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1.
Ann Intern Med ; 174(1): 1-7, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33017564

RESUMO

BACKGROUND: Economic analyses of medical scribes have been limited to individual, specialty-specific clinics. OBJECTIVE: To determine the number of additional patient visits various specialties would need to recover the costs of implementing scribes in their practice at 1 year. DESIGN: Modeling study based on 2015 data from the Centers for Medicare & Medicaid Services (CMS) and National Ambulatory Medical Care Survey. Scribe costs were based on literature review and a third-party contractor model. Revenue was calculated from direct visit billing, CPT (Current Procedural Terminology) billing, and data from the National Ambulatory Medical Care Survey. DATA SOURCES: 2015 data from CMS and the National Ambulatory Medical Care Survey. TARGET POPULATION: Health care providers. TIME HORIZON: 1 year. PERSPECTIVE: Office-based clinic. OUTCOME MEASURES: The number of additional patient visits a physician must have to recover the costs of a scribe program at 1 year. RESULTS OF BASE-CASE ANALYSIS: An average of 1.34 additional new patient visits per day (295 per year) were required to recover scribe costs (range, 0.89 [cardiology] to 1.80 [orthopedic surgery] new patient visits per day). For returning patients, an average of 2.15 additional visits per day (472 per year) were required (range, 1.65 [cardiology] to 2.78 [orthopedic surgery] returning visits per day). The addition of 2 new patient (or 3 returning) visits per day was profitable for all specialties. RESULTS OF SENSITIVITY ANALYSIS: Results were not sensitive to most inputs, with the exception of hourly scribe cost and inclusion of CPT revenue. LIMITATION: Use of Medicare data and failure to account for indirect costs, downstream revenue, or changes in documentation quality. CONCLUSION: For all specialties, modest increases in productivity due to scribes may allow physicians to see more patients and offset scribe costs, making scribe programs revenue-neutral. PRIMARY FUNDING SOURCE: University of Chicago Medicine's Center for Healthcare Delivery Science and Innovation and the Bucksbaum Institute.


Assuntos
Médicos/economia , Atenção Primária à Saúde/economia , Avaliação de Programas e Projetos de Saúde , Custos e Análise de Custo , Documentação , Eficiência , Seguimentos , Humanos , Estudos Prospectivos , Estados Unidos
2.
Am J Physiol Cell Physiol ; 320(3): C253-C263, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33356943

RESUMO

Breast cancer is the most prevalent cancer in women worldwide. In the United Kingdom, approximately 5% of all breast cancers are already metastatic at the time of diagnosis. An abundance of literature shows that exercise can have beneficial effects on the outcome and prognosis of breast cancer patients, yet the molecular mechanisms remain poorly understood. There are several in vitro models that aim to recapitulate the response of breast cancer to exercise in vivo; this systematic review and meta-analysis summarizes the existing literature. The following search terms were used to conduct a systematic literature search using a collection of databases (last search performed May 2020): "in vitro," "exercise," and "breast cancer." Only studies that investigated the effects of exercise on breast cancer in vitro were included. Standardized mean differences (SMD) were calculated to determine pooled effect sizes. This meta-analysis has successfully demonstrated that various identified exercise interventions on breast cancer cells in vitro significantly reduced breast cancer cell viability, proliferation, and tumorigenic potential (SMD = -1.76, P = 0.004, SMD = -2.85, P = 0.003, and SMD = -3.15, P = 0.0008, respectively). A clear direction of effect was found with exercise on breast cancer cell migration in vitro, however this effect was not significant (SMD = -0.62, P = 0.317). To our knowledge, this is the first meta-analysis and systematic review investigating and summarizing literature on exercise and breast cancer in vitro, highlighting models used and priority areas for future research focus.


Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/fisiopatologia , Exercício Físico/fisiologia , Animais , Mama/patologia , Mama/fisiopatologia , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Progressão da Doença , Feminino , Humanos
3.
MMWR Morb Mortal Wkly Rep ; 69(40): 1457-1459, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33031365

RESUMO

There is increasing evidence that children and adolescents can efficiently transmit SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19) (1-3). During July-August 2020, four state health departments and CDC investigated a COVID-19 outbreak that occurred during a 3-week family gathering of five households in which an adolescent aged 13 years was the index and suspected primary patient; 11 subsequent cases occurred.


Assuntos
Infecções por Coronavirus/epidemiologia , Surtos de Doenças , Família , Pneumonia Viral/epidemiologia , Adolescente , Adulto , Idoso , COVID-19 , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Estados Unidos/epidemiologia , Adulto Jovem
4.
MMWR Morb Mortal Wkly Rep ; 69(31): 1023-1025, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32759921

RESUMO

Limited data are available about transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), among youths. During June 17-20, an overnight camp in Georgia (camp A) held orientation for 138 trainees and 120 staff members; staff members remained for the first camp session, scheduled during June 21-27, and were joined by 363 campers and three senior staff members on June 21. Camp A adhered to the measures in Georgia's Executive Order* that allowed overnight camps to operate beginning on May 31, including requiring all trainees, staff members, and campers to provide documentation of a negative viral SARS-CoV-2 test ≤12 days before arriving. Camp A adopted most† components of CDC's Suggestions for Youth and Summer Camps§ to minimize the risk for SARS-CoV-2 introduction and transmission. Measures not implemented were cloth masks for campers and opening windows and doors for increased ventilation in buildings. Cloth masks were required for staff members. Camp attendees were cohorted by cabin and engaged in a variety of indoor and outdoor activities, including daily vigorous singing and cheering. On June 23, a teenage staff member left camp A after developing chills the previous evening. The staff member was tested and reported a positive test result for SARS-CoV-2 the following day (June 24). Camp A officials began sending campers home on June 24 and closed the camp on June 27. On June 25, the Georgia Department of Public Health (DPH) was notified and initiated an investigation. DPH recommended that all attendees be tested and self-quarantine, and isolate if they had a positive test result.


Assuntos
Acampamento , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Surtos de Doenças , Pneumonia Viral/epidemiologia , Pneumonia Viral/transmissão , Adolescente , Adulto , COVID-19 , Criança , Feminino , Georgia/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Adulto Jovem
6.
Breast Cancer Res Treat ; 177(2): 395-399, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31172406

RESUMO

PURPOSE: This pilot study evaluated adherence to anti-estrogen therapy in women with hormone receptor-positive breast cancer utilizing bubble packaging. METHODS: This was a single-arm prospective investigational pilot study that enrolled 86 patients between August 2012 and April 2014. Descriptive statistics for patient age, race, insurance, stage, duration of treatment, and comorbidities were computed. All patients received routine prescriptions in a "bubble" pack or daily blister pack dispensed by one pharmacy. Participants were considered adherent if they had taken ≥ 80% of the dispensed drug. Disease-free survival (DFS) and overall survival (OS) data were obtained at 78 months. RESULTS: Fifty patients were included in the analysis. The overall adherence rate was 97%. None of the variables examined (race, age, insurance status, and stage) had an impact on adherence rate. Only duration of endocrine therapy had a marginal effect on adherence (p value = 0.06). The late cohort (duration of therapy 37-60 months) was least likely to be compliant at 89.53%. Our 5-year DFS was 94% and 5-year OS was 96%. There was no statistically significant difference in DFS and OS between patients with adherence rate > 90% and < 90%. CONCLUSION: Adherence rate to bubble packaging was higher than that in historical studies. Although this is a single-arm pilot study, these data suggest bubble packaging of anti-estrogen may be a reasonable option to improve adherence in hormone receptor-positive breast cancer patients.


Assuntos
Antineoplásicos Hormonais/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Adesão à Medicação , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Terapia Combinada , Comorbidade , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Projetos Piloto , Receptores de Estrogênio/genética , Receptores de Progesterona/genética , Resultado do Tratamento
8.
Clin Chem ; 61(3): 487-97, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25524438

RESUMO

BACKGROUND: Application of metabolite profiling could expand the etiological knowledge of type 2 diabetes mellitus (T2D). However, few prospective studies apply broad untargeted metabolite profiling to reveal the comprehensive metabolic alterations preceding the onset of T2D. METHODS: We applied untargeted metabolite profiling in serum samples obtained from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort comprising 300 individuals who developed T2D after a median follow-up time of 6 years and 300 matched controls. For that purpose, we used ultraperformance LC-MS with a protocol specifically designed for large-scale metabolomics studies with regard to robustness and repeatability. After multivariate classification to select metabolites with the strongest contribution to disease classification, we applied multivariable-adjusted conditional logistic regression to assess the association of these metabolites with T2D. RESULTS: Among several alterations in lipid metabolism, there was an inverse association with T2D for metabolites chemically annotated as lysophosphatidylcholine(dm16:0) and phosphatidylcholine(O-20:0/O-20:0). Hexose sugars were positively associated with T2D, whereas higher concentrations of a sugar alcohol and a deoxyhexose sugar reduced the odds of diabetes by approximately 60% and 70%, respectively. Furthermore, there was suggestive evidence for a positive association of the circulating purine nucleotide isopentenyladenosine-5'-monophosphate with incident T2D. CONCLUSIONS: This study constitutes one of the largest metabolite profiling approaches of T2D biomarkers in a prospective study population. The findings might help generate new hypotheses about diabetes etiology and develop further targeted studies of a smaller number of potentially important metabolites.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Adulto , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
9.
Breast Cancer (Auckl) ; 17: 11782234221145385, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36710995

RESUMO

Purpose: Breast cancer is the most diagnosed cancer and the leading cause of cancer death in women globally, and mesenchymal stem cells have been widely implicated in tumour progression. This systematic review and meta-analysis seeks to identify and summarise existing literature on the effects of human mesenchymal stem cells (hMSCs) on the migration of breast cancer cells (BCCs) in vitro, to determine the direction of this relationship according to existing research and to identify the directions for future research. Methods: A systematic literature search was conducting using a collection of databases, using the following search terms: in vitro AND mesenchymal stem cells AND breast cancer. Only studies that investigated the effects of human, unmodified MSCs on the migration of human, unmodified BCCs in vitro were included. Standardised mean differences (SMDs) were calculated to determine pooled effect sizes. Results: This meta-analysis demonstrates that hMSCs (different sources combined) increase the migration of both MDA-MB-231 and MCF-7 cell lines in vitro (SMD = 1.84, P = .03 and SMD = 2.69, P < .00001, respectively). Importantly, the individual effects of hMSCs from different sources were also analysed and demonstrated that MSCs derived from human adipose tissue increase BCC migration (SMD = 1.34, P = .0002) and those derived from umbilical cord increased both MDA-MB-231 and MCF-7 migration (SMD = 3.93, P < .00001 and SMD = 3.01, P < .00001, respectively). Conclusions: To our knowledge, this is the first systematic review and meta-analysis investigating and summarising the effects of hMSCs from different sources on the migration of BCCs, in vitro.

10.
Biopreserv Biobank ; 21(5): 450-457, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36094454

RESUMO

Introduction: For stem cell therapies to be adopted in mainstream health care, robust, reliable, and cost-effective storage and transport processes must be developed. Cryopreservation remains the best current platform for this purpose, and freezing cells at high concentration may have many benefits, including savings on cost and storage space, facilitating transport logistics, and reducing cryoprotectant volume. Cells, such as mesenchymal stem cells (MSCs), are typically frozen at 1 million cells per milliliter (mL), but the aim of this study is to examine the post-thaw attributes of human bone marrow derived MSCs (hBM-MSCs) frozen at 1, 5, and 10 million cells per mL. Methods: Thawed cells were assessed for their morphology, phenotypic marker expression, viability, apoptosis level, metabolic activity, proliferation, and osteogenic and adipogenic differentiation. Results: In this study, for the first time, it is shown that all assessed cells expressed the typical MSC markers (CD90, CD105, and CD73) and lacked the expression of CD14, CD20, CD34, CD45, and HLA-DR. In addition, all cells showed elongated fibroblastic morphology. Post-thaw viability was retained with no difference among the three concentrations. Moreover, no significant statistical difference was observed in the post-thaw apoptosis level, metabolic activity, proliferation, and osteogenic potential, indicating that these cells are amenable to cryopreservation at higher concentrations. Conclusion: The results of this study are of paramount importance to the development of manufacturing processes around a useful freezing concentration when cells are targeted to be stored for at least 6 months.

11.
Psychiatr Serv ; 74(2): 166-172, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-35983659

RESUMO

As reviewers, editors, and researchers with lived experience of mental health challenges, addiction, and/or psychosocial distress/disability, the authors have struggled to find an adequate way to address inappropriate or misleading use of the term "participatory methods" to describe research that involves people with lived experience in only a superficial or tokenistic manner. The authors of this article have found that, in their experience, editors or other reviewers often appear to give authors extensive leeway on claims of participatory methods that more accurately reflect tokenism or superficial involvement. The problem of co-optation is described, examples from the authors' experiences are given, the potential harms arising from co-optation are articulated, and a series of concrete actions that journal editors, reviewers, and authors can take to preserve the core intent of participatory approaches are offered. The authors conclude with a call to action: the mental health field must ensure that power imbalances that sustain epistemic injustice against people with lived experience are not worsened by poorly conducted or reported studies or by tokenistic participatory methods.


Assuntos
Serviços de Saúde Mental , Saúde Mental , Humanos , Empoderamento
12.
Psychiatr Serv ; 74(9): 902-910, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-36935620

RESUMO

OBJECTIVE: A growing consensus has emerged regarding the importance of stakeholder involvement in mental health services research. To identify barriers to and the extent of stakeholder involvement in participatory research, the authors undertook a mixed-methods study of researchers and community members who reported participation in such research. METHODS: Eight consultative focus groups were conducted with diverse groups of stakeholders in mental health services research (N=51 unique participants, mostly service users), followed by a survey of service users, family members, community providers, and researchers (N=98) with participatory research experience. Focus groups helped identify facilitators and barriers to meaningful research collaboration, which were operationalized in the national survey. Participants were also asked about high-priority next steps. RESULTS: The barrier most strongly endorsed as a large or very large problem in the field was lack of funding for stakeholder-led mental health services research (76%), followed by lack of researcher training in participatory methods (74%) and insufficiently diverse backgrounds among stakeholders (69%). The two most frequently identified high-priority next steps were ensuring training and continuing education for researchers and stakeholders (33%) and authentically centering lived experience and reducing tokenism in research (26%). CONCLUSIONS: These findings suggest a need for increased attention to and investment in the development, implementation, and sustainment of participatory methods that prioritize collaboration with direct stakeholders, particularly service users, in U.S. mental health services research. The findings also underscore the presence and potentially important role of researchers who dually identify as service users and actively contribute a broader orientation from the service user-survivor movement.


Assuntos
Serviços de Saúde Mental , Humanos , Grupos Focais , Inquéritos e Questionários , Encaminhamento e Consulta , Pesquisa sobre Serviços de Saúde
13.
Bioinformatics ; 27(8): 1108-12, 2011 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-21325300

RESUMO

MOTIVATION: The study of metabolites (metabolomics) is increasingly being applied to investigate microbial, plant, environmental and mammalian systems. One of the limiting factors is that of chemically identifying metabolites from mass spectrometric signals present in complex datasets. RESULTS: Three workflows have been developed to allow for the rapid, automated and high-throughput annotation and putative metabolite identification of electrospray LC-MS-derived metabolomic datasets. The collection of workflows are defined as PUTMEDID_LCMS and perform feature annotation, matching of accurate m/z to the accurate mass of neutral molecules and associated molecular formula and matching of the molecular formulae to a reference file of metabolites. The software is independent of the instrument and data pre-processing applied. The number of false positives is reduced by eliminating the inaccurate matching of many artifact, isotope, multiply charged and complex adduct peaks through complex interrogation of experimental data. AVAILABILITY: The workflows, standard operating procedure and further information are publicly available at http://www.mcisb.org/resources/putmedid.html. CONTACT: warwick.dunn@manchester.ac.uk.


Assuntos
Cromatografia Líquida , Espectrometria de Massas , Metabolômica/métodos , Software , Fluxo de Trabalho
14.
Nephrol Dial Transplant ; 27(6): 2502-10, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22294777

RESUMO

BACKGROUND: Prolonged peritoneal dialysis (PD) therapy can result in the development of encapsulating peritoneal sclerosis (EPS), characterized by extensive sclerosis of the peritoneum with bowel adhesions often causing obstruction. METHODS: As a proof-of-principle study, holistic profiling of endogenous metabolites has been applied in a prospective collection of PD effluent collected in multiple UK renal centres over 6 years in order to investigate metabolic differences in PD effluent between PD therapy patients who later developed clinically defined EPS (n = 11) and controls, who were matched for PD vintage, age and gender (n = 11). RESULTS: 'Fit-for-purpose' analytical methods employing gas chromatography-mass spectrometry (MS), direct injection MS and quality control samples were developed and validated. These methods were applied in a proof-of-principle study to define metabolic differences in PD effluent related to subsequent development of EPS. Changes in amino acids, amines and derivatives, short-chain fatty acids and derivatives and sugars were observed prior to EPS developing, and changes in the metabolomic profiles could be detected. CONCLUSION: There is potential for applying metabolic profiles to identify patients at risk of developing EPS although long-term prospective studies with larger patient cohorts are required.


Assuntos
Metabolômica , Diálise Peritoneal Ambulatorial Contínua/efeitos adversos , Peritônio/metabolismo , Peritonite/metabolismo , Esclerose/metabolismo , Estudos de Casos e Controles , Estudos Transversais , Seguimentos , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Técnicas In Vitro , Falência Renal Crônica , Peritônio/patologia , Peritonite/diagnóstico , Peritonite/etiologia , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Esclerose/diagnóstico , Esclerose/etiologia
15.
Top Antivir Med ; 29(5): 430-439, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35191659

RESUMO

Vaccine hesitancy is one of the greatest health care challenges of our time, as recently highlighted by the experience with COVID-19 vaccines. It is now clear that several current COVID-19 vaccines are highly effective in preventing severe disease, hospitalization, and death from the disease, but their effectiveness has been greatly undermined by the many unfounded conspiracy theories, active disinformation, and fears (real or imagined) circulating through social media and through society in general, persuading millions of people worldwide not to receive the vaccine. Fortunately, there are numerous practical strategies that physicians and other health care professionals can employ in communicating effectively with vaccine-hesitant individuals, including using humble inquiry, compassionate listening, and storytelling, as well as engaging the entire health care team in providing accurate information. This article summarizes the major points of an IAS-USA-sponsored webinar held on August 3, 2021, titled COVID-19 Vaccine Hesitancy, Crucial Conversations, and Effective Messaging for Patients and Health Care Teams by Marie T. Brown, MD, an expert on adult immunization. The webinar was moderated by Constance A. Benson, MD.


Assuntos
COVID-19 , Infecções por HIV , Vacinas , Adulto , Vacinas contra COVID-19 , Humanos , SARS-CoV-2 , Hesitação Vacinal
16.
Psychiatry Res ; 317: 114799, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36037743

RESUMO

Metamotivation is defined as the ability to identify, monitor, and self-regulate motivation in service of goal attainment. As metamotivation is becoming an area of increased interest for intervention among people with psychiatric disorders, there is a need for valid and reliable self-report measures. The current pilot study adapted the Brief Regulation of Motivation Scale (BRoMS; Kim et al., 2018), a self-report measure validated among college students, for use with individuals with schizophrenia spectrum disorders, as a first step towards identifying a metamotivation measure. Thirty-four participants diagnosed with schizophrenia or schizoaffective disorder completed the adapted BRoMS measure and a measure of community functioning. The BRoMS was found to be acceptable, feasible and internally consistent. Higher BRoMs scores were associated with better work related skills. Concurrent and predictive validity were further evaluated among a subsample (n = 21), with comparisons between the BRoMS and participant responses on a semi-structured interview, and measures of self-motivation, and quality of life. The BRoMS demonstrated limited concurrent validity with the interview responses and motivation-related subscales; however, there was modest predictive validity regarding quality of life. This pilot data informs the need for continued efforts to develop and validate metamotivation scales.


Assuntos
Esquizofrenia , Humanos , Esquizofrenia/diagnóstico , Psicologia do Esquizofrênico , Motivação , Projetos Piloto , Escalas de Graduação Psiquiátrica , Qualidade de Vida , Psicometria , Reprodutibilidade dos Testes
17.
Sci Rep ; 12(1): 3504, 2022 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-35241723

RESUMO

Breast cancer is a persisting global burden for health services with cases and deaths projected to rise in future years. Surgery complemented by adjuvant therapy is commonly used to treat breast cancer, however comes with detrimental side effects to physical fitness and mental wellbeing. The aim of this systematic review and meta-analysis is to determine whether resistance and endurance interventions performed during adjuvant treatment can lastingly ameliorate these side effects. A systematic literature search was performed in various electronic databases. Papers were assessed for bias and grouped based on intervention design. RStudio was used to perform the meta-analyses for each group using the 'meta' package. Publication bias and power analyses were also conducted. These methods conform to PRISMA guidelines. Combined resistance and endurance interventions elicited significant long-lasting improvements in global fatigue and were beneficial to the remaining side effects. Individually, resistance and endurance interventions non-significantly improved these side effects. Resistance interventions elicited higher benefits overall. Exercise interventions have lasting clinical benefits in ameliorating adjuvant therapy side effects, which negatively impact physical fitness and mental wellbeing. These interventions are of clinical value to enhance adherence rates and avoid comorbidities such as sarcopenia, thus improving disease prognosis.


Assuntos
Neoplasias da Mama , Neoplasias da Mama/terapia , Terapia por Exercício , Fadiga/terapia , Feminino , Humanos , Resistência Física , Aptidão Física , Prognóstico , Qualidade de Vida
18.
J Proteome Res ; 10(8): 3660-73, 2011 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-21671558

RESUMO

Being born small for gestational age (SGA) confers increased risks of perinatal morbidity and mortality and increases the risk of cardiovascular complications and diabetes in later life. Accumulating evidence suggests that the etiology of SGA is usually associated with poor placental vascular development in early pregnancy. We examined metabolomic profiles using ultra performance liquid chromatography-mass spectrometry (UPLC-MS) in three independent studies: (a) venous cord plasma from normal and SGA babies, (b) plasma from a rat model of placental insufficiency and controls, and (c) early pregnancy peripheral plasma samples from women who subsequently delivered a SGA baby and controls. Multivariate analysis by cross-validated Partial Least Squares Discriminant Analysis (PLS-DA) of all 3 studies showed a comprehensive and similar disruption of plasma metabolism. A multivariate predictive model combining 19 metabolites produced by a Genetic Algorithm-based search program gave an Odds Ratio for developing SGA of 44, with an area under the Receiver Operator Characteristic curve of 0.9. Sphingolipids, phospholipids, carnitines, and fatty acids were among this panel of metabolites. The finding of a consistent discriminatory metabolite signature in early pregnancy plasma preceding the onset of SGA offers insight into disease pathogenesis and offers the promise of a robust presymptomatic screening test.


Assuntos
Recém-Nascido Pequeno para a Idade Gestacional , Primeiro Trimestre da Gravidez/metabolismo , Animais , Cromatografia Líquida , Feminino , Retardo do Crescimento Fetal , Humanos , Recém-Nascido , Espectrometria de Massas , Modelos Animais , Análise Multivariada , Gravidez , Curva ROC , Ratos , Ratos Sprague-Dawley
19.
Lab Invest ; 91(2): 181-9, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20921952

RESUMO

For decades, superoxic ex vivo dual perfusion of the human placental lobule has been used as a model to study the physiology and metabolism of the placenta. The aim of this study was to further develop the technique to enable perfusion at soluble oxygen concentrations similar to those in normal pregnancy (normoxia) and in pre-eclampsia (PE; hypoxia). Our design involved reducing the mean soluble oxygen tension in the maternal-side intervillous space (IVS) perfusate to 5-7% and <3% for normoxia and hypoxia, respectively, while providing a more ubiquitous delivery of perfusate into the IVS, using 22 maternal-side cannulae. We achieved quasi-steady states in [O2](fetal venous (soluble)), which were statistically different between the two adaptations at t=150 to t=240 min of dual perfusion (2.1, 1.2, 2.8 and 0.4, 0.0, 1.5%; median, 25th, 75th percentiles, n=20 and 24 readings in n=5 and n=6 lobules, normoxic and hypoxic perfusion, respectively; P<0.001, Mann-Whitney U-test). Lactate dehydrogenase (LDH) levels in fetal and maternal venous outflow perfusates were unaffected by the adaptations. There was also no difference in tissue lactate release between the two adaptations. Glucose consumption from the fetal circulation and maternal-side 'venous' pyruvate release were higher under normoxic conditions, indicative of a greater metabolic flux through glycolysis. Furthermore, there was greater release of the hypoxic-sensitive marker, macrophage inflammatory protein-1α, into the maternal venous perfusate in the hypoxic model. Also, during hypoxic perfusion, we found that fetal-side venous placental growth factor (PlGF) levels were higher compared with normoxic perfusion. We conclude that these ex vivo adapted methods of placental perfusion provide a means of studying aspects of placental metabolism in relation to normal oxygenation and hypoxia-associated pregnancy disease.


Assuntos
Oxigênio/sangue , Perfusão/métodos , Placenta/metabolismo , Pré-Eclâmpsia/sangue , Catéteres , Feminino , Humanos , Técnicas In Vitro , L-Lactato Desidrogenase/sangue , Pré-Eclâmpsia/metabolismo , Gravidez , Estatísticas não Paramétricas , Fatores de Tempo
20.
Anal Chem ; 83(17): 6689-97, 2011 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-21766834

RESUMO

In clinical analyses, the most appropriate biofluid should be analyzed for optimal assay performance. For biological fluids, the most readily accessible is blood, and metabolomic analyses can be performed either on plasma or serum. To determine the optimal agent for analysis, metabolic profiles of matched human serum and plasma were assessed by gas chromatography/time-of-flight mass spectrometry and ultrahigh-performance liquid chromatography mass spectrometry (in positive and negative electrospray ionization modes). Comparison of the two metabolomes, in terms of reproducibility, discriminative ability and coverage, indicated that they offered similar analytical opportunities. An analysis of the variation between 29 small-cell lung cancer (SCLC) patients revealed that the differences between individuals are markedly similar for the two biofluids. However, significant differences between the levels of some specific metabolites were identified, as were differences in the intersubject variability of some metabolite levels. Glycerophosphocholines, erythritol, creatinine, hexadecanoic acid, and glutamine in plasma, but not in serum, were shown to correlate with life expectancy for SCLC patients, indicating the utility of metabolomic analyses in clinical prognosis and the particular utility of plasma in relation to the clinical management of SCLC.


Assuntos
Neoplasias Pulmonares/metabolismo , Metabolômica/métodos , Plasma/metabolismo , Soro/metabolismo , Carcinoma de Pequenas Células do Pulmão/metabolismo , Cromatografia Líquida de Alta Pressão/métodos , Creatinina/sangue , Eritritol/sangue , Cromatografia Gasosa-Espectrometria de Massas/métodos , Glutamina/sangue , Glicerilfosforilcolina/sangue , Humanos , Espectrometria de Massas/métodos , Ácido Palmítico/sangue
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