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1.
Birth ; 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38563087

RESUMO

OBJECTIVE: We sought to understand the lived experiences of Black women diagnosed with severe maternal morbidity (SMM) in communities with high maternal mortality to inform practices that reduce obstetric racism and improve patient outcomes. METHODS: From August 2022 through December 2022, we conducted a phenomenological, qualitative study among Black women who experienced SMM. Participants were recruited via social media and met inclusion criteria if they self-identified as Black cisgender women, were 18-40 years old, had SMM diagnosed, and lived within zip codes in the United States that have the top-five highest maternal mortality rates. Family members participated on behalf of women who were deceased but otherwise met all other criteria. We conducted in-depth interviews (IDIs), and transcripts were analyzed using inductive and deductive methods to explore birth story experiences. RESULTS: Overall, 12 participants completed IDIs; 10 were women who experienced SMM and 2 were mothers of women who died due to SMM. The mean age for women who experienced SMM was 31 years (range 26-36 years) at the time of the IDI or death. Most participants had graduate-level education, and the average annual household income was 123,750 USD. Women were especially interested in study participation because of their high-income status as they did not fit the stereotypical profile of Black women who experience racial discrimination. The average time since SMM diagnosis was 2 years. Participants highlighted concrete examples of communication failures, stereotyping by providers, differential treatment, and medical errors which patients experienced as manifestations of racism. Medical personnel dismissing and ignoring concerns during emergent situations, even when raised through strong self-advocacy, was a key factor in racism experienced during childbirth. CONCLUSIONS: Future interventions to reduce racism and improve maternal health outcomes should center on the experiences of Black women and focus on improving patient-provider communication, as well as the quality and effectiveness of responses during emergent situations. Précis statement: This study underscores the need to center Black women's experiences, enhance patient-provider communication, and address emergent concerns to mitigate obstetric racism and enhance maternal health outcomes.

2.
ACS Appl Mater Interfaces ; 16(2): 2593-2605, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38175180

RESUMO

The advancement of anion exchange membranes (AEMs) with superior ionic conductivity has been greatly hindered due to the inherent "trade-off" between membrane swelling and ionic conductivity. To resolve this dilemma, macromolecular covalently cross-linked C-FPVBC-x AEMs were fabricated by combining partially functionalized ether-bond-free polystyrene (FPVBC) with poly(arylene piperidinium). The results from atomic force microscopy reveal that an increase in the ratio of FPVBC promotes the fabrication of microphase separation morphology, resulting in a high ionic conductivity of 40.15 mS cm-1 (30 °C) for the C-FPVBC-1.7 membrane. Molecular dynamics simulations further examine the ionic conduction effect of cross-linked AEMs. Besides, the unique cross-linking structure significantly improves mechanical and alkaline stability. After treatment in 1 M KOH at 50 °C for 1200 h, the C-FPVBC-1.7 membrane shows only a 6.9% decrease in conductivity. The C-FPVBC-1.7 AEM-based water electrolyzer achieves a high current density of 890 mA cm-2 at 2.4 V (80 °C) and maintains good stability, enduring over 100 h at 100 mA cm-2 (50 °C). These results demonstrate the significant potential of macromolecularly cross-linked AEMs for practical applications in water electrolysis.

4.
ACS Chem Biol ; 18(8): 1808-1820, 2023 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-37498174

RESUMO

The constant and the sudden emergence of zoonotic human and animal viruses is a significant threat to human health, the world economy, and the world food supply. This has necessitated the development of broad-spectrum therapeutic strategies to combat these emerging pathogens. Mechanisms that are essential for viral replication and propagation have been successfully targeted in the past to develop broad-spectrum therapeutics that can be readily repurposed to combat new zoonotic pathogens. Because of the importance of viral RNA capping enzymes to viral replication and pathogenesis, as well as their presence in both DNA and RNA viruses, these viral proteins have been a long-standing therapeutic target. Here, we use genome sequencing information and yeast-based platforms (YeRC0M) to identify, characterize, and target viral genome-encoded essential RNA capping enzymes from emerging strains of DNA viruses, i.e., Monkeypox virus and African Swine Fever Virus, which are a significant threat to human and domestic animal health. We first identified and biochemically characterized these viral RNA capping enzymes and their necessary protein domains. We observed significant differences in functional protein domains and organization for RNA capping enzymes from emerging DNA viruses in comparison to emerging RNA viruses. We also observed several differences in the biochemical properties of these viral RNA capping enzymes using our phenotypic yeast-based approaches (YeRC0M) as compared to the previous in vitro studies. Further, using directed evolution, we were able to identify inactivation and attenuation mutations in these essential viral RNA capping enzymes; these data could have implications on virus biocontainment as well as live attenuated vaccine development. We also developed methods that would facilitate high-throughput phenotypic screening to identify broad-spectrum inhibitors that selectively target viral RNA capping enzymes over host RNA capping enzymes. As demonstrated here, our approaches to identify, characterize, and target viral genome-encoded essential RNA capping enzymes are highly modular and can be readily adapted for targeting emerging viral pathogens as well as their variants that emerge in the future.


Assuntos
Vírus da Febre Suína Africana , Vírus , Animais , Humanos , Suínos , Saccharomyces cerevisiae/metabolismo , Vírus da Febre Suína Africana/genética , Vírus da Febre Suína Africana/metabolismo , Vírus/genética , RNA Viral/genética , RNA Viral/metabolismo , Replicação Viral , Vírus de DNA/genética , Vírus de DNA/metabolismo
5.
PLoS One ; 18(4): e0283815, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37053233

RESUMO

BACKGROUND: The District of Columbia (DC) has striking disparities in maternal and infant outcomes comparing Black to White women and babies. Social determinants of health (SDoH) are widely recognized as a significant contributor to these disparities in health outcomes. Screening for social risk factors and referral for appropriate services is a critical step in addressing social needs and reducing outcome disparities. METHODS: We conducted interviews among employees (n = 18) and patients (n = 9) across three diverse, urban clinics within a healthcare system and one community-based organization involved in a five-year initiative to reduce maternal and infant disparities in DC. Interviews were guided by the Consolidated Framework for Implementation Research to understand current processes and organizational factors that contributed to or impeded delivery of social risk factor screening and referral for indicated needs. RESULTS: We found that current processes for social risk factor screening and referral differed between and within clinics depending on the patient population. Key facilitators of successful screening included a supportive organizational culture and adaptability of more patient-centered screening processes. Key barriers to delivery included high patient volume and limited electronic health record capabilities to record results and track the status of internal and community referrals. Areas identified for improvement included additional social risk factor assessment training for new providers, patient-centered approaches to screening, improved tracking processes, and facilitation of connections to social services within clinical settings. CONCLUSION: Despite proliferation of social risk factor screeners and recognition of their importance within health care settings, few studies detail implementation processes for social risk factor screening and referrals. Future studies should test implementation strategies for screening and referral services to address identified barriers to implementation.


Assuntos
Atenção à Saúde , Família , Lactente , Humanos , Feminino , Criança , District of Columbia , Encaminhamento e Consulta , Programas de Rastreamento , Cuidado do Lactente
6.
J Patient Saf ; 19(2): 67-70, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36728348

RESUMO

OBJECTIVES: This study aimed to determine whether potential malpractice events reported by employees, malpractice events involving claims, and malpractice lawsuits differ based on patient race in a large 10-hospital healthcare system. METHODS: Data in a healthcare system's malpractice database from July 1, 2012, to June 30, 2017, were stratified by patient race using "Black," "White," and "other" categories. χ2 Goodness-of-fit tests were used to compare differences in race proportions in employee-reported observations of events that could lead to payment of a claim, claims not involving the court, and lawsuits involving the court. RESULTS: There were significantly more employee-reported observations and claims for White patients and significantly fewer observations and claims for Black patients than expected based on the race proportions in the overall healthcare system patient population ( P < 0.001). There were no significant race differences in lawsuits (Black patients, P = 0.146; White patients, P = 0.061; other patients, P = 0.458). Four of the 10 hospitals in the healthcare system had significant race differences in potential malpractice events (hospital A, P < 0.001; hospital B, P = 0.011; hospital E, P < 0.001; hospital G, P = 0.010). CONCLUSIONS: Our findings reveal the existence of race differences in potential malpractice events in a large healthcare system. By proactively investigating, understanding, and addressing racial disparities in patient safety events, including those recorded in malpractice databases, healthcare systems can help advance initiatives to provide high-quality and equitable care to patients.


Assuntos
Imperícia , Humanos , Fatores Raciais , Hospitais , Bases de Dados Factuais , Estudos Retrospectivos
7.
ACS Synth Biol ; 11(11): 3759-3771, 2022 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-36331143

RESUMO

Essential viral enzymes have been successfully targeted to combat the diseases caused by emerging pathogenic RNA viruses (e.g., viral RNA-dependent RNA polymerase). Because of the conserved nature of such viral enzymes, therapeutics targeting these enzymes have the potential to be repurposed to combat emerging diseases, e.g., remdesivir, which was initially developed as a potential Ebola treatment, then was repurposed for COVID-19. Our efforts described in this study target another essential and highly conserved, but relatively less explored, step in RNA virus translation and replication, i.e., capping of the viral RNA genome. The viral genome cap structure disguises the genome of most RNA viruses to resemble the mRNA cap structure of their host and is essential for viral translation, propagation, and immune evasion. Here, we developed a synthetic, phenotypic yeast-based complementation platform (YeRC0M) for molecular characterization and targeting of SARS-CoV-2 genome-encoded RNA cap-0 (guanine-N7)-methyltransferase (N7-MTase) enzyme (nsp14). In YeRC0M, the lack of yeast mRNA capping N7-MTase in yeast, which is an essential gene in yeast, is complemented by the expression of functional viral N7-MTase or its variants. Using YeRC0M, we first identified important protein domains and amino acid residues that are essential for SARS-CoV-2 nsp14 N7-MTase activity. We also expanded YeRC0M to include key nsp14 variants observed in emerging variants of SARS-CoV-2 (e.g., delta variant of SARS-CoV-2 encodes nsp14 A394V and nsp14 P46L). We also combined YeRC0M with directed evolution to identify attenuation mutations in SARS-CoV-2 nsp14. Because of the high sequence similarity of nsp14 in emerging coronaviruses, these observations could have implications on live attenuated vaccine development strategies. These data taken together reveal key domains in SARS-CoV-2 nsp14 that can be targeted for therapeutic strategies. We also anticipate that these readily tractable phenotypic platforms can also be used for the identification of inhibitors of viral RNA capping enzymes as antivirals.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , RNA Viral/genética , Proteínas não Estruturais Virais/química , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/metabolismo , Saccharomyces cerevisiae/genética , Metiltransferases/metabolismo , RNA Mensageiro
8.
J Clin Microbiol ; 60(11): e0066522, 2022 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-36222515

RESUMO

A surge in hematopoietic stem cell transplantation (HSCT) human adenovirus A31 (HAdV-A31) infections was initially observed in late 2014/2015 at SickKids (SK) Hospital, Toronto, Canada. In response, enhanced laboratory monitoring for all adenovirus infections was conducted. Positive samples underwent genotyping, viral culture, and, in selected cases, whole-genome sequencing (WGS). HAdV-A31 specimens/DNA obtained from four international pediatric HSCT centers also underwent WGS. During the SK outbreak period (27 October 2014 to 31 October 2018), 17/20 HAdV-A31 isolates formed a distinct clade with 0 to 8 mutations between the closest neighbors. Surveillance before and after the outbreak detected six additional HAdV-A31 HSCT cases; three of the four sequenced cases clustered within the outbreak clade. Two SK outbreak isolates were identical to sequences from two patients in an outbreak in England. Three SK non-outbreak sequences also had high sequence similarity to strains from three international centers. Environmental PCR testing of the HSCT ward showed significant adenovirus contamination. Despite intense infection control efforts, we observed re-occurrence of infection with the outbreak strain. Severe but nonfatal infection was observed more commonly with HAdV-A31 compared to other genotypes, except HAdV-C1. Our findings strongly implicate nosocomial spread of HAdV-A31 over 10 years on a HSCT unit and demonstrate the value of WGS in defining and mapping the outbreak. Close linkages among strains in different countries suggest international dissemination, though the mechanism is undetermined. This large, extended outbreak emphasizes the pre-eminent role of HAdV-A31 in causing intractable pediatric HSCT outbreaks of severe illness worldwide.


Assuntos
Infecções por Adenoviridae , Infecções por Adenovirus Humanos , Adenovírus Humanos , Transplante de Células-Tronco Hematopoéticas , Humanos , Criança , Infecções por Adenovirus Humanos/epidemiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Sequenciamento Completo do Genoma , Hospitais , Filogenia
9.
J Patient Saf ; 17(8): e1605-e1608, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34852418

RESUMO

OBJECTIVES: This study aimed to determine if race differences exist in voluntarily reported near-miss patient safety events in a large integrated, 10-hospital health care system on its journey to become a high reliability organization. METHODS: From July 1, 2015, to June 30, 2017, employees in a mid-Atlantic health care system voluntarily reported near-miss events by type using an occurrence reporting system referred to as the Patient Safety Event Management System. Inpatients, outpatients, and observation patients were identified as "Black," "White," or "other" (n = 39,390). Using retrospective analysis and χ2 goodness of fit, comparisons of race proportions were conducted to determine differences at the health system level, by hospital, and by event type. RESULTS: Significant race differences existed: (1) overall across the health care system with higher proportions of events reported for Whites and lower proportions of events reported for Blacks in the Patient Safety Event Management System, (2) by site in 9 of 10 hospitals, and (3) by type. All differences were significant at P < 0.05. CONCLUSIONS: Race differences in near-miss patient safety events exist in voluntary reporting systems by type. Health care organizations, particularly health care high reliability organizations, can use these findings to help to identify areas of further study and investigation. Further study and investigation should include efforts to understand the root cause of the differences found in this study, including the role of reporting bias by race.


Assuntos
Organizações de Alta Confiabilidade , Segurança do Paciente , Atenção à Saúde , Humanos , Fatores Raciais , Reprodutibilidade dos Testes , Estudos Retrospectivos
10.
Behav Pharmacol ; 32(6): 524-532, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34397448

RESUMO

3,4-Methylenedioxypyrovalerone (MDPV), one of several synthetic cathinones, is a popular constituent of illicit 'bath salts'. In preclinical studies utilizing drug discrimination methods with male rodents, MDPV has been characterized as similar to both cocaine and 3,4-methylenedioxymethamphetamine-hydrochloride (MDMA). Whereas few drug discrimination studies have utilized female rats, the current study evaluated the discriminative stimulus effects of MDPV in 12 adult female Sprague-Dawley rats trained to discriminate 0.5 mg/kg MDPV from saline under a fixed ratio 20 schedule of food reinforcement. Stimulus substitution was assessed with MDPV and its enantiomers, other synthetic cathinones [alpha pyrrolidinopentiophenone-hydrochloride(α-PVP), 4-methylmethcathinone (4-MMC)], other dopamine agonists (cocaine, [+)-methamphetamine] and serotonin agonists [MDMA, lysergic acid diethylamide (LSD)] Stimulus antagonism was assessed with the dopamine D1 receptor antagonist, Sch 23390 and the D2 receptor antagonist, haloperidol. Cocaine and (+)-methamphetamine engendered full stimulus generalization to MDPV with minimal effects on response rate. LSD produced partial substitution, whereas MDMA and 4-MMC produced complete substitution, and all these serotonergic compounds produced dose-dependent response suppression. (S)-MDPV and α-PVP engendered full substitution with similar potency to the racemate, while (R)-MDPV failed to substitute up to 5 mg/kg. Both Sch 23390 and haloperidol attenuated the discrimination of low MDPV doses and essentially shifted the dose-response curve to the right but failed to block discrimination of the training dose. These findings are generally consistent with previous reports based exclusively on male rodents. Moreover, they confirm the contribution of dopaminergic mechanisms but do not rule out the possible contribution of other neurotransmitter actions to the interoceptive stimulus effects of MDPV.


Assuntos
Benzodioxóis/farmacologia , Pirrolidinas/farmacologia , Receptores de Dopamina D1 , Receptores de Dopamina D2 , Animais , Benzazepinas/farmacologia , Estimulantes do Sistema Nervoso Central/farmacologia , Cocaína/farmacologia , Antagonistas de Dopamina/farmacologia , Inibidores da Captação de Dopamina/farmacologia , Relação Dose-Resposta a Droga , Feminino , Alucinógenos/farmacologia , N-Metil-3,4-Metilenodioxianfetamina/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores de Dopamina D1/antagonistas & inibidores , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D2/análise , Receptores de Dopamina D2/metabolismo , Fatores Sexuais , Transmissão Sináptica/fisiologia , Catinona Sintética
11.
J R Coll Physicians Edinb ; 51(S1): S7-S11, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34185032

RESUMO

The entire College, notably officers and staff, responded with resilience and versatility to COVID-19. We strove to remain at the forefront of medical education during rapid change in both medical care and the scientific evidence that supports it. Every department has had to adapt, indeed evolve, to tackle the pandemic, which affected all aspects of College work, notably education, training, examinations, heritage, policy and public affairs. Several of the resulting changes will provide a strong foundation for the future development of the College. These innovations, especially in the nature and delivery of education, will both extend the reach of the College in years to come, and enhance its relevance. Effective though electronic communication has proved over the last 15 months, however, it cannot replace the social coherence and innate teamwork of a Royal College. So we look forward to re-engaging colleagues in the revitalised College.


Assuntos
COVID-19 , Médicos , Humanos , Pandemias , SARS-CoV-2 , Universidades
12.
J Org Chem ; 86(9): 6184-6194, 2021 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-33835804

RESUMO

In contrast to methyl phenylacetates, methyl arylacetates do not provide syn-aldols in the dicyclohexylboron triflate/triethylamine (Chx2BOTf/Et3N)-mediated enolboration-aldolization reaction. However, a combination of a less bulky boron reagent (dibutylboron triflate, n-Bu2BOTf), a bulky amine (i-Pr2NEt), and ambient temperature is required to obtain syn-aldols from methyl arylacetates. The corresponding anti-aldol products have been synthesized by the enolboration-aldolization of methyl arylacetates in the presence of Chx2BOTf/Et3N at a lower temperature. We report the first example of a complementary syn- and anti-selective enolboration-aldolization of arylacetates.


Assuntos
Boro , Fenilacetatos , Indicadores e Reagentes , Estereoisomerismo , Temperatura
13.
Infect Control Hosp Epidemiol ; 42(3): 261-267, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32782038

RESUMO

OBJECTIVE: In this study, we aimed to capture perspectives of healthcare workers (HCWs) on coronavirus disease 2019 (COVID-19) and infection prevention and control (IPAC) measures implemented during the early phase of the COVID-19 pandemic. DESIGN: A cross-sectional survey of HCWs. PARTICIPANTS: HCWs from the Hospital for Sick Children, Toronto, Canada. INTERVENTION: A self-administered survey was distributed to HCWs. We analyzed factors influencing HCW knowledge and self-reported use of personal protective equipment (PPE), concerns about contracting COVID-19 and acceptance of the recommended IPAC precautions for COVID-19. RESULTS: In total, 175 HCWs completed the survey between March 6 and March 10: 35 staff physicians (20%), 24 residents or fellows (14%), 72 nurses (41%), 14 respiratory therapists (8%), 14 administration staff (8%), and 14 other employees (8%). Most of the respondents were from the emergency department (n = 58, 33%) and the intensive care unit (n = 58, 33%). Only 86 respondents (50%) identified the correct donning order; only 60 (35%) identified the correct doffing order; but the majority (n = 113, 70%) indicated the need to wash their hands immediately prior to removal of their mask and eye protection. Also, 91 (54%) respondents felt comfortable with recommendations for droplet and/or contact precautions for routine care of patients with COVID-19. HCW occupation and concerns about contracting COVID-19 outside work were associated with nonacceptance of the recommendations (P = .016 and P = .036 respectively). CONCLUSION: As part of their pandemic response plans, healthcare institutions should have ongoing training for HCWs that focus on appropriate PPE doffing and discussions around modes of transmission of COVID-19.


Assuntos
COVID-19/prevenção & controle , Fidelidade a Diretrizes/estatística & dados numéricos , Conhecimentos, Atitudes e Prática em Saúde , Pessoal de Saúde , Equipamento de Proteção Individual , Adulto , COVID-19/transmissão , Canadá , Estudos Transversais , Luvas Protetoras , Hospitais Pediátricos , Humanos , Controle de Infecções/métodos , Controle de Infecções/normas , Pessoa de Meia-Idade , Percepção , Dispositivos de Proteção Respiratória , Inquéritos e Questionários , Centros de Atenção Terciária
14.
J Pediatr ; 220: 249-253, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31987650

RESUMO

There are few biomarkers to predict efficacy of glucocorticoid treatment in childhood acute lymphoblastic leukemia (ALL) at diagnosis. Here, we demonstrate reciprocal regulation of 11beta-hydroxysteroid dehydrogenase (11ß-HSD), may predict the apoptotic response of ALL to glucocorticoid treatment. Our data may be useful to refine glucocorticoid treatment, to retain benefit while minimizing side effects.


Assuntos
11-beta-Hidroxiesteroide Desidrogenase Tipo 1/fisiologia , 11-beta-Hidroxiesteroide Desidrogenase Tipo 2/fisiologia , Dexametasona/uso terapêutico , Glucocorticoides/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Prednisolona/uso terapêutico , Adolescente , Células Cultivadas , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Resultado do Tratamento
15.
J Patient Saf ; 16(4): e235-e239, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-30585888

RESUMO

OBJECTIVES: The aim of the study was to determine whether race differences exist in voluntarily reported harmful patient safety events in a large 10 hospital healthcare system on a high reliability organization journey. METHODS: From July 1, 2015, to June 30, 2017, employees in a healthcare system based in Washington, District of Columbia, and Maryland voluntarily reported harmful patient safety events by type using a Patient Safety Event Management System. Inpatients, outpatients, and observation patients were identified as "black," "white," or "other" (N = 5038). Using retrospective analysis and χ goodness of fit, comparisons of race proportions were conducted to determine differences at the health system level, by hospital, by event type, and by severity. RESULTS: Significant race differences existed: (1) overall with higher proportions of whites and lower proportions of other in a Patient Safety Event Management System; (2) by type across races; (3) in six hospitals across races; and (4) by type and by hospital for blacks and whites. All differences were significant at P < 0.05. CONCLUSIONS: Race differences in harmful events exist in voluntary reporting systems by type and by hospital setting. Healthcare organizations, particularly healthcare high reliability organizations, can use these findings to help identify areas of further study and investigation. Further study and investigation should include efforts to understand the root cause of the differences found in this study, including the role of reporting bias.


Assuntos
Atenção à Saúde/normas , Organizações de Alta Confiabilidade , Segurança do Paciente/normas , Feminino , Humanos , Masculino , Fatores Raciais , Estudos Retrospectivos
16.
Regen Med ; 13(8): 935-944, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30488776

RESUMO

Human pluripotent stem cells (hPSCs) have the potential to transform medicine. However, hurdles remain to ensure safety for such cellular products. Science-based understanding of the requirements for source materials is required as are appropriate materials. Leaders in hPSC biology, clinical translation, biomanufacturing and regulatory issues were brought together to define requirements for source materials for the production of hPSC-derived therapies and to identify other key issues for the safety of cell therapy products. While the focus of this meeting was on hPSC-derived cell therapies, many of the issues are generic to all cell-based medicines. The intent of this report is to summarize the key issues discussed and record the consensus reached on each of these by the expert delegates.


Assuntos
Terapia Baseada em Transplante de Células e Tecidos/normas , Segurança do Paciente , Células-Tronco Pluripotentes/transplante , Medicina Regenerativa/normas , Terapia Baseada em Transplante de Células e Tecidos/efeitos adversos , Terapia Baseada em Transplante de Células e Tecidos/métodos , Guias de Prática Clínica como Assunto , Medicina Regenerativa/métodos , Reino Unido
17.
J Chem Phys ; 149(6): 064702, 2018 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-30111156

RESUMO

Extensive molecular dynamics simulations of xenon in two classes of zeolite crystal systems, one consisting of purely intra-crystalline space and the other with both intra- and inter-crystalline space are reported. The latter mimics a typical poly-crystalline sample of zeolite. Comparison of results from these two systems provides insights into the structure and dynamics in the presence of inter-crystalline space. The temperature, as well as the distance between the crystallites, has been varied. The density distribution and diffusivities calculated inside the poly-crystalline system show that the interfacial region between the crystal and the inter-crystalline region acts as a bottleneck for diffusion through the system. At lower temperatures, the particles are trapped at the interface due to the pronounced energy minima present in that region. With the increase in temperature, the particles are able to overcome this barrier frequently, and the transport across the inter-crystalline region is increased. A ballistic or superdiffusive motion is seen in the inter-crystalline region along all the axes except along the axis which has the inter-crystalline space. The transition time for ballistic to diffusive motion increases with the increase in the length of the inter-crystalline space. Velocity auto- and cross correlation functions exhibit strong oscillations and exchange of kinetic energy along directions perpendicular to the direction of the inter-crystalline space. These results explain why uptake and PFG-NMR measurements exhibit lower values for diffusivity for the same system when compared to Quasi-Elastic Neutron Scattering. Thus, using molecular dynamics simulations, we were able to correlate the difference of diffusivity values measured using various experimental methods where these inter-crystalline regions are common.

18.
J Eat Disord ; 6: 6, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29619220

RESUMO

BACKGROUND: There is limited evidence to inform nutrition and dietetic interventions for individuals with eating disorders even though it is recommended as an essential part of multidisciplinary management. There is minimal guidance, an absence of standardised nutrition educational material, and no research on how best to educate patients on healthy eating and how to achieve nutrition adequacy. Therefore the REAL Food Guide was developed. METHODS: The REAL Food Guide is a pyramid with four layers and key nutrition messages beside each layer that was conceived to address gaps in nutrition education and intervention for individuals with eating disorders. Written and verbal consumer feedback was obtained from consumers receiving treatment regarding the acceptability and usefulness of the REAL Food Guide. A unique database was developed to reflect the types of foods and realistic portion sizes that patients are likely to select. This database was used for nutrition modelling to assess the nutrition adequacy of three meal patterns (meat containing, vegetarian and semi-vegan) for both weight maintenance and weight regain. Each meal pattern was compared to the Nutrient Reference Values for Australia and New Zealand. RESULTS: Nutritional analysis demonstrated nutritional adequacy of meal patterns for energy, macronutrients and most micronutrients when the recommended number of serves from the REAL Food Guide were assessed. All meal patterns were adequate in micronutrients except for the semi-vegan meal pattern that was inadequate in vitamin D. Feedback from individuals with eating disorders demonstrates the nutrition education tool was acceptable to them as they felt it was more helpful for their recovery than general nutrition guidelines. CONCLUSION: The REAL Food Guide is a comprehensive and user-friendly guide that clinicians can use to educate patients about components of a balanced and healthy diet. The guide can educate all eating disorder clinicians, including those who are new to the field, about the basics of nutrition. Clinicians using the guide can be confident that, if followed, patient's energy and nutritional requirements will be met and important nutrition education messages are reinforced, that are tailored to the beliefs and concerns of individuals with eating disorders.

19.
Arch Dis Child ; 102(12): 1110-1117, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-27449675

RESUMO

OBJECTIVE: The extent that inherited bleeding disorders affect; number, size and location of bruises in young children <6 years. DESIGN: Prospective, longitudinal, observational study. SETTING: Community. PATIENTS: 105 children with bleeding disorders, were compared with 328 without a bleeding disorder and classified by mobility: premobile (non-rolling/rolling over/sitting), early mobile (crawling/cruising) and walking and by disease severity: severe bleeding disorder factor VIII/IX/XI <1 IU/dL or type 3 von Willebrand disease. INTERVENTIONS: Number, size and location of bruises recorded in each child weekly for up to 12 weeks. OUTCOMES: The interventions were compared between children with severe and mild/moderate bleeding disorders and those without bleeding disorders. Multiple collections for individual children were analysed by multilevel modelling. RESULTS: Children with bleeding disorders had more and larger bruises, especially when premobile. Compared with premobile children without a bleeding disorder; the modelled ratio of means (95% CI) for number of bruises/collection was 31.82 (8.39 to 65.42) for severe bleeding disorders and 5.15 (1.23 to 11.17) for mild/moderate, and was 1.81 (1.13 to 2.23) for size of bruises. Children with bleeding disorders rarely had bruises on the ears, neck, cheeks, eyes or genitalia. CONCLUSIONS: Children with bleeding disorder have more and larger bruises at all developmental stages. The differences were greatest in premobile children. In this age group for children with unexplained bruising, it is essential that coagulation studies are done early to avoid the erroneous diagnosis of physical abuse when the child actually has a serious bleeding disorder, however a blood test compatible with a mild/moderate bleeding disorder cannot be assumed to be the cause of bruising.


Assuntos
Transtornos Herdados da Coagulação Sanguínea/complicações , Contusões/etiologia , Transtornos Herdados da Coagulação Sanguínea/epidemiologia , Transtornos Plaquetários/complicações , Transtornos Plaquetários/epidemiologia , Desenvolvimento Infantil , Pré-Escolar , Contusões/epidemiologia , Contusões/patologia , Feminino , Humanos , Lactente , Estudos Longitudinais , Masculino , Estudos Prospectivos , Índice de Gravidade de Doença , País de Gales/epidemiologia , Caminhada
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