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1.
Mycoses ; 67(9): e13799, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39289823

RESUMEN

BACKGROUND: Several clinical signs in dermatoscopy are very characteristic of onychomycosis and can be a quick complement for the diagnosis of onychomycosis. OBJECTIVES: The aim of this study was to evaluate the diagnostic accuracy of dermatoscopy compared to microbiological culture and polymerase chain reaction (PCR), as well as the clinical signs associated with onychomycosis. METHODS: The clinical signs of 125 patients were assessed cross-sectionally using dermatoscopy, and a positive or negative result was assigned. A sample was then taken for PCR and microbiological culture. RESULTS: Of the 125 patients, 69.6% (87/125) had positive results when both laboratory tests were combined. When they were not combined, the prevalence was lower at 48% (60/125) with PCR and at 43.2% (54/125) with culture. Furthermore, 76.8% (96/125) were classified as positive with dermatoscopy with a sensitivity of 1, a specificity of 0.76, positive predictive value of 0.91 and negative predictive value of 1 (with 95% confidence intervals). Of the 96 dermatoscopy-positive samples, 36 were negative with PCR (p < 0.001), 42 were negative with culture (p < 0.001) and nine were negative when both tests were combined (p < 0.001). Clinical signs that were significantly associated with the presence of onychomycosis were subungual hyperkeratosis (dermatoscopy: p = 0.004, odds ratio (OR) = 2.438; PCR + microbiological culture: p = 0.004, OR = 3.221), subungual detritus (p = 0.033, OR = 3.01, only with dermatoscopy) and dermatophytoma (dermatoscopy: p = 0.049, OR = 3.02; PCR + microbiological culture: p = 0.022, OR = 2.40). CONCLUSIONS: The results suggest that dermatoscopy is a good tool for the diagnosis of onychomycosis but should be used as a complementary test or for screening patients to be sampled for laboratory testing. The combination of the three tests can lead to a reduction of false-positive and false-negative clinical and laboratory results. This allows for early diagnosis and specific treatment based on test results.


Asunto(s)
Dermoscopía , Onicomicosis , Reacción en Cadena de la Polimerasa , Sensibilidad y Especificidad , Humanos , Onicomicosis/diagnóstico , Onicomicosis/microbiología , Estudios Transversales , Reacción en Cadena de la Polimerasa/métodos , Femenino , Masculino , Persona de Mediana Edad , Adulto , Anciano , Dermoscopía/métodos , Adulto Joven , Anciano de 80 o más Años , Adolescente , Técnicas Microbiológicas/métodos , Hongos/aislamiento & purificación , Hongos/genética , Valor Predictivo de las Pruebas
2.
Artículo en Inglés | MEDLINE | ID: mdl-39234867

RESUMEN

A polycrystalline sample LuCrO3 has been characterized by neutron powder diffraction (NPD) and magnetization measurements. Its crystal structure has been Rietveld refined from NPD data in space group Pnma; this perovskite contains strongly tilted CrO6 octahedra with extremely bent Cr-O-Cr superexchange angles of ∼142°. The NPD data show that below Néel temperature (TN ≃ 131 K), the magnetic structure can be defined as an A-type antiferromagnetic arrangement of Cr3+ magnetic moments, aligned along the b axis, with a canting along the c axis. A noticeable magnetostrictive effect is observed in the unit-cell parameters and volume upon cooling down across TN. The AC magnetic susceptibility indicates the onset of magnetic ordering below 112.6 K; the magnetization isotherms below TN show a nonlinear behaviour that is associated with the described canting of the Cr3+ magnetic moments. From the Curie-Weiss law, the effective moment of the Cr3+ sublattice is found to be µeff = 3.55 µB (calculated 3.7 µB) while the ΘCW parameter yields a value of -155 K, indicating antiferromagnetic interactions. There is a conspicuous increase of TN upon the application of external pressure, which must be due to shortening of the Cr-O bond length under compression that increases the orbital overlap integral.

3.
ACS Sens ; 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39241167

RESUMEN

The detection and monitoring of Pseudomonas aeruginosa and its virulence factors, such as the LasB protease, are crucial for managing bacterial infections. Traditional fluorescent sensors for this protease face limitations in bacterial cultures due to interference from pigments like pyoverdine secreted by this opportunistic pathogen. We report here a Ln(III)-metallopeptide that combines a DO3A-Ln(III) complex and a sensitizing unit via a short peptide sequence as a simple, tunable, and selective probe for detecting P. aeruginosa's LasB. The probe's luminescence switches off in the presence of P. aeruginosa's secretome due to LasB cleavage but remains stable in other bacterial environments, such as non-LasB-secreting P. aeruginosa strains or E. coli cultures. It also resists degradation by other proteases, like human leukocyte elastase and trypsin, and remains stable in the presence of bioanalytes related to P. aeruginosa infections, such as glutathione, H2O2, and pyocyanin, and in complex media like FBS. Importantly, time-gated experiments completely remove the background fluorescence of P. aeruginosa pigments, thus demonstrating the potential of the developed Ln(III)-metallopeptide for real-time monitoring of LasB activity in bacterial cultures.

4.
Nanoscale ; 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39221766

RESUMEN

Arrays of 50 nm diameter Fe85Pd15 cylindrical nanowires were electrochemically grown, crystallizing in a metastable γ-Fe(Pd) fcc A1 disordered solid solution. After performing a heating-cooling thermal cycle between 300 K and 1000 K, the γ-Fe(Pd) fcc metastable phase still predominates (97%), coexisting with a not-fully-identified minority phase. The thermal cycling induces a moderate increase in the crystallite size and a reduction of the lattice parameter although leading to a significant heating-cooling magnetic hysteresis. No further changes in temperature-dependent magnetization, M(T), are observed during subsequent cycling. The full-range (5 K to 800 K) saturation magnetization Ms(T) curve is quite accurately described by a phenomenological expression, which provides a Bloch-type contribution as T → 0 and undergoes the critical behavior near the Curie temperature TC. An upturn in Ms(T) is observed below 100 K which is described by a spin-glass-like second contribution, with freezing temperature Tf = (80 ± 2) K, and kBTf comparable to the exchange interactions in Fe-Pd systems. A Curie temperature of TC = 830 K, and a critical exponent value ß = 0.42 ± 0.05 are estimated. These regimes (below and above 100 K) are also observed in the magnetization process. The temperature dependence of coercivity between 100 K and 800 K is consistent with a nucleation/propagation remagnetization mechanism, with activation energy of (320 ± 20) kJ mol-1 and critical field for magnetization reversal of (65 ± 1) mT, at 0 K. The analysis of the effective magnetic anisotropy as a function of temperature allows us to conclude that it essentially arises from the balance between different magnetostatic contributions.

5.
Int J Low Extrem Wounds ; : 15347346241275186, 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39140372

RESUMEN

The objective of this study was to identify bone fractures and joint dislocations that have greater association with the severity of arch collapse in patients with Charcot foot involving the midfoot.A retrospective study in 28 (N = 29 feet) patients who had Charcot foot deformity of the midfoot. The study included stage III of Eichenholtz classification, and Schon classification types I to III. Talar-first metatarsal and calcaneal pitch angles and cuboid height were used to evaluate the severity of the midfoot deformity in a weightbearing lateral radiograph. Two investigators evaluated the bone fracture and joint dislocation involved in weightbearing antero-posterior and lateral radiographs.There were 13 (46%) feet that showed pattern 1, 9 (31%) feet with pattern 2, and 7 (25%) feet with pattern 3 according to the Schon classification. One foot had a combination of patterns 1 and 2. Midfoot ulceration occurred in 64% (n = 19) of feet. In the multivariate analysis, plantarflexion of talar-first metatarsal angle was predicted by navicular-medial cuneiform dislocation (p = .007 [-20.620-3.683]), an increase of the negative calcaneal pitch angle by fragmentation of the cuboid (p = .003 [-15.568-3.626]), and increment of the negative cuboid height by navicular-medial cuneiform and medial cuneiform-first metatarsal dislocations (p = .040 [-12.779-0.317], p = .002 [-13.437-3.267], respectively).Bone fractures and dislocations in the sagittal plane seem to contribute to midfoot collapse, but navicular-medial cuneiform dislocation/non-union and cuboid fragmentation predict severe rocker-bottom deformity in cases of Charcot foot.

6.
Behav Sci (Basel) ; 14(8)2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39199081

RESUMEN

Regular physical activity (PA) improves the psychological well-being of those who practice it. However, female university students are a risk group due to their low level of PA. Based on the transtheoretical model of behavioural change, the main aim of this study was to examine whether the relationship between PA and subjective vitality was mediated by cognitive-emotional variables such as decisional balance (perceived benefits and barriers) and enjoyment associated with PA in a group of female university students. Participants were asked to complete self-administered questionnaires, which were available for one month via a Google Form. The results showed the existence of a statistically significant, relative, and indirect effect between the stage of change and subjective vitality via both mediating variables. Compared to females in the pre-contemplation stage, those in the action and maintenance stages achieved higher subjective vitality scores as a result of the effect of being in a more advanced stage on decisional balance and enjoyment of PA. It is concluded that female university students who reported regular PA found the activity to be more revitalising, stimulating, and exciting; all positive feelings and cognitions that translated into a more energetic and vital perception of themselves.

7.
Healthcare (Basel) ; 12(16)2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39201221

RESUMEN

BACKGROUND/OBJECTIVES: To analyze the best noninvasive tests prognosis marker in patients with diabetic foot ulcer (DFU) who underwent endovascular revascularization based on clinical outcomes, such as healing rate, time to heal, and free amputation survival after at least a six-month follow-up. METHODS: A multicentric prospective observational study was performed with 28 participants with ischemic or neuroischemic DFU who came to the participant centers and underwent endovascular revascularization between January 2022 and March 2023. Toe systolic pressure (TP), ankle systolic pressure (AP), the ankle brachial pressure index (ABPI), the toe brachial pressure index (TBPI), transcutaneous pressure of oxygen (TcPO2), and skin perfusion pressure (SPP) were evaluated using PeriFlux 6000 System, Perimed, Sweden, before (Visit 0) and four weeks after revascularization (Visit 1). The primary clinical outcome was an evaluation of the clinical evolution of noninvasive tests comparing Visit 0 and Visit 1, estimating the sensitivity for predicting wound healing of noninvasive tests at six months following initial recruitment. RESULTS: After six months, 71.43% (n = 20) of DFU healed, four patients (14.3%) received major amputations, and one (3.5%) died. The two tests that best predicted wound healing after revascularization according to the ROC curve were TcPO2 and TP with sensitivities of 0.89 and 0.70 for the cut-off points of 24 mmHg and 46 mmHg, respectively. CONCLUSIONS: TcPO2 and TP were the two tests that best predicted wound healing in patients who underwent endovascular revascularization. Clinicians should consider the importance of the evaluation of microcirculation in the healing prognosis of patients with diabetic foot ulcers.

8.
Viruses ; 16(8)2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39205281

RESUMEN

BACKGROUND: There are multiple conservative treatment options for plantar warts, but none have proven to be universally effective. Nitric acid is often used empirically by podiatrists in the treatment of plantar warts. A novel medical device or topical solution of nitric-zinc complex solution (NZCS) could potentially offer an effective and safe alternative for the targeted treatment of plantar warts. OBJECTIVE: To observe the rate of complete healing of NZCS in a series of plantar wart cases and to establish the minimum number of product applications and time needed for healing. This will help standardize and protocolize its use. METHODS: A descriptive study was conducted involving 72 patients who exhibited symptoms of plantar warts. These patients underwent chemical treatment using a nitric-zinc complex. RESULTS: The cure rate with NZCS was 59.2%. The average number of NZCS applications was 5.9 ± 3.0 and the mean duration of treatment was 9.4 ± 7.1 weeks. A recurrence rate of 6.7% was observed. CONCLUSIONS: The topical solution of the nitric-zinc complex is an effective treatment for plantar warts, which can be considered a first-line treatment option in the general population.


Asunto(s)
Verrugas , Zinc , Verrugas/tratamiento farmacológico , Humanos , Zinc/uso terapéutico , Masculino , Femenino , Adulto , Adulto Joven , Adolescente , Resultado del Tratamiento , Persona de Mediana Edad , Niño , Ácido Nítrico/química , Administración Tópica
9.
Int J Biol Macromol ; 277(Pt 3): 134298, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39097051

RESUMEN

Antibiotic resistance is one of most important health concerns nowadays, and ß-lactamases are the most important resistance determinants. These enzymes, based on their structural and functional characteristics, are grouped in four categories (A, B, C and D). We have solved the structure of PIB-1, a Pseudomonas aeruginosa chromosomally-encoded ß-lactamase, in its apo form and in complex with meropenem and zinc. These crystal structures show that it belongs to the Class C ß-lactamase group, although it shows notable differences, especially in the Ω- and P2-loops, which are important for the enzymatic activity. Functional analysis showed that PIB-1 is able to degrade carbapenems but not cephalosporins, the typical substrate of Class C ß-lactamases, and that its catalytic activity increases in the presence of metal ions, especially zinc. They do not bind to the active-site but they induce the formation of trimers that show an increased capacity for the degradation of the antibiotics, suggesting that this oligomer is more active than the other oligomeric species. While PIB-1 is structurally a Class C ß-lactamase, the low sequence conservation, substrate profile and its metal-dependence, prompts us to position this enzyme as the founder of a new group inside the Class C ß-lactamases. Consequently, its diversity might be wider than expected.


Asunto(s)
Carbapenémicos , Pseudomonas aeruginosa , Zinc , beta-Lactamasas , Pseudomonas aeruginosa/enzimología , beta-Lactamasas/química , beta-Lactamasas/metabolismo , Carbapenémicos/farmacología , Carbapenémicos/metabolismo , Carbapenémicos/química , Zinc/metabolismo , Zinc/química , Modelos Moleculares , Dominio Catalítico , Hidrólisis , Especificidad por Sustrato , Metales/metabolismo , Metales/química , Metales/farmacología , Relación Estructura-Actividad , Meropenem/farmacología , Meropenem/química , Meropenem/metabolismo , Secuencia de Aminoácidos , Cristalografía por Rayos X
10.
Int Wound J ; 21(7): e14964, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38994863

RESUMEN

Negative pressure wound therapy is currently one of the most popular treatment approaches that provide a series of benefits to facilitate healing, including increased local blood perfusion with reduced localized oedema and control of wound exudate. The porous foam dressing is a critical element in the application of this therapy and its choice is based on its ability to manage exudate. Industry standards often employ aqueous solutions devoid of proteins to assess dressing performance. However, such standardized tests fail to capture the intricate dynamics of real wounds, oversimplifying the evaluation process. This study aims to evaluate the technical characteristics of two different commercial polyurethane foam dressings during negative pressure wound therapy. We introduce an innovative experimental model designed to evaluate the effects of this therapy on foam dressings in the presence of viscous exudates. Our findings reveal a proportional increase in dressing fibre occupancy as pressure intensifies, leading to a reduction in dressing pore size. The tests underscore the pressure system's diminished efficacy in fluid extraction with increasing fluid viscosity. Our discussion points to the need of establishing standardized guidelines for foam dressing selection based on pore size and the necessity of incorporating real biological exudates into industrial standards.


Asunto(s)
Exudados y Transudados , Microscopía Confocal , Terapia de Presión Negativa para Heridas , Poliuretanos , Cicatrización de Heridas , Terapia de Presión Negativa para Heridas/métodos , Humanos , Viscosidad , Microscopía Confocal/métodos , Vendajes , Heridas y Lesiones/terapia
11.
Nanomaterials (Basel) ; 14(13)2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38998771

RESUMEN

Bimetallic nanomaterials have generated significant interest across diverse scientific disciplines, due to their unique and tunable properties arising from the synergistic combination of two distinct metallic elements. This study presents a novel approach for synthesizing branched gold-platinum nanoparticles by utilizing poly(allylamine hydrochloride) (PAH)-stabilized branched gold nanoparticles, with a localized surface plasmon resonance (LSPR) response of around 1000 nm, as a template for platinum deposition. This approach allows precise control over nanoparticle size, the LSPR band, and the branching degree at an ambient temperature, without the need for high temperatures or organic solvents. The resulting AuPt branched nanoparticles not only demonstrate optical activity but also enhanced catalytic properties. To evaluate their catalytic potential, we compared the enzymatic capabilities of gold and gold-platinum nanoparticles by examining their peroxidase-like activity in the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB). Our findings revealed that the incorporation of platinum onto the gold surface substantially enhanced the catalytic efficiency, highlighting the potential of these bimetallic nanoparticles in catalytic applications.

12.
Microb Biotechnol ; 17(7): e14528, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39016996

RESUMEN

Different international agencies recognize that antibiotic resistance is one of the most severe human health problems that humankind is facing. Traditionally, the introduction of new antibiotics solved this problem but various scientific and economic reasons have led to a shortage of novel antibiotics at the pipeline. This situation makes mandatory the implementation of approaches to preserve the efficacy of current antibiotics. The concept is not novel, but the only action taken for such preservation had been the 'prudent' use of antibiotics, trying to reduce the selection pressure by reducing the amount of antibiotics. However, even if antibiotics are used only when needed, this will be insufficient because resistance is the inescapable outcome of antibiotics' use. A deeper understanding of the alterations in the bacterial physiology upon acquisition of resistance and during infection will help to design improved strategies to treat bacterial infections. In this article, we discuss the interconnection between antibiotic resistance (and antibiotic activity) and bacterial metabolism, particularly in vivo, when bacteria are causing infection. We discuss as well how understanding evolutionary trade-offs, as collateral sensitivity, associated with the acquisition of resistance may help to define evolution-based therapeutic strategies to fight antibiotic resistance and to preserve currently used antibiotics.


Asunto(s)
Antibacterianos , Bacterias , Infecciones Bacterianas , Farmacorresistencia Bacteriana , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Bacterias/efectos de los fármacos , Bacterias/genética , Bacterias/metabolismo , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/microbiología , Humanos , Animales
13.
Eur. j. nucl. med. mol. imaging ; 51(8): 2229-2246, 20240701. tab
Artículo en Inglés | BIGG - guías GRADE | ID: biblio-1562449

RESUMEN

Consensus on the choice of the most accurate imaging strategy in diabetic foot infective and non-infective complications is still lacking. This document provides evidence-based recommendations, aiming at defining which imaging modality should be preferred in different clinical settings. This working group includes 8 nuclear medicine physicians appointed by the European Association of Nuclear Medicine (EANM), 3 radiologists and 3 clinicians (one diabetologist, one podiatrist and one infectious diseases specialist) selected for their expertise in diabetic foot. The latter members formulated some clinical questions that are not completely covered by current guidelines. These questions were converted into statements and addressed through a systematic analysis of available literature by using the PICO (Population/Problem­Intervention/Indicator­Comparator­Outcome) strategy. Each consensus statement was scored for level of evidence and for recommendation grade, according to the Oxford Centre for Evidence-Based Medicine (OCEBM) criteria. Nine clinical questions were formulated by clinicians and used to provide 7 evidence-based recommendations: (1) A patient with a positive probe-to-bone test, positive plain X-rays and elevated ESR should be treated for presumptive osteomyelitis (OM). (2) Advanced imaging with MRI and WBC scintigraphy, or [18F]FDG PET/CT, should be considered when it is needed to better evaluate the location, extent or severity of the infection, in order to plan more tailored treatment. (3) In a patient with suspected OM, positive PTB test but negative plain X-rays, advanced imaging with MRI or WBC scintigraphy + SPECT/CT, or with [18F]FDG PET/CT, is needed to accurately assess the extent of the infection. (4) There are no evidence-based data to definitively prefer one imaging modality over the others for detecting OM or STI in fore- mid- and hind-foot. MRI is generally the first advanced imaging modality to be performed. In case of equivocal results, radiolabelled WBC imaging or [18F]FDG PET/CT should be used to detect OM or STI. (5) MRI is the method of choice for diagnosing or excluding Charcot neuro-osteoarthropathy; [18F]FDG PET/CT can be used as an alternative. (6) If assessing whether a patient with a Charcot foot has a superimposed infection, however, WBC scintigraphy may be more accurate than [18F]FDG PET/CT in differentiating OM from Charcot arthropathy. (7) Whenever possible, microbiological or histological assessment should be performed to confirm the diagnosis. (8) Consider appealing to an additional imaging modality in a patient with persisting clinical suspicion of infection, but negative imaging. These practical recommendations highlight, and should assist clinicians in understanding, the role of imaging in the diagnostic workup of diabetic foot complications.


Asunto(s)
Humanos , Osteomielitis/tratamiento farmacológico , Pie Diabético/diagnóstico por imagen , Espectroscopía de Resonancia Magnética , Antibacterianos/uso terapéutico
14.
ACS Appl Electron Mater ; 6(5): 2969-2977, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38828031

RESUMEN

Thermoelectric materials offer a promising avenue for energy management, directly converting heat into electrical energy. Among them, AgSbTe2 has gained significant attention and continues to be a subject of research at further improving its thermoelectric performance and expanding its practical applications. This study focuses on Ag-deficient Ag0.7Sb1.12Te2 and Ag0.7Sb1.12Te1.95Se0.05 materials, examining the impact of compositional engineering within the AgSbTe2 thermoelectric system. These materials have been rapidly synthesized using an arc-melting technique, resulting in the production of dense nanostructured pellets. Detailed analysis through scanning electron microscopy (SEM) reveals the presence of a layered nanostructure, which significantly influences the thermoelectric properties of these materials. Synchrotron X-ray diffraction reveals significant changes in the lattice parameters and atomic displacement parameters (ADPs) that suggest a weakening of bond order in the structure. The thermoelectric characterization highlights the enhanced power factor of Ag-deficient materials that, combined with the low glass-like thermal conductivity, results in a significant improvement in the figure of merit, achieving zT values of 1.25 in Ag0.7Sb1.12Te2 and 1.01 in Ag0.7Sb1.12Te1.95Se0.05 at 750 K.

15.
Inorg Chem ; 63(27): 12641-12650, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38920333

RESUMEN

Metal halide perovskites with a two-dimensional structure are utilized in photovoltaics and optoelectronics. High-crystallinity CsSn2Br5 specimens have been synthesized via ball milling. Differential scanning calorimetry curves show melting at 553 K (endothermic) and recrystallization at 516 K (exothermic). Structural analysis using synchrotron X-ray diffraction data, collected from 100 to 373 K, allows for the determination of Debye model parameters. This analysis provides insights into the relative Cs-Br and Sn-Br chemical bonds within the tetragonal structure (space group: I4/mcm), which remains stable throughout the temperature range studied. Combined with neutron data, X-N techniques permit the identification of the Sn2+ lone electron pair (5s2) in the two-dimensional framework, occupying empty space opposite to the four Sn-Br bonds of the pyramidal [SnBr4] coordination polyhedra. Additionally, diffuse reflectance UV-vis spectroscopy unveils an indirect optical gap of approximately ∼3.3 eV, aligning with the calculated value from the B3LYP-DFT method (∼3.2 eV). The material exhibits a positive Seebeck coefficient as high as 6.5 × 104 µV K-1 at 350 K, which evolves down to negative values of -3.0 × 103 µV K-1 at 550 K, surpassing values reported for other halide perovskites. Notably, the thermal conductivity remains exceptionally low, between 0.32 and 0.25 W m-1 K-1.

18.
EBioMedicine ; 105: 105185, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38848648

RESUMEN

BACKGROUND: In order to prevent the emergence and spread of future variants of concern of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), developing vaccines capable of stopping transmission is crucial. The SARS-CoV-2 vaccine NDV-HXP-S can be administered live intranasally (IN) and thus induce protective immunity in the upper respiratory tract. The vaccine is based on Newcastle disease virus (NDV) expressing a stabilised SARS-CoV-2 spike protein. NDV-HXP-S can be produced as influenza virus vaccine at low cost in embryonated chicken eggs. METHODS: The NDV-HXP-S vaccine was genetically engineered to match the Omicron variants of concern (VOC) BA.1 and BA.5 and tested as an IN two or three dose vaccination regimen in female mice. Furthermore, female mice intramuscularly (IM) vaccinated with mRNA-lipid nanoparticles (LNPs) were IN boosted with NDV-HXP-S. Systemic humoral immunity, memory T cell responses in the lungs and spleens as well as immunoglobulin A (IgA) responses in distinct mucosal tissues were characterised. FINDINGS: NDV-HXP-S Omicron variant vaccines elicited high mucosal IgA and serum IgG titers against respective SARS-CoV-2 VOC in female mice following IN administration and protected against challenge from matched variants. Additionally, antigen-specific memory B cells and local T cell responses in the lungs were induced. Host immunity against the NDV vector did not interfere with boosting. Intramuscular vaccination with mRNA-LNPs was enhanced by IN NDV-HXP-S boosting resulting in improvement of serum neutralization titers and induction of mucosal immunity. INTERPRETATION: We demonstrate that NDV-HXP-S Omicron variant vaccines utilised for primary immunizations or boosting efficiently elicit humoral and cellular immunity. The described induction of systemic and mucosal immunity has the potential to reduce infection and transmission. FUNDING: This work was partially funded by the NIAIDCenters of Excellence for Influenza Research and Response (CEIRR) and by the NIAID Collaborative Vaccine Innovation Centers and by institutional funding from the Icahn School of Medicine at Mount Sinai. See under Acknowledgements for details.


Asunto(s)
Administración Intranasal , Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , Inmunidad Humoral , Inmunidad Mucosa , Virus de la Enfermedad de Newcastle , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Animales , Femenino , SARS-CoV-2/inmunología , SARS-CoV-2/genética , Ratones , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , COVID-19/prevención & control , COVID-19/inmunología , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/genética , Virus de la Enfermedad de Newcastle/inmunología , Virus de la Enfermedad de Newcastle/genética , Inmunidad Celular , Inmunoglobulina A/inmunología , Nanopartículas/administración & dosificación , Nanopartículas/química , Anticuerpos Neutralizantes/inmunología , Vacunación/métodos , Humanos , Liposomas
19.
World J Microbiol Biotechnol ; 40(7): 226, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38822187

RESUMEN

Multidrug efflux pumps are protein complexes located in the cell envelope that enable bacteria to expel, not only antibiotics, but also a wide array of molecules relevant for infection. Hence, they are important players in microbial pathogenesis. On the one hand, efflux pumps can extrude exogenous compounds, including host-produced antimicrobial molecules. Through this extrusion, pathogens can resist antimicrobial agents and evade host defenses. On the other hand, efflux pumps also have a role in the extrusion of endogenous compounds, such as bacterial intercommunication signaling molecules, virulence factors or metabolites. Therefore, efflux pumps are involved in the modulation of bacterial behavior and virulence, as well as in the maintenance of the bacterial homeostasis under different stresses found within the host. This review delves into the multifaceted roles that efflux pumps have, shedding light on their impact on bacterial virulence and their contribution to bacterial infection. These observations suggest that strategies targeting bacterial efflux pumps could both reinvigorate the efficacy of existing antibiotics and modulate the bacterial pathogenicity to the host. Thus, a comprehensive understanding of bacterial efflux pumps can be pivotal for the development of new effective strategies for the management of infectious diseases.


Asunto(s)
Antibacterianos , Bacterias , Infecciones Bacterianas , Proteínas Bacterianas , Farmacorresistencia Bacteriana Múltiple , Proteínas de Transporte de Membrana , Factores de Virulencia , Antibacterianos/farmacología , Proteínas de Transporte de Membrana/metabolismo , Proteínas Bacterianas/metabolismo , Bacterias/metabolismo , Bacterias/patogenicidad , Infecciones Bacterianas/microbiología , Virulencia , Factores de Virulencia/metabolismo , Humanos , Animales
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