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1.
Magn Reson Med ; 91(1): 325-336, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37799019

RESUMO

PURPOSE: Sodium MRI can be used to quantify tissue sodium concentration (TSC) in vivo; however, UTE sequences are required to capture the rapidly decaying signal. 2D MRI enables high in-plane resolution but typically has long TEs. Half-sinc excitation may enable UTE; however, twice as many readouts are necessary. Scan time can be minimized by reducing the number of signal averages (NSAs), but at a cost to SNR. We propose using compressed sensing (CS) to accelerate 2D half-sinc acquisitions while maintaining SNR and TSC. METHODS: Ex vivo and in vivo TSC were compared between 2D spiral sequences with full-sinc (TE = 0.73 ms, scan time ≈ 5 min) and half-sinc excitation (TE = 0.23 ms, scan time ≈ 10 min), with 150 NSAs. Ex vivo, these were compared to a reference 3D sequence (TE = 0.22 ms, scan time ≈ 24 min). To investigate shortening 2D scan times, half-sinc data was retrospectively reconstructed with fewer NSAs, comparing a nonuniform fast Fourier transform to CS. Resultant TSC and image quality were compared to reference 150 NSAs nonuniform fast Fourier transform images. RESULTS: TSC was significantly higher from half-sinc than from full-sinc acquisitions, ex vivo and in vivo. Ex vivo, half-sinc data more closely matched the reference 3D sequence, indicating improved accuracy. In silico modeling confirmed this was due to shorter TEs minimizing bias caused by relaxation differences between phantoms and tissue. CS was successfully applied to in vivo, half-sinc data, maintaining TSC and image quality (estimated SNR, edge sharpness, and qualitative metrics) with ≥50 NSAs. CONCLUSION: 2D sodium MRI with half-sinc excitation and CS was validated, enabling TSC quantification with 2.25 × 2.25 mm2 resolution and scan times of ≤5 mins.


Assuntos
Imageamento por Ressonância Magnética , Sódio , Humanos , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Simulação por Computador , Análise de Fourier , Imageamento Tridimensional/métodos
2.
Nature ; 559(7712): 114-119, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29950719

RESUMO

Prolonged exposure to microbial products such as lipopolysaccharide can induce a form of innate immune memory that blunts subsequent responses to unrelated pathogens, known as lipopolysaccharide tolerance. Sepsis is a dysregulated systemic immune response to disseminated infection that has a high mortality rate. In some patients, sepsis results in a period of immunosuppression (known as 'immunoparalysis')1 characterized by reduced inflammatory cytokine output2, increased secondary infection3 and an increased risk of organ failure and mortality4. Lipopolysaccharide tolerance recapitulates several key features of sepsis-associated immunosuppression5. Although various epigenetic changes have previously been observed in tolerized macrophages6-8, the molecular basis of tolerance, immunoparalysis and other forms of innate immune memory has remained unclear. Here we perform a screen for tolerance-associated microRNAs and identify miR-221 and miR-222 as regulators of the functional reprogramming of macrophages during lipopolysaccharide tolerization. Prolonged stimulation with lipopolysaccharide in mice leads to increased expression of miR-221 and mir-222, both of which regulate brahma-related gene 1 (Brg1, also known as Smarca4). This increased expression causes the transcriptional silencing of a subset of inflammatory genes that depend on chromatin remodelling mediated by SWI/SNF (switch/sucrose non-fermentable) and STAT (signal transducer and activator of transcription), which in turn promotes tolerance. In patients with sepsis, increased expression of miR-221 and miR-222 correlates with immunoparalysis and increased organ damage. Our results show that specific microRNAs can regulate macrophage tolerization and may serve as biomarkers of immunoparalysis and poor prognosis in patients with sepsis.


Assuntos
Montagem e Desmontagem da Cromatina/genética , Imunidade Inata/imunologia , Memória Imunológica/genética , Memória Imunológica/imunologia , MicroRNAs/genética , Animais , DNA Helicases/metabolismo , Feminino , Células HEK293 , Humanos , Tolerância Imunológica/genética , Tolerância Imunológica/imunologia , Imunidade Inata/genética , Inflamação/genética , Inflamação/imunologia , Mediadores da Inflamação/imunologia , Lipopolissacarídeos/imunologia , Macrófagos/imunologia , Masculino , Camundongos , Proteínas Nucleares/metabolismo , Células RAW 264.7 , Fatores de Transcrição STAT/metabolismo , Sepse/imunologia , Choque Séptico/imunologia , Fatores de Transcrição/metabolismo
3.
Pediatr Blood Cancer ; 66(10): e27895, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31286672

RESUMO

Data regarding micronutrient deficiencies in children with cancer are lacking. We measured micronutrients in a subset of children with cancer (n = 23) participating in a randomized trial of the neutropenic diet. Ninety-six percent of children had ≥1 micronutrient deficiency and 39% had ≥3 micronutrient deficiencies. Eighty-six percent of children had vitamin C deficiency, 87% had 25-hydroxyvitamin D deficiency, 50% had zinc deficiency, and 13% had vitamin A deficiency. Dietary intake did not correlate with micronutrient deficiency status. More data are needed regarding the prevalence and etiology of micronutrient deficiencies in children with cancer to further understand their implications and treatment.


Assuntos
Dieta , Micronutrientes/deficiência , Neoplasias , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estado Nutricional , Prevalência , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos
4.
Pediatr Blood Cancer ; 65(1)2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28696047

RESUMO

BACKGROUND: The neutropenic diet (ND) is prescribed to avoid introduction of bacteria into a host's gastrointestinal tract and reduce infection. Due to a lack of evidence to support the ND, there continues to be debate among pediatric oncologists regarding its usefulness. This prospective randomized controlled trial evaluated the difference in neutropenic infection rates in pediatric oncology patients randomized to Food and Drug Administration approved food safety guidelines (FSGs) versus the ND plus FSGs during one cycle of chemotherapy. PROCEDURE: Pediatric patients receiving cancer treatment with myelosuppressive chemotherapy were eligible. Neutropenic infection was the primary outcome and defined as (i) fever with neutropenia or (ii) hospital admission and treatment for clinical infection and neutropenia. The rate of neutropenic infection was compared with Student's t-test for independent samples. Documented infections were identified by comprehensive chart review and compared between groups using a χ2 test. RESULTS: One hundred fifty patients were randomly assigned to FSGs (n = 73) or ND + FSGs (n = 77). The most common diagnoses were acute lymphoblastic leukemia (32%) and sarcoma (32%). There was no significant difference between the groups in the percentage of patients who developed neutropenic infection: FSGs 33% versus ND + FSGs 35% (P = 0.78). Patients randomized to ND + FSGs reported that following the diet required more effort than those on FSGs alone. CONCLUSION: The ND offers no benefit over FSGs in the prevention of infection in pediatric oncology patients undergoing myelosuppressive chemotherapy and adherence requires more effort for patients and families. Institutions caring for children with cancer should consider replacing ND guidelines with FSGs.


Assuntos
Inocuidade dos Alimentos , Neoplasias/tratamento farmacológico , Neutropenia , Adolescente , Adulto , Criança , Pré-Escolar , Método Duplo-Cego , Feminino , Humanos , Lactente , Infecções/induzido quimicamente , Infecções/terapia , Masculino , Neutropenia/induzido quimicamente , Neutropenia/dietoterapia , Guias de Prática Clínica como Assunto , Estudos Prospectivos
6.
J Clin Immunol ; 35(2): 119-24, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25516070

RESUMO

PURPOSE: Combined immunodeficiency (CID) presents a unique challenge to clinicians. Two patients presented with the prior clinical diagnosis of common variable immunodeficiency (CVID) disorder marked by an early age of presentation, opportunistic infections, and persistent lymphopenia. Due to the presence of atypical clinical features, next generation sequencing was applied documenting RAG deficiency in both patients. METHODS: Two different genetic analysis techniques were applied in these patients including whole exome sequencing in one patient and the use of a gene panel designed to target genes known to cause primary immunodeficiency disorders (PIDD) in a second patient. Sanger dideoxy sequencing was used to confirm RAG1 mutations in both patients. RESULTS: Two young adults with a history of recurrent bacterial sinopulmonary infections, viral infections, and autoimmune disease as well as progressive hypogammaglobulinemia, abnormal antibody responses, lymphopenia and a prior diagnosis of CVID disorder were evaluated. Compound heterozygous mutations in RAG1 (1) c256_257delAA, p86VfsX32 and (2) c1835A>G, pH612R were documented in one patient. Compound heterozygous mutations in RAG1 (1) c.1566G>T, p.W522C and (2) c.2689C>T, p. R897X) were documented in a second patient post-mortem following a fatal opportunistic infection. CONCLUSION: Astute clinical judgment in the evaluation of patients with PIDD is necessary. Atypical clinical findings such as early onset, granulomatous disease, or opportunistic infections should support the consideration of atypical forms of late onset CID secondary to RAG deficiency. Next generation sequencing approaches provide powerful tools in the investigation of these patients and may expedite definitive treatments.


Assuntos
Imunodeficiência de Variável Comum/genética , Proteínas de Homeodomínio/genética , Mutação , Agamaglobulinemia/diagnóstico , Agamaglobulinemia/etiologia , Biópsia , Pré-Escolar , Imunodeficiência de Variável Comum/complicações , Imunodeficiência de Variável Comum/diagnóstico , Análise Mutacional de DNA , Evolução Fatal , Feminino , Humanos , Imuno-Histoquímica , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/etiologia , Linfopenia/diagnóstico , Linfopenia/etiologia , Tomografia Computadorizada por Raios X , Adulto Jovem
7.
Magn Reson Imaging ; 110: 184-194, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38642779

RESUMO

PURPOSE: 23Na MRI can be used to quantify in-vivo tissue sodium concentration (TSC), but the inherently low 23Na signal leads to long scan times and/or noisy or low-resolution images. Reconstruction algorithms such as compressed sensing (CS) have been proposed to mitigate low signal-to-noise ratio (SNR); although, these can result in unnatural images, suboptimal denoising and long processing times. Recently, machine learning has been increasingly used to denoise 1H MRI acquisitions; however, this approach typically requires large volumes of high-quality training data, which is not readily available for 23Na MRI. Here, we propose using 1H data to train a denoising convolutional neural network (CNN), which we subsequently demonstrate on prospective 23Na images of the calf. METHODS: 1893 1H fat-saturated transverse slices of the knee from the open-source fastMRI dataset were used to train denoising CNNs for different levels of noise. Synthetic low SNR images were generated by adding gaussian noise to the high-quality 1H k-space data before reconstruction to create paired training data. For prospective testing, 23Na images of the calf were acquired in 10 healthy volunteers with a total of 150 averages over ten minutes, which were used as a reference throughout the study. From this data, images with fewer averages were retrospectively reconstructed using a non-uniform fast Fourier transform (NUFFT) as well as CS, with the NUFFT images subsequently denoised using the trained CNN. RESULTS: CNNs were successfully applied to 23Na images reconstructed with 50, 40 and 30 averages. Muscle and skin apparent TSC quantification from CNN-denoised images were equivalent to those from CS images, with <0.9 mM bias compared to reference values. Estimated SNR was significantly higher in CNN-denoised images compared to NUFFT, CS and reference images. Quantitative edge sharpness was equivalent for all images. For subjective image quality ranking, CNN-denoised images ranked equally best with reference images and significantly better than NUFFT and CS images. CONCLUSION: Denoising CNNs trained on 1H data can be successfully applied to 23Na images of the calf; thus, allowing scan time to be reduced from ten minutes to two minutes with little impact on image quality or apparent TSC quantification accuracy.


Assuntos
Algoritmos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Redes Neurais de Computação , Razão Sinal-Ruído , Imageamento por Ressonância Magnética/métodos , Humanos , Processamento de Imagem Assistida por Computador/métodos , Perna (Membro)/diagnóstico por imagem , Masculino , Adulto , Feminino , Isótopos de Sódio , Estudos Prospectivos , Sódio , Voluntários Saudáveis , Músculo Esquelético/diagnóstico por imagem
8.
Comput Struct Biotechnol J ; 24: 412-419, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38831762

RESUMO

In anticipation of potential future pandemics, we examined the challenges and opportunities presented by the COVID-19 outbreak. This analysis highlights how artificial intelligence (AI) and predictive models can support both patients and clinicians in managing subsequent infectious diseases, and how legislators and policymakers could support these efforts, to bring learning healthcare system (LHS) from guidelines to real-world implementation. This report chronicles the trajectory of the COVID-19 pandemic, emphasizing the diverse data sets generated throughout its course. We propose strategies for harnessing this data via AI and predictive modelling to enhance the functioning of LHS. The challenges faced by patients and healthcare systems around the world during this unprecedented crisis could have been mitigated with an informed and timely adoption of the three pillars of the LHS: Knowledge, Data and Practice. By harnessing AI and predictive analytics, we can develop tools that not only detect potential pandemic-prone diseases early on but also assist in patient management, provide decision support, offer treatment recommendations, deliver patient outcome triage, predict post-recovery long-term disease impacts, monitor viral mutations and variant emergence, and assess vaccine and treatment efficacy in real-time. A patient-centric approach remains paramount, ensuring patients are both informed and actively involved in disease mitigation strategies.

9.
Eur J Immunol ; 42(10): 2736-43, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22806433

RESUMO

Rapid arrest of T cells at target sites upon engagement of chemokine receptors is crucial to the proper functioning of the immune system. Although T-cell arrest always occurs under hydrodynamic forces in vivo, most studies investigating the molecular mechanisms of arrest have been performed under static conditions. While the requirement of the adapter protein SLP-76 (Src homology 2-domain containing leukocyte-specific phosphoprotein of 76 kDa) in TCR-induced integrin activation has been demonstrated, its role in chemokine-triggered T-cell adhesion is unknown. Using a flow chamber system, we show that SLP-76 plays an important role in regulating the transition from tethering and rolling to firm adhesion of T cells under physiological shear flow in response to CXCL12α (stromal cell-derived factor-1α); SLP-76-deficient primary T cells exhibited defective adhesion with a significant decrease in the number of firmly arrested cells. We further demonstrate the N-terminal phosphotyrosines of SLP-76 play a critical role in T-cell adhesion under flow. These findings reveal a novel role for SLP-76 in CXCR4-mediated T lymphocyte trafficking.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Fosfoproteínas/metabolismo , Receptores CXCR/metabolismo , Linfócitos T/fisiologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Adesão Celular/genética , Quimiocina CXCL12/metabolismo , Cultura em Câmaras de Difusão , Humanos , Células Jurkat , Migração e Rolagem de Leucócitos/genética , Camundongos , Camundongos Knockout , Fosfoproteínas/genética , Fosfotirosina/metabolismo , RNA Interferente Pequeno/genética
10.
Front Pain Res (Lausanne) ; 4: 1266783, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38090537

RESUMO

This article presents an overview of the pain research programs within the National Institutes of Health (NIH) Helping to End Addiction Long-term® Initiative, or NIH HEAL Initiative®. Launched in 2018 to address the opioid crisis, the NIH HEAL Initiative supports research on addiction prevention and treatment. A key component of addiction prevention is the development of new, effective, non-addictive treatments for acute and chronic pain. HEAL's innovate research portfolio spans the spectrum from therapeutic discovery and development through clinical trials and into clinical practice.

11.
Nurs Open ; 10(6): 3962-3972, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36808483

RESUMO

AIMS: The aim of the study was to explore the physician associate role in patient care, integration and collaboration with team members, within the hospital setting. DESIGN: Convergent mixed methods case study design. METHODS: Questionnaires with some open-ended questions and semi-structured interviews were analysed with descriptive statistics and thematic analysis. RESULTS: Participants included 12 physician associates, 31 health professionals and 14 patients/relatives. Physician associates provide effective, safe and, importantly, continuity of care and patients received patient-centred care. Integration into teams was variable, and there was a lack of knowledge about the physician associate role amongst staff and patients. Views towards physician associates were mostly positive, but support for physician associates differed across the three hospitals. CONCLUSION: This study further consolidates the role of physician associates to multiprofessional teams and patient care and emphasises the importance of providing support to individuals and teams when integrating new professions. Interprofessional learning throughout healthcare careers can develop interprofessional working within multiprofessional teams. IMPACT: Leaders in healthcare will see that clarity about the role of physician associates must be given to staff members and patients. Employers and team members will see the need to properly integrate new professions and team members within the workplace and to enhance professional identities. The research will also impact on educational establishments to provide more interprofessional training. PATIENT AND PUBLIC INVOLVEMENT: There is no patient and public involvement.


Assuntos
Médicos , Humanos , Assistência ao Paciente , Pessoal de Saúde , Hospitais , Equipe de Assistência ao Paciente
12.
BMJ Open ; 12(5): e059324, 2022 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-35589341

RESUMO

OBJECTIVE: To study the trends of hyperkalaemia in USA inpatient hospitalisation records with heart failure (HF), chronic kidney disease (CKD), acute kidney injury (AKI) and/or type II diabetes mellitus (T2DM) from 2004 to 2014 with respect to prevalence and inpatient mortality. DESIGN: Observational cross-sectional and propensity score-matched case-control study. SETTING: The National Inpatient Sample (representing up to 97% of inpatient hospital discharge records in the USA) from 2004 to 2014 PARTICIPANTS: 120 513 483 (±2 312 391) adult inpatient hospitalisation records with HF, CKD/end-stage renal disease (ESRD), AKI and/or T2DM. EXPOSURE: Hyperkalaemia, defined as the presence of an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code of '276.7' in any of the first 15 diagnostic codes. PRIMARY AND SECONDARY OUTCOME MEASURES: The outcomes of interest are the annual rates of hyperkalaemia prevalence and inpatient mortality. RESULTS: Among 120 513 483 (±2 312 391) adult inpatient hospitalisations with HF, CKD/ESRD, AKI and/or T2DM, we found a 28.9% relative increase of hyperkalaemia prevalence from 4.94% in 2004 to 6.37% in 2014 (p<0.001). Hyperkalaemia was associated with an average of 4 percentage points higher rate of inpatient mortality (1.71 post-matching, p<0.0001). Inpatient mortality rates decreased from 11.49%±0.17% to 6.43%±0.08% and 9.67%±0.13% to 5.05%±0.07% for matched cases with and without hyperkalaemia, respectively (p<0.001). CONCLUSIONS: Hyperkalaemia prevalence increased over time and was associated with greater inpatient mortality, even after accounting for presentation characteristics. We detected a decreasing trend in inpatient mortality risk, regardless of hyperkalaemia presence.


Assuntos
Injúria Renal Aguda , Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Hiperpotassemia , Falência Renal Crônica , Insuficiência Renal Crônica , Injúria Renal Aguda/epidemiologia , Adulto , Estudos de Casos e Controles , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Hospitalização , Humanos , Hiperpotassemia/complicações , Hiperpotassemia/epidemiologia , Pacientes Internados , Falência Renal Crônica/complicações , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/terapia , Pontuação de Propensão , Insuficiência Renal Crônica/epidemiologia , Fatores de Risco , Estados Unidos/epidemiologia
13.
Front Mol Neurosci ; 15: 964632, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36117909

RESUMO

Chronic hypertension is a major risk factor for the development of neurodegenerative disease, yet the etiology of hypertension-driven neurodegeneration remains poorly understood. Forming a unique interface between the systemic circulation and the brain, the blood-cerebrospinal fluid barrier (BCSFB) at the choroid plexus (CP) has been proposed as a key site of vulnerability to hypertension that may initiate downstream neurodegenerative processes. However, our ability to understand BCSFB's role in pathological processes has, to date, been restricted by a lack of non-invasive functional measurement techniques. In this work, we apply a novel Blood-Cerebrospinal Fluid Barrier Arterial Spin Labeling (BCSFB-ASL) Magnetic resonance imaging (MRI) approach with the aim of detecting possible derangement of BCSFB function in the Spontaneous Hypertensive Rat (SHR) model using a non-invasive, translational technique. SHRs displayed a 36% reduction in BCSFB-mediated labeled arterial water delivery into ventricular cerebrospinal fluid (CSF), relative to normotensive controls, indicative of down-regulated choroid plexus function. This was concomitant with additional changes in brain fluid biomarkers, namely ventriculomegaly and changes in CSF composition, as measured by T1 lengthening. However, cortical cerebral blood flow (CBF) measurements, an imaging biomarker of cerebrovascular health, revealed no measurable change between the groups. Here, we provide the first demonstration of BCSFB-ASL in the rat brain, enabling non-invasive assessment of BCSFB function in healthy and hypertensive rats. Our data highlights the potential for BCSFB-ASL to serve as a sensitive early biomarker for hypertension-driven neurodegeneration, in addition to investigating the mechanisms relating hypertension to neurodegenerative outcomes.

14.
Intern Emerg Med ; 17(6): 1759-1768, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35349005

RESUMO

Intravenous vitamin C (IV-VitC) has been suggested as a treatment for severe sepsis and acute respiratory distress syndrome; however, there are limited studies evaluating its use in severe COVID-19. Efficacy and safety of high-dose IV-VitC (HDIVC) in patients with severe COVID-19 were evaluated. This observational cohort was conducted at a single-center, 530 bed, community teaching hospital and took place from March 2020 through July 2020. Inverse probability treatment weighting (IPTW) was utilized to compare outcomes in patients with severe COVID-19 treated with and without HDIVC. Patients were enrolled if they were older than 18 years of age and were hospitalized secondary to severe COVID-19 infection, indicated by an oxygenation index < 300. Primary study outcomes included mortality, mechanical ventilation, intensive care unit (ICU) admission, and cardiac arrest. From a total of 100 patients enrolled, 25 patients were in the HDIVC group and 75 patients in the control group. The average time to death was significantly longer for HDIVC patients (P = 0.0139), with an average of 22.9 days versus 13.7 days for control patients. Patients who received HDIVC also had significantly lower rates of mechanical ventilation (52.93% vs. 73.14%; ORIPTW = 0.27; P = 0.0499) and cardiac arrest (2.46% vs. 9.06%; ORIPTW = 0.23; P = 0.0439). HDIVC may be an effective treatment in decreasing the rates of mechanical ventilation and cardiac arrest in hospitalized patients with severe COVID-19. A longer hospital stay and prolonged time to death may suggest that HDIVC may protect against clinical deterioration in severe COVID-19.


Assuntos
Antineoplásicos , Tratamento Farmacológico da COVID-19 , COVID-19 , Parada Cardíaca , Ácido Ascórbico/uso terapêutico , COVID-19/complicações , Parada Cardíaca/terapia , Humanos , Respiração Artificial , SARS-CoV-2
15.
Adv Sci (Weinh) ; 9(12): e2105333, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35106965

RESUMO

Medical therapies achieve their control at expense to the patient in the form of a range of toxicities, which incur costs and diminish quality of life. Magnetic resonance navigation is an emergent technique that enables image-guided remote-control of magnetically labeled therapies and devices in the body, using a magnetic resonance imaging (MRI) system. Minimally INvasive IMage-guided Ablation (MINIMA), a novel, minimally invasive, MRI-guided ablation technique, which has the potential to avoid traditional toxicities, is presented. It comprises a thermoseed navigated to a target site using magnetic propulsion gradients generated by an MRI scanner, before inducing localized cell death using an MR-compatible thermoablative device. The authors demonstrate precise thermoseed imaging and navigation through brain tissue using an MRI system (0.3 mm), and they perform thermoablation in vitro and in vivo within subcutaneous tumors, with the focal ablation volume finely controlled by heating duration. MINIMA is a novel theranostic platform, combining imaging, navigation, and heating to deliver diagnosis and therapy in a single device.


Assuntos
Imagem por Ressonância Magnética Intervencionista , Neoplasias , Humanos , Imageamento por Ressonância Magnética/métodos , Imagem por Ressonância Magnética Intervencionista/métodos , Neoplasias/diagnóstico por imagem , Neoplasias/cirurgia , Qualidade de Vida
16.
Adv Sci (Weinh) ; 9(6): e2104194, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34927381

RESUMO

Astrocytes play crucial and diverse roles in brain health and disease. The ability to selectively control astrocytes provides a valuable tool for understanding their function and has the therapeutic potential to correct dysfunction. Existing technologies such as optogenetics and chemogenetics require the introduction of foreign proteins, which adds a layer of complication and hinders their clinical translation. A novel technique, magnetomechanical stimulation (MMS), that enables remote and selective control of astrocytes without genetic modification is described here. MMS exploits the mechanosensitivity of astrocytes and triggers mechanogated Ca2+ and adenosine triphosphate (ATP) signaling by applying a magnetic field to antibody-functionalized magnetic particles that are targeted to astrocytes. Using purpose-built magnetic devices, the mechanosensory threshold of astrocytes is determined, a sub-micrometer particle for effective MMS is identified, the in vivo fate of the particles is established, and cardiovascular responses are induced in rats after particles are delivered to specific brainstem astrocytes. By eliminating the need for device implantation and genetic modification, MMS is a method for controlling astroglial activity with an improved prospect for clinical application than existing technologies.


Assuntos
Astrócitos/fisiologia , Encéfalo/fisiologia , Campos Magnéticos , Mecanotransdução Celular/fisiologia , Estimulação Física/métodos , Animais , Tronco Encefálico/fisiologia , Células Cultivadas , Feminino , Masculino , Modelos Animais , Ratos , Ratos Sprague-Dawley
17.
J Immunol ; 182(9): 5183-7, 2009 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-19380761

RESUMO

SLP-76 (Src homology 2 domain-containing leukocyte phosphoprotein of 76 kDa) organizes signaling from immunoreceptors, including the platelet collagen receptor, the pre-TCR, and the TCR, and is required for T cell development. In this study we examine a mouse in which wild-type SLP-76 is replaced with a mutant constitutively targeted to the cell membrane. Membrane-targeted SLP-76 (MTS) supports ITAM signaling in platelets and from the pre-TCR. Signaling from the mature TCR, however, is defective in MTS thymocytes, resulting in failed T cell differentiation. Defective thymic selection by MTS is not rescued by a SLP-76 mutant whose localization is restricted to the cytosol. Thus, fixed localization of SLP-76 reveals differential requirements for the subcellular localization of signaling complexes downstream of the pre-TCR vs mature TCR.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/biossíntese , Proteínas Adaptadoras de Transdução de Sinal/genética , Membrana Celular/metabolismo , Glicoproteínas de Membrana/fisiologia , Fosfoproteínas/biossíntese , Fosfoproteínas/genética , Precursores de Proteínas/fisiologia , Receptores de Antígenos de Linfócitos T alfa-beta/fisiologia , Transdução de Sinais/imunologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/fisiologia , Animais , Diferenciação Celular/genética , Diferenciação Celular/imunologia , Membrana Celular/genética , Membrana Celular/imunologia , Técnicas de Introdução de Genes , Marcação de Genes , Humanos , Células Jurkat , Glicoproteínas de Membrana/biossíntese , Glicoproteínas de Membrana/genética , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Fosfoproteínas/fisiologia , Precursores de Proteínas/biossíntese , Precursores de Proteínas/genética , Receptores de Antígenos de Linfócitos T alfa-beta/biossíntese , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Transdução de Sinais/genética , Linfócitos T/citologia
18.
PLoS One ; 16(1): e0245783, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33481944

RESUMO

Mistrust of health care providers among persons of color is a significant barrier to engaging them in research studies. Underrepresentation of persons of color is particularly problematic when the health problem under study disproportionately affects minoritized communities. The purpose of this study was to test the validity and reliability of an abbreviated and adapted version of the Group Based Medical Mistrust Scale. The GBMMS is a 12-item scale with three subscales that assess suspicion, experiences of discrimination, and lack of support in the health care setting. To adapt for use in the research setting, we shortened the scale to six items, and replaced "health care workers" and "health care" with "medical researchers" and "medical research," respectively. Using panelists from a market research firm, we recruited and enrolled a racially and ethnically diverse sample of American adults (N = 365) and adolescents aged 14-17 (N = 250). We administered the adapted scale in a web-based survey. We used Cronbach's alpha to evaluate measure internal reliability of the scale and external factor analysis to evaluate the relationships between the revised scale items. Five of the six items loaded onto a single factor, with (α = 0.917) for adolescents and (α = 0.912) for adults. Mean scores for each item ranged from 2.5-2.9, and the mean summary score (range 6-25) was 13.3 for adults and 13.1 for adolescents. Among adults, Black respondents had significantly higher mean summary scores compared to whites and those in other racia/ethnic groups (p<0.001). There was a trend toward significance for Black adolescents as compared to white respondents and those in other racial/ethnic groups (p = 0.09). This five-item modified version of the GBMMS is reliable and valid for measuring research mistrust with American adults and adolescents of diverse racial and ethnic identities.


Assuntos
Psicometria/métodos , Confiança/psicologia , Adolescente , Adulto , Atenção à Saúde/estatística & dados numéricos , Análise Fatorial , Feminino , Humanos , Masculino , Grupos Raciais/psicologia , Reprodutibilidade dos Testes , Inquéritos e Questionários
19.
Palliat Med Rep ; 2(1): 93-100, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34223508

RESUMO

Objective: The primary objective was to evaluate the efficacy of a weekly palliative care-guided, case-based discussion of high-risk infants on Neonatal Intensive Care Unit (NICU) physician (MD) and Advanced Practice Provider (APP) perceptions of pediatric palliative care (PPC). Study Design: The study setting was a level IV academic NICU in a United States midwestern children's hospital. A pre/post design was used to evaluate the effects of a weekly palliative care-guided, case-based discussion of high-risk infants on neonatology providers' (MD and APP) perspectives of palliative and end-of-life care in the NICU using a previously published survey instrument. Surveys were completed at baseline and after 12 months of implementation. Data was analyzed with a Wilcoxon Signed Rank test with significance set at p < 0.05. Results: Thirty-one providers (13 APPs and 18 MDs) completed both pre- and post-intervention surveys. Post-intervention, providers were more likely to endorse that they "are comfortable with PPC", "feel comfortable teaching PPC to trainees", "feel confident handling end-of-life care", "have time to discuss PPC", and "were satisfied with the transition to end-of-life care for their most recent patient". They also were more likely to report, "families' perception of burden is relevant when making ethical decisions", that "parents are involved in decisions regarding palliative care", and that their "institution is supportive of palliative care." (p-values < 0.05 for all). Conclusion: NICU provider perceptions of palliative care can be improved through the implementation of a case-based interdisciplinary conference that emphasizes palliative care domains in the context of Neonatal ICU care.

20.
Proc (Bayl Univ Med Cent) ; 34(4): 437-441, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-34219921

RESUMO

The prevalence and seroconversion rate of SARS-CoV-2 infection among asymptomatic health care workers in the US is unclear. Our study utilized real-time polymerase chain reaction (RT-PCR) SARS-CoV-2 testing and serological evaluation to detect IgG antibodies specific to SARS-CoV-2 antigens in asymptomatic health care workers. A total of 197 subjects with a mean age of 35 years were recruited into the study. While most (67%) reported prolonged contact with known COVID-19 patients, only 8 (4.2%) tested positive on RT-PCR and 23 (11.7%) had detectable levels of IgG antibody to SARS-CoV-2. Out of 19 subjects with detectable IgG antibody at week 1, 11 (57.9%) lost their antibody response by week 3. No statistically significant difference was found in baseline characteristics or exposure status between subjects with positive and negative results on RT-PCR or antibody positivity. In conclusion, we found a low incidence of PCR positivity for SARS-CoV-2 in a high-risk group. This likely demonstrates the effectiveness of proper personal protective equipment use and low transmission risk in health care settings. The detectable IgG antibody titer was low, and a significant portion of subjects lost their antibody response on repeat testing. This may mean that antibody response in asymptomatic patients is categorically different than in symptomatic hospitalized patients with COVID-19.

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