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2.
EClinicalMedicine ; 40: 101121, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34527894

RESUMO

Background: Academic bullying is a topic of significant interest of late, with high profile cases featured in scientific journals. Our aim is to document the nature and extent of academic bullying behaviors, examining who are the primary targets and perpetrators as well as the responses to and outcomes of bullying. Methods: We developed a cross-sectional global survey aimed primarily at those in academic science institutions. The survey was administered via Qualtrics and data were collected (between November 2019 and July 2021) from 2006 individuals whose participation was solicited through various means including advertisements in Science and Nature magazines and the American Chemical Society. Findings: Among the 2006 survey participants, the majority of targets were graduate students or postdocs. An overwhelming proportion of participants reported either experiencing (84%) or witnessing (59%) abusive supervision, or both (49%). While a majority of perpetrators were male, they were proportionately no more likely to abuse than females. Perpetrators were more likely from the highest-ranked institutions and they were most likely PIs. Females were more likely to report being bullied but their scores on the Tepper abusive supervision scale and the contextual behavior checklist we developed were not greater than male targets. Male targets actually reported higher levels of certain bullying behaviors. While international scholars were no more likely to report being bullied, the severity of the behaviors they reported was significantly greater. Targets (64%) were most likely to use avoidant tactics (not reporting and relying on family/friends for support) in response to bullying due to fear of retaliation (61%). The small percentage that did report the abuse (29%) overwhelmingly reported unfair and biased (58%) outcomes. Additional qualitative analysis of open-ended comments revealed similar patterns. We also noticed that the COVID-19 pandemic has exacerbated academic bullying and changed the patterns of behaviors possibly due to the remote nature of interactions. Open-ended responses from targets are analyzed with examples provided. Interpretation: Our results elucidated the various forms of abuse, the most likely perpetrators and targets, as well as the typical reactions of targets and witnesses. We investigated the results of targets' actions following chronic bullying. Our findings highlight the domain, extent, and dynamics of academic bullying to hopefully motivate the scientific community to take action.

4.
Adv Sci (Weinh) ; : e2100556, 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34558234

RESUMO

The emergence of nanotechnology has created unprecedented hopes for addressing several unmet industrial and clinical issues, including the growing threat so-termed "antibiotic resistance" in medicine. Over the last decade, nanotechnologies have demonstrated promising applications in the identification, discrimination, and removal of a wide range of pathogens. Here, recent insights into the field of bacterial nanotechnology are examined that can substantially improve the fundamental understanding of nanoparticle and bacteria interactions. A wide range of developed nanotechnology-based approaches for bacterial detection and removal together with biofilm eradication are summarized. The challenging effects of nanotechnologies on beneficial bacteria in the human body and environment and the mechanisms of bacterial resistance to nanotherapeutics are also reviewed.

5.
Science ; 373(6558): 974, 2021 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-34446599
6.
Mol Pharm ; 18(8): 3171-3180, 2021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-34279974

RESUMO

Current treatment of chronic wounds has been critically limited by various factors, including bacterial infection, biofilm formation, impaired angiogenesis, and prolonged inflammation. Addressing these challenges, we developed a multifunctional wound dressing-based three-pronged approach for accelerating wound healing. The multifunctional wound dressing, composed of nanofibers, functional nanoparticles, natural biopolymers, and selected protein and peptide, can target multiple endogenous repair mechanisms and represents a promising alternative to current wound healing products.

7.
Adv Drug Deliv Rev ; 174: 337-347, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33957181

RESUMO

Males and females have physiological, hormonal, and genetic differences that can cause different responses to medicinal treatments. The role of sex in the pharmacokinetics and pharmacodynamics of drugs is well established in the literature. However, researchers have yet to robustly and consistently consider the impact of sex differences on the pharmacokinetics and pharmacodynamics of nanomedicine formulations when designing nanomedicine therapeutics and/or constructing clinical trials. In this review, we highlight the physiological and anatomical differences between sexes and discuss how these differences can influence the therapeutic efficacy, side effects, and drug delivery safety of nanomedicine products. A deep understanding of the effects of sex on nano-based drug delivery agents will robustly improve the risk assessment process, resulting in safer formulations, successful clinical translation, and improved therapeutic efficacies for both sexes.

8.
Mol Pharm ; 18(6): 2448-2453, 2021 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-33983745

RESUMO

Nanomedicine has demonstrated a substantial role in vaccine development against severe acute respiratory syndrome coronavirus (SARS-CoV-2 and COVID-19). Although nanomedicine-based vaccines have now been validated in millions of individuals worldwide in phase 4 and tracking of sex-disaggregated data on COVID-19 is ongoing, immune responses that underlie COVID-19 disease outcomes have not been clarified yet. A full understanding of sex-role effects on the response to nanomedicine products is essential to building an effective and unbiased response to the pandemic. Here, we exposed model lipid nanoparticles (LNPs) to whole blood of 18 healthy donors (10 females and 8 males) and used flow cytometry to measure cellular uptake by circulating leukocytes. Our results demonstrated significant differences in the uptake of LNP between male and female natural killer (NK) cells. The results of this proof-of-concept study show the importance of recipient sex as a critical factor which enables researchers to better consider sex in the development and administration of vaccines for safer and more-efficient sex-specific outcomes.


Assuntos
Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , Nanopartículas/química , SARS-CoV-2/imunologia , COVID-19/epidemiologia , COVID-19/imunologia , COVID-19/virologia , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/química , Composição de Medicamentos/métodos , Ácidos Graxos Monoinsaturados/química , Feminino , Voluntários Saudáveis , Humanos , Imunogenicidade da Vacina , Lipossomos , Masculino , Pandemias/prevenção & controle , Compostos de Amônio Quaternário/química , Fatores Sexuais , Resultado do Tratamento
9.
Nat Commun ; 12(1): 2984, 2021 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-34017011

RESUMO

Nanomedicine has demonstrated substantial potential to improve the quality and efficacy of healthcare systems. Although the promise of nanomedicine to transform conventional medicine is evident, significant numbers of therapeutic nanomedicine products have failed in clinical trials. Most studies in nanomedicine have overlooked several important factors, including the significance of sex differences at various physiological levels. This report attempts to highlight the importance of sex in nanomedicine at cellular and molecular level. A more thorough consideration of sex physiology, among other critical variations (e.g., health status of individuals), would enable researchers to design and develop safer and more-efficient sex-specific diagnostic and therapeutic nanomedicine products.


Assuntos
Nanomedicina/métodos , Nanopartículas/uso terapêutico , Fatores Sexuais , Ensaios Clínicos como Assunto , Feminino , Humanos , Masculino , Resultado do Tratamento
10.
Adv Exp Med Biol ; 1318: 825-837, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33973214

RESUMO

Pandemics are enormous threats to the world that impact all aspects of our lives, especially the global economy. The COVID-19 pandemic has emerged since December 2019 and has affected the global economy in many ways. As the world becomes more interconnected, the economic impacts of the pandemic become more serious. In addition to increased health expenditures and reduced labor force, the pandemic has hit the supply and demand chain massively and caused trouble for manufacturers who have to fire some of their employees or delay their economic activities to prevent more loss. With the closure of manufacturers and companies and reduced travel rates, usage of oil after the beginning of the pandemic has decreased significantly that was unprecedented in the last 30 years. The mining industry is a critical sector in several developing countries, and the COVID-19 pandemic has hit this industry too. Also, world stock markets declined as investors started to become concerned about the economic impacts of the COVID-19 pandemic. The tourism industry and airlines have also experienced an enormous loss too. The GDP has reduced, and this pandemic will cost the world more than 2 trillion at the end of 2020.


Assuntos
COVID-19 , Pandemias , Humanos , Indústrias , Pandemias/prevenção & controle , SARS-CoV-2 , Viagem
12.
Biomater Sci ; 9(13): 4671-4678, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34018505

RESUMO

Glioblastoma multiforme (GBM) is the most aggressive form of gliomas. The development of supplementary approaches for glioblastoma diagnosis, limited to imaging techniques and tissue biopsies so far, is a necessity of clinical relevance. In this context, nanotechnology might afford tools to enable early diagnosis. Upon exposure to biological media, nanoparticles are coated with a layer of proteins, the protein corona (PC), whose composition is individual and personalized. Here we show that the PC of graphene oxide nanosheets has a capacity to detect GBM using a simple one-dimensional gel electrophoresis technique. In a range of molecular weights between 100 and 120 kDa, the personalized PC from GBM patients is completely discernible from that of healthy donors and that of cancer patients affected by pancreatic adenocarcinoma and colorectal cancer. Using tandem mass spectrometry, we found that inter-alpha-trypsin inhibitor (ITI) heavy chain H4 is enriched in the PC of all tested individuals but not in the GBM patients. Overall, if confirmed on a larger cohort series, this approach could be advantageous at the first level of investigation to decide whether to carry out more invasive analyses and/or to follow up patients after surgery and/or pharmacological treatment.


Assuntos
Adenocarcinoma , Glioblastoma , Neoplasias Pancreáticas , Coroa de Proteína , Eletroforese , Glioblastoma/diagnóstico , Grafite , Humanos
13.
Expert Opin Drug Deliv ; 18(10): 1379-1394, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33887999

RESUMO

Introduction:Current challenges to successful clinical translation of therapeutic nanomedicine have discouraged many stakeholders, including patients. Significant effort has been devoted to uncovering the reasons behind the less-than-expected success, beyond failures or ineffectiveness, of therapeutic nanomedicine products (e.g. cancer nanomedicine). Until we understand and address the factors that limit the safety and efficacy of NPs, both individually and in combination, successful clinical development will lag.Areas covered:This review highlights the critical roles of interdependent factors affecting the safety and therapeutic efficacy of therapeutic NPs for drug delivery applications.Expert opinion:Deep analysis of the current nanomedical literature reveals ahistory of unanticipated complexity by awide range of stakeholders including researchers. In the manufacture of nanomedicines themselves, there have been persistent difficulties with reproducibility and batch-to-batch variation. The unanticipated complexity and interdependency of nano-bio parameters has delayed our recognition of important factors affecting the safety and therapeutic efficacy of nanomedicine products. These missteps have had many factors including our lack of understanding of the interdependency of various factors affecting the biological identity and fate of NPs and biased interpretation of data. All these issues could raise significant concern regarding the reproducibility- or even the validity- of past publications that in turn formed the basis of many clinical trials of therapeutic nanomedicines. Therefore, the individual and combined effects of previously overlooked factors on the safety and therapeutic efficacy of NPs need to be fully considered in nanomedicine reports and product development.


Assuntos
Nanomedicina , Neoplasias , Sistemas de Liberação de Medicamentos , Humanos , Reprodutibilidade dos Testes
14.
Polymers (Basel) ; 13(7)2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33808295

RESUMO

Current strategies for regeneration of large bone fractures yield limited clinical success mainly due to poor integration and healing. Multidisciplinary approaches in design and development of functional tissue engineered scaffolds are required to overcome these translational challenges. Here, a new generation of hyperelastic bone (HB) implants, loaded with superparamagnetic iron oxide nanoparticles (SPIONs), are 3D bioprinted and their regenerative effect on large non-healing bone fractures is studied. Scaffolds are bioprinted with the geometry that closely correspond to that of the bone defect, using an osteoconductive, highly elastic, surgically friendly bioink mainly composed of hydroxyapatite. Incorporation of SPIONs into HB bioink results in enhanced bacteriostatic properties of bone grafts while exhibiting no cytotoxicity. In vitro culture of mouse embryonic cells and human osteoblast-like cells remain viable and functional up to 14 days on printed HB scaffolds. Implantation of damage-specific bioprinted constructs into a rat model of femoral bone defect demonstrates significant regenerative effect over the 2-week time course. While no infection, immune rejection, or fibrotic encapsulation is observed, HB grafts show rapid integration with host tissue, ossification, and growth of new bone. These results suggest a great translational potential for 3D bioprinted HB scaffolds, laden with functional nanoparticles, for hard tissue engineering applications.

15.
Bioimpacts ; 11(2): 157-164, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33842286

RESUMO

Introduction: The study examined the behavior of vasculature in conditions of eliminated cardiac function using mathematical modeling. In addition, we addressed the question of whether the stretch-recoil capability of veins, at least in part accounts for the slower response to simulated cardiac arrest. Methods: In the first set of computational experiments, blood flow and pressure patterns in veins and arteries during the first few seconds after cardiac arrest were assessed via a validated multi-scale mathematical model of the whole cardiovascular system, comprising cardiac dynamics, arterial and venous blood flow dynamics, and microcirculation. In the second set of experiments, the effects of stretch-recoil zones of venous vessels with different diameters and velocities on blood velocity and dynamic pressure analyzed using computational fluid dynamics (CFD) modeling. Results: In the first set of experiments, measurement of changes in velocity, dynamic pressure, and fluid flow revealed that the venous system responded to cardiac arrest more slowly compared to the arteries. This disparity might be due to the intrinsic characteristics of the venous system, including stretch-recoil and elastic fiber composition. In the second set of experiments, we attempted to determine the role of the stretch-recoil capability of veins in the slower response to cardiac arrest. During the second set of experiments, we found that this recoil behavior increased dynamic pressure, velocity, and blood flow. The enhancement in dynamic pressure through combining the results from both experiments yielded a 15-40% increase in maximum dynamic pressure due to stretch-recoil, depending on vein diameter under normal conditions. Conclusion: In the situation of cardiac arrest, the vein geometry changes continue, promoting smooth responses of the venous system. Moreover, the importance of such vein behavior in blood displacement may grow as the pressure on the venous side gradually decreases with time. Our experiments suggest that the driving force for venous return is the pressure difference that remains within the venous system after the energy coming from every ventricular systole spent to overcome the resistance created by arterial and capillary systems.

16.
Biointerphases ; 16(1): 011008, 2021 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-33706522

RESUMO

Ferumoxytol nanoparticles are being used clinically for the treatment of anemia and molecular imaging in patients. It is well documented that while most patients tolerate ferumoxytol well, a small percentage of patients (i.e., 0.01%) develop severe allergic reactions. The purpose of our proof-of-concept study was to determine whether patients with or without hypersensitivity reactions have specific protein corona profiles around ferumoxytol nanoparticles. In a retrospective, institutional review board approved pilot study, we enrolled 13 pediatric patients (5 girls, 8 boys, mean age 16.9 ± 8.2 years) who received a ferumoxytol-enhanced magnetic resonance imaging and who did (group 1, n = 5) or did not (group 2, n = 8) develop an allergic reaction. Blood samples of these patients were incubated with ferumoxytol, and the formation of a hard protein corona around ferumoxytol nanoparticles was measured by dynamic light scattering, zeta potential, and liquid chromatography-mass spectrometry. We also performed in vitro immune response analyses to randomly selected coronas from each group. Our results provide preliminary evidence that ex vivo analysis of the biomolecular corona may provide useful and predictive information on the possibility of severe allergic reactions to ferumoxytol nanoparticles. In the future, patients with predisposition of an allergic reaction to ferumoxytol may be diagnosed based on the proteomic patterns of the corona around ferumoxytol in their blood sample.

17.
Trends Biotechnol ; 39(5): 425-427, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33568314

RESUMO

The role of the 'file drawer' problem in nanomedicine, which partly drives the current limited clinical success of therapeutic nanoparticles, has been poorly investigated. We propose an integrated functioning of all stakeholders as the only effective way to address the file drawer problem in an efficient and timely manner.


Assuntos
Nanomedicina , Publicações Periódicas como Assunto , Nanomedicina/normas , Nanomedicina/tendências , Pesquisa/normas
19.
Nat Commun ; 12(1): 573, 2021 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-33495475

RESUMO

The biological identity of nanoparticles (NPs) is established by their interactions with a wide range of biomolecules around their surfaces after exposure to biological media. Understanding the true nature of the biomolecular corona (BC) in its native state is, therefore, essential for its safe and efficient application in clinical settings. The fundamental challenge is to visualize the biomolecules within the corona and their relationship/association to the surface of the NPs. Using a synergistic application of cryo-electron microscopy, cryo-electron tomography, and three-dimensional reconstruction, we revealed the unique morphological details of the biomolecules and their distribution/association with the surface of polystyrene NPs at a nanoscale resolution. The analysis of the BC at a single NP level and its variability among NPs in the same sample, and the discovery of the presence of nonspecific biomolecules in plasma residues, enable more precise characterization of NPs, improving predictions of their safety and efficacies.


Assuntos
Microscopia Crioeletrônica/métodos , Tomografia com Microscopia Eletrônica/métodos , Nanopartículas/química , Nanopartículas/ultraestrutura , Plasma/química , Poliestirenos/química , Simulação por Computador , Humanos , Imageamento Tridimensional/métodos , Microscopia Eletrônica de Transmissão/métodos , Coroa de Proteína/química , Reprodutibilidade dos Testes
20.
Mol Pharm ; 18(2): 476-482, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-32379456

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 and COVID-19) has produced an unprecedented global pandemic. Though the death rate from COVID-19 infection is ∼2%, many infected people recover at home. Among patients for whom COVID-19 is deadly are those with pre-existing comorbidities. Therefore, identification of populations at highest risk of COVID-19 mortality could significantly improve the capacity of healthcare providers to take early action and minimize the possibility of overwhelming care centers, which in turn would save many lives. Although several approaches have been used/developed (or are being developed/suggested) to diagnose COVID-19 infection, no approach is available/proposed for fast diagnosis of COVID-19 infections likely to be fatal. The central aim of this short perspective is to suggest a few possible nanobased technologies (i.e., protein corona sensor array and magnetic levitation) that could discriminate COVID-19-infected people while still in the early stages of infection who are at high risk of death. Such discrimination technologies would not only be useful in protecting health care centers from becoming overwhelmed but would also provide a powerful tool to better control possible future pandemics with a less social and economic burden.


Assuntos
COVID-19/diagnóstico , COVID-19/mortalidade , COVID-19/virologia , SARS-CoV-2/patogenicidade , Humanos , Pandemias/estatística & dados numéricos , Fatores de Risco
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