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1.
Neurocrit Care ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38955930

RESUMO

BACKGROUND: Cerebrospinal fluid creatine kinase BB isoenzyme (CSF CK-BB) after cardiac arrest (CA) has been shown to have a high positive predictive value for poor neurological outcome, but it has not been evaluated in the setting of targeted temperature management (TTM) and modern CA care. We aimed to evaluate CSF CK-BB as a prognostic biomarker after CA. METHODS: We performed a retrospective cohort study of patients with CA admitted between 2010 and 2020 to a three-hospital health system who remained comatose and had CSF CK-BB assayed between 36 and 84 h after CA. We examined the proportion of patients at hospital discharge who achieved favorable or intermediate neurological outcome, defined as Cerebral Performance Category score of 1-3, compared with those with poor outcome (Cerebral Performance Category score 4-5) for various CSF CK-BB thresholds. We also evaluated additive value of bilateral absence of somatosensory evoked potentials (SSEPs). RESULTS: Among 214 eligible patients, the mean age was 54.7 ± 4.8 years, 72% of patients were male, 33% were nonwhite, 17% had shockable rhythm, 90% were out-of-hospital CA, and 83% received TTM. A total of 19 (9%) awakened. CSF CK-BB ≥ 230 U/L predicted a poor outcome at hospital discharge, with a specificity of 100% (95% confidence interval [CI] 82-100%) and sensitivity of 69% (95% CI 62-76%). When combined with bilaterally absent N20 response on SSEP, specificity remained 100% while sensitivity increased to 80% (95% CI 73-85%). Discordant CK-BB and SSEP findings were seen in 13 (9%) patients. CONCLUSIONS: Cerebrospinal fluid creatine kinase BB isoenzyme levels accurately predicted poor neurological outcome among CA survivors treated with TTM. The CSF CK-BB cutoff of 230 U/L optimizes sensitivity to 69% while maintaining a specificity of 100%. CSF CK-BB could be a useful addition to multimodal neurological prognostication after CA.

2.
Adv Physiol Educ ; 48(3): 609-615, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38870267

RESUMO

This interventional study was designed to evaluate the effectiveness of buzz session teaching in large groups and assess undergraduate medical students' perceptions of the buzz session teaching method. The study involved 100 first-year medical students divided into two groups, i.e., group I as "buzz first" and group II as "didactic first" comprising 50 students each. The topic "Physiology of the Cerebellum" was taught to group I through a buzz session and to group II through a didactic lecture. After a week, group I received a didactic lecture on the topic "Anterolateral Pathway in the Spinal Cord," whereas group II was taught the same by a buzz session. The students of both groups underwent a multiple choice question exam related to the taught topic immediately and again after 15 days of the teaching session. All students were provided feedback on a five-point Likert scale for the buzz session. According to students' perceptions, buzz sessions boosted communication skills and confidence levels by 94.8% and 96.3%, respectively. Of the students, 93.7% felt that the buzz session helped them retain more information and 94.1% thought they made the classroom environment more lively. More buzz sessions were desired by 94.8% of the participants. There was no difference in the marks gained for the acquired topics using buzz sessions and didactic lectures as teaching methods (P > 0.05). The students scored more marks in the tests taken after the buzz session than after the didactic lecture at 15 days of instruction (P < 0.05). The study concluded that students enjoyed the buzz session teaching method. The buzz session increased short-term retention.NEW & NOTEWORTHY In this current interventional study, we assessed the effectiveness of a buzz session as a novel teaching tool for large-group physiology instruction in first-year undergraduate medical students. Furthermore, we assessed student responses to see how the buzz session was perceived. Experimental evidence indicates that the buzz sessions led to greater retention after 15 days than the didactic lecture approach for physiology teaching in a preclinical context.


Assuntos
Educação de Graduação em Medicina , Estudantes de Medicina , Ensino , Humanos , Estudantes de Medicina/psicologia , Educação de Graduação em Medicina/métodos , Feminino , Masculino , Percepção , Avaliação Educacional/métodos , Fisiologia/educação , Adulto Jovem
3.
Adv Physiol Educ ; 48(2): 407-413, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38545641

RESUMO

Emotional intelligence (EI) has a positive correlation with the academic performance of medical students. However, why there is a positive correlation needs further exploration. We hypothesized that the capability of answering higher-order knowledge questions (HOQs) is higher in students with higher EI. Hence, we assessed the correlation between EI and the capability of medical students to answer HOQs in physiology. First-year undergraduate medical students (n = 124) from an Indian medical college were recruited as a convenient sample. EI was assessed by the Schutte Self-Report Emotional Intelligence Test (SSEIT), a 33-item self-administered validated questionnaire. A specially designed objective examination with 15 lower-order and 15 higher-order multiple-choice questions was conducted. The correlation between the examination score and the EI score was tested by Pearson's correlation coefficient. Data from 92 students (33 females and 59 males) with a mean age of 20.14 ± 1.87 yr were analyzed. Overall, students got a percentage of 53.37 ± 14.07 in the examination, with 24.46 ± 9.1 in HOQs and 28.91 ± 6.58 in lower-order knowledge questions (LOQs). They had a mean score of 109.58 ± 46.2 in SSEIT. The correlation coefficient of SSEIT score with total marks was r = 0.29 (P = 0.0037), with HOQs was r = 0.41 (P < 0.0001), and with LOQs was r = 0.14 (P = 0.19). Hence, there is a positive correlation between EI and the capability of medical students to answer HOQs in physiology. This study may be the foundation for further exploration of the capability of answering HOQs in other subjects.NEW & NOTEWORTHY This study assessed the correlation between emotional intelligence (EI) and the capability of medical students to answer higher-order knowledge questions (HOQs) in the specific context of physiology. The finding reveals one of the multifaceted dimensions of the relationship between EI and academic performance. This novel perspective opens the door to further investigations to explore the relationship in other subjects and other dimensions to understand why students with higher EI have higher academic performance.


Assuntos
Educação de Graduação em Medicina , Inteligência Emocional , Fisiologia , Estudantes de Medicina , Humanos , Estudantes de Medicina/psicologia , Inteligência Emocional/fisiologia , Feminino , Masculino , Fisiologia/educação , Adulto Jovem , Educação de Graduação em Medicina/métodos , Avaliação Educacional/métodos , Inquéritos e Questionários
4.
Microb Pathog ; 162: 105326, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34863878

RESUMO

AIDS restriction genes (ARGs) like APOBEC3, TRIM5α, and BST2 can act as immunological detectors of the innate protective mechanism of the body. ARGs influence the course of viral pathogenesis and progression of the disease. The infection caused by different viruses including HIV activates the innate immune receptors leading to production of proinflammatory cytokines, interferons and signals that recruit and activate cells involved in the process of inflammation following induction of adaptive immunity. Differential expression of genes involved in viral infection decide the fate and subsequent susceptibility to infection and its clinical outcome. Nevertheless, comprehensive reports on the incidence of genetic polymorphism of APOBEC3s, TRIM5α, and BST-2 in the general population and its association with pathological conditions have not been described well. Therefore, the occurrence of APOBEC3, TRIM5α, and BST2 polymorphism in healthy individuals and its impact on HIV transmission was analyzed. We conducted an extensive search using the several databases including, EMBASE, PubMed (Medline), and Google Scholar. APOBEC3-D, -F, -G, and -H out of the seven human APOBEC3s, help in the control of viral infection. Amongst various restriction factors, TRIM5α and BST-2 also restrict the viral infection followed by the development of the disease. In the current review, a brief account of the polymorphism in the APOBEC3G, TRIM5α, and BST2 genes are explored among different populations along with the interaction of APOBEC3G with Vif protein. Furthermore, this review specifically focus on ARGs polymorphism (APOBEC3G, TRIM5α, and BST2) associated with HIV transmission.


Assuntos
Síndrome da Imunodeficiência Adquirida , Infecções por HIV , HIV-1 , Desaminases APOBEC , Antígenos CD/genética , Proteínas Ligadas por GPI/genética , Infecções por HIV/genética , Humanos , Polimorfismo Genético
5.
J Cardiovasc Magn Reson ; 24(1): 27, 2022 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-35410226

RESUMO

BACKGROUND: Theoretically, artificial intelligence can provide an accurate automatic solution to measure right ventricular (RV) ejection fraction (RVEF) from cardiovascular magnetic resonance (CMR) images, despite the complex RV geometry. However, in our recent study, commercially available deep learning (DL) algorithms for RVEF quantification performed poorly in some patients. The current study was designed to test the hypothesis that quantification of RV function could be improved in these patients by using more diverse CMR datasets in addition to domain-specific quantitative performance evaluation metrics during the cross-validation phase of DL algorithm development. METHODS: We identified 100 patients from our prior study who had the largest differences between manually measured and automated RVEF values. Automated RVEF measurements were performed using the original version of the algorithm (DL1), an updated version (DL2) developed from a dataset that included a wider range of RV pathology and validated using multiple domain-specific quantitative performance evaluation metrics, and conventional methodology performed by a core laboratory (CORE). Each of the DL-RVEF approaches was compared against CORE-RVEF reference values using linear regression and Bland-Altman analyses. Additionally, RVEF values were classified into 3 categories: ≤ 35%, 35-50%, and ≥ 50%. Agreement between RVEF classifications made by the DL approaches and the CORE measurements was tested. RESULTS: CORE-RVEF and DL-RVEFs were obtained in all patients (feasibility of 100%). DL2-RVEF correlated with CORE-RVEF better than DL1-RVEF (r = 0.87 vs. r = 0.42), with narrower limits of agreement. As a result, DL2 algorithm also showed increasing accuracy from 0.53 to 0.80 for categorizing RV function. CONCLUSIONS: The use of a new DL algorithm cross-validated on a dataset with a wide range of RV pathology using multiple domain-specific metrics resulted in a considerable improvement in the accuracy of automated RVEF measurements. This improvement was demonstrated in patients whose images were the most challenging and resulted in the largest RVEF errors. These findings underscore the critical importance of this strategy in the development of DL approaches for automated CMR measurements.


Assuntos
Inteligência Artificial , Disfunção Ventricular Direita , Ventrículos do Coração/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Imagem Cinética por Ressonância Magnética/métodos , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Volume Sistólico , Disfunção Ventricular Direita/diagnóstico por imagem , Função Ventricular Direita
6.
Curr Cardiol Rep ; 24(12): 1907-1916, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36301406

RESUMO

PURPOSE OF REVIEW: The athlete's heart exhibits unique structural and functional adaptations in the setting of strenuous and repetitive athletic training which may be similarly found in pathologic states. The purpose of this review is to highlight the morphologic and functional changes associated with the athlete's heart, with a focus upon the insights that echocardiography provides into exercise-induced cardiac remodeling. RECENT FINDINGS: Recent studies are aiming to investigate the long-term effects and clinical consequences of an athlete's heart. The "gray-zone" continues to pose a clinical challenge and may indicate scenarios where additional imaging modalities, or longitudinal follow-up, provide a definitive answer. Echocardiography is likely to remain the first-line imaging modality for the cardiac evaluation of elite athletes. Multimodality imaging combined with outcome and long-term follow-up studies both during training and after retirement in both men and women may help further clarify the remaining mysteries in the coming years.


Assuntos
Cardiomegalia Induzida por Exercícios , Masculino , Feminino , Humanos , Ecocardiografia , Coração/diagnóstico por imagem , Atletas
7.
Neurocrit Care ; 36(2): 504-510, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34476722

RESUMO

BACKGROUND: Tracheostomy represents one important and value-laden treatment decision after severe acute brain injury (SABI). Whether to pursue this life-sustaining treatment typically hinges on intense conversations between family and clinicians. The aim of this study was, among a cohort of patient who had undergone tracheostomy after SABI, to explore the long-term reflections of patients and their families as they look back on this decision. METHODS: For this qualitative study, we reviewed the electronic medical records of patients with SABI who underwent tracheostomy. We included all patients who were admitted to our 30-bed neuro-intensive care unit with SABI and underwent tracheostomy between November 2017 and October 2019. Using purposive sampling, we invited survivors and family members to participate in telephone interviews greater than 3 months after SABI until thematic saturation was reached. Interviews were audiotaped, transcribed, and analyzed by using thematic analysis. RESULTS: Overall, 38 patients with SABI in the neuro-intensive care unit underwent tracheostomy. The mean age of patients was 49 (range 18-81), with 19 of 38 patients diagnosed with traumatic brain injury and 19 of 38 with stroke. We interviewed 20 family members of 18 of 38 patients at a mean of 16 (SD 9) months after hospitalization. The mean patient age among those with an interview was 50 (range 18-76); the mean modified Rankin Scale score (mRS) was 4.7 (SD 0.8) at hospital discharge. At the time of the interview, ten patients lived at home and two in a skilled nursing facility and had a mean mRS of 2.6 (SD 0.9), and six had died. As families reflected on the decision to proceed with a tracheostomy, two themes emerged. First, families did not remember tracheostomy as a choice because the uncertain chance of recovery rendered the certain alternative of death unacceptable or because they valued survival above all and therefore could not perceive an alternative to life-sustaining treatment. Second, families identified a fundamental need to receive supportive, consistent communication centering around compassion, clarity, and hope. When this need was met, families were able to reflect on the tracheostomy decision with peace, regardless of their loved one's eventual outcome. CONCLUSIONS: After SABI, prognostic uncertainty almost transcends the concept of choice. Families who proceeded with a tracheostomy saw it as the only option at the time. High-quality communication may mitigate the stress surrounding this high-stakes decision.


Assuntos
Lesões Encefálicas Traumáticas , Lesões Encefálicas , Lesões Encefálicas/cirurgia , Lesões Encefálicas Traumáticas/terapia , Família , Humanos , Unidades de Terapia Intensiva , Traqueostomia
8.
J Stroke Cerebrovasc Dis ; 31(12): 106794, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36215903

RESUMO

OBJECTIVES: Based on a 16-year case series, we sought lessons about diagnosis and treatment of cerebral fat embolism syndrome. MATERIALS AND METHODS: Using discharge codes at a Level 1 Trauma Center, we performed a retrospective chart review of clinical characteristics, diagnostic studies, treatments, and outcome in cerebral fat embolism syndrome. RESULTS: Thirty-nine (40%) of 97 patients with fat embolism syndrome were diagnosed with cerebral fat embolism syndrome, with 29 (74%) presenting with coma. All had abnormal brain magnetic resonance imaging, with scattered cytotoxic edema (starfield pattern) in 29 (74%). All but two of the 21 patients with dilated fundoscopy showed retinal embolism. Among 29 patients with transcranial Doppler, the presence of microembolic signals in 15 (52%) was associated with fever (p = 0.039), right-to-left intracardiac shunting (p = 0.046) and a trend towards initial coma. In 11 patients with serial transcranial Dopplers and treatment with high-intensity statin therapy, the frequency of microembolic signals tended to decrease after therapy was initiated. Of the 28 (72%) of the 39 patients discharged, 16 (57%) had mild to moderate disability at last follow up. CONCLUSIONS: The recognition of cerebral fat embolism syndrome may be improved with routine inclusion of brain magnetic resonance imaging, dilated fundoscopy, and transcranial Doppler. We share our empiric management algorithm for cerebral fat embolism syndrome using these studies and with consideration of experimental therapies in select patients to prevent ongoing cerebral injury.


Assuntos
Embolia Gordurosa , Embolia Intracraniana , Humanos , Centros de Traumatologia , Embolia Intracraniana/diagnóstico por imagem , Embolia Intracraniana/etiologia , Embolia Intracraniana/terapia , Coma , Estudos Retrospectivos , Embolia Gordurosa/diagnóstico por imagem , Embolia Gordurosa/etiologia , Embolia Gordurosa/terapia
9.
Antimicrob Agents Chemother ; 65(9): e0039821, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34152811

RESUMO

Dengue fever, caused by dengue virus (DENV), is the most prevalent arthropod-borne viral disease and is endemic in many tropical and subtropical parts of the world, with an increasing incidence in temperate regions. The closely related flavivirus Zika virus (ZIKV) can be transmitted vertically in utero and causes congenital Zika syndrome and other birth defects. In adults, ZIKV is associated with Guillain-Barré syndrome. There are no approved antiviral therapies against either virus. Effective antiviral compounds are urgently needed. Amaryllidaceae alkaloids (AAs) are a specific class of nitrogen-containing compounds produced by plants of the Amaryllidaceae family with numerous biological activities. Recently, the AA lycorine was shown to present strong antiflaviviral properties. Previously, we demonstrated that Crinum jagus contained lycorine and several alkaloids of the cherylline, crinine, and galanthamine types with unknown antiviral potential. In this study, we explored their biological activities. We show that C. jagus crude alkaloid extract inhibited DENV infection. Among the purified AAs, cherylline efficiently inhibited both DENV (50% effective concentration [EC50], 8.8 µM) and ZIKV replication (EC50, 20.3 µM) but had no effect on HIV-1 infection. Time-of-drug-addition and -removal experiments identified a postentry step as the one targeted by cherylline. Consistently, using subgenomic replicons and replication-defective genomes, we demonstrate that cherylline specifically hinders the viral RNA synthesis step but not viral translation. In conclusion, AAs are an underestimated source of antiflavivirus compounds, including the effective inhibitor cherylline, which could be optimized for new therapeutic approaches.


Assuntos
Alcaloides , Alcaloides de Amaryllidaceae , Amaryllidaceae , Vírus da Dengue , Dengue , Infecção por Zika virus , Zika virus , Adulto , Alcaloides/farmacologia , Alcaloides de Amaryllidaceae/farmacologia , Humanos , Isoquinolinas , Replicação Viral , Infecção por Zika virus/tratamento farmacológico
10.
Small ; 17(13): e2006977, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33690965

RESUMO

A low-temperature polarization-resolved magneto-photoluminescence experiment is performed on individual PbS/CdS core/shell quantum dots (QDs). The experiment enables a direct measurement of the exciton Landé g factor and the anisotropic zero-field splitting of the lowest emissive bright exciton triplet in PbS/CdS QDs. While anisotropic splittings of individual QDs distribute randomly in 104-325 µeV range, the exciton Landé g factors increase from 0.95 to 2.70 as the emission energy of the QD increases from 1.0 to 1.2 eV. The tight-binding calculations allow to rationalize these trends as a direct consequence of reducing a cubic symmetry of QD via addition/removal of a few (<70) atoms from the surfaces of the PbS core. Furthermore, it is observed that while right (σ  + ) and left (σ  - ) circularly polarized photoluminescence (PL) peaks split linearly with magnetic field as expected for Zeeman effect, the energy splitting between X and Y linearly polarized PL peaks remains nearly unchanged. The theoretical study reveals rich and complex magnetic field-induced interplay of bright triplet and dark exciton states explaining this puzzling behavior. These findings fill the missing gaps in the understanding of lead salt QDs and provide foundation for development of classical and quantum light sources operating at telecommunication wavelengths.

11.
Microb Pathog ; 158: 105023, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34090983

RESUMO

BACKGROUND: Long period of SARS-CoV-2 infection has been associated with psychiatric and cognitive disorders in adolescents and children. SARS-CoV-2 remains dormant in the CNS leading to neurological complications. The wide expression of ACE2 in the brain raises concern for its involvement in SARS-CoV-2 infection. Though, the mechanistic insights about blood-brain barriers (BBB) crossing by SARS-CoV-2 and further brain infection are still not clear. Moreover, the mechanism behind dormant SARS-CoV-2 infections leading to chronic neurological disorders needs to be unveiled. There is an urgent need to find out the risk factor involved in COVID-19-associated neurological disease. Therefore, the role of immune-associated genes in the pathogenesis of COVID-19 associated neurological diseases is presented which could contribute to finding associated genetic risk factors. METHOD: The search utilizing multiple databases, specifically, EMBASE, PubMed (Medline), and Google Scholar was performed. Moreover, the literature survey on the involvement of COVID-19, neuropathogenesis, and its consequences was done. DESCRIPTION: Persistent inflammatory stimuli may promote the progression of neurodegenerative diseases. An increased expression level of cytokine, chemokine, and decreased expression level of immune cells has been associated with the COVID-19 patient. Cytokine storm was observed in severe COVID-19 patients. The nature of SARS-CoV-2 infection can be neuroinflammatory. Genes of immune response could be associated with neurodegenerative diseases. CONCLUSION: The present review will provide a useful framework and help in understanding COVID-19-associated neuropathogenesis. Experimental studies on immune-associated genes in COVID-19 patients with neurological manifestations could be helpful to establish its neuropathogenesis.


Assuntos
COVID-19 , Doenças Neurodegenerativas , Adolescente , Encéfalo , Citocinas , Humanos , SARS-CoV-2
12.
J Magn Reson Imaging ; 54(4): 1257-1265, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33742522

RESUMO

BACKGROUND: Late gadolinium enhancement (LGE) imaging in patients with implantable cardioverter-defibrillators (ICD) is limited by device-related artifacts (DRA). The use of wideband (WB) LGE protocols improves LGE images, but their efficacy with different ICD types is not well known. PURPOSE: To assess the effects of WB LGE imaging on DRA in different non-MR conditional ICD subtypes. STUDY TYPE: Retrospective. POPULATION: A total of 113 patients undergoing cardiac magnetic resonance imaging with three ICD subtypes: transvenous (TV-ICD, N = 48), cardiac-resynchronization therapy device (CRT-D, N = 48), and subcutaneous (S-ICD, N = 17). FIELD STRENGTH/SEQUENCE: 5 T scanner, standard LGE, and WB LGE imaging with a phase-sensitive inversion recovery segmented gradient echo sequence. ASSESSMENT: DRA burden was defined as the number of artifact-positive short-axis LGE slices as percentage of the total number of short-axis slices covering the left ventricle from based to apex, and was determined for WB and standard LGE studies for each patient. Additionally, artifact area on each slice was quantified. STATISTICAL TESTS: Shapiro-Wilks, Kruskal-Wallis analysis of variance, Dunn tests with Bonferroni correction, and Mann-Whitney U-test. RESULTS: In patients with TV-ICD, DRA burden was significantly reduced and nearly eliminated with WB LGE compared to standard LGE imaging (median [interquartile range]: 0 [0-7]% vs. 18 [0-50]%, P < 0.05), but WB imaging had less of an impact on DRA in the CRT-D (8 [0-23]% vs. 16 [0-45]%, p = 0.12) and S-ICD (60 [15-71]% vs. 67 [50-92]%, P = 0.09) patients. Residual DRA was significantly greater (P < 0.05) for S-ICD compared to other device types with WB LGE imaging, despite the generators of all three ICD types having similar proximity to the heart. The area of S-ICD associated DRA was smaller with WB LGE (P < 0.001) than with standard LGE imaging and the artifacts had different characteristics (dark signal void instead of a bright hyperenhancement artifact). DATA CONCLUSION: Although WB LGE imaging reduced the burden of DRA caused by S-ICD, the residual artifact was greater than that observed with TV-ICD and CRT-D devices. Further developments are needed to better resolve S-ICD artifacts. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: STAGE: 5.


Assuntos
Desfibriladores Implantáveis , Gadolínio , Artefatos , Meios de Contraste , Humanos , Imageamento por Ressonância Magnética , Estudos Retrospectivos
13.
Am J Hum Genet ; 96(2): 194-207, 2015 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-25620205

RESUMO

Mutations in genes encoding the ERCC3 (XPB), ERCC2 (XPD), and GTF2H5 (p8 or TTD-A) subunits of the transcription and DNA-repair factor TFIIH lead to three autosomal-recessive disorders: xeroderma pigmentosum (XP), XP associated with Cockayne syndrome (XP/CS), and trichothiodystrophy (TTD). Although these diseases were originally associated with defects in DNA repair, transcription deficiencies might be also implicated. By using retinoic acid receptor beta isoform 2 (RARB2) as a model in several cells bearing mutations in genes encoding TFIIH subunits, we observed that (1) the recruitment of the TFIIH complex was altered at the activated RARB2 promoter, (2) TFIIH participated in the recruitment of nucleotide excision repair (NER) factors during transcription in a manner different from that observed during NER, and (3) the different TFIIH variants disturbed transcription by having distinct consequences on post-translational modifications of histones, DNA-break induction, DNA demethylation, and gene-loop formation. The transition from heterochromatin to euchromatin was disrupted depending on the variant, illustrating the fact that TFIIH, by contributing to NER factor recruitment, orchestrates chromatin remodeling. The subtle transcriptional differences found between various TFIIH variants thus participate in the phenotypic variability observed among XP, XP/CS, and TTD individuals.


Assuntos
Montagem e Desmontagem da Cromatina/genética , Complexos Multiproteicos/metabolismo , Receptores do Ácido Retinoico/genética , Fator de Transcrição TFIIH/genética , Transcrição Gênica/fisiologia , Síndromes de Tricotiodistrofia/genética , Xeroderma Pigmentoso/genética , Imunoprecipitação da Cromatina , DNA Helicases/genética , Reparo do DNA/genética , Reparo do DNA/fisiologia , Proteínas de Ligação a DNA/genética , Humanos , Imunoprecipitação , Modelos Moleculares , Complexos Multiproteicos/genética , Mutação/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Transcrição/genética , Transcrição Gênica/genética , Proteína Grupo D do Xeroderma Pigmentoso/genética
14.
Nano Lett ; 17(6): 3421-3428, 2017 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-28485598

RESUMO

Assembly of anisotropic nanocrystals into ordered superstructures is an area of intense research interest due to its relevance to bring nanocrystal properties to macroscopic length scales and to impart additional collective properties owing to the superstructure. Numerous routes have been explored to assemble such nanocrystal superstructures ranging from self-directed to external field-directed methods. Most of the approaches require sensitive control of experimental parameters that are largely environmental and require extra processing steps, increasing complexity and limiting reproducibility. Here, we demonstrate a simple approach to assemble colloidal nanorods in situ, wherein dopant incorporation during the particle synthesis results in the formation of preassembled 2D sheets of close-packed ordered arrays of vertically oriented nanorods in solution.

15.
Nano Lett ; 17(4): 2611-2620, 2017 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-28337921

RESUMO

Doped metal oxides are plasmonic materials that boast both synthetic and postsynthetic spectral tunability. They have already enabled promising smart window and optoelectronic technologies and have been proposed for use in surface enhanced infrared absorption spectroscopy (SEIRA) and sensing applications. Herein, we report the first step toward realization of the former utilizing cubic F and Sn codoped In2O3 nanocrystals (NCs) to couple to the C-H vibration of surface-bound oleate ligands. Electron energy loss spectroscopy is used to map the strong near-field enhancement around these NCs that enables localized surface plasmon resonance (LSPR) coupling between adjacent nanocrystals and LSPR-molecular vibration coupling. Fourier transform infrared spectroscopy measurements and finite element simulations are applied to observe and explain the nature of the coupling phenomena, specifically addressing coupling in mesoscale assembled films. The Fano line shape signatures of LSPR-coupled molecular vibrations are rationalized with two-port temporal coupled mode theory. With this combined theoretical and experimental approach, we describe the influence of coupling strength and relative detuning between the molecular vibration and LSPR on the enhancement factor and further explain the basis of the observed Fano line shape by deconvoluting the combined response of the LSPR and molecular vibration in transmission, absorption and reflection. This study therefore illustrates various factors involved in determining the LSPR-LSPR and LSPR-molecular vibration coupling for metal oxide materials and provides a fundamental basis for the design of sensing or SEIRA substrates.

16.
Langmuir ; 32(1): 329-37, 2016 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-26653672

RESUMO

The objective of this work is to demonstrate that conjugated polymer:fullerene hybrid nanoparticles encapsulated in the hydrophobic cores of triblock copolymer micelles may successfully act as spatially confined donor-acceptor systems capable of facilitating photoinduced charge carrier separation. To this end, aqueous dispersions of poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene] (MEH-PPV) nanoparticles were first prepared by solubilization of the polymer in the cores of poly(oxyethylene)-poly(oxypropylene)-poly(oxyethylene) triblock copolymer, Pluronic F-127 micelles. A number of significant optical spectroscopic changes were observed on transfer of the conjugated polymer from a nonaqueous solvent to the aqueous micellar environment. These were primarily attributed to increased interchain interactions due to conjugated polymer chain collapse during encapsulation in the micellar cores. When prepared in buffer solution, the micelles exhibited good long-term collodial stability. When MEH-PPV micelles were blended by the addition of controlled amounts of [6,6]-phenyl-C61-butyric acid methyl ester (PCBM), the observed correspondence of photoluminescence emission quenching, quantum yield decreases, and emission lifetime shortening with increasing PCBM concentration indicated efficient photoinduced donor-to-acceptor charge transfer between MEH-PPV and the fullerenes in the cores of the micelles, an assignment that was confirmed by transient absorption spectroscopic monitoring of carrier photogeneration and recombination.

17.
Nanotechnology ; 27(24): 245601, 2016 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-27159927

RESUMO

Stable, aqueous dispersions of nanoparticles based on the low band gap polymers poly [2,7-(9,9-dioctyl-fluorene)-alt-5,5-(4',7'-di-2-thienyl-2',1',3'-benzothiadiazole)] (APFO-3) and poly [N-9'-heptadecanyl-2,7-carbazole-alt-5,5-(4',7'-di-2-thienyl-2',1',3'-benzothiadiazole)] (PCDTBT) were prepared, using a flexible, surfactant-free reprecipitation method, and characterized by a variety of optical techniques. Light scattering measurements indicated average nanoparticle hydrodynamic diameters of approximately 40 nm. The particles presented wide-bandwidth absorption and photoluminescence excitation spectra with high absorption cross-sections on the order of 10(-12) cm(2). Nanoparticle emission spectra were significantly red-shifted, with decreased emission quantum yields and lifetimes, consistent with increased inter-polymer chain interactions in the condensed phase. Single particle photoluminescence studies highlighted the multi-chromophoric nature of the polymer nanoparticles and confirmed their favorable photostabilities. When the nanoparticles were doped with [6,6]-phenyl-C61-butyric acid methyl ester (PCBM), the correspondence of photoluminescence emission quenching, quantum yield decreases, emission lifetime shortening, and increased non-radiative rates with increasing PCBM concentration suggested efficient photo-induced donor-to-acceptor charge transfer between the conjugated polymers and the fullerene dopants co-localized in the nanoparticle cores. Taken together, the data suggest that these surfactant-free hybrid nanomaterials may be useful for integration with future nanostructured organic photovoltaics technologies.

18.
Nanotechnology ; 27(30): 305603, 2016 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-27306338

RESUMO

The functionalization of polyfluorene (PFO) nanoparticles by coprecipitation of the conjugated polymer with an amphiphilic comb polymer, consisting of a hydrophobic polystyrene backbone with hydrophilic, carboxylic acid-terminated polyethylene oxide side-chains (PS-PEG-COOH), is investigated. The comb polymer affects the properties of the formed hybrid nanoparticles. Non-functionalized particles are typically larger (28 nm) than functionalized ones (20 nm); peak molar extinction coefficients are found to differ in a similar trend. Zeta potentials are negative, consistent with negative surface charge on PFO particles due to chemical defect formation, with additional charge on functionalized particles due to the pendant carboxylic acid groups. Emission quantum yields of functionalized particles are typically larger, consistent with lower efficiency of energy transfer to quenchers in smaller particles and weaker PFO interchain interactions due to chain dilution. The trend in per-particle fluorescence brightness values, as confirmed by single particle fluorescence imaging, reflects the nanoparticle extinction coefficients. Photostability studies on aqueous dispersions of hybrid particles indicate mild photobrightening under continuous illumination while PFO particles exhibit slow exponential emission decay. Functionalized particles are also resistant to aggregation during exposure to adenocarcinoma cells. Generally, the hybrid particles exhibit more favorable time-, pH- and medium-dependent stabilities, likely due to steric and electrostatic stabilization by PEG-carboxylic acid functionalities. Overall, the functionalized particles exhibit attractive properties: Reasonably small size, tight size distribution, high absorption cross section, radiative rate and emission quantum yield, excellent brightness and photostability, and good colloidal stability.

19.
Curr Cardiol Rep ; 18(9): 93, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27553788

RESUMO

The current climate in healthcare is increasingly emphasizing a value-based approach to diagnostic testing. Cardiac imaging, including echocardiography, has been a primary target of ongoing reforms in healthcare delivery and reimbursement. The Appropriate Use Criteria (AUC) for echocardiography is a physician-derived tool intended to guide utilization in optimal patient care. To date, the AUC have primarily been employed solely as justification for reimbursement, though evolving broader applications to guide clinical decision-making suggest a far more valuable role in the delivery of high-quality and high-value healthcare.


Assuntos
Doenças Cardiovasculares/diagnóstico por imagem , Ecocardiografia/estatística & dados numéricos , Técnicas de Imagem Cardíaca/economia , Técnicas de Imagem Cardíaca/normas , Técnicas de Imagem Cardíaca/estatística & dados numéricos , Técnicas de Imagem Cardíaca/tendências , Ecocardiografia/economia , Ecocardiografia/normas , Humanos , Guias de Prática Clínica como Assunto , Regionalização da Saúde , Aquisição Baseada em Valor
20.
J Am Chem Soc ; 137(20): 6464-7, 2015 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-25974290

RESUMO

The presence of antimony, as a dopant in the colloidal growth reaction for CuIn(1-x)Ga(x)S2 (CIGS) nanocrystals, causes end-to-end fusion of nanorod pairs into nanodumbbells at high yield. The influence of the dopant on shape is indirect; antimony catalyzes the incorporation of gallium, which is found in high concentration at the junction between the fused nanorods.

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