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1.
Hum Vaccin Immunother ; 20(1): 2334084, 2024 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-38563792

RESUMO

We conducted a national in-depth analysis including pharmacovigilance reports and clinical study to assess the reporting rate (RR) and to determine the clinical profile of polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) in COVID-19-vaccinated individuals. First, based on the French pharmacovigilance database, we estimated the RR of PMR and GCA cases in individuals aged over 50 who developed their initial symptoms within one month of receiving the BNT162b2 mRNA, mRNA-1273, ChAdOx1 nCoV-19, and Ad26.COV2.S vaccines. We then conducted a nationwide survey to gather clinical profiles, therapeutic management, and follow-up data from individuals registered in the pharmacovigilance study. A total of 70 854 684 COVID-19 vaccine doses were administered to 25 260 485 adults, among which, 179 cases of PMR (RR 7. 1 cases/1 000 000 persons) and 54 cases of GCA (RR 2. 1 cases/1 000 000 persons) have been reported. The nationwide survey allowed the characterization of 60 PMR and 35 GCA cases. Median time to the onset of first symptoms was 10 (range 2-30) and 7 (range 2-25) days for PMR and GCA, respectively. Phenotype, GCA-related ischemic complications and -large vessel vasculitis as well as therapeutic management and follow-up seemed similar according to the number of vaccine shots received and when compared to the literature data of unvaccinated population. Although rare, the short time between immunization and the onset of first symptoms of PMR and GCA suggests a temporal association. Physician should be aware of this potential vaccine-related phenomenon.


Assuntos
COVID-19 , Arterite de Células Gigantes , Polimialgia Reumática , Adulto , Humanos , Pessoa de Meia-Idade , Arterite de Células Gigantes/epidemiologia , Polimialgia Reumática/epidemiologia , Vacinas contra COVID-19/efeitos adversos , Ad26COVS1 , Vacina BNT162 , ChAdOx1 nCoV-19 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinação/efeitos adversos
2.
Front Psychol ; 15: 1336202, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38449752

RESUMO

Introduction: This study was conducted to determine the effectiveness of coloring activity of circular symmetrical shape with complex patterns, so-called mandala, on anxiety associated with chronic illness in three different ambulatory medical situations (general consultation, psychiatric day hospital, and hemodialysis session). Methods: Thirty patients were included in three groups and came from three different ambulatory medical situations: a hemodialysis group (n = 10), a psychiatric day hospital group (n = 10), and a nephrology consultation group (n = 10). We asked the patients to fill STAI-S and STAI-T questionnaires before to color complex circular shape with complex patterns, then to fill the STAI-S questionnaire again and a questionnaire on the experience of the activity. Results: The results show that the STAI-S score was significantly lower after coloring for the hemodialysis (p = 0.02) and psychiatric groups (p = 0.005) but not for the general consultation group (p = 0.26). STAI-T scores did not differ between groups. The distribution of colors in the mandala was different in the three groups of patients. A positive subjective experience of the activity was found in all groups. Discussion: These results show the effectiveness of a coloring activity of a circular shape with complex patterns on anxiety associated with chronic illness in care environment. The different distribution of the colors of the mandala in the three groups raises the question of the influence of the context on the mood of the patients and the deeper meaning of the choice of colors and their placement in the mandala. Our study reinforces the multiple applications of art activities in different medical disciplines and encourages their development within healthcare settings.

3.
JTCVS Tech ; 23: 146-153, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38352000

RESUMO

Objectives: Pulmonary hypertension (PH) is an important physiologic variable in the assessment of patients undergoing major thoracic operations but all too often neglected because of the need for right heart catheterization (RHC) due to the inaccuracy of transthoracic echocardiography. Patients with lung cancer often require endobronchial ultrasound (EBUS) as part of the staging of the cancer. We sought to investigate whether EBUS can be used to screen these patients for PH. Methods: Patients undergoing a major thoracic operation requiring EBUS for staging were included prospectively in the study. All patients had also a RHC (gold standard). We aimed to compare the pulmonary artery pressure measurements by EBUS with the RHC values. Results: A total of 20 patients were enrolled in the study. The prevalence of abnormal pulmonary artery pressure was 65% based on RHC. All patients underwent measurement of the pulmonary vascular acceleration time (PVAT) by EBUS with no adverse events. Linear regression analysis comparing PVAT and RHC showed a correlation (r = -0.059, -0.010 to -0.018, P = .007). A receiver operator characteristic curve (area under the curve = 0.736) was used to find the optimal PVAT threshold (140 milliseconds) to predict PH; this was used to calculate a positive and negative likelihood ratio following a positive diagnosis of 2.154 and 0.538, respectively. Conclusions: EBUS interrogation of pulmonary artery hemodynamic is safe and feasible. EBUS may be used as a screening test for PH in high-risk individuals.

4.
J Neurosci Res ; 102(1): e25279, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38284833

RESUMO

An observer willing to cross a street must first estimate if the approaching cars offer enough time to safely complete the task. The brain areas supporting this perception, known as Time-To-Contact (TTC) perception, have been mainly studied through noninvasive correlational approaches. We carried out an experiment in which patients were tested during an awake brain surgery electrostimulation mapping to examine the causal implication of various brain areas in the street-crossing decision process. Forty patients were tested in a gap acceptance task before their surgery to establish a baseline performance. The task was individually adapted upon this baseline level and carried out during their surgery. We acquired and normalized to MNI space the coordinates of the functional areas that influenced task performance. A total of 103 stimulation sites were tested, allowing to establish a large map of the areas involved in the street-crossing decision. Multiple sites were found to impact the gap acceptance decision. A direct implication was however found mostly for sites within the right parietal lobe, while indirect implication was found for sites within the language, motor, or attentional networks. The right parietal lobe can be considered as causally influencing the gap acceptance decision. Other positive sites were all accompanied with dysfunction in other cognitive functions, and therefore should probably not be considered as the site of TTC estimation.


Assuntos
Mapeamento Encefálico , Encéfalo , Humanos , Encéfalo/cirurgia , Cognição , Idioma , Lobo Parietal
5.
Nanomaterials (Basel) ; 13(24)2023 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-38133052

RESUMO

The synthesis of core-shell magnetic mesoporous nanoparticles (MMSNs) through a phase transfer process is usually performed at the 100-250 mg scale. At the gram scale, nanoparticles without cores or with multicore systems are observed. Iron oxide core nanoparticles (IO) were synthesized through a thermal decomposition procedure of α-FeO(OH) in oleic acid. A phase transfer from chloroform to water was then performed in order to wrap the IO nanoparticles with a mesoporous silica shell through the sol-gel procedure. MMSNs were then functionalized with DTPA (diethylenetriaminepentacetic acid) and used for the separation of metal ions. Their toxicity was evaluated. The phase transfer procedure was crucial to obtaining MMSNs on a large scale. Three synthesis parameters were rigorously controlled: temperature, time and glassware. The homogeneous dispersion of MMSNs on the gram scale was successfully obtained. After functionalization with DTPA, the MMSN-DTPAs were shown to have a strong affinity for Ni ions. Furthermore, toxicity was evaluated in cells, zebrafish and seahorse cell metabolic assays, and the nanoparticles were found to be nontoxic. We developed a method of preparing MMSNs at the gram scale. After functionalization with DTPA, the nanoparticles were efficient in metal ion removal and separation; furthermore, no toxicity was noticed up to 125 µg mL-1 in zebrafish.

6.
Nanoscale ; 15(28): 12008-12024, 2023 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-37403617

RESUMO

Biodegradable periodic mesoporous organosilica nanoparticles (nanoPMOs) are widely used as responsive drug delivery platforms for targeted chemotherapy of cancer. However, the evaluation of their properties such as surface functionality and biodegradability is still challenging, which has a significant impact on the efficiency of chemotherapy. In this study, we have applied direct stochastic optical reconstruction microscopy (dSTORM), a single-molecule super-resolution microscopy technique, to quantify the degradation of nanoPMOs triggered by glutathione and the multivalency of antibody-conjugated nanoPMOs. Subsequently, the effect of these properties on cancer cell targeting, drug loading and release capability, and anticancer activity is also studied. Due to the higher spatial resolution at the nanoscale, dSTORM imaging is able to reveal the structural properties (i.e., size and shape) of fluorescent and biodegradable nanoPMOs. The quantification of nanoPMOs' biodegradation using dSTORM imaging demonstrates their excellent structure-dependent degradation behavior at a higher glutathione concentration. The surface functionality of anti-M6PR antibody-conjugated nanoPMOs as quantified by dSTORM imaging plays a key role in prostate cancer cell labeling: oriented antibody is more effective than random ones, while high multivalency is also effective. The higher biodegradability and cancer cell-targeting properties of nanorods conjugated with oriented antibody (EAB4H) effectively deliver the anticancer drug doxorubicin to cancer cells, exhibiting potent anticancer effects.


Assuntos
Nanopartículas , Neoplasias da Próstata , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/tratamento farmacológico , Anticorpos/química , Anticorpos/imunologia , Porosidade , Dióxido de Silício/química , Nanopartículas/química , Sistemas de Liberação de Medicamentos , Oxirredução , Propriedades de Superfície , Humanos , Linhagem Celular Tumoral
7.
Molecules ; 28(14)2023 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-37513209

RESUMO

Dendritic mesoporous organosilica nanoparticles (DMON) are a new class of biodegradable nanoparticles suitable for biomolecule delivery. We studied the photochemical internalization (PCI) and photodynamic therapy (PDT) of DMON to investigate new ways for DMON to escape from the endosomes-lysosomes and deliver biomolecules into the cytoplasm of cells. We added photosensitizers in the framework of DMON and found that DMON were loaded with siRNA or FVIII factor protein. We made four formulations with four different photosensitizers. The photosensitizers allowed us to perform imaging of DMON in cancer cells, but the presence of the tetrasulfide bond in the framework of DMON quenched the formation of singlet oxygen. Fortunately, one formulation allowed us to efficiently deliver proapoptotic siRNA in MCF-7 cancer cells leading to 31% of cancer cell death, without irradiation. As for FVIII protein, it was loaded in two formulations with drug-loading capacities (DLC) up to 25%. In conclusion, DMON are versatile nanoparticles capable of loading siRNA and delivering it into cancer cells, and also loading FVIII protein with good DLC. Due to the presence of tetrasulfide, it was not possible to perform PDT or PCI.


Assuntos
Nanopartículas , Fotoquimioterapia , Humanos , Fármacos Fotossensibilizantes/farmacologia , RNA Interferente Pequeno/metabolismo , Nanopartículas/química , Fotoquimioterapia/métodos , Células MCF-7 , Linhagem Celular Tumoral
8.
Bioengineering (Basel) ; 10(7)2023 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-37508879

RESUMO

To date, bone regeneration techniques use many biomaterials for bone grafting with limited efficiencies. For this purpose, tissue engineering combining biomaterials and stem cells is an important avenue of development to improve bone regeneration. Among potentially usable non-toxic and bioresorbable scaffolds, porous silicon (pSi) is an interesting biomaterial for bone engineering. The possibility of modifying its surface can allow a better cellular adhesion as well as a control of its rate of resorption. Moreover, release of silicic acid upon resorption of its nanostructure has been previously proved to enhance stem cell osteodifferentiation by inducing calcium phosphate formation. In the present study, we used a rat tail model to experiment bone tissue engineering with a critical size defect. Two groups with five rats per group of male Wistar rats were used. In each rat, four vertebrae were used for biomaterial implantation. Randomized bone defects were filled with pSi particles alone or pSi particles carrying dental pulp stem cells (DPSC). Regeneration was evaluated in comparison to empty defect and defects filled with xenogenic bone substitute (Bio-Oss®). Fluorescence microscopy and SEM evaluations showed adhesion of DPSCs on pSi particles with cells exhibiting distribution throughout the biomaterial. Histological analyzes revealed the formation of a collagen network when the defects were filled with pSi, unlike the positive control using Bio-Oss®. Overall bone formation was objectivated with µCT analysis and showed a higher bone mineral density with pSi particles combining DPSC. Immunohistochemical assays confirmed the increased expression of bone markers (osteocalcin) when pSi particles carried DPSC. Surprisingly, no grafted cells remained in the regenerated area after one month of healing, even though the grafting of DPSC clearly increased bone regeneration for both bone marker expression and overall bone formation objectivated with µCT. In conclusion, our results show that the association of pSi with DPSCs in vivo leads to greater bone formation, compared to a pSi graft without DPSCs. Our results highlight the paracrine role of grafted stem cells by recruitment and stimulation of endogenous cells.

9.
Adv Healthc Mater ; 12(27): e2301052, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37499629

RESUMO

The concept of using two-photon excitation in the NIR for the spatiotemporal control of biological processes holds great promise. However, its use for the delivery of nucleic acids has been very scarcely described and the reported procedures are not optimal as they often involve potentially toxic materials and irradiation conditions. This work prepares a simple system made of biocompatible porous silicon nanoparticles (pSiNP) for the safe siRNA photocontrolled delivery and gene silencing in cells upon two-photon excitation. PSiNP are linked to an azobenzene moiety, which possesses a lysine group (pSiNP@ICPES-azo@Lys) to efficiently complex siRNA. Non-linear excitation of the two-photon absorber system (pSiNP) followed by intermolecular energy transfer (FRET) to trans azobenzene moiety, result in the photoisomerization of the azobenzene from trans to cis and in the destabilization of the azobenzene-siRNA complex, thus inducing the delivery of the cargo siRNA to the cytoplasm of cells. Efficient silencing in MCF-7 expressing stable firefly luciferase with siRNAluc against luciferase is observed. Furthermore, siRNA against inhibitory apoptotic protein (IAP) leads to over 70% of MCF-7 cancer cell death. The developed technique using two-photon light allows a unique high spatiotemporally controlled and safe siRNA delivery in cells in few seconds of irradiation.


Assuntos
Nanopartículas , Neoplasias , Humanos , RNA Interferente Pequeno/genética , Silício , Porosidade , Transfecção , Linhagem Celular Tumoral
10.
Neuroimage ; 276: 120217, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37271304

RESUMO

Neurophysiological investigations over the past decades have demonstrated the involvement of the primate insula in a wide array of sensory, cognitive, affective and regulatory functions, yet the complex functional organization of the insula remains unclear. Here we examined to what extent non-invasive task-based and resting-state fMRI provides support for functional specialization and integration of sensory and motor information in the macaque insula. Task-based fMRI experiments suggested a functional specialization related to processing of ingestive/taste/distaste information in anterior insula, grasping-related sensorimotor responses in middle insula and vestibular information in posterior insula. Visual stimuli depicting social information involving conspecific`s lip-smacking gestures yielded responses in middle and anterior portions of dorsal and ventral insula, overlapping partially with the sensorimotor and ingestive/taste/distaste fields. Functional specialization/integration of the insula was further corroborated by seed-based whole brain resting-state analyses, showing distinct functional connectivity gradients across the anterio-posterior extent of both dorsal and ventral insula. Posterior insula showed functional correlations in particular with vestibular/optic flow network regions, mid-dorsal insula with vestibular/optic flow as well as parieto-frontal regions of the sensorimotor grasping network, mid-ventral insula with social/affiliative network regions in temporal, cingulate and prefrontal cortices and anterior insula with taste and mouth motor networks including premotor and frontal opercular regions.


Assuntos
Macaca , Imageamento por Ressonância Magnética , Animais , Vias Neurais/fisiologia , Córtex Insular , Encéfalo , Mapeamento Encefálico
11.
Transl Oncol ; 34: 101709, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37302348

RESUMO

Background: Data regarding outcomes among patients with cancer and co-morbid cardiovascular disease (CVD)/cardiovascular risk factors (CVRF) after SARS-CoV-2 infection are limited. Objectives: To compare Coronavirus disease 2019 (COVID-19) related complications among cancer patients with and without co-morbid CVD/CVRF. Methods: Retrospective cohort study of patients with cancer and laboratory-confirmed SARS-CoV-2, reported to the COVID-19 and Cancer Consortium (CCC19) registry from 03/17/2020 to 12/31/2021. CVD/CVRF was defined as established CVD or no established CVD, male ≥ 55 or female ≥ 60 years, and one additional CVRF. The primary endpoint was an ordinal COVID-19 severity outcome including need for hospitalization, supplemental oxygen, intensive care unit (ICU), mechanical ventilation, ICU or mechanical ventilation plus vasopressors, and death. Secondary endpoints included incident adverse CV events. Ordinal logistic regression models estimated associations of CVD/CVRF with COVID-19 severity. Effect modification by recent cancer therapy was evaluated. Results: Among 10,876 SARS-CoV-2 infected patients with cancer (median age 65 [IQR 54-74] years, 53% female, 52% White), 6253 patients (57%) had co-morbid CVD/CVRF. Co-morbid CVD/CVRF was associated with higher COVID-19 severity (adjusted OR: 1.25 [95% CI 1.11-1.40]). Adverse CV events were significantly higher in patients with CVD/CVRF (all p<0.001). CVD/CVRF was associated with worse COVID-19 severity in patients who had not received recent cancer therapy, but not in those undergoing active cancer therapy (OR 1.51 [95% CI 1.31-1.74] vs. OR 1.04 [95% CI 0.90-1.20], pinteraction <0.001). Conclusions: Co-morbid CVD/CVRF is associated with higher COVID-19 severity among patients with cancer, particularly those not receiving active cancer therapy. While infrequent, COVID-19 related CV complications were higher in patients with comorbid CVD/CVRF. (COVID-19 and Cancer Consortium Registry [CCC19]; NCT04354701).

12.
Int J Mol Sci ; 24(12)2023 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-37373219

RESUMO

In the present work, superparamagnetic adsorbents based on 3-aminopropyltrimethoxy silane (APTMS)-coated maghemite (γFe2O3@SiO2-NH2) and cobalt ferrite (CoFe2O4@SiO2-NH2) nanoparticles were prepared and characterized using transmission-electron microscopy (TEM/HRTEM/EDXS), Fourier-transform infrared spectroscopy (FTIR), specific surface-area measurements (BET), zeta potential (ζ) measurements, thermogravimetric analysis (TGA), and magnetometry (VSM). The adsorption of Dy3+, Tb3+, and Hg2+ ions onto adsorbent surfaces in model salt solutions was tested. The adsorption was evaluated in terms of adsorption efficiency (%), adsorption capacity (mg/g), and desorption efficiency (%) based on the results of inductively coupled plasma optical emission spectrometry (ICP-OES). Both adsorbents, γFe2O3@SiO2-NH2 and CoFe2O4@SiO2-NH2, showed high adsorption efficiency toward Dy3+, Tb3+, and Hg2+ ions, ranging from 83% to 98%, while the adsorption capacity reached the following values of Dy3+, Tb3+, and Hg2+, in descending order: Tb (4.7 mg/g) > Dy (4.0 mg/g) > Hg (2.1 mg/g) for γFe2O3@SiO2-NH2; and Tb (6.2 mg/g) > Dy (4.7 mg/g) > Hg (1.2 mg/g) for CoFe2O4@SiO2-NH2. The results of the desorption with 100% of the desorbed Dy3+, Tb3+, and Hg2+ ions in an acidic medium indicated the reusability of both adsorbents. A cytotoxicity assessment of the adsorbents on human-skeletal-muscle derived cells (SKMDCs), human fibroblasts, murine macrophage cells (RAW264.7), and human-umbilical-vein endothelial cells (HUVECs) was conducted. The survival, mortality, and hatching percentages of zebrafish embryos were monitored. All the nanoparticles showed no toxicity in the zebrafish embryos until 96 hpf, even at a high concentration of 500 mg/L.


Assuntos
Mercúrio , Poluentes Químicos da Água , Humanos , Animais , Camundongos , Peixe-Zebra , Dióxido de Silício/química , Células Endoteliais , Mercúrio/química , Íons , Nanopartículas Magnéticas de Óxido de Ferro , Adsorção , Cinética , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/química
13.
J Fish Biol ; 103(2): 202-219, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37190911

RESUMO

This review examines the published literature on the distribution and species richness of the family Mugilidae around six continents as well as their phylogenetic relationships in a time-calibrated tree. Three mugilid species-rich regions were identified globally, namely the Coral Triangle, southern Asia and southern Africa, all of which have between 16 and 18 morphologically recognized species. Two of the species hotspots are tropical, and only southern Africa incorporates temperate waters. The centre of mugilid evolution and then global dispersion appears to be located in the tropical waters of the Indo-Pacific. Speciation within the family was promoted mainly by plate tectonics, eustatic sea-level changes, tropical climate and high habitat diversity within this region. The number of these tropical species that radiated out to the coastal waters of Africa and America was clearly less than the number that remained in the central Indo-Pacific region. Nonetheless, access by tropical mugilid species was greater to Africa than the Americas because of the direct tropical and subtropical coastal connectivity to the former continent. This enabled more tropical mugilids to reach Africa than America, with the latter probably relying on Palaeocene "island hopping" or "rafting" to move eastwards across the Pacific Ocean. In addition, tropical mugilids were able to access warm western and central African coastal waters from the Pacific prior to the closure of the Tethys Sea gap in the eastern Mediterranean and prior to the development of the cool Benguela Current upwelling off the southwest African coast, and from America through at least two transatlantic rafting events.


Assuntos
Antozoários , Smegmamorpha , Animais , Filogenia , Ecossistema , África Austral
14.
Int J Pharm ; 641: 123083, 2023 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-37245740

RESUMO

Photodynamic therapy (PDT) and photochemical internalization (PCI) are two methods that use light to provoke cell death or disturbance of cellular membranes, respectively, via excitation of a photosensitizer and the formation of reactive oxygen species (ROS). In this context, two-photon excitation (TPE) is of high interest for PCI and/or PDT due to spatiotemporal resolution of two-photon light and deeper penetration of near-infrared light in biological tissues. Here, we report that Periodic Mesoporous Ionosilica Nanoparticles (PMINPs) containing porphyrin groups allow the complexation of pro-apoptotic siRNA. These nano-objects were incubated with MDA-MB-231 breast cancer cells, and TPE-PDT led to significant cell death. Finally, MDA-MB-231 breast cancer cells were pre-incubated with the nanoparticles and then injected in the pericardial cavity of zebrafish embryos. After 24 h, the xenografts were irradiated with femtosecond pulsed laser and the size monitoring by imaging showed a decrease 24 h after irradiation. Pro-apoptotic siRNA was complexed with the nanoparticles and incubation with MDA-MB-231 cells did not lead to cancer cell death in dark conditions, but with two-photon irradiation, TPE-PCI was observed and a synergic effect between pro-apoptotic siRNA and TPE-PDT was noticed, leading to 90% of cancer cell death. Therefore, PMINPs represent an interesting system for nanomedicine applications.


Assuntos
Neoplasias da Mama , Nanopartículas , Fotoquimioterapia , Animais , Humanos , Feminino , Peixe-Zebra , RNA Interferente Pequeno/uso terapêutico , Fármacos Fotossensibilizantes/uso terapêutico , Fotoquimioterapia/métodos , Neoplasias da Mama/tratamento farmacológico , Inativação Gênica , Linhagem Celular Tumoral
15.
Cancer ; 129(14): 2192-2200, 2023 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-37016930

RESUMO

BACKGROUND: Continuous ibrutinib administration is needed to maintain efficacy in patients with chronic lymphocytic leukemia (CLL) and, as such, long-term toxicity is a concern. The authors report the 5-year follow-up of patients with CLL who received treatment with ibrutinib with a focus on hypertension and cardiovascular toxicities. METHODS: Patient characteristics were assessed, including blood pressure, cardiovascular disease, disease progression, and death. Univariate logistic regression analysis assessed the relation of patient characteristics and the development of new or worsened hypertension. The incidence of hypertensive outcomes was evaluated using competing risk. Survival was estimated using the Kaplan-Meier method. RESULTS: Three hundred patients with CLL who were treated with ibrutinib on clinical trials were included. The median patient age at study enrollment was 65 years (range, 29-83 years). Seventy percent of patients were men, and 88% were Caucasian. Sixty-nine percent of patients had hypertension at baseline, and 47% were on antihypertensive medication. Eighty-eight percent had relapsed or refractory CLL. New-onset and worsening hypertension were common, occurring in 68.5% and 38% of patients, respectively. Systolic blood pressure ≥160 mm Hg or diastolic blood pressure ≥100 mm Hg was observed in 16.9% of patients. Hypertension was reversible after ibrutinib discontinuation. Older age, male sex, tobacco use, and chronic kidney disease were associated with ibrutinib-related hypertension. Baseline hypertension was not associated with major adverse cardiovascular events in ibrutinib-treated patients nor with event-free or overall survival. CONCLUSIONS: Hypertension is a common toxicity in patients with CLL who receive ibrutinib but is manageable in most patients. Other than chronic kidney disease, baseline cardiovascular disease did not affect ibrutinib-related hypertension nor was hypertension associated with major adverse cardiovascular events or survival. PLAIN LANGUAGE SUMMARY: Ibrutinib is an effective treatment for patients with chronic lymphocytic leukemia. Ibrutinib is a well tolerated therapy, however hypertension can develop or worsen in patients receiving ibrutinib and other cardiovascular events are significant challenges to the use of this drug. This may be particularly true in patients with heart disease. Short-term side effects may worsen heart disease, but the long-term impact is unknown. The long-term results of ibrutinib on heart disease and hypertension are described.


Assuntos
Doenças Cardiovasculares , Cardiopatias , Hipertensão , Leucemia Linfocítica Crônica de Células B , Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Feminino , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/epidemiologia , Resultado do Tratamento , Hipertensão/induzido quimicamente , Hipertensão/epidemiologia , Hipertensão/tratamento farmacológico , Cardiopatias/induzido quimicamente , Inibidores de Proteínas Quinases/efeitos adversos
16.
Chempluschem ; 88(3): e202300021, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36779542

RESUMO

Periodic Mesoporous Ionosilica Nanoparticles (PMINPs) made via co-condensation reactions starting from an ionosilica precursor and a porphyrin derivative were used for simultaneous BODIPY/siRNA delivery in cancer cells. We observed high BODIPY loading capacities and efficiencies of the PMINPs that are triggered by anion exchange. siRNA adsorption took place on the surface of the nanoparticles, whereas BODIPY was encapsulated within the core of the nanoparticles. BODIPY release was found to be pH-dependent. Our results indicate 94 % BODIPY release after 16 h at pH 4, whereas only 2 % were released at pH 7.4. Furthermore, complexation with siRNA against luciferase gene was observed at the surface of PMINPs and gene silencing through its delivery via photochemical internalization (PCI) mechanism was efficient in MDA-MB-231 breast cancer cells expressing stable luciferase.


Assuntos
Nanopartículas , Fotoquimioterapia , RNA Interferente Pequeno/genética , Luciferases/genética
17.
Neuroimage ; 270: 119959, 2023 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-36822249

RESUMO

Non-human primate (NHP) neuroimaging can provide essential insights into the neural basis of human cognitive functions. While functional magnetic resonance imaging (fMRI) localizers can play an essential role in reaching this objective (Russ et al., 2021), they often differ substantially across species in terms of paradigms, measured signals, and data analysis, biasing the comparisons. Here we introduce a functional frequency-tagging face localizer for NHP imaging, successfully developed in humans and outperforming standard face localizers (Gao et al., 2018). FMRI recordings were performed in two awake macaques. Within a rapid 6 Hz stream of natural non-face objects images, human or monkey face stimuli were presented in bursts every 9 s. We also included control conditions with phase-scrambled versions of all images. As in humans, face-selective activity was objectively identified and quantified at the peak of the face-stimulation frequency (0.111 Hz) and its second harmonic (0.222 Hz) in the Fourier domain. Focal activations with a high signal-to-noise ratio were observed in regions previously described as face-selective, mainly in the STS (clusters PL, ML, MF; also, AL, AF), both for human and monkey faces. Robust face-selective activations were also found in the prefrontal cortex of one monkey (PVL and PO clusters). Face-selective neural activity was highly reliable and excluded all contributions from low-level visual cues contained in the amplitude spectrum of the stimuli. These observations indicate that fMRI frequency-tagging provides a highly valuable approach to objectively compare human and monkey visual recognition systems within the same framework.


Assuntos
Mapeamento Encefálico , Imageamento por Ressonância Magnética , Animais , Humanos , Imageamento por Ressonância Magnética/métodos , Neuroimagem , Reconhecimento Psicológico , Macaca , Reconhecimento Visual de Modelos/fisiologia , Estimulação Luminosa/métodos
18.
Eur J Dent Educ ; 27(4): 888-897, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36484087

RESUMO

AIM: The purpose of this study was to evaluate if the use of intraoral scanner analysis could help students to optimise their performance and their self-assessment abilities in prosthetic preparation without the teacher's assistance in the preclinical course. MATERIALS AND METHODS: Ninety-five second-year dental students were randomly divided into three groups: Control group (C), CeRec group (CR) and PrepCheck group (PC). Group C only use silicon keys to control the preparation thickness. The students in Group CR analysed their work with Cerec™ software. The Group PC use a pedagogic software (PrepCheck™) which allowed comparison with the "master" preparation. They used control tools preparations for three consecutive training sessions. Then a final assessment session without control tool to evaluate their performance was organised. All preparations were objectively evaluated thanks to stl. analysis software (Geomagic® Control X). Each preparation was compared with the master preparation by defining tolerance ranges. An objective overall score out of 20 was assigned to each preparation according to their degree of correspondence. In addition, a questionnaire was performed to analyse the students' perceptions regarding the use of intraoral camera. RESULTS: During the assessment session, no significant difference was revealed between the different groups with respect to the students' performance. The comparative analysis between the self-assessment scores and the objective scores using Geomagic® software showed that digital control tools did not help the student to improve their self-assessment abilities without the teacher's assistance. CONCLUSIONS: The intraoral cameras and specific pedagogic software in autonomy could not improve students' performance for teeth preparation and self-assessment abilities in second year. These digital tools facilitate objective feedback on preparation defects, but constructive criticism needs human reflection. The teacher's opinions and advice remain essential to develop their students' performance and self-assessment skills. The use of digital tools must be integrated in dentistry course to develop the interpret of the results and optimise feedback.


Assuntos
Avaliação Educacional , Estudantes de Odontologia , Humanos , Avaliação Educacional/métodos , Prostodontia/educação , Educação em Odontologia/métodos , Software , Competência Clínica
19.
Life (Basel) ; 12(12)2022 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-36556409

RESUMO

BACKGROUND: In addition to their great optical properties, nanodiamonds (NDs) have recently proved useful for two-photon-excited photodynamic therapy (TPE-PDT) applications. Indeed, they are able to produce reactive oxygen species (ROS) directly upon two-photon excitation but not with one-photon excitation; Methods: Fluorescent NDs (FNDs) with a 100 nm diameter and detonation NDs (DNDs) of 30 nm were compared. In order to use the gems for cancer-cell theranostics, they were encapsulated in a bis(triethoxysilyl)ethylene-based (ENE) periodic mesoporous organosilica (PMO) shell, and the surface of the formed nanoparticles (NPs) was modified by the direct grafting of polyethylene glycol (PEG) and amino groups using PEG-hexyltriethoxysilane and aminoundecyltriethoxysilane during the sol-gel process. The NPs' phototoxicity and interaction with MDA-MB-231 breast cancer cells were evaluated afterwards; Results: Transmission electronic microscopy images showed the formation of core-shell NPs. Infrared spectra and zeta-potential measurements confirmed the grafting of PEG and NH2 groups. The encapsulation of the NDs allowed for the imaging of cancer cells with NDs and for the performance of TPE-PDT of MDA-MB-231 cancer cells with significant mortality. CONCLUSIONS: Multifunctional ND@PMO core-shell nanosystems were successfully prepared. The NPs demonstrated high biocompatibility and TPE-PDT efficiency in vitro in the cancer cell model. Such systems hold good potential for two-photon-excited PDT applications.

20.
Clin Nutr ESPEN ; 51: 412-418, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36184236

RESUMO

BACKGROUND: Sarcopenia is observed in about 50% of cancer patients. Cancer-related sarcopenia negatively affects survival and is a predictive factor of anticancer drug toxicity. Sarcopenia diagnosis is challenging in routine care. We investigated whether plasma creatinine and cystatin C predict sarcopenia diagnosis in the specific population of cancer patients. METHODS: Two common diagnostic criteria of cancer-related sarcopenia based on skeletal muscle mass ± handgrip strength were separately applied as the "gold standard" sarcopenia definition. Four sarcopenia indexes based on creatinine and cystatin C values were evaluated: Creatinine/Cystatin C, Glomerular Filter rate (GFR) Cockroft-Gault/GFR CKD-EPI, GFR Cockroft-Gault/GFR Grubb and GFR Cockroft-Gault/GFR simple. The receiver operating characteristic (ROC) curves and the area under the ROC curves were applied to evaluate the sarcopenia diagnostic accuracy of the four different sarcopenia indexes. RESULTS: A total of 99 patients were included. Among them, 47.5% were overweight or obese. The ratio creatinine/cystatin C (ratio value at 0.8) more accurately predicts the diagnosis of sarcopenia in the entire population based on low skeletal muscle mass and low handgrip strength (sensitivity, specificity, accuracy and Youden index at 0.77, 0.57, 0.90, 0.34 respectively). The other evaluated ratios predict sarcopenia with a lower specificity in all conditions. In the overweight/obese group, the results are similar. The ratio creatinine/cystatin C (ratio value at 1) accurately predicts sarcopenia with a sensitivity, a specificity, an accuracy and a Youden index at 0.50, 0.86, 0.95, 0.36 respectively in overweight/obese population. CONCLUSIONS: The creatinine/cystatin C ratio is a useful and simple biomarker to predict sarcopenia in cancer patients. Moreover, this sarcopenia index also seems to be a strong sarcopenia diagnosis biomarker in overweight and obese cancer patients. Our results must be confirmed in a larger cohort.


Assuntos
Antineoplásicos , Nefropatias , Neoplasias , Sarcopenia , Biomarcadores , Creatinina , Cistatina C , Taxa de Filtração Glomerular/fisiologia , Força da Mão , Humanos , Nefropatias/diagnóstico , Músculos , Neoplasias/complicações , Obesidade , Sobrepeso , Sarcopenia/diagnóstico , Tomografia Computadorizada por Raios X
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