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1.
J Cancer Educ ; 39(2): 180-185, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38049567

RESUMO

Family caregivers (FCs) of a patient with chronic lymphocytic leukemia (CLL) can encounter unpredictable challenges and care demands. They can experience high levels of burden, a loss of self-care, and poor quality of life. Their receipt of social support and ability to communicate with clinicians may impact their burden. FCs would benefit from educational resources that teach them communication skills central to their ability to obtain the support they need-support that is imperative to reducing burden. To better target psychosocial educational interventions focused on social support and communication skills, we aimed to explore the relationship between social support, sources of support, and burden; the relationship between FCs' clinical communication and their perceptions of support and burden; and any unmet support needs. A total of 575 CLL FCs completed an online survey of validated scales about social support, burden, and clinical communication, as well as an open-ended item in which they reported any unmet support needs. Statistical analyses showed that FCs who perceived they were more supported reported less burden, and female FCs reported more burden than males. Support from family, friends, and professionals collectively contributed to FCs' support. FCs who perceived they had stronger communication skills with their loved one's clinicians reported more social support. FCs identified six areas of unmet support needs: financial, emotional, informational, instrumental, peer, and communication support. Collectively, findings show that increased social support can reduce FCs' burden and qualitative findings provide a roadmap of social support domains to target that could potentially improve the caregiving experience.


Assuntos
Cuidadores , Leucemia Linfocítica Crônica de Células B , Masculino , Humanos , Feminino , Cuidadores/psicologia , Sobrecarga do Cuidador , Leucemia Linfocítica Crônica de Células B/terapia , Qualidade de Vida/psicologia , Apoio Social
2.
J Physiol ; 601(17): 3961-3974, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37470310

RESUMO

High gestational weight gain (GWG) is a cardiovascular risk factor and may disturb neonatal endothelial function. Long non-coding RNAs (lncRNAs) regulate gene expression epigenetically and can modulate endothelial function. Endothelial colony forming cells (ECFCs), circulating endothelial precursors, are a recruitable source of endothelial cells and sustain endothelial function, vascular growth and repair. We here investigated whether higher GWG affects neonatal ECFC function and elucidated the role of lncRNAs herein. Wound healing of umbilical cord blood-derived ECFCs after pregnancies with GWG <13 kg versus >13 kg was determined in a scratch assay and based on monolayer impedance after electric wounding (electric cell-substrate impedance sensing, ECIS). LncRNA expression was analysed by RNA sequencing. The function of killer cell lectin-like receptor K1 antisense RNA (KLRK1-AS1) was investigated after siRNA-based knockdown. Closure of the scratch was delayed by 25% (P = 0.041) in the higher GWG group and correlated inversely with GWG (R = -0.538, P = 0.012) in all subjects (n = 22). Similarly, recovery of the monolayer barrier after electric wounding was delayed (-11% after 20 h; P = 0.014; n = 15). Several lncRNAs correlated with maternal GWG, the most significant one being KLRK1-AS1 (log2 fold change = -0.135, P < 0.001, n = 35). KLRK1-AS1 knockdown (n = 4) reduced barrier recovery after electric wounding by 21% (P = 0.029) and KLRK1-AS1 expression correlated with the time required for wound healing for both scratch (R = 0.447, P = 0.033) and impedance-based assay (R = 0.629, P = 0.014). Higher GWG reduces wound healing of neonatal ECFCs, and lower levels of the lncRNA KLRK1-AS1 may underlie this. KEY POINTS: Maternal cardiovascular risk factors such as diabetes, obesity and smoking in pregnancy disturb fetal endothelial function, and we here investigated whether also high gestational weight gain (GWG) has an impact on fetal endothelial cells. Circulating endothelial progenitor cells (endothelial colony forming cells, ECFCs) are highly abundant in the neonatal blood stream and serve as a circulating pool for vascular growth and repair. We revealed that higher GWG delays wound healing capacity of ECFCs in vitro. We identified the regulatory RNA lncRNA KLRK1-AS1 as a link between GWG and delayed ECFC wound healing. Our data show that high GWG, independent of pre-pregnancy BMI, affects neonatal ECFC function.


Assuntos
Células Progenitoras Endoteliais , Ganho de Peso na Gestação , RNA Longo não Codificante , Gravidez , Recém-Nascido , Feminino , Humanos , RNA Longo não Codificante/genética , Células Cultivadas , Cicatrização , Subfamília K de Receptores Semelhantes a Lectina de Células NK
3.
J Cancer Educ ; 38(5): 1562-1570, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37097340

RESUMO

Cancer clinical trials (CCTs) are imperative for advancing cancer treatment and providing treatment options for patients; however, many barriers exist to offering and enrolling interested and eligible patients. It is crucial to equip patients and caregivers with communication skills that help them initiate and navigate conversations about the option of receiving treatment within a CCT. The aim was to assess the acceptability and impact of a novel video training for patients and caregivers that models strategies for patient-provider communication using the PACES method of healthcare communication and provides information about CCTs. The three-module training was implemented among blood cancer patients and caregivers. Using a single-arm pre-post study design, self-report surveys assessed changes in knowledge, confidence in using the PACES method, and perceived importance of, confidence in, and behavioral intention related to talking with doctors about CCTs. The Patient Report of Communication Behavior (PRCB) scale was administered. Among 192 participants, post-intervention knowledge gains were evident (p < 0.001). Confidence, importance, and likelihood to communicate about CCTs and confidence about using PACES also increased (p < 0.001); females who had never previously spoken to a provider about CCTs demonstrated greater impact (p = 0.045) than other genders. PRCB mean scores increased among patients 65+ who had never spoken to a provider about CCTs, with greater change than patients <65 (p = 0.001). This educational intervention for patients and caregivers increased knowledge about CCTs, skills in communicating with doctors about care and CCTs, and readiness to initiate conversations about CCTs as a potential treatment option.


Assuntos
Neoplasias Hematológicas , Neoplasias , Médicos , Humanos , Masculino , Feminino , Cuidadores/educação , Neoplasias/tratamento farmacológico , Comunicação
4.
Palliat Support Care ; : 1-7, 2023 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-37606295

RESUMO

OBJECTIVES: This study investigated the challenges and support needs of adults aged 75 and older during and after treatment for a blood cancer to aid targeted supportive resource development. METHODS: Adults aged 75 and older with a blood cancer participated in in-depth, semi-structured interviews about challenges and unmet support needs. Participants recruited through The Leukemia & Lymphoma Society were (1) in treatment or previously in treatment for a blood cancer at age 75 or older and (2) living in the United States or its territories. A thematic analysis was conducted with findings compared between 2 groups: (1) chronic -living with a chronic blood cancer; (2) acute -living with an acute blood cancer or both an acute and chronic blood cancer. RESULTS: Participants (n = 50) ranged from 75 to 91 years old. Both groups described similar experiences and identified 5 challenges and support needs: (1) socioemotional impact, (2) activities of daily living and instrumental activities of daily living (ADLs/iADLs), (3) uncertainty management, (4) treatment-related stressors, and (5) COVID-19-related strain. Properties for these themes illustrate challenges and support needs, with some differences between groups. For instance, those living with a chronic blood cancer highlighted financial strain with treatment-related stressors, while those with an acute blood cancer focused more on iADLs. SIGNIFICANCE OF RESULTS: Findings inform an agenda for targeted resource development for older adults with a blood cancer nearing the end of the life span. Results demonstrate the need for supportive services and family communication interventions to help patients manage iADLs and navigate socioemotional needs and challenges.

5.
Pediatr Res ; 92(6): 1590-1597, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35184136

RESUMO

BACKGROUND: Maternal cardiovascular risk factors (CVRF) in pregnancy, i.e., obesity and hyperglycemia, transmit to the fetus and affect placental and fetal endothelial function. Moreover, a sex dimorphism in endothelial function and susceptibility towards CVRF exists already in utero. Endothelial colony-forming cells (ECFC) are circulating endothelial progenitors highly present in neonatal cord blood and sensitive to CVRF. This study investigated whether fetal sex or subtle maternal metabolic changes within healthy range alter fetal ECFC outgrowth. METHODS: Outgrowth of ECFC from cord blood of male (n = 31) and female (n = 26) neonates was analyzed after healthy pregnancies and related to fetal sex and maternal metabolic parameters. RESULTS: Male ECFC grew out earlier (-20.57% days; p = 0.031) than female. Although all women were non-diabetic, higher levels of fasting plasma glucose (FPG) at midpregnancy increased the time required for colony outgrowth (OR: 1.019; p = 0.030), which, after stratifying for fetal sex, was significant only in the males. Gestational weight gain and BMI did not affect outgrowth. Colony number was unchanged by all parameters. CONCLUSIONS: Fetal sex and maternal FPG within normal range alter ECFC function in utero. A role of ECFC in postnatal angiogenesis and vasculogenesis has been suggested, which may be affected by altered outgrowth dynamics. IMPACT: This study is the first to report that a sexual dimorphism exists in ECFC function, as cells of female progeny require a longer period of time until colony outgrowth than ECFC of male progeny. Our data show that ECFC function is highly sensitive and affected by maternal glucose levels even in a normal, non-diabetic range. Our data raise the question of whether maternal plasma glucose in pregnancy should be considered to play a critical role even in the non-diabetic setting.


Assuntos
Células Progenitoras Endoteliais , Recém-Nascido , Humanos , Feminino , Masculino , Gravidez , Glucose , Sangue Fetal , Glicemia/metabolismo , Células Cultivadas , Placenta , Jejum
6.
Psychooncology ; 31(7): 1212-1220, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35218278

RESUMO

OBJECTIVE: We examined the effects of the family communication environment (conversation orientation) on adult child caregivers' burden and clinical interactions and if the effects are mediated by openness to communicate about cancer, avoidant cancer communication, and social support (SS). METHOD: Caregivers of a parent diagnosed with a blood cancer (N = 121) completed an online survey of validated measures of conversation orientation (i.e., the extent to which families openly communicate), SS, cancer openness, avoidance, caregiver burden, clinical communication skills, and quality of clinical interactions (QCI). RESULTS: Conversation orientation had significant indirect effects on caregiver burden, mediated by SS (ß = -0.11, p < 0.001), as well as cancer openness and avoidance (ß = -0.07, p < 0.001). Conversation orientation also had significant indirect effects on caregivers' communication skills with a parent's clinician, mediated by avoidance (ß = 0.08, p < 0.01) and SS (ß = 0.06, p < 0.001). Finally, conversation orientation had significant indirect effects on caregivers' QCI mediated by avoidance (ß = 0.71, p < 0.05). CONCLUSIONS: Adult child caregivers whose families communicate more openly exhibit less caregiver burden and report better clinical interaction skills and perceived quality of the clinical interaction. Avoidance emerged as a key mediating factor. Caregivers from less open communication environments may benefit from interventions that help them navigate challenging but critical caregiving conversations.


Assuntos
Sobrecarga do Cuidador , Comunicação , Neoplasias Hematológicas , Relações Interpessoais , Adulto , Filhos Adultos , Cuidadores , Família , Neoplasias Hematológicas/terapia , Humanos , Apoio Social , Inquéritos e Questionários
7.
Future Oncol ; 18(17): 2075-2085, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35209721

RESUMO

Aim: We examined the preferences of adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) for benefits and risks of tyrosine kinase inhibitors combined with chemotherapy for first-line treatment. Methods: In a discrete choice experiment, 201 patients chose between hypothetical treatment alternatives with varied levels of remission duration and overall survival (OS), and risks of major cardiovascular (CV) events and myelosuppression. Results: Although OS was the most important attribute to patients with Ph+ ALL, they were willing to tolerate a 2.9% increase in CV risk for 1 additional month of OS. Older patients (>59 years) and patients not in remission were less likely to tolerate increased CV risk. Conclusion: Preferences and risk tolerance varied between patients, highlighting the importance of shared decision making when selecting treatments for Ph+ ALL.


Treatments differ in their potential benefits and side effects they may come with. Patients should be involved in deciding which treatments they receive. This is because patients may have different views than physicians on how the benefits and side effects of treatment would affect their quality of life. Additionally, patients may have different risk tolerances. This study shows how patients with a form of leukemia valued survival benefits and side effects of treatments, and the trade-offs that they were willing to make between these. On average, longer survival had most value to patients. They were willing to accept a higher risk of a major cardiovascular side effect (e.g., having a stroke) if the treatment would allow them to live longer. However, not all patients had the same opinion, and some groups of patients were less willing to accept risks to receive longer survival. By involving patients in treatment decisions, we can help ensure they receive treatments that match their personal preferences.


Assuntos
Preferência do Paciente , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adulto , Humanos , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética
8.
Palliat Support Care ; 20(1): 22-29, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-33890563

RESUMO

OBJECTIVES: The study examined the diagnosis experience of midlife family caregivers of a patient with a blood cancer, exploring similarities and differences between parent caregivers and adult-child caregivers. METHODS: Participants were between 30 and 65 years old and were family caregivers of a living patient with acute myeloid leukemia, acute lymphoblastic leukemia, or lymphoma. We conducted semi-structured interviews with parent caregivers (n = 20) and adult-child caregivers (n = 19) and a thematic analysis of the interview data. RESULTS: Both types of caregivers report the patient experiencing (1) mis- and missed diagnosis (facing delayed diagnosis or treatment and having symptoms dismissed or overlooked) and (2) emotional distress (being in shock and survival mode, struggling with uncertainty, and confronting mortality). Adult-child caregivers also experienced relational shifts in assuming control of their parent's care, sometimes despite geographic distance, and struggled to distribute the care burden among family members. SIGNIFICANCE OF RESULTS: Differences between the caregivers' experiences emerged based on the relational role and the patient's place in the lifespan. Findings can be used to inform the development of support resources to address the needs of each group.


Assuntos
Cuidadores , Neoplasias , Adulto , Filhos Adultos , Idoso , Cuidadores/psicologia , Família/psicologia , Humanos , Longevidade , Pessoa de Meia-Idade , Incerteza
9.
Histochem Cell Biol ; 156(4): 363-375, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34169358

RESUMO

Human umbilical vein and artery endothelial cells (HUVEC; HUAEC), placental endothelial cells (fpAEC), and endothelial colony-forming cells (ECFC) from cord blood are a widely used model for researching placental vascular development, fetal and placental endothelial function, and the effect of adverse conditions in pregnancy thereon. However, placental vascular development and angiogenesis start in the first weeks of gestation, and adverse conditions in pregnancy may also affect endothelial function before term, suggesting that endothelial cells from early pregnancy may respond differently. Thus, we established a novel, gentle flow-through method to isolate pure human umbilical endothelial cells from first trimester (FTUEC). FTUEC were characterized and their phenotype was compared to the umbilical endothelium in situ as well as to other fetal endothelial cell models from term of gestation, i.e. HUVEC, fpAEC, ECFC. FTUEC possess a CD34-positive, juvenile endothelial phenotype, and can be expanded and passaged. We regard FTUEC as a valuable tool to study developmental processes as well as the effect of adverse insults in pregnancy in vitro.


Assuntos
Células Endoteliais/citologia , Primeiro Trimestre da Gravidez/sangue , Feminino , Citometria de Fluxo , Humanos , Gravidez
10.
Support Care Cancer ; 29(6): 3069-3076, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33051829

RESUMO

PURPOSE: Research on the impact of family cancer caregiving is primarily dyadic in focus. How caregiving affects the larger family system is less understood, yet knowing this is vital to developing supportive resources for caregivers, patients, and their families. To better understand how blood cancer caregiving impacts the family system, we explored the experiences of adult child caregivers of diagnosed parents and parent caregivers of diagnosed children. METHODS: We conducted semi-structured interviews with 39 midlife parent and adult child caregivers of patients with leukemia or lymphoma. Using a family systems theory lens, we conducted a thematic analysis using the constant comparative method to identify how caregiving impacts the larger family system. RESULTS: Caregivers ranged from age 30 to 64 (M = 43). They described four ways that caregiving impacted themselves and the larger family system: (1) disruption of home life, (2) emotional (dis)connection, (3) juggling competing roles, and (4) developing resiliency and intimacy. Perspectives within each category differed based on their relational role to the patient or in the broader family. CONCLUSIONS: Themes identify ways to provide support to both caregiver types. Support care resources could help families navigate gains and losses impacting the family system after a blood cancer diagnosis. Both caregiver types described experiencing (and/or their family experiencing) a loss in relational connection, feeling alone, and members distancing themselves. Both caregiver types also described gains in family functioning, like strengthened bonds and togetherness. Findings validate the need for family-centered support with key areas to address for healthy family functioning.


Assuntos
Cuidadores/psicologia , Família/psicologia , Neoplasias Hematológicas/psicologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
11.
Int J Mol Sci ; 22(24)2021 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-34948175

RESUMO

Gestational diabetes (GDM) and preeclampsia (PE) are associated with fetal hyperglycemia, fetal hypoxia, or both. These adverse conditions may compromise fetal and placental endothelial cells. In fact, GDM and PE affect feto-placental endothelial function and also program endothelial function and cardiovascular disease risk of the offspring in the long-term. MicroRNAs are short, non-coding RNAs that regulate protein translation and fine tune biological processes. A group of microRNAs termed angiomiRs is particularly involved in the regulation of endothelial function. We hypothesized that transient hyperglycemia and hypoxia may alter angiomiR expression in feto-placental endothelial cells (fpEC). Thus, we isolated primary fpEC after normal, uncomplicated pregnancy, and induced hyperglycemia (25 mM) and hypoxia (6.5%) for 72 h, followed by reversal to normal conditions for another 72 h. Current vs. transient effects on angiomiR profiles were analyzed by RT-qPCR and subjected to miRNA pathway analyses using DIANA miRPath, MIENTURNET and miRPathDB. Both current and transient hypoxia affected angiomiR profile stronger than current and transient hyperglycemia. Both stimuli altered more angiomiRs transiently, i.e., followed by 72 h culture at control conditions. Pathway analysis revealed that hypoxia significantly altered the pathway 'Proteoglycans in cancer'. Transient hypoxia specifically affected miRNAs related to 'adherens junction'. Our data reveal that hyperglycemia and hypoxia induce memory effects on angiomiR expression in fpEC. Such memory effects may contribute to long-term adaption and maladaption to hyperglycemia and hypoxia.


Assuntos
MicroRNAs/genética , Placenta/citologia , Placentação/genética , Adulto , Diabetes Gestacional/metabolismo , Células Endoteliais/metabolismo , Feminino , Feto/metabolismo , Expressão Gênica/genética , Humanos , Hiperglicemia/genética , Hiperglicemia/metabolismo , Hipóxia/genética , Hipóxia/metabolismo , Neovascularização Fisiológica , Placenta/metabolismo , Pré-Eclâmpsia/metabolismo , Gravidez , Cultura Primária de Células , Transcriptoma/genética
12.
J Cancer Educ ; 36(3): 538-546, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-31820416

RESUMO

Access to reliable, up-to-date information and resources can assist individuals managing and living with cancer. The Leukemia & Lymphoma Society, through its Information Resource Center, provides personalized information and support to individuals affected by blood cancer. To examine its value and impact, we conducted qualitative interviews (n = 18) and an online survey of patients and caregivers (N = 515) after they talked with an Information Resource Center Information Specialist by phone, with a follow-up survey about 6 months later. Respondents most commonly contacted the Information Resource Center to get referrals to support programs (40.4%) and to obtain information about getting a second opinion (36.5%) and financial assistance (36.2%). After talking with an Information Specialist, respondents felt more hopeful (85.9%), more confident in managing care (82.9%), and more knowledgeable about their diagnosis (49.5%) and financial resources (42.4%). After speaking with an Information Specialist, respondents changed how they advocated for themselves/loved one (23.8%), changed how they communicated with doctors/other providers and family/friends (both 15.9%), received financial assistance (22.2%), and took other actions. Among respondents who took actions, most said that the conversation(s) had positively impacted the action. Respondents who spoke with an Information Specialist more than once were more likely to report positive impacts, including changing how they advocate for themselves/loved one and communicate with providers (both p < 0.05). Respondents diagnosed more recently were also more likely to report positive impact, including changing the way they communicate with providers (p < 0.05). Findings highlight the value of cancer helplines and suggest ways they can be most effective.


Assuntos
Cuidadores , Neoplasias , Amigos , Humanos , Estudos Longitudinais , Neoplasias/terapia , Assistência Centrada no Paciente
13.
J Cancer Educ ; 36(5): 1039-1044, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-32157570

RESUMO

Participation in cancer clinical trials (CCTs) is critical to improving cancer treatments and quality of care. However, rates of patient participation remain low. Research has shown that a trusted physician recommendation is an important influence on patients' decisions to enroll in a CCT. Improving primary care providers' (PCPs') knowledge, attitudes, and beliefs about CCTs is a promising potential path for improving CCT participation. The aim of this pilot study was to test the effect of an online educational course for PCPs about clinical trials on primary care providers' knowledge, attitudes and beliefs, and behavior. Forty-one PCPs in the New York City area participated in a 1-h online training session on cancer clinical trials. These PCPs had self-selected to complete the training in a previous survey. The objectives of the training module were to (1) educate the PCPs about clinical trials, with a focus on overcoming misconceptions; and (2) discuss roles of PCPs in partnering with oncologists to help patients gain access to clinical trials. The training module included didactics, audio excerpts, and case descriptions. Participants completed a pre-test immediately before taking the course, a post-test immediately after taking the course, and a 3-month post-course survey. All three assessments included a general T/F knowledge test, a 7-item attitude/belief scale, and a knowledge test focused specifically on local resources and access for clinical trials. Forty-one PCPs completed the module and the pre-post course surveys. Eighty percent (33/41) also completed the 3-month post-course survey. General knowledge and local knowledge increased significantly (p < .05) from pre- to post-course. At 3 months post-training, both general and local knowledge scores remained significantly increased from baseline. For those who completed the 3-month post-course survey, attitudes and beliefs increased significantly from pre- to post-course, but this change was not sustained at 3 months post-training. At 3 months post-training, 52% of the PCPs who had an interaction with a recently diagnosed cancer patient reported speaking with patients about CCTs as a result of the training. A brief online course showed significant and sustained improvement in PCPs' general and local knowledge about cancer clinical trials, which translated into self-reported behavior change. Future dissemination of the course and further research into its impact are important next steps.


Assuntos
Neoplasias , Médicos de Atenção Primária , Atitude do Pessoal de Saúde , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Neoplasias/terapia , Projetos Piloto , Inquéritos e Questionários
14.
Clin Sci (Lond) ; 134(1): 39-51, 2020 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-31825070

RESUMO

Endothelial function and the risk for endothelial dysfunction differ between males and females. Besides the action of estrogen, sex chromosome gene expression and programming effects also provoke this sexual dimorphism. MicroRNAs (miRNAs) have emerged as regulators of endothelial cell function and dysfunction. We here hypothesized distinct miRNA expression patterns in male versus female human endothelial cells that contribute to the functional differences. We used our well-established model of fetal endothelial cells isolated from placenta (fpEC) and analyzed sexual dimorphic miRNA expression and potentially affected biological functions. Next-generation miRNA sequencing of fpEC isolated after pregnancies with male and female neonates identified sex-dependent miRNA expression patterns. Potential biological pathways regulated by the altered set of miRNAs were determined using mirPath and mirSystem softwares, and suggested differences in barrier function and actin organization. The identified pathways were further investigated by monolayer impedance measurements (ECIS) and analysis of F-actin organization (Phalloidin). Nine miRNAs were differentially expressed in fpEC of male versus female neonates. Functional pathways most significantly regulated by these miRNAs included 'Adherens junction', 'ECM receptor interaction' and 'Focal adhesion'. These pathways control monolayer barrier function and may be paralleled by altered cytoskeletal organization. In fact, monolayer impedance was higher in fpEC of male progeny, and F-actin staining revealed more pronounced peripheral stress fibers in male versus female fpEC. Our data highlight that endothelial cell function differs between males and females already in utero, and that altered miRNAs are associated with sex dependent differences in barrier function and actin organization.


Assuntos
Actinas/metabolismo , Células Endoteliais/metabolismo , MicroRNAs/genética , Caracteres Sexuais , Diabetes Gestacional/genética , Estrogênios/metabolismo , Feminino , Feto/metabolismo , Humanos , Masculino , Placenta/metabolismo , Gravidez
15.
Int J Mol Sci ; 21(3)2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-32012940

RESUMO

Maternal overweight in pregnancy alters the metabolic environment and generates chronic low-grade inflammation. This affects fetal development and programs the offspring's health for developing cardiovascular and metabolic disease later in life. MME (membrane-metalloendopeptidase, neprilysin) cleaves various peptides regulating vascular tone. Endothelial cells express membrane-bound and soluble MME. In adults, the metabolic environment of overweight and obesity upregulates endothelial and circulating MME. We here hypothesized that maternal overweight increases MME in the feto-placental endothelium. We used primary feto-placental endothelial cells (fpEC) isolated from placentas after normal vs. overweight pregnancies and determined MME mRNA, protein, and release. Additionally, soluble cord blood MME was analyzed. The effect of oxygen and tumor necrosis factor α (TNFα) on MME protein in fpEC was investigated in vitro. Maternal overweight reduced MME mRNA (-39.9%, p < 0.05), protein (-42.5%, p = 0.02), and MME release from fpEC (-64.7%, p = 0.02). Both cellular and released MME protein negatively correlated with maternal pre-pregnancy BMI. Similarly, cord blood MME was negatively associated with pre-pregnancy BMI (r = -0.42, p = 0.02). However, hypoxia and TNFα, potential negative regulators of MME expression, did not affect MME protein. Reduction of MME protein in fpEC and in cord blood may alter the balance of vasoactive peptides. Our study highlights the fetal susceptibility to maternal metabolism and inflammatory state.


Assuntos
Regulação para Baixo , Células Endoteliais/enzimologia , Sangue Fetal/enzimologia , Regulação da Expressão Gênica no Desenvolvimento , Regulação Enzimológica da Expressão Gênica , Neprilisina/biossíntese , Obesidade Materna/enzimologia , Placenta/enzimologia , Adulto , Linhagem Celular , Células Endoteliais/patologia , Feminino , Humanos , Obesidade Materna/patologia , Placenta/patologia , Gravidez
16.
Histochem Cell Biol ; 152(5): 377-390, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31541300

RESUMO

Function and dysfunction of endothelial cells are regulated by a multitude of factors. Endothelial cell research often requires in vitro cell culture experiments. Hence, various culture media specifically designed to promote endothelial cell growth are available. These strikingly differ in their composition: complex media contain endothelial cell growth supplement (ECGS), an extract produced of bovine brain with undefined amounts of biologically active compounds, whilst defined media contain selected growth factors in defined concentrations. We here compared the effect of seven purchasable endothelial cell culture media on colony outgrowth, proliferation, viability, in vitro angiogenesis and phenotype of mature primary human endothelial cells using feto-placental endothelial cells isolated from chorionic arteries (fpEC). The effect of media on colony outgrowth was additionally tested on umbilical cord blood-derived endothelial progenitor cells (ECFCs). Outgrowth, purity, proliferation and viability differed between media. Outgrowth of fpEC and ECFCs was best in a defined medium containing EGF, FGF2 and VEGF. By contrast, established fpEC isolations proliferated best in complex media containing ECGS, heparin and ascorbic acid. Also viability of cells was higher in complex media. In vitro angiogenesis was most intense in a defined medium containing the highest number of individual growth factors. FACS analysis of surface markers for endothelial cell subtypes revealed that endothelial phenotype of fpEC was unaffected by media composition. Our data demonstrate the fundamental effect of endothelial cell culture media on primary cell isolation success and behaviour. Whether the composition of supplements is suitable also for individual experiments needs to be tested specifically.


Assuntos
Meios de Cultivo Condicionados/farmacologia , Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Neovascularização Fisiológica/efeitos dos fármacos , Animais , Bovinos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Humanos , Fenótipo
17.
Clin Trials ; 14(5): 518-525, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28693389

RESUMO

BACKGROUND/AIMS: Cancer clinical trials give patients access to state-of-the-art treatments and facilitate the translation of findings into mainstream clinical care. However, patients from racial and ethnic minority groups remain underrepresented in clinical trials. Primary care physicians are a trusted source of information for patients, yet their role in decision-making about cancer treatment and referrals to trial participation has received little attention. The aim of this study was to determine physicians' knowledge, attitudes, and beliefs about cancer clinical trials, their experience with trials, and their interest in appropriate training about trials. METHODS: A total of 613 physicians in the New York City area primarily serving patients from ethnic and racial minority groups were invited via email to participate in a 20-min online survey. Physicians were asked about their patient population, trial knowledge and attitudes, interest in training, and personal demographics. Using calculated scale variables, we used descriptive statistical analyses to better understand physicians' knowledge, attitudes, and beliefs about trials. RESULTS: A total of 127 physicians completed the survey. Overall, they had low knowledge about and little experience with trials. However, they generally had positive attitudes toward trials, with 41.4% indicating a strong interest in learning more about their role in trials, and 35.7% indicating that they might be interested. Results suggest that Black and Latino physicians and those with more positive attitudes and beliefs were more likely to be interested in future training opportunities. CONCLUSION: Primary care physicians may be an important group to target in trying to improve cancer clinical trial participation among minority patients. Future work should explore methods of educational intervention for such interested providers.


Assuntos
Atitude do Pessoal de Saúde , Ensaios Clínicos como Assunto , Conhecimentos, Atitudes e Prática em Saúde , Neoplasias/terapia , Médicos de Atenção Primária/psicologia , Adulto , Negro ou Afro-Americano/psicologia , Negro ou Afro-Americano/estatística & dados numéricos , Asiático/psicologia , Asiático/estatística & dados numéricos , Feminino , Hispânico ou Latino/psicologia , Hispânico ou Latino/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque , Pesquisa Qualitativa , Encaminhamento e Consulta , Inquéritos e Questionários , População Branca/psicologia , População Branca/estatística & dados numéricos
18.
Am J Community Psychol ; 60(1-2): 145-159, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28913882

RESUMO

Reduction of cancer-related disparities requires strategies that link medically underserved communities to preventive care. In this community-based participatory research project, a public library system brought together stakeholders to plan and undertake programs to address cancer screening and risk behavior. This study was implemented over 48 months in 20 large urban neighborhoods, selected to reach diverse communities disconnected from care. In each neighborhood, Cancer Action Councils were organized to conduct a comprehensive dynamic trial, an iterative process of program planning, implementation and evaluation. This process was phased into neighborhoods in random, stepped-wedge sequence. Population-level outcomes included self-reported screening adherence and smoking cessation, based on street intercept interviews. Event-history regressions (n = 9374) demonstrated that adherence outcomes were associated with program implementation, as were mediators such as awareness of screening programs and cancer information seeking. Findings varied by ethnicity, and were strongest among respondents born outside the U.S. or least engaged in care. This intervention impacted health behavior in diverse, underserved and vulnerable neighborhoods. It has been sustained as a routine library system program for several years after conclusion of grant support. In sum, participatory research with the public library system offers a flexible, scalable approach to reduce cancer health disparities.


Assuntos
Etnicidade , Conhecimentos, Atitudes e Prática em Saúde , Disparidades em Assistência à Saúde , Bibliotecas , Neoplasias/diagnóstico , Logradouros Públicos , Pesquisa Participativa Baseada na Comunidade , Detecção Precoce de Câncer , Feminino , Fidelidade a Diretrizes , Comportamentos Relacionados com a Saúde , Humanos , Masculino , Área Carente de Assistência Médica , Pessoa de Meia-Idade , Neoplasias/prevenção & controle , Cidade de Nova Iorque , Razão de Chances , Desenvolvimento de Programas , Abandono do Hábito de Fumar , População Urbana , Populações Vulneráveis
19.
Med Care ; 54(4): 380-5, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26759984

RESUMO

BACKGROUND: The high prices of chronic myeloid leukemia (CML) therapy are well recognized, but less discussion has focused on the value of health care spending on the disease. This study examined whether the added costs have been "worth" the benefits among older adults with CML. MATERIALS AND METHODS: We analyzed trends in health care costs and survival over time of 2164 CML patients over age 65 using the Surveillance, Epidemiology and End Results-Medicare-linked database. We estimated life expectancy over a 15-year duration after diagnosis using a Weibull survival model and projected the corresponding costs using a 2-part model, adjusting for patient characteristics. We estimated population-level survival, total health care costs, and incremental cost-effectiveness ratios (expressed as cost per life year gained) over the period of 1995-2007. RESULTS: We found that therapeutic improvements in the treatment of CML have been associated with survival gains among older adults. Mean life expectancy was 2.2 years in 1995 and increased to 4.2 years in 2007. During the same timeframe, CML care costs have increased, from $127,000 in 1995 to $278,000 in 2007 (2010 dollars), mostly due to increasing tyrosine kinase inhibitor costs. The aggregated incremental cost-effectiveness ratio was $74,000/life year gained. CONCLUSIONS: Our findings showed that, despite high costs, CML care may provide reasonable value for money among older patients between 1995-2007. Our study sheds light on the value of health care spending on CML by considering both the costs and the benefits. Future research should investigate strategies to improve treatment adherence to maximize the value of CML care.


Assuntos
Análise Custo-Benefício , Custos de Cuidados de Saúde/estatística & dados numéricos , Leucemia Mielogênica Crônica BCR-ABL Positiva/economia , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/economia , Antineoplásicos/uso terapêutico , Feminino , Humanos , Estimativa de Kaplan-Meier , Expectativa de Vida/tendências , Masculino , Medicare/estatística & dados numéricos , Anos de Vida Ajustados por Qualidade de Vida , Programa de SEER/estatística & dados numéricos , Estados Unidos
20.
Cancer ; 121(6): 908-15, 2015 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-25377382

RESUMO

BACKGROUND: Research has demonstrated that communication and care coordination improve cancer patient outcomes. To improve communication and care coordination, it is important to understand primary care providers' (PCPs') perceptions of communication with oncologists as well as PCPs' communication needs. METHODS: A mixed-methods approach was used in the present study. In the qualitative phase of the study, 18 PCPs practicing in underserved, minority communities were interviewed about their experiences communicating with oncologists. In the quantitative phase of the study, 128 PCPs completed an online survey about their preferences, experiences, and satisfaction with communication with oncologists. RESULTS: Results indicated a PCP-oncologist gap in communication occurred between diagnosis and treatment. PCPs wanted more communication with oncologists, updates on their patients' prognosis throughout treatment, and to be contacted via telephone or email and saw their role as crucial in providing supportive care for their patients. CONCLUSIONS: Although PCPs recognize that they play a critical, proactive role in supporting patients throughout the continuum of their cancer care experience, existing norms regarding postreferral engagement and oncologist-PCP communication often hinder activation of this role among PCPs. Expected standards regarding the method, frequency, and quality of postreferral communication should be jointly articulated and made accountable between PCPs and oncologists to help improve cancer patients' quality of care, particularly in minority communities.


Assuntos
Atitude do Pessoal de Saúde , Comunicação , Oncologia , Área Carente de Assistência Médica , Médicos de Atenção Primária , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Papel do Médico , Inquéritos e Questionários
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