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3.
BMC Pregnancy Childbirth ; 22(1): 956, 2022 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-36550457

RESUMO

BACKGROUND: This study aims to explore the prevalence of symptoms of depression and traumatic stress in fathers in the setting of poor fetal, neonatal, and maternal outcomes. METHODS: A prospective mixed-methods study was conducted at an outer metropolitan public teaching hospital in Brisbane, Australia, with quantitative results presented here. Subjects included 28 fathers whose male partners had experienced pregnancy or childbirth complicated by a significant congenital abnormality or aneuploidy, termination of pregnancy, fetal death in-utero, stillbirth, admission to the neonatal intensive care unit or special care nursery or significant maternal morbidity, such as a postpartum haemorrhage or an emergency postpartum hysterectomy. These experiences were classified into two groups: anticipatory (time to prepare) and sudden (no warning). The fathers were screened using the Edinburgh Postnatal Depression Scale (EPDS) and the Impact of Events Scale-Revised (IES-R) to assess subjective distress at 2-3 weeks (timepoint 1) and 3-4 months (timepoint 2) after the event. RESULTS: Data for both the EPDS and IES-R scales was available for 26 fathers (92.9%) at timepoint 1 and for 15 fathers (53.6%) at timepoint 2. High overall EPDS scores (≥10) were noted in 16/27 (59.3%) fathers at timepoint 1 and 6/15 fathers (40.0%) at timepoint 2. High overall IES-R scores ≥33 were noted in 12/26 (46.2%) fathers at timepoint 1 and 4/15 fathers (26.7%) at timepoint 2. A higher percentage of fathers who experienced anticipatory events had EPDS and IES-R score above these cut-offs at timepoint 1 (8/13 or 61.5%) compared to those experiencing sudden events (8/14 or 57.1%), however, percentages were similar between groups at time point 2 (2/7 or 28.6%% and 4/8 or 50.0%, respectively). More fathers who experienced anticipatory events had IES-R scores ≥33 at timepoint 1 (7/13 or 53.8%) compared to those experiencing sudden events (5/14 or 38.0%). CONCLUSION: Our study indicates high rates of distress in fathers exposed to poor fetal, neonatal, and maternal outcomes, which can persist for months after the event. Increased support for fathers in this setting may be required to prevent poor mental health. Further research on the long-term effects of these adverse events is warranted.


Assuntos
Depressão Pós-Parto , Depressão , Gravidez , Feminino , Recém-Nascido , Masculino , Humanos , Depressão/epidemiologia , Depressão Pós-Parto/epidemiologia , Estudos Prospectivos , Pai/psicologia , Parto/psicologia , Escalas de Graduação Psiquiátrica
4.
BMC Pregnancy Childbirth ; 22(1): 434, 2022 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-35610624

RESUMO

BACKGROUND: This study aims to explore the emotional and behavioural responses and coping strategies of fathers or expectant fathers who faced a significant traumatic event during a partner's pregnancy, labour, or the postpartum period. METHODS: This prospective qualitative study of 24 fathers was conducted at a public teaching hospital in Brisbane, Australia. 'Traumatic pregnancy' was defined as a pregnancy complicated by life-threatening or severe risk to the mother and the fetus, termination of pregnancy, intrauterine fetal death or stillbirth. Semi-structured interviews of participants were conducted 3-4 months after the traumatic event. An initial qualitative analysis with automatic coding was performed using Leximancer and later followed by a six-phase manual thematic analysis. RESULTS: A pregnancy-related traumatic event had significant mental and physical impacts on fathers. Participants' reactions and coping strategies were varied and influenced by their background history, pre-existing vulnerabilities, and the gap between expectation and reality. Most fathers described a fluctuating state between their needs 'not being met' and 'being met'. These needs were conceptualised using Maslow's hierarchy and Calman's gap theory to construct a composite thematic model to depict the universal requirements of men facing a traumatic pregnancy or childbirth. CONCLUSIONS: A greater understanding of the needs of men and gaps in their care is urgently needed. A targeted effort is required to make maternity services father-inclusive. This approach may assist in preventing long term consequences on fathers, partners, and their children.


Assuntos
Pai , Parto , Criança , Parto Obstétrico , Pai/psicologia , Feminino , Humanos , Masculino , Dor , Parto/psicologia , Gravidez , Estudos Prospectivos , Pesquisa Qualitativa
6.
Implement Sci Commun ; 1: 20, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32885181

RESUMO

BACKGROUND: Increasingly, health researchers must demonstrate the impact and real-life applications of their research. We investigated how health researchers with expertise in knowledge translation report research translation activities and impact on their curriculum vitae (CV). METHODS: We conducted a cross-sectional survey of health researchers with expertise in knowledge translation as we anticipated best practices in CV reporting from this specialized group. Our survey asked participants about their reporting of research translation and impact activities on their CVs, intention to report, and barriers and facilitators to reporting such activities on their CVs. We calculated univariate descriptive statistics for all quantitative data. Linear regression models determined predictors of researchers' intention to report research translation and impact activities on their CVs. We analyzed open-ended qualitative responses using content analysis. RESULTS: One hundred and fifty-three health researchers responded to the survey (response rate = 29%). Most respondents were Canadian, were female, and had a doctoral degree. Eighty-two percent indicated they reported at least one research translation and/or impact indicator on their CVs. Of those, health researchers commonly reported the following: advisory/regulatory committee membership related to research program (83%), research translation award(s) (61%), and academic performance assessments (59%). Researchers least commonly indicated the following: citation metric scores (31%), summaries of impact (21%), and requests to use research materials and/or products (19%). Fewer than half of the health researchers intended to report knowledge translation (43%) and impact (33%) on their CVs. Strong beliefs about capabilities and consequences of reporting research translation and/or impact were significant predictors of intention. Main barriers were as follows: CV templates do not include research translation and impact activities, participants perceived employers do not value research translation and impact activities, and lack of metrics to evaluate research translation and impact. Ninety-six percent were unaware of a CV template formatted to include research translation and/or impact reporting. CONCLUSIONS: Knowledge translation and impact indicators on the CV are inconsistently reported by our sample of health researchers. Modifiable barriers should be addressed to support more consistent reporting of such activities, including providing a CV template that includes research translation and impact as well as clear metrics to quantify them.

7.
Health Res Policy Syst ; 18(1): 8, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31959184

RESUMO

BACKGROUND: Integrated knowledge translation (IKT) is a model of research co-production, whereby researchers partner with knowledge users throughout the research process and who can use the research recommendations in practice or policy. IKT approaches are used to improve the relevance and impact of research. As an emerging field, however, the evidence underpinning IKT is in active development. The Integrated Knowledge Translation Research Network represents a collaborative interdisciplinary team that aims to advance the state of IKT science. METHODS: In 2017, the Integrated Knowledge Translation Research Network issued a call to its members for concept papers to further define IKT, outline an IKT research agenda, and inform the Integrated Knowledge Translation Research Network's special meeting entitled, Integrated Knowledge Translation State of the Science Colloquium, in Ottawa, Canada (2018). At the colloquium, authors presented concept papers and discussed knowledge-gaps for a research agenda and implications for advancing the IKT field. We took detailed field notes, audio-recorded the meeting and analysed the data using qualitative content analysis. RESULTS: Twenty-four participants attended the meeting, including researchers (n = 11), trainees (n = 6) and knowledge users (n = 7). Seven overarching categories emerged from these proceedings - IKT theory, IKT methods, IKT process, promoting partnership, definitions and distinctions of key IKT terms, capacity-building, and role of funders. Within these categories, priorities identified for future IKT research included: (1) improving clarity about research co-production/IKT theories and frameworks; (2) describing the process for engaging knowledge users; and (3) identifying research co-production/IKT outcomes and methods for evaluation. CONCLUSION: The Integrated Knowledge Translation State of the Science Colloquium initiated a research agenda to advance IKT science and practice. Next steps will focus on building a theoretical and evidence base for IKT.


Assuntos
Comportamento Cooperativo , Prática Clínica Baseada em Evidências/organização & administração , Pesquisa Translacional Biomédica/organização & administração , Fortalecimento Institucional/organização & administração , Prática Clínica Baseada em Evidências/normas , Humanos , Pesquisa Translacional Biomédica/normas
8.
Eur J Surg Oncol ; 46(4 Pt A): 522-526, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31740186

RESUMO

INTRODUCTION: Determining the extent of residual disease in the breast and axilla following neoadjuvant chemotherapy (NACT) is vital for surgical planning. Traditionally patients with incomplete radiological response in the breast after NACT undergo axillary node clearance, regardless of axillary clinical and radiological response. The aim of this study was to determine whether radiological and/or pathological response in the breast to NACT were predictive of axillary response. MATERIALS AND METHODS: A retrospective cohort study of patients with operable breast cancer with histologically proven axillary lymph node involvement who received NACT and underwent definitive surgical treatment between 1/1/2016 and 31/12/2018 were included. All had MRI and/or US of the breast and axilla before, mid-treatment and at the end of NACT. RESULTS: The 83 patients had a median age of 50 years (range 25-77). MRI had a positive predictive value (PPV) of 52.6% and negative predictive value (NPV) of 81.8% for breast pathological complete response (pCR). For axillary pCR, US had a PPV of 60.0% and NPV of 89.6%. Only 71% of patients had radiological concordance; 15.9% had radiological complete response (rCR) in breast and axilla whilst 55.1% had neither breast nor axillary rCR. 85.6% of patients had pathological concordance (20.5% with breast and axillary pCR: 65.1% with residual disease in both). CONCLUSION: Radiological and pathological response in the breast to NACT does not accurately predict axillary response. The axilla and the breast should be viewed and assessed as two separate entities for treatment plans.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Linfonodos/diagnóstico por imagem , Adulto , Idoso , Axila , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Excisão de Linfonodo , Linfonodos/patologia , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Terapia Neoadjuvante , Neoplasia Residual , Valor Preditivo dos Testes , Estudos Retrospectivos , Biópsia de Linfonodo Sentinela , Resultado do Tratamento , Ultrassonografia
9.
Obstet Med ; 12(2): 57-65, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31217809

RESUMO

The role of fathers prior to conception, during pregnancy, and in the post-partum period has generally not been a key consideration for Obstetric Physicians. However, this view may need challenging. This paper outlines the key importance of fathers in all phases of obstetric medical care. We review the contribution of paternal factors such as genetics, health, and lifestyle to fetal development, pregnancy complications, and maternal and neonatal wellbeing. The role of fathers in complex care decisions during pregnancy is also reviewed. Postpartum, fathers have a substantial role in shaping the future of the family unit through encouraging breastfeeding and creating a supportive environment for motherhood. This review proposes areas for future research and recommends an evidence-based change in practice in obstetric medicine that focuses on recognizing the role of fathers in the pregnancy journey.

10.
J Med Microbiol ; 68(6): 848-859, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31136294

RESUMO

PURPOSE: The purpose of the present study was to determine the relatedness of Staphylococcus aureus strains successively isolated over a 7-day period from a single bacteraemic patient undergoing antibiotic treatment with vancomycin. METHODS: The S. aureus strains had been isolated and sequenced previously. Antibiotic susceptibility testing, population analysis profiling, and lysostaphin sensitivity and phagocytic killing assays were used to characterize these clonal isolates. RESULTS: The seven isolates (MEH1-MEH7) were determined to belong to a common multilocus sequence type (MLST) and spa type. Within the third and fifth day of vancomycin treatment, mutations were observed in the vraS and rpsU genes, respectively. Population analysis profiles revealed that the initial isolate (MEH1) was vancomycin-susceptible S. aureus (VSSA), while those isolated on day 7 were mostly heteroresistant vancomycin-intermediate S. aureus (hVISA). Supporting these findings, MEH7 was also observed to be slower in growth, to have an increase in cell wall width and to have reduced sensitivity to lysostaphin, all characteristics of VISA and hVISA strains. In addition, MEH7, although phagocytosed at numbers comparable to the initial isolate, MEH1, survived in higher numbers in RAW 264.7 macrophages. Macrophages infected with MEH7 also released more TNF-α and IFN-1ß. CONCLUSION: We report an increasing resistance to vancomycin coupled with daptomycin that occurred within approximately 3 days of receiving vancomycin and steadily increased until the infection was cleared with an alternative antibiotic therapy. This study reiterates the need for rapid, efficient and accurate detection of hVISA and VISA infections, especially in high-bacterial load, metastatic infections like bacteraemia.


Assuntos
Antibacterianos/farmacologia , Macrófagos/fisiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/genética , Resistência a Vancomicina/genética , Vancomicina/farmacologia , Idoso , Bacteriemia/microbiologia , Parede Celular/efeitos dos fármacos , Daptomicina/farmacologia , Humanos , Lisostafina/farmacologia , Masculino , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Mutação , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/virologia
11.
J Child Orthop ; 13(2): 167-171, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30996741

RESUMO

PURPOSE: The ability to monitor and study developmental dysplasia of the hip (DDH) requires validated radiographic outcome measures. The sourcil method of acetabular index measurement (AI-S) has not yet been shown to be a reliable measure of acetabular dysplasia in a DDH population, despite its widespread use. The aims of this study were to test the reliability of the AI-S method in a DDH population, and to compare the reliability of the AI-S method with that of the classic lateral edge method (AI-L). METHODS: From an institutional database, standardized anteroposterior hip radiographs were obtained from a cohort of 35 female patients (70 hips) at two and five years of age who had been treated nonoperatively for DDH. Three observers independently measured the acetabular index using the AI-L and AI-S methods on all 70 hips at two time points, four weeks apart. RESULTS: The inter-rater reliability intraclass correlation coefficient (ICC) for the AI-L and AI-S methods was between good and excellent at 0.94 (confidence interval (CI) 0.89 to 0.96) and 0.91 (CI 0.87 to 0.94), respectively. The ICCs for intra-rater reliability for the AI-L method were excellent at 0.93 (CI 0.90 to 0.95), 0.95 (CI 0.93 to 0.97) and 0.95 (CI 0.94 to 0.97) for raters 1, 2 and 3, respectively. The ICCs for intra-rater reliability for the AI-S method were between good and excellent at 0.91 (CI 0.87 to 0.93), 0.93 (CI 0.90 to 0.95) and 0.90 (CI 0.86 to 0.93) for raters 1, 2 and 3 respectively. CONCLUSION: Both AI-S and AI-L methods are equally reliable radiographic measures of DDH. LEVEL OF EVIDENCE: Level III (diagnostic).

12.
Eur Rev Med Pharmacol Sci ; 22(21): 7333-7342, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30468478

RESUMO

OBJECTIVE: The main goal of oncoplastic breast surgery (OBS) is to optimize cosmetic outcomes and reduce patient morbidity, while still providing an oncologically-safe surgical outcome and extending the target population of conservative surgery. Although the growing number of reported experiences with oncoplastic surgery, few studies account for the long-term outcomes. PATIENTS AND METHODS: Between January 2000 and December 2010, 1024 consecutive oncoplastic surgeries were performed and prospectively included in a database. Demographic data, histological and oncological evaluation and surgical complications were recorded. The role of tumor and patients' characteristics on the development of local recurrence and metastases were assessed by multivariate analysis. RESULTS: Median follow up was 74.2 months. The average age of patients was 56.24. In 869 patients (84.9%) an invasive tumor and in 155 (15.1%) an in situ tumor (11% DCIS and 4% LIN) was found. The average size of the tumor was 24.5 mm. A positive margin presented in 67 (6.5%) patients. Forty patients (50%) underwent re-excision and 39 (49.4%) underwent mastectomy. The overall breast conservation rate was 96.2%. Reported complications were: 17 wound infections (1.7%); 106 hematomas (10.4%); 94 lymphorrheas (9.2%), 48 partial wound dehiscence (4.7%). Local recurrences (LR) were observed in 49 patients (4.7%). The risk of local recurrence was significantly higher in the group of patients with lymphovascular invasion and with high grade (G) (p < 0.05). 52 (5.07%) distant metastases were reported and the related risk was significantly higher in the group of patients with lymphovascular invasion and with negative receptors (p < 0.05). CONCLUSIONS: Oncoplastic surgery provides an acceptable oncological long-term outcome and can be used to treat with conservative surgery also a selected population of patients who would had otherwise undergone mastectomy in the past.


Assuntos
Neoplasias da Mama/cirurgia , Mastectomia Segmentar , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Tomada de Decisão Clínica , Bases de Dados Factuais , Progressão da Doença , Feminino , Humanos , Margens de Excisão , Mastectomia Segmentar/efeitos adversos , Mastectomia Segmentar/mortalidade , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia , Seleção de Pacientes , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Carga Tumoral
13.
Eur Rev Med Pharmacol Sci ; 22(15): 4768-4777, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30070312

RESUMO

OBJECTIVE: Autologous fat transfer (AFT) is commonly used to treat implant palpability and prevent fibrosis and thinning in mastectomy skin flaps. A major limit to this procedure is volume retention over time, leading to the introduction of fat enrichment with stromal vascular fraction (SVF+AFT). Oncological concerns have been raised over the injection of an increased concentration of progenitors cells (ASCs) in the SVF. The aim of the study is to evaluate the long-term cancer recurrence risk of SVF+AFT cases compared to AFT, in patients undergoing Nipple Sparing Mastectomy (NSM). PATIENTS AND METHODS: A prospective study was designed to compare three groups of patients undergoing NSM followed by SVF+AFT, AFT or none (control group), after a two-stage breast reconstruction. Patients were strictly followed-up for at least 5-years from the second stage reconstructive procedure. Loco-regional and systemic recurrence rate were evaluated over time as the primary outcome. Logistic regression was used to investigate which factors were associated with recurrence events and independent variables of interest were: surgical technique, age above 50 years old, lympho-vascular invasion, oncological stage, adjuvant or neoadjuvant chemotherapy, adjuvant radiotherapy and adjuvant hormone therapy. RESULTS: 41 women were included in G1 (SVF+AFT), 64 in G2 (AFT), and 64 in G3 (control group). Loco-regional recurrence rate was 2.4% for G1, 4.7% for G2, and 1.6% for G3. Systemic recurrence was 7.3%, 3.1%, and 3.1%, respectively. Among the variables included, there were no significant risk factors influencing a recurrence event, either loco-regional or systemic. In particular, SVF+AFT (G1) did not increase the oncological recurrence. CONCLUSIONS: Our data suggest that both centrifuged and SVF-enhanced fat transfer have a similar safety level in comparison to patients who did not undergo fat grafting in breast reconstruction after NSM.


Assuntos
Tecido Adiposo/transplante , Neoplasias da Mama/cirurgia , Mamoplastia/métodos , Mastectomia , Adulto , Neoplasias da Mama/patologia , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Tratamentos com Preservação do Órgão/métodos , Estudos Prospectivos , Transplante Autólogo
14.
Breast ; 39: 8-13, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29455110

RESUMO

BACKGROUND: Although demand for prophylactic mastectomy is increasing over time among women at a high risk for breast cancer, there is a paucity of studies on long term patient-reported outcomes after this procedure. METHODS: Between January 2011 and January 2015, 46 patients documented BRCA1/2 mutation carriers, eligible for prophylactic nipple-sparing mastectomy (NSM) and immediate breast prosthetic reconstruction were registered at our Institution. Patients underwent NSM and subcutaneous reconstruction with implant covered by a titanium-coated polypropylene mesh (TiLoop®). The BREAST-Q questionnaire was given to patients prior to surgery and at 1 and 2 years follow-up points. Capsular contracture was evaluated by Baker scale. Surgical outcomes along with the changes in BREAST-Q score were analyzed over time. RESULTS: Complications were reported in only one case and after two years the capsular contracture rates were acceptable (grade I: 65,2%; grade II: 32,6%; grade III 2,2%). At one year and two year follow-ups patients reported high rates in the measures of overall satisfaction with breasts (72,5 and 73,7 respectively), psychosocial well-being (78,4 and 78,6), sexual well-being (58,8 and 59,4), physical well-being (77,6 and 80,6) and overall satisfaction with outcome (75,7 and 79,7). A statistically significant increase in all BREAST-domains from the preoperative to the postoperative period was reported at one and two years follow-ups (p < 0,05). CONCLUSION: Following bilateral prophylactic NSM and immediate subcutaneous reconstruction with TiLoop®, patients demonstrated high levels of satisfaction and quality of life as measured by BREAST-Q. 2-years outcomes confirmed high patient comfort with increased scores from the preoperative baseline level.


Assuntos
Neoplasias da Mama/prevenção & controle , Mamoplastia/instrumentação , Mastectomia Segmentar/métodos , Mamilos/cirurgia , Tratamentos com Preservação do Órgão/métodos , Mastectomia Profilática/métodos , Adulto , Idoso , Implantes de Mama , Neoplasias da Mama/genética , Neoplasias da Mama/psicologia , Feminino , Genes BRCA1 , Genes BRCA2 , Humanos , Mamoplastia/métodos , Mamoplastia/psicologia , Mastectomia Segmentar/psicologia , Pessoa de Meia-Idade , Mutação , Medidas de Resultados Relatados pelo Paciente , Satisfação do Paciente , Mastectomia Profilática/psicologia , Estudos Prospectivos , Qualidade de Vida , Telas Cirúrgicas , Resultado do Tratamento , Adulto Jovem
15.
Anaesthesia ; 73(4): 438-443, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29327341

RESUMO

Avoidance of general anaesthesia for breast surgery may be because of clinical reasons or patient choice. There is emerging evidence that the use of regional anaesthesia and the avoidance of volatile anaesthetics and opioid analgesia may have beneficial effects on oncological outcomes. We conducted a prospective observational case series of 16 breast cancer surgeries performed under thoracic paravertebral plus pectoral nerve block with propofol sedation to demonstrate feasibility of technique, patient acceptability and surgeon satisfaction. Fifteen out of 16 cases were successfully completed under sedation and regional anaesthesia, with one conversion to general anaesthesia. Eleven out of 16 cases required low-dose intra-operative opioid analgesia. Out of the 15 surgical procedures completed under regional anaesthesia with sedation, all patients experienced either no or minimal intra-operative pain, and all would choose this anaesthetic technique again. Surgeon-reported operating conditions were 'indistinguishable from general anaesthesia' in most cases, and surgeons were 'extremely satisfied' or 'satisfied' with the technique after every procedure. Combined thoracic paravertebral plus pectoral nerve block with intra-operative sedation is a feasible technique for breast surgery.


Assuntos
Neoplasias da Mama/cirurgia , Sedação Consciente/métodos , Mastectomia/métodos , Bloqueio Nervoso/métodos , Idoso , Anestésicos Combinados/administração & dosagem , Anestésicos Locais/administração & dosagem , Atitude do Pessoal de Saúde , Esquema de Medicação , Estudos de Viabilidade , Feminino , Humanos , Hipnóticos e Sedativos/administração & dosagem , Levobupivacaína/administração & dosagem , Lidocaína/administração & dosagem , Pessoa de Meia-Idade , Satisfação do Paciente , Propofol/administração & dosagem , Estudos Prospectivos , Nervos Torácicos , Vértebras Torácicas
16.
Genome Announc ; 5(23)2017 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-28596388

RESUMO

Staphylococcus aureus strains MEH1 and MEH7 were successively isolated from the blood of a patient with recurrent bacteremia. The submitted draft genomes of strains MEH1 and MEH7 are 2,914,972 and 2,911,704 bp, respectively.

17.
Leukemia ; 31(11): 2479-2490, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28321121

RESUMO

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematopoietic neoplasm resulting from the malignant transformation of T-cell progenitors, and comprises ~15% and 25% of pediatric and adult ALL cases, respectively. It is well-established that activating NOTCH1 mutations are the major genetic lesions driving T-ALL in most patients, but efforts to develop targeted therapies against this pathway have produced limited success in decreasing leukemic burden and come with significant clinical side effects. A finer detailed understanding of the genetic and molecular mechanisms underlying T-ALL is required identify patients at increased risk for treatment failure and the development of precision medicine strategies. Generation of genetic models that more accurately reflect the normal developmental history of T-ALL are necessary to identify new avenues for treatment. The DNA methyltransferase enzyme DNMT3A is also recurrently mutated in T-ALL patients, and we show here that inactivation of Dnmt3a combined with Notch1 gain-of-function leads to an aggressive T-ALL in mouse models. Moreover, conditional inactivation of Dnmt3a in mouse hematopoietic cells leads to an accumulation of immature progenitors in the thymus, which are less apoptotic. These data demonstrate that Dnmt3a is required for normal T-cell development, and acts as a T-ALL tumor suppressor.


Assuntos
DNA (Citosina-5-)-Metiltransferases/fisiologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Linfócitos T/citologia , Animais , Apoptose , Linhagem Celular , DNA (Citosina-5-)-Metiltransferases/genética , Metilação de DNA , DNA Metiltransferase 3A , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
18.
Am J Surg ; 213(3): 516-520, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27890332

RESUMO

BACKGROUND: Examine effects of hospital transfer into a quaternary care center on surgical outcomes of intestinal atresia. METHODS: Children <1 yo principally diagnosed with intestinal atresia were identified using the Kids' Inpatient Database (2012). Exposure variable was patient transfer status. Outcomes measured were inpatient mortality, hospital length of stay (LOS) and discharge status. Linearized standard errors, design-based F tests, and multivariable logistic regression were performed. RESULTS: 1672 weighted discharges represented a national cohort. The highest income group and those with private insurance had significantly lower odds of transfer (OR:0.53 and 0.74, p < 0.05). Rural patients had significantly higher transfer rates (OR: 2.73, p < 0.05). Multivariate analysis revealed no difference in mortality (OR:0.71, p = 0.464) or non-home discharge (OR: 0.79, p = 0.166), but showed prolonged LOS (OR:1.79, p < 0.05) amongst transferred patients. CONCLUSIONS: Significant differences in hospital LOS and treatment access reveal a potential healthcare gap. Post-acute care resources should be improved for transferred patients.


Assuntos
Atresia Intestinal/mortalidade , Atresia Intestinal/cirurgia , Transferência de Pacientes , Feminino , Mortalidade Hospitalar , Humanos , Renda , Lactente , Seguro Saúde , Tempo de Internação/estatística & dados numéricos , Masculino , Análise Multivariada , Setor Privado , População Rural , Estados Unidos/epidemiologia
19.
PLoS One ; 11(12): e0167435, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27935974

RESUMO

Osteopontin (OPN) promotes hepatic fibrosis, and developing therapies targeting OPN expression in settings of hepatic injury holds promise. The polyphenol epigallocatechin-3-gallate (EGCG), found in high concentrations in green tea, downregulates OPN expression through OPN mRNA degradation, but the mechanism is unknown. Previous work has shown that microRNAs can decrease OPN mRNA levels, and other studies have shown that EGCG modulates the expression of multiple microRNAs. In our study, we first demonstrated that OPN induces hepatic stellate cells to transform into an activated state. We then identified three microRNAs which target OPN mRNA: miR-181a, miR-10b, and miR-221. In vitro results show that EGCG upregulates all three microRNAs, and all three microRNAs are capable of down regulating OPN mRNA when administered alone. Interestingly, only miR-221 is necessary for EGCG-mediated OPN mRNA degradation and miR-221 inhibition reduces the effects of EGCG on cell function. In vivo experiments show that thioacetamide (TAA)-induced cell cytotoxicity upregulates OPN expression; treatment with EGCG blocks the effects of TAA. Furthermore, chronic treatment of EGCG in vivo upregulates all three microRNAs equally, suggesting that in more chronic treatment all three microRNAs are involved in modulating OPN expression. We conclude that in in vitro and in vivo models of TAA-induced hepatic fibrosis, EGCG inhibits OPN-dependent injury and fibrosis. EGCG works primarily by upregulating miR-221 to accelerate OPN degradation. EGCG may therefore have utility as a protective agent in settings of liver injury.


Assuntos
Antioxidantes/uso terapêutico , Catequina/análogos & derivados , Cirrose Hepática/tratamento farmacológico , MicroRNAs/genética , Regulação para Cima/efeitos dos fármacos , Animais , Antioxidantes/química , Catequina/química , Catequina/uso terapêutico , Linhagem Celular , Células Hep G2 , Células Estreladas do Fígado/efeitos dos fármacos , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Humanos , Cirrose Hepática/genética , Cirrose Hepática/patologia , Masculino , Osteopontina/metabolismo , Ratos Sprague-Dawley , Chá/química
20.
Clin Transl Imaging ; 4(5): 353-366, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27738626

RESUMO

Cerenkov luminescence imaging (CLI) is a novel molecular optical imaging technique based on the detection of optical Cerenkov photons emitted by positron emission tomography (PET) imaging agents. The ability to use clinically approved tumour-targeted tracers in combination with small-sized imaging equipment makes CLI a particularly interesting technique for image-guided cancer surgery. The past few years have witnessed a rapid increase in proof-of-concept preclinical studies in this field, and several clinical trials are currently underway. This article provides an overview of the basic principles of Cerenkov radiation and outlines the challenges of CLI-guided surgery for clinical use. The preclinical and clinical trial literature is examined including applications focussed on image-guided lymph node detection and Cerenkov luminescence endoscopy, and the ongoing clinical studies and technological developments are highlighted. By intraoperatively guiding the oncosurgeon towards more accurate and complete resections, CLI has the potential to transform current surgical practice, and improve oncological and cosmetic outcomes for patients.

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