitoring by flow cytometry. The ex vivo evaluation from CL patients demonstrated a modulatory profile before treatment, with a decrease in TLR‐2, FcγRII, HLA‐DR, CD86, IFN‐γR, TNF, IL‐12, NO, and an increase in FcγRIII and IL‐10R. Conversely, treatment changes some of these biomarker expressions by decreasing FcγRIII and IL‐10R and increasing IFN‐γR, IL‐12 and NO. Moreover, an in vitro analysis of these patients showed a reduced phagocytic capacity of Leishmania braziliensis and higher levels of IL‐10 and TGF‐β modulating functional profile. Regardless of the compromised L. braziliensis phagocytic capacity, treatment re‐established the production of IL‐12, IL‐10, TGF‐β and NO at the basal level. Notably, monocytes from patients with early cicatrization showed enhanced FcγRI and FcγRII expressions and reduced IL‐10, which was further corroborated by a baseline fold change analysis. Finally, the logistic regression model emphasized the performance of FcγRI, FcγRII and IL‐10 as robust predictive biomarkers for post‐therapeutic cicatrization during cutaneous leishmaniasis.
IntroductionLeptospirosis is a globally distributed zoonotic and environmentally mediated disease that has emerged as a major health problem in urban slums in developing countries. Its aetiological ...agent is bacteria of the genus Leptospira, which are mainly spread in the urine of infected rodents, especially in an environment where adequate sanitation facilities are lacking, and it is known that open sewers are key transmission sources of the disease. Therefore, we aim to evaluate the effectiveness of a simplified sewerage intervention in reducing the risk of exposure to contaminated environments and Leptospira infection and to characterise the transmission mechanisms involved.Methods and analysisThis matched quasi-experimental study design using non-randomised intervention and control clusters was designed to assess the effectiveness of an urban simplified sewerage intervention in the low-income communities of Salvador, Brazil. The intervention consists of household-level piped sewerage connections and community engagement and public involvement activities. A cohort of 1400 adult participants will be recruited and grouped into eight clusters consisting of four matched intervention-control pairs with approximately 175 individuals in each cluster in baseline. The primary outcome is the seroincidence of Leptospira infection assessed through five serological measurements: one preintervention (baseline) and four postintervention. As a secondary outcome, we will assess Leptospira load in soil, before and after the intervention. We will also assess Leptospira exposures before and after the intervention, through transmission modelling, accounting for residents' movement, contact with flooding, contaminated soil and water, and rat infestation, to examine whether and how routes of exposure for Leptospira change following the introduction of sanitation.Ethics and disseminationThis study protocol has been reviewed and approved by the ethics boards at the Federal University of Bahia and the Brazilian National Research Ethics Committee. Results will be disseminated through peer-reviewed publications and presentations to implementers, researchers and participating communities.Trial registration numberBrazilian Clinical Trials Registry (RBR-8cjjpgm).
Abstract
The Spodoptera complex of the family Noctuidae, represented here by S. frugiperda (J.E. Smith), S. eridania (Stoll), S. albula (Walker), and S. cosmioides (Walker), is an important group of ...crop pests in Brazil. Spodoptera frugiperda and S. eridania are invasive in Africa, and the former also in Asia and Oceania. The egg parasitoids Telenomus remus Nixon (Hymenoptera: Scelionidae) and Trichogramma spp. (Hymenoptera: Trichogrammatidae) are potential control agents for field use against these noctuids. We evaluated the parasitism efficiency, development, and flight capacity of an isofemale line and a regular line of T. remus, and 2 genetically variable populations of Trichogramma pretiosum Riley and Trichogramma atopovirilia Oatman and Platner (Hymenoptera: Trichogrammatidae) in these 4 members of the Spodoptera complex. All parasitoids were able to develop in the 4 hosts. The parasitoids showed good flight capacity, except for the regular line of T. remus. The Trichogramma species, despite having high viability and female:male sex ratios, showed poorer parasitism performances than T. remus. The regular T. remus line also showed good parasitism capacity and high viability but had a predominance of males. In general, the isofemale line of T. remus showed good rates of parasitism and flight capacity as well as a high viability and sex ratio, proving to be a potential candidate for an augmentative biological-control program for Spodoptera spp Guenée (Lepidoptera: Noctuidae).
Single layer behavior in multilayer epitaxial graphene has been a matter of intense investigation. This is due to the layer decoupling that occurs during growth of graphene on some types of ...substrates, such as carbon-terminated silicon carbide. We show here that near-edge X-ray absorption spectroscopy can be used to observe the signature of this decoupling. To this end, samples of multilayer graphene from silicon carbide sublimation were grown with different degrees of decoupling. Raman spectroscopy was used to infer the degree of structural decoupling. X-ray grazing-incidence diffraction and scanning tunneling microscopy showed that growth initiates with the presence of bilayer graphene commensurate structures, while layer decoupling is associated to the formation of incommensurate structures observed for longer sublimation time. Near-edge X-ray absorption spectroscopy was used to probe the electronic states above the Fermi energy. Besides the σ* and π* empty states, image potential states are observed and show a clear change of intensity as a function of incident angle. These image potential states evolve from a graphite- to graphene-like behavior as a function of growth time and can be used to infer the degree of structural coupling among layers.
Display omitted
•Multilayer graphene was grown with different degrees of electronic decoupling•Raman spectroscopy was used to infer the degree of decoupling•Growth initiates with the presence of bilayer graphene commensurate structures•Near-edge X-ray absorption spectroscopy probed change of intensity of image potential states•These image potential states evolve from a graphite- to graphene-like behavior
To assess whether medical orders within Physician Orders for Life-Sustaining Treatment (POLST) forms reflect patients' preferences for care at the end of life.
This cross-sectional study assessed the ...agreement between medical orders in POLST forms and the free-form text documentation of an advance care planning conversation performed by an independent researcher during a single episode of hospitalization.
Inpatients at a single public university hospital, aged 21 years or older, and for whom one of their attending physicians provided a negative answer to the following question: "Would I be surprised if this patient died in the next year?" Data collection occurred between October 2016 and September 2017.
Agreement between medical orders in POLST forms and the free-form text documentation of an advance care planning conversation was measured by kappa statistics.
Sixty-two patients were interviewed. Patients' median (interquartile range) age was 62 (56-70) years, and 21 patients (34%) were women. Overall, in 7 (11%) cases, disagreement in at least 1 medical order for life-sustaining treatment was found between POLST forms and the content of the independent advance care planning conversation. The kappa statistic for cardiopulmonary resuscitation was 0.92 95% confidence interval (CI): 0.82-1.00; for level of medical intervention, 0.90 (95% CI: 0.81-0.99); and for artificially administered nutrition, 0.87 (95% CI: 0.75-0.98).
The high level of agreement between medical orders in POLST forms and the documentation in an independent advance care planning conversation offers further support for the POLST paradigm. In addition, the finding that the agreement was not 100% underscores the need to confirm frequently that POLST medical orders accurately reflect patients' current values and preferences of care.
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