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1.
J Neurosurg Case Lessons ; 7(16)2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38621303

RESUMO

BACKGROUND: Phantom limb pain and traumatic neuromas are not commonly seen in neurosurgical practice. These conditions can present with similar symptoms; however, management of traumatic neuroma is often surgical, whereas phantom limb pain is treated with conservative measures. OBSERVATIONS: A 77-year-old female patient with a long-standing history of an above-the-knee amputation experienced severe pain in her right posterior buttocks area for several years' duration, attributed to phantom limb pain, which radiated down the stump of her leg and was treated with a variety of conservative measures. A recent exacerbation of her pain led to a prolonged hospitalization with magnetic resonance imaging of her leg stump, revealing a mass in the sciatic notch, at a relative distance from the stump. The anatomical location of the mass on the sciatic nerve in the notch led to a presumed radiological diagnosis of nerve sheath tumor, for which she underwent excision. At surgery, a neuroma of the proximal portion of the transected sciatic nerve that had retracted from the amputated stump to the notch was diagnosed. LESSONS: Traumatic neuromas of transected major nerves after limb amputation should be considered in the differential diagnosis of phantom limb pain.

2.
PLoS Negl Trop Dis ; 18(4): e0012117, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38630833

RESUMO

Filariasis, a neglected tropical disease caused by roundworms, is a significant public health concern in many tropical countries. Microscopic examination of blood samples can detect and differentiate parasite species, but it is time consuming and requires expert microscopists, a resource that is not always available. In this context, artificial intelligence (AI) can assist in the diagnosis of this disease by automatically detecting and differentiating microfilariae. In line with the target product profile for lymphatic filariasis as defined by the World Health Organization, we developed an edge AI system running on a smartphone whose camera is aligned with the ocular of an optical microscope that detects and differentiates filarias species in real time without the internet connection. Our object detection algorithm that uses the Single-Shot Detection (SSD) MobileNet V2 detection model was developed with 115 cases, 85 cases with 1903 fields of view and 3342 labels for model training, and 30 cases with 484 fields of view and 873 labels for model validation before clinical validation, is able to detect microfilarias at 10x magnification and distinguishes four species of them at 40x magnification: Loa loa, Mansonella perstans, Wuchereria bancrofti, and Brugia malayi. We validated our augmented microscopy system in the clinical environment by replicating the diagnostic workflow encompassed examinations at 10x and 40x with the assistance of the AI models analyzing 18 samples with the AI running on a middle range smartphone. It achieved an overall precision of 94.14%, recall of 91.90% and F1 score of 93.01% for the screening algorithm and 95.46%, 97.81% and 96.62% for the species differentiation algorithm respectively. This innovative solution has the potential to support filariasis diagnosis and monitoring, particularly in resource-limited settings where access to expert technicians and laboratory equipment is scarce.

3.
Microsc Microanal ; 30(1): 151-159, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38302194

RESUMO

Analysis of bone marrow aspirates (BMAs) is an essential step in the diagnosis of hematological disorders. This analysis is usually performed based on a visual examination of samples under a conventional optical microscope, which involves a labor-intensive process, limited by clinical experience and subject to high observer variability. In this work, we present a comprehensive digital microscopy system that enables BMA analysis for cell type counting and differentiation in an efficient and objective manner. This system not only provides an accessible and simple method to digitize, store, and analyze BMA samples remotely but is also supported by an Artificial Intelligence (AI) pipeline that accelerates the differential cell counting process and reduces interobserver variability. It has been designed to integrate AI algorithms with the daily clinical routine and can be used in any regular hospital workflow.


Assuntos
Inteligência Artificial , Doenças Hematológicas , Humanos , Medula Óssea , Microscopia , Doenças Hematológicas/diagnóstico , Algoritmos
4.
Am J Trop Med Hyg ; 109(5): 1192-1198, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37918001

RESUMO

Low-income countries carry approximately 90% of the global burden of visual impairment, and up to 80% of this could be prevented or cured. However, there are only a few studies on the prevalence of retinal disease in these countries. Easier access to retinal information would allow differential diagnosis and promote strategies to improve eye health, which are currently scarce. This pilot study aims to evaluate the functionality and usability of a tele-retinography system for the detection of retinal pathology, based on a low-cost portable retinal scanner, manufactured with 3D printing and controlled by a mobile phone with an application designed ad hoc. The study was conducted at the Manhiça Rural Hospital in Mozambique. General practitioners, with no specific knowledge of ophthalmology or previous use of retinography, performed digital retinographies on 104 hospitalized patients. The retinographies were acquired in video format, uploaded to a web platform, and reviewed centrally by two ophthalmologists, analyzing the image quality and the presence of retinal lesions. In our sample there was a high proportion of exudates and hemorrhages-8% and 4%, respectively. In addition, the presence of lesions was studied in patients with known underlying risk factors for retinal disease, such as HIV, diabetes, and/or hypertension. Our tele-retinography system based on a smartphone coupled with a simple and low-cost 3D printed device is easy to use by healthcare personnel without specialized ophthalmological knowledge and could be applied for the screening and initial diagnosis of retinal pathology.


Assuntos
Doenças Retinianas , Smartphone , Humanos , Moçambique/epidemiologia , Projetos Piloto , Programas de Rastreamento/métodos , Doenças Retinianas/diagnóstico por imagem , Doenças Retinianas/epidemiologia , Impressão Tridimensional
5.
J Chem Phys ; 159(15)2023 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-37861120

RESUMO

The phase behavior and structural properties of hard anisotropic particles (prisms and dumbbells) are examined in one-dimensional channels using the Parsons-Lee (PL) theory, and the transfer-matrix and neighbor-distribution methods. The particles are allowed to move freely along the channel, while their orientations are constrained such that one particle can occupy only two or three different lengths along the channel. In this confinement setting, hard prisms behave as an additive mixture, while hard dumbbells behave as a non-additive one. We prove that all methods provide exact results for the phase properties of hard prisms, while only the neighbor-distribution and transfer-matrix methods are exact for hard dumbbells. This shows that non-additive effects are incorrectly included into the PL theory, which is a successful theory of the isotropic-nematic phase transition of rod-like particles in higher dimensions. In the one-dimensional channel, the orientational ordering develops continuously with increasing density, i.e., the system is isotropic only at zero density, while it becomes perfectly ordered at the close-packing density. We show that there is no orientational correlation in the hard prism system, while the hard dumbbells are orientationally correlated with diverging correlation length at close packing. On the other hand, positional correlations are present for all the systems, the associated correlation length diverging at close packing.

6.
Nature ; 623(7985): 157-166, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37853118

RESUMO

Immunotherapy failures can result from the highly suppressive tumour microenvironment that characterizes aggressive forms of cancer such as recurrent glioblastoma (rGBM)1,2. Here we report the results of a first-in-human phase I trial in 41 patients with rGBM who were injected with CAN-3110-an oncolytic herpes virus (oHSV)3. In contrast to other clinical oHSVs, CAN-3110 retains the viral neurovirulence ICP34.5 gene transcribed by a nestin promoter; nestin is overexpressed in GBM and other invasive tumours, but not in the adult brain or healthy differentiated tissue4. These modifications confer CAN-3110 with preferential tumour replication. No dose-limiting toxicities were encountered. Positive HSV1 serology was significantly associated with both improved survival and clearance of CAN-3110 from injected tumours. Survival after treatment, particularly in individuals seropositive for HSV1, was significantly associated with (1) changes in tumour/PBMC T cell counts and clonal diversity, (2) peripheral expansion/contraction of specific T cell clonotypes; and (3) tumour transcriptomic signatures of immune activation. These results provide human validation that intralesional oHSV treatment enhances anticancer immune responses even in immunosuppressive tumour microenvironments, particularly in individuals with cognate serology to the injected virus. This provides a biological rationale for use of this oncolytic modality in cancers that are otherwise unresponsive to immunotherapy (ClinicalTrials.gov: NCT03152318 ).


Assuntos
Neoplasias Encefálicas , Glioblastoma , Herpesvirus Humano 1 , Terapia Viral Oncolítica , Vírus Oncolíticos , Humanos , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/patologia , Glioblastoma/imunologia , Glioblastoma/patologia , Nestina/genética , Terapia Viral Oncolítica/efeitos adversos , Vírus Oncolíticos/genética , Vírus Oncolíticos/imunologia , Vírus Oncolíticos/fisiologia , Reprodutibilidade dos Testes , Análise de Sobrevida , Linfócitos T/citologia , Linfócitos T/imunologia , Resultado do Tratamento , Microambiente Tumoral/imunologia , Herpesvirus Humano 1/genética , Herpesvirus Humano 1/imunologia , Herpesvirus Humano 1/fisiologia
7.
Front Microbiol ; 14: 1197399, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37538842

RESUMO

Plant-microbiota interactions have significant effects on plant growth, health, and productivity. Rhizosphere microorganisms are involved in processes that promote physiological responses to biotic and abiotic stresses in plants. In recent years, the interest in microorganisms to improve plant productivity has increased, mainly aiming to find promising strains to overcome the impact of climate change on crops. In this work, we hypothesize that given the desertic environment of the Antarctic and the Atacama Desert, different plant species inhabiting these areas might share microbial taxa with functions associated with desiccation and drought stress tolerance. Therefore, in this study, we described and compared the composition of the rhizobacterial community associated with Deschampsia antarctica (Da), Colobanthus quitensis (Cq) from Antarctic territories, and Croton chilensis (Cc), Eulychnia iquiquensis (Ei) and Nicotiana solanifolia (Ns) from coastal Atacama Desert environments by using 16S rRNA amplicon sequencing. In addition, we evaluated the putative functions of that rhizobacterial community that are likely involved in nutrient acquisition and stress tolerance of these plants. Even though each plant microbial rhizosphere presents a unique taxonomic pattern of 3,019 different sequences, the distribution at the genus level showed a core microbiome with a higher abundance of Haliangium, Bryobacter, Bacillus, MND1 from the Nitrosomonadaceae family, and unclassified taxa from Gemmatiamonadaceae and Chitinophagaceae families in the rhizosphere of all samples analyzed (781 unique sequences). In addition, species Gemmatirosa kalamazoonesis and Solibacter usitatus were shared by the core microbiome of both Antarctic and Desert plants. All the taxa mentioned above had been previously associated with beneficial effects in plants. Also, this microbial core composition converged with the functional prediction related to survival under harsh conditions, including chemoheterotrophy, ureolysis, phototrophy, nitrogen fixation, and chitinolysis. Therefore, this study provides relevant information for the exploration of rhizospheric microorganisms from plants in extreme conditions of the Atacama Desert and Antarctic as promising plant growth-promoting rhizobacteria.

8.
Phys Rev E ; 108(1-1): 014902, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37583179

RESUMO

The importance of roughness in the modeling of granular gases has been increasingly considered in recent years. In this paper, a freely evolving homogeneous granular gas of inelastic and rough hard disks or spheres is studied under the assumptions of the Boltzmann kinetic equation. The homogeneous cooling state is studied from a theoretical point of view using a Sonine approximation, in contrast to a previous Maxwellian approach. A general theoretical description is done in terms of d_{t} translational and d_{r} rotational degrees of freedom, which accounts for the cases of spheres (d_{t}=d_{r}=3) and disks (d_{t}=2, d_{r}=1) within a unified framework. The non-Gaussianities of the velocity distribution function of this state are determined by means of the first nontrivial cumulants and by the derivation of non-Maxwellian high-velocity tails. The results are validated by computer simulations using direct simulation Monte Carlo and event-driven molecular dynamics algorithms.

9.
J Chem Phys ; 159(3)2023 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-37477217

RESUMO

The structural properties of confined single-file hard-disk fluids are studied analytically by means of a mapping of the original system onto a one-dimensional mixture of non-additive hard rods, the mapping being exact in the polydisperse limit. Standard statistical-mechanical results are used as a starting point to derive thermodynamic and structural properties of the one-dimensional mixture, where the condition that all particles have the same chemical potential must be taken into account. Analytical results are then provided for the nth neighbor probability distribution function, the radial distribution function, and the structure factor, a very good agreement being observed upon comparison with simulation data from the literature. Moreover, we have analyzed the scaling form for the disappearance of defects in the zigzag configuration for high pressure and have obtained the translational correlation length and the structural crossover in the oscillation frequency for asymptotically large distances.

10.
J Chem Phys ; 158(15)2023 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-37094005

RESUMO

The exact transfer-matrix solution for the longitudinal equilibrium properties of the single-file hard-disk fluid is used to study the limiting low- and high-pressure behaviors analytically as functions of the pore width. In the low-pressure regime, the exact third and fourth virial coefficients are obtained, which involve single and double integrals, respectively. Moreover, we show that the standard irreducible diagrams do not provide a complete account of the virial coefficients in confined geometries. The asymptotic equation of state in the high-pressure limit is seen to present a simple pole at the close-packing linear density, as in the hard-rod fluid, but, in contrast to the latter case, the residue is 2. Since, for an arbitrary pressure, the exact transfer-matrix treatment requires the numerical solution of an eigenvalue integral equation, we propose here two simple approximations to the equation of state, with different complexity levels, and carry out an extensive assessment of their validity and practical convenience vs the exact solution and available computer simulations.

11.
Curr Opin Biotechnol ; 81: 102918, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36972633

RESUMO

The Antarctic continent is undergoing a rapid warming, affecting microbial communities throughout its ecosystems. This continent is a natural laboratory for studying the effect of climate change, however, assessing the microbial communities' responses to environmental changes is challenging from a methodological point of view. We suggest novel experimental designs, including multivariable assessments that apply multiomics methods in combination with continuous environmental data recording and new warming simulation systems. Moreover, we propose that climate change studies in Antarctica should consider three main objectives, including descriptive studies, short-term temporary adaptation studies, and long-term adaptive evolution studies. This will help us to understand and manage the effects of climate change on the Earth.


Assuntos
Mudança Climática , Microbiota , Ecossistema , Regiões Antárticas
12.
Anim Microbiome ; 5(1): 7, 2023 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-36739423

RESUMO

BACKGROUND: Anthropogenic disturbance has the potential to negatively affect wildlife health by altering food availability and diet composition, increasing the exposure to agrochemicals, and intensifying the contact with humans, domestic animals, and their pathogens. However, the impact of these factors on the fecal microbiome composition of wildlife hosts and its link to host health modulation remains barely explored. Here we investigated the composition of the fecal bacterial microbiome of the insectivorous bat Kuhl's pipistrelle (Pipistrellus kuhlii) dwelling in four environmental contexts with different levels of anthropogenic pressure. We analyzed their microbiome composition, structure and diversity through full-length 16S rRNA metabarcoding using the nanopore long-read sequencer MinION™. We hypothesized that the bacterial community structure of fecal samples would vary across the different scenarios, showing a decreased diversity and richness in samples from disturbed ecosystems. RESULTS: The fecal microbiomes of 31 bats from 4 scenarios were sequenced. A total of 4,829,302 reads were obtained with a taxonomic assignment percentage of 99.9% at genus level. Most abundant genera across all scenarios were Enterococcus, Escherichia/Shigella, Bacillus and Enterobacter. Alpha diversity varied significantly between the four scenarios (p < 0.05), showing the lowest Shannon index in bats from urban and intensive agriculture landscapes, while the highest alpha diversity value was found in near pristine landscapes. Beta diversity obtained by Bray-Curtis distance showed weak statistical differentiation of bacterial taxonomic profiles among scenarios. Furthermore, core community analysis showed that 1,293 genera were shared among localities. Differential abundance analyses showed that the highest differentially abundant taxa were found in near pristine landscapes, with the exception of the family Alcaligenaceae, which was also overrepresented in urban and intensive agriculture landscapes. CONCLUSIONS: This study suggests that near pristine and undisturbed landscapes could promote a more resilient gut microbiome in wild populations of P. kuhlii. These results highlight the potential of the fecal microbiome as a non-invasive bioindicator to assess insectivorous bats' health and as a key element of landscape conservation strategies.

13.
IEEE Trans Med Imaging ; 42(3): 810-822, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36288233

RESUMO

Magnetic resonance imaging of whole fetal body and placenta is limited by different sources of motion affecting the womb. Usual scanning techniques employ single-shot multi-slice sequences where anatomical information in different slices may be subject to different deformations, contrast variations or artifacts. Volumetric reconstruction formulations have been proposed to correct for these factors, but they must accommodate a non-homogeneous and non-isotropic sampling, so regularization becomes necessary. Thus, in this paper we propose a deep generative prior for robust volumetric reconstructions integrated with a diffeomorphic volume to slice registration method. Experiments are performed to validate our contributions and compare with ifdefined tmiformat R2.5a state of the art method methods in the literature in a cohort of 72 fetal datasets in the range of 20-36 weeks gestational age. Results suggest improved image resolution Quantitative as well as radiological assessment suggest improved image quality and more accurate prediction of gestational age at scan is obtained when comparing to a state of the art reconstruction method methods. In addition, gestational age prediction results from our volumetric reconstructions compare favourably are competitive with existing brain-based approaches, with boosted accuracy when integrating information of organs other than the brain. Namely, a mean absolute error of 0.618 weeks ( R2=0.958 ) is achieved when combining fetal brain and trunk information.


Assuntos
Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Gravidez , Feminino , Humanos , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Feto/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Idade Gestacional
14.
Int J Mol Sci ; 23(22)2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36430385

RESUMO

Extensive burns represent a significant challenge in biomedicine due to the multiple systemic and localized complications resulting from the major skin barrier loss. The functionalization of xenografts with nanostructured antibacterial agents proposes a fast and accessible application to restore barrier function and prevent localized bacterial contamination. Based on this, the objective of this work was to functionalize a xenograft by electrospray deposition with silver nanoparticles (AgNPs) and to evaluate its antibiofilm and cytotoxic effects on human fibroblasts. Initially, AgNPs were synthesized by a green microwave route with sizes of 2.1, 6.8, and 12.2 nm and concentrations of 0.055, 0.167, and 0.500 M, respectively. The AgNPs showed a size relationship directly proportional to the concentration of AgNO3, with a spherical and homogeneous distribution determined by high-resolution transmission electron microscopy. The surface functionalization of radiosterilized porcine skin (RPS) via electrospray deposition with the three AgNP concentrations (0.055, 0.167, and 0.500 M) in the epidermis and the dermis showed a uniform distribution on both surfaces by energy-dispersive X-ray spectroscopy. The antibiofilm assays of clinical multidrug-resistant Pseudomonas aeruginosa showed significant effects at the concentrations of 0.167 and 0.500 M, with a log reduction of 1.3 and 2.6, respectively. Additionally, viability experiments with human dermal fibroblasts (HDF) exposed to AgNPs released from functionalized porcine skin showed favorable tolerance, with retention of viability more significant than 90% for concentrations of 0.05 and 0.167 M after 24 h exposure. Antibacterial activity combined with excellent biocompatibility makes this biomaterial a candidate for antibacterial protection by inhibiting bacterial biofilms in deep burns during early stages of development.


Assuntos
Queimaduras , Nanopartículas Metálicas , Humanos , Suínos , Prata/química , Nanopartículas Metálicas/uso terapêutico , Nanopartículas Metálicas/química , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Antibacterianos/química , Biofilmes , Bactérias , Queimaduras/tratamento farmacológico
15.
Microorganisms ; 10(7)2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35889151

RESUMO

Antibiotic resistance genes (ARGs) are undergoing a remarkably rapid geographic expansion in various ecosystems, including pristine environments such as Antarctica. The study of ARGs and environmental resistance genes (ERGs) mechanisms could provide a better understanding of their origin, evolution, and dissemination in these pristine environments. Here, we describe the diversity of ARGs and ERGs and the importance of mobile genetic elements as a possible mechanism for the dissemination of resistance genes in Antarctica. We analyzed five soil metagenomes from Deception Island in Antarctica. Results showed that detected ARGs are associated with mechanisms such as antibiotic efflux, antibiotic inactivation, and target alteration. On the other hand, resistance to metals, surfactants, and aromatic hydrocarbons were the dominant ERGs. The taxonomy of ARGs showed that Pseudomonas, Psychrobacter, and Staphylococcus could be key taxa for studying antibiotic resistance and environmental resistance to stress in Deception Island. In addition, results showed that ARGs are mainly associated with phage-type mobile elements suggesting a potential role in their dissemination and prevalence. Finally, these results provide valuable information regarding the ARGs and ERGs in Deception Island including the potential contribution of mobile genetic elements to the spread of ARGs and ERGs in one of the least studied Antarctic ecosystems to date.

16.
Phys Rev E ; 105(5-1): 054140, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35706208

RESUMO

Loosely speaking, the Mpemba effect appears when hotter systems cool sooner or, in a more abstract way, when systems further from equilibrium relax faster. In this paper, we investigate the Mpemba effect in a molecular gas with nonlinear drag, both analytically (by employing the tools of kinetic theory) and numerically (direct simulation Monte Carlo of the kinetic equation and event-driven molecular dynamics). The analysis is carried out via two alternative routes, recently considered in the literature: first, the kinetic or thermal route, in which the Mpemba effect is characterized by the crossing of the evolution curves of the kinetic temperature (average kinetic energy), and, second, the stochastic thermodynamics or entropic route, in which the Mpemba effect is characterized by the crossing of the distance to equilibrium in probability space. In general, a nonmutual correspondence between the thermal and entropic Mpemba effects is found, i.e., there may appear the thermal effect without its entropic counterpart or vice versa. Furthermore, a nontrivial overshoot with respect to equilibrium of the thermal relaxation makes it necessary to revise the usual definition of the thermal Mpemba effect, which is shown to be better described in terms of the relaxation of the local equilibrium distribution. Our theoretical framework, which involves an extended Sonine approximation in which not only the excess kurtosis but also the sixth cumulant is retained, gives an excellent account of the behavior observed in simulations.

17.
PLoS One ; 17(5): e0268494, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35587505

RESUMO

Worldwide, TB is one of the top 10 causes of death and the leading cause from a single infectious agent. Although the development and roll out of Xpert MTB/RIF has recently become a major breakthrough in the field of TB diagnosis, smear microscopy remains the most widely used method for TB diagnosis, especially in low- and middle-income countries. This research tests the feasibility of a crowdsourced approach to tuberculosis image analysis. In particular, we investigated whether anonymous volunteers with no prior experience would be able to count acid-fast bacilli in digitized images of sputum smears by playing an online game. Following this approach 1790 people identified the acid-fast bacilli present in 60 digitized images, the best overall performance was obtained with a specific number of combined analysis from different players and the performance was evaluated with the F1 score, sensitivity and positive predictive value, reaching values of 0.933, 0.968 and 0.91, respectively.


Assuntos
Crowdsourcing , Mycobacterium tuberculosis , Tuberculose dos Linfonodos , Tuberculose Pulmonar , Humanos , Sensibilidade e Especificidade , Escarro/microbiologia , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/microbiologia
18.
Mod Pathol ; 35(9): 1175-1180, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35361888

RESUMO

Current public health initiatives to contain the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) global pandemic focus on expanding vaccination efforts to include vulnerable populations such as pregnant people. Vaccines using messenger ribonucleic acid (mRNA) technology rely on translation by immune cells, primarily at the injection site. Hesitancy remains among the general population regarding the safety of mRNA vaccines during gestation, and it remains unknown whether the SARS-CoV-2 Spike protein (the product of mRNA vaccines available) accumulates in the placenta after vaccination. Objective: To determine whether Spike protein translation and accumulation occurs in placental tissue in the context of recent mRNA SARC-CoV-2 vaccination during pregnancy. We identified 48 patients receiving one or two doses of mRNA SARS-CoV-2 vaccine during gestation and used immunohistochemistry against SARS-CoV-2 Spike protein in formalin-fixed, paraffin-embedded placental tissue. One placenta, positive for SARS-CoV-2 RNA by in situ hybridization (ISH) was used as positive control. Seven term placentas collected prior to the emergence of SARS-CoV-2 served as negative controls. Eighty one percent of patients in the study group underwent third-trimester delivery; remaining had a first-trimester spontaneous abortion or elective second-trimester termination. Patients received two (52%) or one (48%) vaccine doses during pregnancy, with a median interval between latest dose and delivery of 13 days (range 2-79 days). Most (63%) cases had their latest dose within 15 days prior to delivery. All the placentas in the study and negative control groups were negative for SARS-CoV-2 immunohistochemistry. Six study cases with short vaccine-delivery intervals (2-7 days) were subjected to SARS-CoV-2 ISH and were negative. Our findings suggest that mRNA vaccines do not reach significant concentrations in the placenta given the absence of definitive SARS-CoV-2 Spike protein accumulation in placental tissue. This observation provides evidence supporting the safety of mRNA vaccines to the placental-fetal unit.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Placenta , Complicações Infecciosas na Gravidez , Glicoproteína da Espícula de Coronavírus , COVID-19/prevenção & controle , Vacinas contra COVID-19/administração & dosagem , Feminino , Humanos , Placenta/virologia , Gravidez , Complicações Infecciosas na Gravidez/prevenção & controle , Complicações Infecciosas na Gravidez/virologia , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/análise , Vacinação
19.
Stem Cells ; 40(3): 273-289, 2022 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-35356986

RESUMO

Insulin-like growth factor I (IGF-1) has been implicated in breast cancer due to its mitogenic and anti-apoptotic effects. Despite substantial research on the role of IGF-1 in tumor progression, the relationship of IGF-1 to tissue stem cells, particularly in mammary tissue, and the resulting tumor susceptibility has not been elucidated. Previous studies with the BK5.IGF-1 transgenic (Tg) mouse model reveals that IGF-1 does not act as a classical, post-carcinogen tumor promoter in the mammary gland. Pre-pubertal Tg mammary glands display increased numbers and enlarged sizes of terminal end buds, a niche for mammary stem cells (MaSCs). Here we show that MaSCs from both wild-type (WT) and Tg mice expressed IGF-1R and that overexpression of Tg IGF-1 increased numbers of MaSCs by undergoing symmetric division, resulting in an expansion of the MaSC and luminal progenitor (LP) compartments in pre-pubertal female mice. This expansion was maintained post-pubertally and validated by mammosphere assays in vitro and transplantation assays in vivo. The addition of recombinant IGF-1 promoted, and IGF-1R downstream inhibitors decreased mammosphere formation. Single-cell transcriptomic profiles generated from 2 related platforms reveal that IGF-1 stimulated quiescent MaSCs to enter the cell cycle and increased their expression of genes involved in proliferation, plasticity, tumorigenesis, invasion, and metastasis. This study identifies a novel, pro-tumorigenic mechanism, where IGF-1 increases the number of transformation-susceptible carcinogen targets during the early stages of mammary tissue development, and "primes" their gene expression profiles for transformation.


Assuntos
Fator de Crescimento Insulin-Like I , Glândulas Mamárias Animais , Animais , Proliferação de Células , Feminino , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Camundongos , Camundongos Transgênicos , Células-Tronco/metabolismo
20.
Entropy (Basel) ; 24(10)2022 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-37420455

RESUMO

We study a dilute granular gas immersed in a thermal bath made of smaller particles with masses not much smaller than the granular ones in this work. Granular particles are assumed to have inelastic and hard interactions, losing energy in collisions as accounted by a constant coefficient of normal restitution. The interaction with the thermal bath is modeled by a nonlinear drag force plus a white-noise stochastic force. The kinetic theory for this system is described by an Enskog-Fokker-Planck equation for the one-particle velocity distribution function. To get explicit results of the temperature aging and steady states, Maxwellian and first Sonine approximations are developed. The latter takes into account the coupling of the excess kurtosis with the temperature. Theoretical predictions are compared with direct simulation Monte Carlo and event-driven molecular dynamics simulations. While good results for the granular temperature are obtained from the Maxwellian approximation, a much better agreement, especially as inelasticity and drag nonlinearity increase, is found when using the first Sonine approximation. The latter approximation is, additionally, crucial to account for memory effects such as Mpemba and Kovacs-like ones.

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