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1.
Actas Dermosifiliogr ; 2024 Jul 18.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-39032781

RESUMO

BACKGROUND AND OBJECTIVE: subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare cytotoxic T-cell lymphoma with indolent behavior, mostly present in women and associated with immunological diseases whose pathogenic background is still poorly understood. SPTCL is associated with lupus erythematosus panniculitis (LEP) and histologically misdiagnosed. OBJECTIVES: the aim of our study was to identify mutations affecting the pathogenesis of both SPTCL and LEP. MATERIALS AND METHODS: we studied a total of 10 SPTCL and 10 LEP patients using targeted Next Generation Sequencing and pyrosequencing. Differences in gene expression between molecular subgroups were investigated using NanoString technology. Clinical data were collected, and correlations sought with the molecular data obtained. RESULTS: the mutational profile of SPTCL and LEP is different. We identified fewer pathogenic mutations than previously reported in SPTCL, noting a single HAVCR2-mutated SPTCL case. Interestingly, 40% of our SPTCL cases showed the pathogenic TP53 (p.Pro72Arg) (P72R) variant. Although cases showing HAVCR2 mutations or the TP53 (P72R) variant had more severe symptomatic disease, none developed hemophagocytic syndrome (HPS). Furthermore, TP53 (P72R)-positive cases were characterized by a lower metabolic signaling pathway and higher levels of CD28 expression and Treg signaling genes. In addition, 30% of our cases featured the same mutation (T735C) of the epigenetic modificatory gene DNMT3A. None of the LEP cases showed mutations in any of the studied genes. CONCLUSIONS: the mutational landscape of SPTCL is broader than previously anticipated. We describe, for the first time, the involvement of the TP53 (P72R) pathogenic variant in this subgroup of tumors, consider the possible role of different genetic backgrounds in the development of SPTCL, and conclude that LEP does not follow the same pathogenic pathway as SPTCL.

2.
Arch Microbiol ; 206(8): 344, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38967798

RESUMO

Uropathogenic Escherichia coli, the most common cause for urinary tract infections, forms biofilm enhancing its antibiotic resistance. To assess the effects of compounds on biofilm formation of uropathogenic Escherichia coli UMN026 strain, a high-throughput combination assay using resazurin followed by crystal violet staining was optimized for 384-well microplate. Optimized assay parameters included, for example, resazurin and crystal violet concentrations, and incubation time for readouts. For the assay validation, quality parameters Z' factor, coefficient of variation, signal-to-noise, and signal-to-background were calculated. Microplate uniformity, signal variability, edge well effects, and fold shift were also assessed. Finally, a screening with known antibacterial compounds was conducted to evaluate the assay performance. The best conditions found were achieved by using 12 µg/mL resazurin for 150 min and 0.023% crystal violet. This assay was able to detect compounds displaying antibiofilm activity against UMN026 strain at sub-inhibitory concentrations, in terms of metabolic activity and/or biomass.


Assuntos
Antibacterianos , Biofilmes , Violeta Genciana , Ensaios de Triagem em Larga Escala , Oxazinas , Escherichia coli Uropatogênica , Xantenos , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Escherichia coli Uropatogênica/efeitos dos fármacos , Escherichia coli Uropatogênica/fisiologia , Ensaios de Triagem em Larga Escala/métodos , Xantenos/química , Antibacterianos/farmacologia , Violeta Genciana/metabolismo , Oxazinas/farmacologia , Oxazinas/metabolismo , Oxazinas/química , Testes de Sensibilidade Microbiana , Infecções Urinárias/microbiologia , Humanos
3.
Phytopathology ; 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38976565

RESUMO

Epidemiological studies to better understand wheat blast (WB) spatial and temporal patterns were conducted in three field environments in Bolivia between 2019 and 2020. The temporal dynamics of wheat leaf blast (WLB) and spike blast (WSB) were best described by the logistic model compared to the Gompertz and exponential models. The non-linear logistic infection rates (rL) were higher under defined inoculation in experiments two and three than under undefined inoculation in experiment one, and they were also higher for WSB than for WLB. The onset of WLB began with a spatial cluster pattern according to autocorrelation analysis and Moran's Index (I) values, with higher severity and earlier onset for defined than for undefined inoculation until the last sampling time. The WSB onset did not start with a spatial cluster pattern; instead, it was detected later until the last sampling date across experiments, with higher severity and earlier onset for defined than for undefined inoculation. Maximum severity (Kmax) was 1.0 for WSB, and less than 1.0 for WLB. Aggregation of WLB and WSB was higher for defined than for undefined inoculation. The directionality of hotspot development was similar for both WLB and WSB, mainly occurring concentrically for defined inoculation. Our results show no evidence of synchronized development but suggest a temporal and spatial progression of disease symptoms on wheat leaves and spikes. Thus, we recommend that monitoring and management of WB should be considered during early growth stages of wheat planted in areas of high risk.

4.
Res Sq ; 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38854052

RESUMO

Repetitive elements (REs) are often expressed at higher levels in tumor cells than normal cells, implicating these genomic regions as an untapped pool of tumor-associated antigens. In ovarian cancer (OC), protein from the RE ERV-K is frequently expressed by tumor cells. Here we determined whether the targeting of a previously identified immunogenic epitope in the envelope gene (env) of ERV-K resulted in target antigen specificity in non-HIV-1 settings. We found that transducing healthy donor T cells with an ERV-K-Env-specific T cell receptor construct resulted in antigen specificity only when co-cultured with HLA-A*03:01 B lymphoblastoid cells. Furthermore, these transduced T cells were not specific for HLA-A*03:01 + OC cells nor for the cognate peptide in HLA-matched systems from multiple healthy donors. These data suggest that the ERV-K-Env epitope recognized by this T cell receptor is of low immunogenicity and has limited potential as a T cell target for OC.

5.
J Intellect Disabil Res ; 68(6): 610-619, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38500391

RESUMO

BACKGROUND: The main objective of this study was to evaluate gait parameters in people with intellectual disability (ID) and without intellectual disability (WID) in two different walking conditions [single task vs. dual task (DT)]. A secondary aim was to evaluate the dual-task cost (DTC) that the DT causes in each group. METHODS: A total of 119 participants joined in this study: 56 ID (30 men) and 63 WID (30 men). The OptoGait system was used to assess gait. In addition, Witty photocells were added to assess gait under the DT condition. RESULTS: Single support time was lower for participants with ID (P < 0.01), while double support time was higher (P < 0.05). All coefficients of variation for gait parameters were higher in participants with ID. Additionally, changes in gait were observed in both groups during the DT condition compared with the single-task condition. These changes were larger for participants with ID in step length, double support time and gait speed (P < 0.001), resulting in a higher DTC in these variables in the ID group (P < 0.01). CONCLUSIONS: Both groups reduced gait performance in the DT condition. However, greater gait variability occurred in the ID group. In addition, DTC was higher for the ID group in all variables analysed. Therefore, people with ID show worse gait performance during a DT than people WID.


Assuntos
Deficiência Intelectual , Humanos , Deficiência Intelectual/fisiopatologia , Masculino , Feminino , Adulto , Desempenho Psicomotor/fisiologia , Adulto Jovem , Pessoa de Meia-Idade , Marcha/fisiologia
6.
J Eur Acad Dermatol Venereol ; 38(2): 265-280, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37750484

RESUMO

Generalized pustular psoriasis (GPP) is a rare, chronic, neutrophilic inflammatory skin disease characterized by episodes of widespread eruption of sterile, macroscopic pustules that can be accompanied by systemic inflammation and symptoms. A systematic literature review and narrative synthesis were conducted to determine the impact of GPP on patients' health-related quality of life (HRQoL) and patient-reported severity of symptoms and to compare its impact to patients with plaque psoriasis (plaque PsO). Searches were undertaken in Embase, MEDLINE and the Cochrane Library from 1 January 2002 to 15 September 2022. Screening was carried out by two reviewers independently. Outcome measures included generic (e.g. EQ-5D, SF-36) and dermatology-specific (e.g. DLQI) clinical outcome assessments, and other relevant patient-reported outcome measures (PROMs) (e.g. severity of pain measured by a numerical rating scale). Overall, 20 studies were found to be eligible for inclusion, of which seven also had data for plaque PsO. The DLQI was the most frequently reported outcome measure (16 out of 20 studies). When reported, mean DLQI (SD) scores varied from 5.7 (1.2) to 15.8 (9.6) across the studies, indicating a moderate to very large effect on HRQoL; the wide range of scores and large SDs were explained by the small population sizes (n ≤ 12 for all studies except two). Similar ranges and large SDs were also observed for other measures within individual studies. However, in general, people with GPP reported a greater impact of their skin condition on HRQoL, when compared to people with plaque PsO (i.e. higher DLQI scores) and higher severity for itch, pain and fatigue. This systematic review highlighted the need for studies with a larger population size, a better understanding of the impact of cutaneous and extracutaneous symptoms and comorbidities on HRQoL during and between GPP flares, and outcome measures specifically tailored to the unique symptoms and the natural course/history of GPP.


Assuntos
Dermatite , Psoríase , Dermatopatias Vesiculobolhosas , Humanos , Qualidade de Vida , Psoríase/diagnóstico , Pele , Doença Crônica , Dor
7.
Plant Methods ; 19(1): 83, 2023 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-37563651

RESUMO

BACKGROUND: Tar spot of corn is a significant and spreading disease in the continental U.S. and Canada caused by the obligate biotrophic fungus Phyllachora maydis. As of 2023, tar spot had been reported in 18 U.S. states and one Canadian Province. The symptoms of tar spot include chlorotic flecking followed by the formation of black stromata where conidia and ascospores are produced. Advancements in research and management for tar spot have been limited by a need for a reliable method to inoculate plants to enable the study of the disease. The goal of this study was to develop a reliable method to induce tar spot in controlled conditions. RESULTS: We induced infection of corn by P. maydis in 100% of inoculated plants with a new inoculation method. This method includes the use of vacuum-collection tools to extract ascospores from field-infected corn leaves, application of spores to leaves, and induction of the disease in the dark at high humidity and moderate temperatures. Infection and disease development were consistently achieved in four independent experiments on different corn hybrids and under different environmental conditions in a greenhouse and growth chamber. Disease induction was impacted by the source and storage conditions of spores, as tar spot was not induced with ascospores from leaves stored dry at 25 ºC for 5 months but was induced using ascospores from infected leaves stored at -20 ºC for 5 months. The time from inoculation to stromata formation was 10 to 12 days and ascospores were present 19 days after inoculation throughout our experiments. In addition to providing techniques that enable in-vitro experimentation, our research also provides fundamental insights into the conditions that favor tar spot epidemics. CONCLUSIONS: We developed a method to reliably inoculate corn with P. maydis. The method was validated by multiple independent experiments in which infection was induced in 100% of the plants, demonstrating its consistency in controlled conditions. This new method facilitates research on tar spot and provides opportunities to study the biology of P. maydis, the epidemiology of tar spot, and for identifying host resistance.

8.
Mol Microbiol ; 120(3): 341-350, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37537859

RESUMO

Respiratory syncytial virus (RSV) is a virus that causes acute respiratory infections in neonates and older adults. To infect host cells, the attachment glycoprotein (G) interacts with a cell surface receptor. This interaction determines the specific cell types that are susceptible to infection. RSV possesses a type I fusion protein F. Type I fusion proteins are metastable when rearrangement of the prefusion F occurs; the fusion peptide is exposed transforming the protein into postfusion form. The transition between the prefusion form and its postfusion form facilitates the viral envelope and the host cell membrane to fuse, enabling the virus to enter the host cell. Understanding the entry mechanism employed by RSV is crucial for developing effective antiviral therapies. In this review, we will discuss the various types of viral fusion proteins and explore the potential entry mechanisms utilized by RSV. A deeper understanding of these mechanisms will provide valuable insights for the development of novel approaches to treat RSV infections.


Assuntos
Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Recém-Nascido , Humanos , Idoso , Anticorpos Neutralizantes , Vírus Sincicial Respiratório Humano/metabolismo , Proteínas Virais de Fusão/metabolismo
9.
Cytotherapy ; 25(7): 718-727, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37278683

RESUMO

BACKGROUND: Adoptive T cell therapy (ATCT) has been successful in treating hematological malignancies and is currently under investigation for solid-tumor therapy. In contrast to existing chimeric antigen receptor (CAR) T cell and/or antigen-specific T cell approaches, which require known targets, and responsive to the need for targeting a broad repertoire of antigens in solid tumors, we describe the first use of immunostimulatory photothermal nanoparticles to generate tumor-specific T cells. METHODS: Specifically, we subject whole tumor cells to Prussian blue nanoparticle-based photothermal therapy (PBNP-PTT) before culturing with dendritic cells (DCs), and subsequent stimulation of T cells. This strategy differs from previous approaches using tumor cell lysates because we use nanoparticles to mediate thermal and immunogenic cell death in tumor cells, rendering them enhanced antigen sources. RESULTS: In proof-of-concept studies using two glioblastoma (GBM) tumor cell lines, we first demonstrated that when PBNP-PTT was administered at a "thermal dose" targeted to induce the immunogenicity of U87 GBM cells, we effectively expanded U87-specific T cells. Further, we found that DCs cultured ex vivo with PBNP-PTT-treated U87 cells enabled 9- to 30-fold expansion of CD4+ and CD8+ T cells. Upon co-culture with target U87 cells, these T cells secreted interferon-É£ in a tumor-specific and dose-dependent manner (up to 647-fold over controls). Furthermore, T cells manufactured using PBNP-PTT ex vivo expansion elicited specific cytolytic activity against target U87 cells (donor-dependent 32-93% killing at an effector to target cell (E:T) ratio of 20:1) while sparing normal human astrocytes and peripheral blood mononuclear cells from the same donors. In contrast, T cells generated using U87 cell lysates expanded only 6- to 24-fold and killed 2- to 3-fold less U87 target cells at matched E:T ratios compared with T cell products expanded using the PBNP-PTT approach. These results were reproducible even when a different GBM cell line (SNB19) was used, wherein the PBNP-PTT-mediated approach resulted in a 7- to 39-fold expansion of T cells, which elicited 25-66% killing of the SNB19 cells at an E:T ratio of 20:1, depending on the donor. CONCLUSIONS: These findings provide proof-of-concept data supporting the use of PBNP-PTT to stimulate and expand tumor-specific T cells ex vivo for potential use as an adoptive T cell therapy approach for the treatment of patients with solid tumors.


Assuntos
Glioblastoma , Nanopartículas , Humanos , Leucócitos Mononucleares , Imunoterapia Adotiva/métodos , Linfócitos T CD8-Positivos , Glioblastoma/terapia , Linhagem Celular Tumoral
10.
Opt Express ; 31(9): 14299-14307, 2023 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-37157297

RESUMO

Using two Michelson interferometers, we describe an experimental scheme for sensitive pump-probe spectral interferometry measurements at long time delays. It has practical advantages over the Sagnac interferometer method typically used when long-time delays are required. First, with the Sagnac interferometer, achieving many nanosecond delays requires expanding the size of the interferometer so that the reference pulse arrives before the probe pulse. Because the two pulses still pass through the same region of the sample, long-lived effects can still affect the measurement. In our scheme, the probe and reference pulses are spatially separated at the sample, alleviating the need for a large interferometer. Second, in our scheme, a fixed delay between probe and reference pulses is straightforward to produce and is continuously adjustable while maintaining alignment. Two applications are demonstrated. First, transient phase spectra are presented in a thin tetracene film with up to 5 ns probe delay. Second, impulsive stimulated Raman measurements are presented in Bi4Ge3O12. The signal-to-noise using the double Michelson technique is comparable to previously described methods with the added advantage of arbitrarily long pump-probe time delays.

11.
J Intellect Disabil Res ; 67(8): 770-781, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37218112

RESUMO

BACKGROUND: The objective of this study was to evaluate the effectiveness of a 14-week resistance training programme implemented with high levels of effort to improve physical fitness in people with intellectual disabilities (IDs) living in group homes. METHODS: Fifty-two individuals with mild to moderate IDs participated in the experimental (n = 27; 15 men) or control groups (n = 25; 14 men). Participants performed 2 familiarisation sessions, 1 pretest, 42 training sessions (14 weeks × 3 sessions; only the experimental group) and 1 posttest. The testing sessions comprised the evaluation of body composition, static balance and muscle strength. The training sessions included four blocks: (1) dynamic bodyweight exercises, (2) dynamic exercises performed against external loads, (3) ballistic exercises and (4) static exercises. RESULTS: The main findings revealed that all variables related to body composition and muscle strength improved more after the intervention period in the experimental group than the control group, whereas the improvements in static balance for the experimental groups were lower than for the remaining variables used as markers of physical fitness. CONCLUSIONS: These findings highlight the importance of prescribing specific moderate-intensity to high-intensity resistance training programmes to improve body composition and muscle strength for people with IDs living in group homes.


Assuntos
Deficiência Intelectual , Treinamento Resistido , Masculino , Humanos , Lares para Grupos , Aptidão Física , Terapia por Exercício , Força Muscular/fisiologia
12.
BMC Res Notes ; 16(1): 69, 2023 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-37143103

RESUMO

OBJECTIVE: Tar spot is a foliar disease of corn caused by Phyllachora maydis, which produces signs in the form of stromata that bear conidia and ascospores. Phyllachora maydis cannot be cultured in media; therefore, the inoculum source for studying tar spot comprises leaves with stromata collected from naturally infected plants. Currently, there is no effective protocol to induce infection under controlled conditions. In this study, an inoculation method was assessed under greenhouse and growth chamber conditions to test whether stromata of P. maydis could be induced on corn leaves. RESULTS: Experiments resulted in incubation periods ranging between 18 and 20 days and stromata development at the beginning of corn growth stage VT-R1 (silk). The induced stromata of P. maydis were confirmed by microscopy, PCR, or both. From thirteen experiments conducted, four (31%) resulted in the successful production of stromata. Statistical analyses indicate that if an experiment is conducted, there are equal chances of obtaining successful or unsuccessful infections. The information from this study will be valuable for developing more reliable P. maydis inoculation methods in the future.


Assuntos
Doenças das Plantas , Zea mays , Doenças das Plantas/microbiologia , Fungos , Phyllachorales , Esporos Fúngicos
13.
Arch Soc Esp Oftalmol (Engl Ed) ; 98(6): 360-364, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37121396

RESUMO

Cryopyrin-associated periodic syndrome is a rare and probably underdiagnosed disease. It presents with various systemic manifestations, including ophthalmological, making its diagnosis a challenge for the clinician. We present the case of a 4-year-old girl for which the identification of papilledema in the ophthalmological examination was the key sign for the diagnosis of cryopyrin-associated periodic syndrome. Our aim is to raise awareness of this syndrome with serious implications for affected patients, so that it is taken into account more frequently as a differential diagnosis, allowing an early diagnosis.


Assuntos
Síndromes Periódicas Associadas à Criopirina , Papiledema , Feminino , Humanos , Pré-Escolar , Síndromes Periódicas Associadas à Criopirina/complicações , Síndromes Periódicas Associadas à Criopirina/diagnóstico , Papiledema/etiologia , Papiledema/complicações , Diagnóstico Diferencial
15.
Eur Ann Allergy Clin Immunol ; 55(6): 261-270, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-36458507

RESUMO

Summary: Background. Polyethylene glycol (PEG) is being used for first time as an excipient for mRNA anti-SARS-CoV-2 vaccines containing PEG 2000, highlighting it as a potential cause of anaphylaxis. Methods. We evaluated 126 patients with moderate-high risk of allergy to SARS-CoV-2 vaccines referred to our department from March-December 2021. Skin tests were performed with PEG 1500 extract (Roxall), using a stepwise approach, with readings at 30 minutes: prick tests with 0.1%, 1% and 10% concentrations; if negative, intradermal tests with 0.0001%, 0.001% and 0.01% concentrations. The same protocol was applied to 5 healthy controls Results. Six patients had positive immediate intradermal tests with PEG 1500, all with severe PEG allergy: one with a near-fatal anaphylaxis after glucocorticoid injection containing PEG 3350 and five with systemic allergic reactions after mRNA vaccines containing PEG 2000 (Pfizer-BioNTech or Moderna). One patient developed anaphylaxis during intradermal test. These six patients were negative to polysorbate 80. The remaining 120 patients had negative tests to PEG 1500; seven had positive tests to polysorbate 80. All controls had negative tests. Conclusions. To our knowledge this is the first study describing the allergy work-up testing with PEG 1500 commercial extract in the scope of SARS-CoV-2 vaccination. The algorithm designed for skin tests revealed to be a useful tool. Severe PEG allergy was diagnosed in 5% of patients, contraindicating PEG-containing vaccines. PEG allergy was excluded in one hundred patients that afterwards took SARS-CoV-2 vaccines containing PEG 2000. Investigation should be conducted in specialized drug allergy centers..


Assuntos
Anafilaxia , Vacinas contra COVID-19 , COVID-19 , Humanos , Anafilaxia/diagnóstico , COVID-19/diagnóstico , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Polietilenoglicóis/efeitos adversos , Polissorbatos , SARS-CoV-2
16.
Artigo em Inglês | MEDLINE | ID: mdl-36468934

RESUMO

Background: Dissecting vertebral artery pseudoaneurysms represent a unique clinical challenge with careful appreciation for location of the posterior inferior cerebellar artery. Limited data is available in terms of outcomes regarding the various treatment modalities. Methods: 11 patients with dissecting pseudoaneurysms were identified from 2013-2021. Pseudoaneurysm size and morphology, clinical presentation, and treatment approach was collected. Success of treatment was recorded based on post-operative imaging as well as documented overall patient outcomes. Three primary treatment modalities emerged: coil embolization, stent assisted coiling, and flow diversion. Results: Of the 11 patients, 5 were female and 6 were male with an age from 36 to 69.7. 7 had ruptured pseudoaneurysms at time of treatment. Size of pseudoaneurysm ranged from 3 to 6 mm. 8 were on the right and 3 were on the left vertebral artery. 8 were proximal to PICA and 3 were distal. Co-dominance of vertebral filling was seen in 5 patients, 5 with dominance through right vertebral artery, and 1 with dominance through left vertebral artery. Variability existed in treatment approaches with 4 patients undergoing coil occlusion, 5 patients undergoing flow diversion stenting, and 2 patients undergoing flow diversion stenting with jailed coiling. 1 patient had enlargement of pseudoaneurysm while inpatient and required a second flow diversion device. 1 patient had two flow diversion devices placed initially at time of treatment due to morphology of PA. 6 patients had repeat angiograms between 6 to 9 months with complete occlusion. 3 had CTA or MRA with complete occlusion for those that had flow diversion, they were transitioned from aspirin and clopidogrel to aspirin monotherapy after first repeat angiogram. 6 patients required shunt placement for hydrocephalus. 1 patient died prior to discharge due to sepsis. 2 patients died post discharge: 1 with myocardial infarction and the 2nd due to urosepsis.Dissecting vertebral pseudoaneurysm has high morbidity and mortality if rupture occurs. Location of PICA origin influences treatment approach. Patients with poor Hunt/Hess scores upon arrival had increased risk for systemic infection and mortality.

17.
Int J Neurobiol ; 4(2)2022.
Artigo em Inglês | MEDLINE | ID: mdl-36081858

RESUMO

Introduction: Recent evidence has demonstrated a close relationship between the cerebral venous and lymphatic systems. Venous congestion has been implicated in a host of neurologic disorders, with relevance for vascular etiologies. Objective: The authors aim to review the literature as it pertains to brain arteriovenous malformations' (BAVMs) venous hemodynamics and glymphatic pathways, as well as the implications of BAVM treatment. Results: BAVMs offer a unique challenge, with sudden alteration in flow dynamics leading to increased hemorrhage risk and difficult challenges post-treatment. Conclusion: Recent progress in the understanding of CNS fluid dynamics and glymphatic pathways have revealed important implications for BAVM pathology and treatment. As imaging techniques and treatment modalities advance, there is a need to further investigate this relationship as it relates to therapeutic options and post-treatment sequalae.

18.
Rev Sci Instrum ; 93(4): 043502, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35489931

RESUMO

Plasma density measurements are key to a wide variety of high-energy-density (HED) and laboratory astrophysics experiments. We present a creative application of photonic Doppler velocimetry (PDV) from which time- and spatially resolved electron density measurements can be made. PDV has been implemented for the first time in close proximity, ∼6 cm, to the high-intensity radiation flux produced by a z-pinch dynamic hohlraum on the Z-machine. Multiple PDV probes were incorporated into the photoionized gas cell platform. Two probes, spaced 4 mm apart, were used to assess plasma density and uniformity in the central region of the gas cell during the formation of the plasma. Electron density time histories with subnanosecond resolution were extracted from PDV measurements taken from the gas cells fielded with neon at 15 Torr. As well, a null shot with no gas fill in the cell was fielded. A major achievement was the low noise high-quality measurements made in the harsh environment produced by the mega-joules of x-ray energy emitted at the collapse of the z-pinch implosion. To evaluate time dependent radiation induced effects in the fiber optic system, two PDV noise probes were included on either side of the gas cell. The success of this alternative use of PDV demonstrates that it is a reliable, precise, and affordable new electron density diagnostic for radiation driven experiments and more generally HED experiments.

19.
Blood Adv ; 6(8): 2520-2534, 2022 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-35244681

RESUMO

Patients with hematologic malignancies relapsing after allogeneic blood or marrow transplantation (BMT) have limited response to conventional salvage therapies, with an expected 1-year overall survival (OS) of <20%. We evaluated the safety and clinical outcomes following administration of a novel T-cell therapeutic targeting 3 tumor-associated antigens (TAA-T) in patients with acute leukemia who relapsed or were at high risk of relapse after allogeneic BMT. Lymphocytes obtained from the BMT donor were manufactured to target TAAs WT1, PRAME, and survivin, which are over-expressed and immunogenic in most hematologic malignancies. Patients received TAA-T infusions at doses of 0.5 to 4 × 107/m2. Twenty-three BMT recipients with relapsed/refractory (n = 11) and/or high-risk (n = 12) acute myeloid leukemia (n = 20) and acute lymphoblastic leukemia (n = 3) were infused posttransplant. No patient developed cytokine-release syndrome or neurotoxicity, and only 1 patient developed grade 3 graft-versus-host disease. Of the patients who relapsed post-BMT and received bridging therapy, the majority (n = 9/11) achieved complete hematologic remission before receiving TAA-T. Relapsed patients exhibited a 1-year OS of 36% and 1-year leukemia-free survival of 27.3% post-TAA-T. The poorest prognosis patients (relapsed <6 months after transplant) exhibited a 1-year OS of 42.8% postrelapse (n = 7). Median survival was not reached for high-risk patients who received preemptive TAA-T posttransplant (n = 12). Although as a phase 1 study, concomitant antileukemic therapy was allowed, TAA-T were safe and well tolerated, and sustained remissions in high-risk and relapsed patients were observed. Moreover, adoptively transferred TAA-T detected by T-cell receptor V-ß sequencing persisted up to at least 1 year postinfusion. This trial was registered at clinicaltrials.gov as #NCT02203903.


Assuntos
Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Leucemia-Linfoma Linfoblástico de Células Precursoras , Doença Aguda , Transplante de Medula Óssea/efeitos adversos , Neoplasias Hematológicas/terapia , Humanos , Leucemia Mieloide Aguda/etiologia , Leucemia Mieloide Aguda/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/etiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Recidiva
20.
Mater Lett ; 311: 131554, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-34963705

RESUMO

COVID-19 pandemic created a global shortage of medical protective equipment. Here, we considered ozone (O3) a disinfectant alternative due to its potent oxidative activity against biological macromolecules. The O3 decontamination assays were done using SARS-CoV-2 obtained from patients to produce artificial contamination of N95 masks and biosecurity gowns. The quantification of SARS-CoV-2 was performed before and after exposing the samples to different ozone gas concentrations for times between 5 and 30 min. Viral loads as a function of the O3 exposure time were estimated from the data obtained by the RT-PCR technique. The genetic material of the virus was no longer detected for any tested concentrations after 15 min of O3 exposure, which means a disinfection Concentration-Time above 144 ppm min. Vibrational spectroscopies were used to follow the modifications of the polymeric fibers after the O3 treatment. The results indicate that the N95 masks could be safely reused after decontamination with treatments of 15 min at the established O3 doses for a maximum of 6 cycles.

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