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1.
J Cell Sci ; 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34635908

RESUMO

Desmosomes, strong cell-cell junctions of epithelia and cardiac muscle, link intermediate filaments to cell membranes and mechanically integrate cells across tissues, dissipating mechanical stress. They comprise five major protein classes - desmocollins and desmogleins (the desmosomal cadherins), plakoglobin, plakophilins and desmoplakin - whose individual contribution to the structure and turnover of desmosomes is poorly understood. Using live-cell imaging together with FRAP and FLAP we show that desmosomes consist of two contrasting protein moieties or modules: a very stable moiety of desmosomal cadherins, desmoplakin and plakoglobin, and a highly mobile plakophilin (Pkp2a). As desmosomes mature from calcium-dependence to calcium-independent hyper-adhesion, their stability increases, but Pkp2a remains highly mobile. We show that desmosome down-regulation during growth-factor-induced cell scattering proceeds by internalisation of whole desmosomes, which still retain a stable moiety and highly mobile Pkp2a. This molecular mobility of Pkp2a suggests a transient and probably regulatory role for Pkp2a in desmosomes.

2.
Sci Rep ; 11(1): 20168, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34635751

RESUMO

High prevalence of non-healing chronic wounds contributes to a huge healthcare burden across the world. Early treatment interventions for non-healing wounds are vital. It was previously shown that accumulation of 15% or more of senescent cells in a chronic wound edge is an indicator that the wound is unlikely to heal. However, determining the presence of senescent cells would require invasive procedures such as tissue biopsies to be taken. In this study, we found a strong correlation between decreased collagen area and presence of senescent cells in human chronic wounds i.e. venous leg ulcer (VLU), diabetic foot ulcer (DFU) and pressure ulcer (PRU). We also report that the lowest collagen levels were found in VLU patients less than 60 years of age, with a persistent wound of > 24 months. Elevated levels of senescent cells were also found in VLU of males. Second harmonic imaging of collagen at the edge of chronic wounds with a handheld multiphoton device could be used to predict the number of senescent cells, indicating if the wound is on a healing trajectory or not. Our data support the use of collagen imaging in cutaneous wound assessment for a faster and non-invasive method to predict cellular senescence and determining wound trajectory of healing.

3.
J Health Care Poor Underserved ; 32(3): 1320-1338, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34421034

RESUMO

To describe the dynamics and forecast the main parameters of the COVID-19 pandemic, the time series of daily cases in the World Health Organization African Region (WHOAR) from February 26th to December 29th, 2020 was analyzed. Estimates for expected values of parameters characterizing an epidemic (size of the epidemic, turning point, maximum value of daily cases, and basic reproductive number) were provided for both the first and the second wave, and for the entire ongoing pandemic in WHOAR. To this aim, the classical SIR (Susceptible-Infected-Removed) model and its approximations were applied to each identified wave. Our results suggest that the turning point of the COVID-19 first wave took place around July 20th, 2020. The first wave was expected to disappear by mid-December 2020, with a total of 1,200,000 expected cases. The second wave apparently started around August 19th, with an expected turning point by January 12th, 2021. The second wave is expected to end by August 9th, 2021, with 1,800,000 cumulative cases, and mounting up to 3,000,000 total cases between February 2020 and August 2021. Estimated basic reproduction numbers (R0) were 1.27 (first wave) and 1.15 (second wave); the expected total number of deaths is around 66,000 victims.


Assuntos
COVID-19/epidemiologia , África ao Sul do Saara/epidemiologia , Número Básico de Reprodução , Humanos , Modelos Biológicos , Pandemias , SARS-CoV-2 , Organização Mundial da Saúde
4.
PLoS Genet ; 17(8): e1009757, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34449766

RESUMO

To complete mitosis, the bridge that links the two daughter cells needs to be cleaved. This step is carried out by the endosomal sorting complex required for transport (ESCRT) machinery. AKTIP, a protein discovered to be associated with telomeres and the nuclear membrane in interphase cells, shares sequence similarities with the ESCRT I component TSG101. Here we present evidence that during mitosis AKTIP is part of the ESCRT machinery at the midbody. AKTIP interacts with the ESCRT I subunit VPS28 and forms a circular supra-structure at the midbody, in close proximity with TSG101 and VPS28 and adjacent to the members of the ESCRT III module CHMP2A, CHMP4B and IST1. Mechanistically, the recruitment of AKTIP is dependent on MKLP1 and independent of CEP55. AKTIP and TSG101 are needed together for the recruitment of the ESCRT III subunit CHMP4B and in parallel for the recruitment of IST1. Alone, the reduction of AKTIP impinges on IST1 and causes multinucleation. Our data altogether reveal that AKTIP is a component of the ESCRT I module and functions in the recruitment of ESCRT III components required for abscission.

5.
Contemp Jew ; : 1-19, 2021 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-34121783

RESUMO

As individuals undergoing a developmental process characterized by identity exploration, Jewish young adults are particularly vulnerable to the disruption of social connections related to the COVID-19 pandemic. Recent research has demonstrated that young adults, including young Jews, have experienced higher rates of mental health difficulties than older individuals during the pandemic. Using data from a survey of Jewish young adults who applied to participate in Birthright Israel summer 2020 trips but were unable to participate due to the pandemic, we examined the factors contributing to young adults' mental health difficulties. We found that loneliness, rather than financial worries or concerns about the health impacts of COVID-19, was the single most important driver of reported emotional or mental health difficulties. Results also suggested that simply increasing the frequency of contacts between individuals is unlikely to reduce loneliness, unless these are positive, substantial connections, such as those among members of a "social support network." Building and rebuilding deep, meaningful social connections between Jewish young adults should be a top priority for Jewish organizations going forward.

6.
J Cardiol Cases ; 2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-34007346

RESUMO

There is growing evidence of the potential for cardiac involvement in patients who have been infected with COVID-19. In this case study, we present a patient with no history of cardiovascular disease, who was hospitalized for COVID-19 pneumonia and subsequently recovered. Despite normal serum troponin levels and left ventricular structure and function, multi-parametric cardiac magnetic resonance imaging revealed a classic myocarditis-like pattern of injury approximately 6 months after his convalescence. Physicians should be aware of the possibility of late myocardial injury/inflammation in patients with recovered COVID-19, even in the absence of elevated troponin levels and/or left ventricular dysfunction.

7.
Magn Reson Imaging ; 79: 1-4, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33652063

RESUMO

The purpose of our study was to assess whether T2 MRI identifies the infarcted myocardium or the true area-at-risk (AAR) and whether edema is present in the salvageable region following acute myocardial infarction (MI). The study involved a porcine model of MI with a coronary occlusion model of either 60 min or 90 min. Imaging was performed on a 3T MRI pre-occlusion and at day 3 post-MI. Prior-MI, myocardial perfusion territory (MPT) maps were obtained under MRI via direct intracoronary injection of contrast agent. Post-MI, edema extent was quantified by T2 mapping while infarction and microvascular obstruction (MVO) were assessed by late gadolinium enhancement (LGE). Anatomically registered short-axis slices were analyzed for MPT, T2-AAR and infarct areas and T2 relaxation values. Animals were divided into groups with (MVO+) and without MVO (MVO-). T2-AAR area was significantly greater than infarct area in both groups. In the MVO+ group, T2-AAR and MPT were comparable and highly correlated, whereas, in the MVO- group, T2-AAR significantly underestimated MPT without any trend. T2 values in the salvageable myocardium were found to be significantly higher than those in remote myocardium. Our methodology offers the advantage that all images are acquired within the same MRI reference as opposed to complex co-registration with gross pathology. Our study suggests that edema may expand beyond the infarct zone over the entire ischemic bed. T2-AAR may be more clinically relevant than true AAR by perfusion territory since it identifies the "salvageable" myocardium.


Assuntos
Meios de Contraste , Infarto do Miocárdio , Animais , Edema/diagnóstico por imagem , Gadolínio , Imagem Cinética por Ressonância Magnética , Infarto do Miocárdio/complicações , Infarto do Miocárdio/diagnóstico por imagem , Miocárdio , Suínos
8.
Dev Cell ; 56(6): 761-780.e7, 2021 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-33725480

RESUMO

Vinculin, a mechanotransducer associated with both adherens junctions (AJs) and focal adhesions (FAs), plays a central role in force transmission through cell-cell and cell-substratum contacts. We generated the conditional knockout (cKO) of vinculin in murine skin that results in the loss of bulge stem cell (BuSC) quiescence and promotes continual cycling of the hair follicles. Surprisingly, we find that the AJs in vinculin cKO cells are mechanically weak and impaired in force generation despite increased junctional expression of E-cadherin and α-catenin. Mechanistically, we demonstrate that vinculin functions by keeping α-catenin in a stretched/open conformation, which in turn regulates the retention of YAP1, another potent mechanotransducer and regulator of cell proliferation, at the AJs. Altogether, our data provide mechanistic insights into the hitherto-unexplored regulatory link between the mechanical stability of cell junctions and contact-inhibition-mediated maintenance of BuSC quiescence.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Junções Aderentes/fisiologia , Folículo Piloso/fisiologia , Mecanotransdução Celular , Células-Tronco/fisiologia , Vinculina/fisiologia , alfa Catenina/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Adesão Celular , Feminino , Folículo Piloso/citologia , Masculino , Potenciais da Membrana , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Células-Tronco/citologia , alfa Catenina/genética
9.
Contemp Jew ; : 1-21, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33612891

RESUMO

Since 2016, a series of horrific acts motivated by antisemitism appear to have caused a fundamental shift in the prevalence of antisemitism in the United States. Little is known, however, about how the events during this time have affected the day-to-day experiences and concerns of American Jews. Using repeated cross-sectional data from surveys of Jewish young adults who applied to Birthright Israel, this paper analyzes recent trends in Jewish young adults' experiences and perceptions of antisemitism. Despite the high-profile incidents during this period, there is no evidence of a major increase in experiences of antisemitic harassment among Jewish young adults-either on or off campus-between 2017 and 2019. At the same time, data show a substantial increase in concerns among young Jews about antisemitism in the United States and on college campuses, with concerns about antisemitism in the United States (but not on campus) being especially concentrated among liberal Jews. These results suggest that Jewish concerns about antisemitism are linked to broader views about the climate for marginalized populations in the United States. They also point to growing Jewish anxieties over violence, safety, and acceptance in the United States. In an era of widely disseminated antisemitic conspiracy theories, even young Jews who have no first-hand experience of antisemitic harassment have become concerned. Supplementary Information: The online version of this article (10.1007/s12397-021-09354-6) contains supplementary material, which is available to authorized users.

10.
Med Phys ; 48(4): 1815-1822, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33417726

RESUMO

PURPOSE: Cardiac relaxometry techniques, particularly T1 mapping, have recently gained clinical importance in various cardiac pathologies. Myocardial T1 and extracellular volume are usually calculated from manual identification of left ventricular epicardial and endocardial regions. This is a laborious process, particularly for large volume studies. Here we present a fully automated relaxometry framework (FASTR) for segmental analysis of T1 maps (both native and postcontrast) and partition coefficient (λ). METHODS: Patients (N = 11) were imaged postacute myocardial infarction on a 1.5T clinical scanner. The scan protocol involved CINE-SSFP imaging, native, and post-contrast T1 mapping using the Modified Look-Locker Inversion (MOLLI) recovery sequence. FASTR consisted of automatic myocardial segmentation of spatio-temporally coregistered CINE images as an initial guess, followed by refinement of the contours on the T1 maps to derive segmental T1 and λ. T1 and λ were then compared to those obtained from two trained expert observers. RESULTS: Robust endocardial and epicardial contours were achieved on T1 maps despite the presence of infarcted tissue. Relative to experts, FASTR resulted in myocardial Dice coefficients (native T1: 0.752 ± 0.041; postcontrast T1: 0.751 ± 0.057) that were comparable to interobserver Dice (native T1: 0.803 ± 0.045; postcontrast T1: 0.799 ± 0.054). There were strong correlations observed for T1 and λ derived from experts and FASTR (native T1: r = 0.83; postcontrast T1: r = 0.87; λ: r = 0.78; P < 0.0001), which were comparable to inter-expert correlation coefficients (native T1: r = 0.90; postcontrast T1: r = 0.93; λ: r = 0.80; P < 0.0001). CONCLUSIONS: Our fully automated framework, FASTR, can generate accurate myocardial segmentations for native and postcontrast MOLLI T1 analysis without the need for manual intervention. Such a design is appealing for high volume clinical protocols.


Assuntos
Infarto do Miocárdio , Miocárdio , Meios de Contraste , Coração/diagnóstico por imagem , Ventrículos do Coração/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Imagem Cinética por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Infarto do Miocárdio/diagnóstico por imagem , Valor Preditivo dos Testes , Reprodutibilidade dos Testes
11.
Nat Commun ; 12(1): 188, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33420028

RESUMO

Nod-like receptor (NLR) proteins activate pyroptotic cell death and IL-1 driven inflammation by assembling and activating the inflammasome complex. Closely related sensor proteins NLRP1 and CARD8 undergo unique auto-proteolysis-dependent activation and are implicated in auto-inflammatory diseases; however, their mechanisms of activation are not understood. Here we report the structural basis of how the activating domains (FIINDUPA-CARD) of NLRP1 and CARD8 self-oligomerize to assemble distinct inflammasome complexes. Recombinant FIINDUPA-CARD of NLRP1 forms a two-layered filament, with an inner core of oligomerized CARD surrounded by an outer ring of FIINDUPA. Biochemically, self-assembled NLRP1-CARD filaments are sufficient to drive ASC speck formation in cultured human cells-a process that is greatly enhanced by NLRP1-FIINDUPA which forms oligomers in vitro. The cryo-EM structures of NLRP1-CARD and CARD8-CARD filaments, solved here at 3.7 Å, uncover unique structural features that enable NLRP1 and CARD8 to discriminate between ASC and pro-caspase-1. In summary, our findings provide structural insight into the mechanisms of activation for human NLRP1 and CARD8 and reveal how highly specific signaling can be achieved by heterotypic CARD interactions within the inflammasome complexes.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Proteínas Adaptadoras de Sinalização CARD/metabolismo , Inflamassomos/química , Inflamassomos/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/química , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Reguladoras de Apoptose/química , Proteínas Reguladoras de Apoptose/genética , Proteínas Adaptadoras de Sinalização CARD/genética , Caspase 1/metabolismo , Microscopia Crioeletrônica , Células HEK293 , Humanos , Inflamassomos/genética , Inflamação , Simulação de Acoplamento Molecular , Mutação , Proteínas de Neoplasias/química , Proteínas de Neoplasias/genética , Transdução de Sinais
12.
Magn Reson Med ; 85(5): 2842-2855, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33226667

RESUMO

PURPOSE: To develop an approach for automated quantification of myocardial infarct heterogeneity in late gadolinium enhancement (LGE) cardiac MRI. METHODS: We acquired 2D short-axis cine and 3D LGE in 10 pigs with myocardial infarct. The 2D cine myocardium was segmented and registered to the LGE images. LGE image signal intensities within the warped cine myocardium masks were analyzed to determine the thresholds of infarct core (IC) and gray zone (GZ) for the standard-deviation (SD) and full-width-at-halfmaximum (FWHM) methods. The initial IC, GZ, and IC + GZ segmentations were postprocessed using a normalized cut approach. Cine segmentation and cine-LGE registration accuracies were evaluated using dice similarity coefficient and average symmetric surface distance. Automated IC, GZ, and IC + GZ volumes were compared with manual results using Pearson correlation coefficient (r), Bland-Altman analyses, and intraclass correlation coefficient. RESULTS: For n = 87 slices containing scar, we achieved cine segmentation dice similarity coefficient = 0.87 ± 0.12, average symmetric surface distance = 0.94 ± 0.74 mm (epicardium), and 1.03 ± 0.82 mm (endocardium) in the scar region. For cine-LGE registration, dice similarity coefficient was 0.90 ± 0.06 and average symmetric surface distance was 0.72 ± 0.39 mm (epicardium) and 0.86 ± 0.53 mm (endocardium) in the scar region. For both SD and FWHM methods, automated IC, GZ, and IC + GZ volumes were strongly (r > 0.70) correlated with manual measurements, and the correlations were not significantly different from interobserver correlations (P > .05). The agreement between automated and manual scar volumes (intraclass correlation coefficient = 0.85-0.96) was similar to that between two observers (intraclass correlation coefficient = 0.81-0.99); automated scar segmentation errors were not significantly different from interobserver segmentation differences (P > .05). CONCLUSIONS: Our approach provides fully automated cine-LGE MRI registration and LGE myocardial infarct heterogeneity quantification in preclinical studies.


Assuntos
Gadolínio , Infarto do Miocárdio , Animais , Meios de Contraste , Imageamento Tridimensional , Imageamento por Ressonância Magnética , Imagem Cinética por Ressonância Magnética , Infarto do Miocárdio/diagnóstico por imagem , Miocárdio , Reprodutibilidade dos Testes , Suínos
13.
J Periodontal Res ; 56(1): 108-120, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32969036

RESUMO

BACKGROUND AND OBJECTIVES: Ageing is associated with an impaired cellular function that can affect tissue architecture and wound healing in gingival and periodontal tissues. However, the impact of oral fibroblast ageing on the structural organization of the extracellular matrix (ECM) proteins is poorly understood. Hence, in this study, we investigated the impact of cellular ageing of oral fibroblasts on the production and structural organization of collagen and other ECM proteins. METHODS: Oral fibroblasts were serially subcultured, and replicative cellular senescence was assessed using population doubling time, Ki67 counts and expression of P21WAFI . The production and structural organization of ECM proteins were assessed at early (young-oFB) and late (aged-oFB) passages. The thickness and pattern of collagen produced by live cultures of young- and aged-oFB were assessed using a label-free and non-invasive second harmonic generation (SHG)-based multiphoton imaging. Expression of other ECM proteins (fibronectin, fibrillin, collagen-IV and laminins) was evaluated using immunocytochemistry and confocal microscopy-based depth profile analysis. RESULTS: Aged-oFB displayed a higher population doubling time, lower Ki67+ cells and higher expression of P21WAFI indicative of slower proliferation rate and senescence phenotype. SHG imaging demonstrated that young-oFB produced a thick, interwoven network of collagen fibres, while the aged-oFB produced thin and linearly organized collagen fibres. Similarly, analysis of immunostained cultures showed that young-oFB produced a rich, interwoven mesh of fibronectin, fibrillin and collagen-IV fibres. In contrast, the aged-oFB produced linearly organized fibronectin, fibrillin and collagen-IV fibres. Lastly, there was no observable difference in production and organization of laminins among the young- and aged-oFB. CONCLUSION: Our results suggest that oral fibroblast ageing impairs ECM production and more importantly the organization of ECM fibres, which could potentially impair wound healing in the elderly.


Assuntos
Colágeno , Fibroblastos , Idoso , Células Cultivadas , Senescência Celular , Matriz Extracelular , Proteínas da Matriz Extracelular , Humanos
14.
Catheter Cardiovasc Interv ; 97(3): 437-442, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-32243080

RESUMO

OBJECTIVE: To create an experimental chronic total occlusion (CTO) model with calcification by dietary modification (cholesterol, calcium carbonate, vitamin D) and local injection of pro-calcification factors (dipotassium phosphate, calcium chloride, and bone morphogenetic protein-2 [BMP-2]). BACKGROUND: Percutaneous revascularization of CTOs frequently fails in heavily calcified occlusions. Development of novel approaches requires a reproducible preclinical model of calcified CTO. METHODS: CTOs were created in 18 femoral arteries of 9 New Zealand White rabbits using the thrombin injection model. Dietary interventions included a high cholesterol diet (0.5% or 0.25%), calcium carbonate (150 mg × 3-5 days/week), and vitamin D (50,000 U × 3-5 days/week). In selected animals, BMP-2 (1-4 µg), dipotassium phosphate, and calcium chloride were injected locally at the time of CTO creation. Animals were sacrificed at 2 weeks (n = 4 arteries), 6 weeks (n = 4 arteries), and 10-12 weeks (n = 14 arteries). RESULTS: CTOs showed evidence of chronic lipid feeding (foam cells) and chronic inflammation (intimal/medial fibrosis and microvessels, inflammatory cells, internal elastic lamina disruption). In calcium/vitamin D supplemented rabbits, mineralization (calcification and/or ossification) was evident as early as 2 weeks post CTO creation, and in 78% of the overall arteries. Mineralization changes were not present in the absence of calcium/vitamin D dietary supplements. Mineralization occurred in 85% of BMP-treated arteries and 60% of arteries without BMP. CONCLUSIONS: Complex mineralization occurs in preclinical CTO models with dietary supplementation of cholesterol with vitamin D and calcium.

15.
NMR Biomed ; 34(1): e4404, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32875632

RESUMO

Hemorrhage is recognized as a new independent predictor of adverse outcomes following acute myocardial infarction. However, the mechanisms of its effects are less understood. The aim of our study was to probe the downstream impact of hemorrhage towards chronic remodeling, including inflammation, vasodilator function and matrix alterations in an experimental model of hemorrhage. Myocardial hemorrhage was induced in the porcine heart by intracoronary injection of collagenase. Animals (N = 18) were subjected to coronary occlusion followed by reperfusion in three groups (six/group): 8 min ischemia with hemorrhage (+HEM), 45 min infarction with no hemorrhage (I - HEM) and 45 min infarction with hemorrhage (I + HEM). MRI was performed up to 4 weeks after intervention. Cardiac function, edema (T2 , T1 ), hemorrhage (T2 *), vasodilator function (T2 BOLD), infarction and microvascular obstruction (MVO) and partition coefficient (pre- and post-contrast T1 ) were computed. Hemorrhage was induced only in the +HEM and I + HEM groups on Day 1 (low T2 * values). Infarct size was the greatest in the I + HEM group, while the +HEM group showed no observable infarct. MVO was seen only in the I + HEM group, with a 40% occurrence rate. Function was compromised and ventricular volume was enlarged only in the hemorrhage groups and not in the ischemia-alone group. In the infarct zone, edema and matrix expansion were the greatest in the I + HEM group. In the remote myocardium, T2 elevation and matrix expansion associated with a transient vasodilator dysfunction were observed in the hemorrhage groups but not in the ischemia-alone group. Our study demonstrates that the introduction of myocardial hemorrhage at reperfusion results in greater myocardial damage, upregulated inflammation, chronic adverse remodeling and remote myocardial alterations beyond the effects of the initial ischemic insult. A systematic understanding of the consequences of hemorrhage will potentially aid in the identification of novel therapeutics for high-risk patients progressing towards heart failure.

16.
Life (Basel) ; 10(12)2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33291615

RESUMO

Despite the great advances in the field of electronic health records (EHRs) over the past 25 years, implementation and adoption challenges persist, and the benefits realized remain below expectations. This scoping review aimed to present current knowledge about the effects of EHR implementation and the barriers to EHR adoption and use. A literature search was conducted in PubMed, Web of Science, IEEE Xplore Digital Library and ACM Digital Library for studies published between January 2005 and May 2020. In total, 7641 studies were identified of which 142 met the criteria and attained the consensus of all researchers on inclusion. Most studies (n = 91) were published between 2017 and 2019 and 81 studies had the United States as the country of origin. Both positive and negative effects of EHR implementation were identified, relating to clinical work, data and information, patient care and economic impact. Resource constraints, poor/insufficient training and technical/educational support for users, as well as poor literacy and skills in technology were the identified barriers to adoption and use that occurred frequently. Although this review did not conduct a quality analysis of the included papers, the lack of uniformity in the use of EHR definitions and detailed contextual information concerning the study settings could be observed.

17.
Neural Netw ; 132: 353-363, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32977280

RESUMO

Immense amount of high-content image data generated in drug discovery screening requires computationally driven automated analysis. Emergence of advanced machine learning algorithms, like deep learning models, has transformed the interpretation and analysis of imaging data. However, deep learning methods generally require large number of high-quality data samples, which could be limited during preclinical investigations. To address this issue, we propose a generative modeling based computational framework to synthesize images, which can be used for phenotypic profiling of perturbations induced by drug compounds. We investigated the use of three variants of Generative Adversarial Network (GAN) in our framework, viz., a basic Vanilla GAN, Deep Convolutional GAN (DCGAN) and Progressive GAN (ProGAN), and found DCGAN to be most efficient in generating realistic synthetic images. A pre-trained convolutional neural network (CNN) was used to extract features of both real and synthetic images, followed by a classification model trained on real and synthetic images. The quality of synthesized images was evaluated by comparing their feature distributions with that of real images. The DCGAN-based framework was applied to high-content image data from a drug screen to synthesize high-quality cellular images, which were used to augment the real image data. The augmented dataset was shown to yield better classification performance compared with that obtained using only real images. We also demonstrated the application of proposed method on the generation of bacterial images and computed feature distributions for bacterial images specific to different drug treatments. In summary, our results showed that the proposed DCGAN-based framework can be utilized to generate realistic synthetic high-content images, thus enabling the study of drug-induced effects on cells and bacteria.


Assuntos
Aprendizado Profundo , Descoberta de Drogas/métodos , Processamento de Imagem Assistida por Computador , Redes Neurais de Computação , Algoritmos , Confiabilidade dos Dados , Humanos , Processamento de Imagem Assistida por Computador/métodos
18.
Cell Death Dis ; 11(9): 809, 2020 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-32978366

RESUMO

Huntington disease (HD) is a hereditary neurodegenerative disorder caused by mutant huntingtin (mHTT). Phosphorylation at serine-421 (pS421) of mHTT has been shown to be neuroprotective in cellular and rodent models. However, the genetic context of these models differs from that of HD patients. Here we employed human pluripotent stem cells (hiPSCs), which express endogenous full-length mHTT. Using genome editing, we generated isogenic hiPSC lines in which the S421 site in mHTT has been mutated into a phospho-mimetic aspartic acid (S421D) or phospho-resistant alanine (S421A). We observed that S421D, rather than S421A, confers neuroprotection in hiPSC-derived neural cells. Although we observed no effect of S421D on mHTT clearance or axonal transport, two aspects previously reported to be impacted by phosphorylation of mHTT at S421, our analysis revealed modulation of several aspects of mitochondrial form and function. These include mitochondrial surface area, volume, and counts, as well as improved mitochondrial membrane potential and oxidative phosphorylation. Our study validates the protective role of pS421 on mHTT and highlights a facet of the relationship between mHTT and mitochondrial changes in the context of human physiology with potential relevance to the pathogenesis of HD.


Assuntos
Doença de Huntington/genética , Doença de Huntington/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismo , Mitocôndrias/metabolismo , Animais , Modelos Animais de Doenças , Humanos , Camundongos , Neuroproteção , Fenótipo
19.
Stud Health Technol Inform ; 272: 28-32, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32604592

RESUMO

It is 200 years since the birth of Florence Nightingale. This keynote paper reviews some of her work relating to health statistics and outlines its continuing legacy to nursing informatics around the world and especially in poorer countries, like South Africa, in the 21st century.


Assuntos
História da Enfermagem , Informática em Enfermagem , Feminino , História do Século XIX , Humanos , África do Sul
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