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1.
Soc Sci Med ; 346: 116671, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38479263

RESUMO

BACKGROUND: The efficacy of vaccination depends on its widespread adoption, making vaccine uptake not just a personal health behavior but also a prosocial one. Previous research has shown that everyday moments of co-experienced positive emotions (positivity resonance) are associated with higher prosocial tendencies, and these moments, in turn, prospectively predict people's pandemic hygiene behaviors. Yet, limited research has explored how moments of positivity resonance may have predicted greater COVID-19 vaccine intentions during the early months of the pandemic. METHODS: We longitudinally surveyed a national U.S. sample across four weeks during the fall of 2020. We tested the hypothesis that positivity resonance with strangers and acquaintances indirectly predicts COVID-19 vaccine intentions, as statistically mediated by prosocial tendencies. We also aimed to replicate the indirect effects of positivity resonance on hygiene behaviors (such as mask wearing and hand washing), effects that have been demonstrated in previous research. RESULTS: In a pre-registered structural equation model, we found that perceived positivity resonance experienced with strangers and acquaintances prospectively predicted prosocial tendencies, which in turn amplified people's COVID-19 vaccine intentions (ß = 0.053) and hygiene behaviors - i.e., social distancing (ß = 0.032), mask wearing (ß = 0.027), hand washing (ß = 0.049). CONCLUSIONS: Understanding the effects of high-quality social interactions with strangers and acquaintances on vaccine intentions and hygiene behaviors is critical, particularly given the likelihood of emerging pandemics and novel vaccines. We discuss theoretical and practical implications related to perceived positivity resonance, prosocial tendencies, and vaccination uptake for novel vaccines.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Humanos , Vacinas contra COVID-19/uso terapêutico , Amigos , Intenção , COVID-19/prevenção & controle , Vacinação , Emoções
2.
J Geriatr Oncol ; 15(3): 101740, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38513534

RESUMO

INTRODUCTION: Studies about clinician acceptability of integrative palliative care interventions in the inpatient and outpatient cancer settings are limited. In this study, we examined clinician acceptability of a NIH-funded interdisciplinary PAlliative and Supportive Care inTervention (PACT) for older adults with acute myeloid leukemia (AML) and their care partners that transcends both inpatient and outpatient settings. MATERIALS AND METHODS: Data was collected using semi-structured interviews with clinicians who were directly involved in PACT. The domains of the Theoretical Framework of Acceptability were used to guide the qualitative analysis. RESULTS: The clinicians consisted of occupational therapists (37%), physical therapists (25%), registered nurses (25%), and a clinical rehabilitation manager (13%). Five themes were identified in the thematic analysis: (1) Emotions and affect towards the intervention, (2) Intervention coherence and self-efficacy, (3) Barriers, burden, and opportunity costs of delivering the intervention, (4) Usefulness and effectiveness of the intervention, and (5) Recommendations to improve intervention delivery. DISCUSSION: All clinicians found the PACT intervention highly acceptable and expressed the positive impact of the intervention on job fulfillment and satisfaction. Our findings provide evidence to inform the delivery and implementation of future large scale integrative palliative care intervention trials.


Assuntos
Cuidadores , Leucemia Mieloide Aguda , Humanos , Idoso , Leucemia Mieloide Aguda/terapia , Cuidados Paliativos
3.
J Adolesc Young Adult Oncol ; 13(1): 147-155, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37262185

RESUMO

Purpose: When a cancer diagnosis coincides with caring for children, it may influence the financial impacts of cancer and decisions to pursue advance care planning (ACP) or genetic testing. We examined associations between caring for children and financial hardship, ACP, and genetic testing among female adolescent and young adult (AYA) cancer survivors in North Carolina and California. Methods: Participants were diagnosed at ages 15-39 years with breast, melanoma, gynecologic, lymphoma, or thyroid cancer during 2004-2016. We estimated adjusted prevalence differences (aPDs) and ratios (aPRs) for each outcome by child caring status using marginal structural binomial regression models. Results: Among 1595 women ages 19-54 years at survey (median = 7 years since diagnosis), 819 (51.3%) reported that they were caring for children at diagnosis. Women caring for children had a higher prevalence of material financial hardship (e.g., medical debt; 30% vs. 21.9%; aPD = 9%, 95% confidence interval [CI]: 3 to 14; aPR = 1.39, 95% CI: 1.12 to 1.72) but similar levels of psychological financial hardship compared to noncaregivers. Women caring for children were more likely to complete ACPs (42.2% vs. 30.7%; aPD = 9%, 95% CI: 3 to 16; aPR = 1.30, 95% CI: 1.08 to 1.57). Among the 723 survivors of breast, endometrial, and ovarian cancer, the prevalence of genetic testing was higher among women caring for children (89%) than noncaregivers (81%); this difference was not statistically significant. Conclusion: Women caring for children at diagnosis may be at elevated risk for adverse financial outcomes and may benefit from additional financial navigation support. Childcare responsibilities may further complicate health decision-making for AYAs diagnosed with cancer.


Assuntos
Planejamento Antecipado de Cuidados , Sobreviventes de Câncer , Neoplasias , Neoplasias da Glândula Tireoide , Criança , Humanos , Feminino , Adulto Jovem , Adolescente , Estresse Financeiro , Neoplasias/epidemiologia , Sobreviventes de Câncer/psicologia , Testes Genéticos
4.
J Contin Educ Nurs ; 55(2): 94-100, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37971228

RESUMO

Nurse practitioner (NP) involvement in professional organizations improves clinical practice, patient outcomes, and health care policy. Results of a survey for a local professional nursing organization showed a need for more NP-level education and NP mentorship and leadership training. Findings were applied to develop a leadership initiative through an NP-led continuing education program. At the conclusion of the program, NP presenters completed a survey. The NP presenters agreed that participating in this program and the mentoring that was provided helped them prepare for their sessions, improve their leadership skills, and prepare for additional speaking engagements. Additionally, each session's attendees completed evaluation surveys. Results from program attendees indicated a high level of agreement about meeting learning objectives in sessions and the effectiveness of the NP presenters. This innovative program may be modeled across a variety of nursing specialties, settings, and organizations to enhance NP professional development and support nursing-led continuing education. [J Contin Educ Nurs. 2024;55(2):94-100.].


Assuntos
Educação em Enfermagem , Tutoria , Profissionais de Enfermagem , Humanos , Liderança , Mentores , Profissionais de Enfermagem/educação
5.
Curr Oncol Rep ; 25(7): 803-812, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37043117

RESUMO

PURPOSE OF REVIEW: The number of older adults with cancer relying on support from caregivers continues to increase. Health disparities in older adults with cancer often extend to their caregivers. This review aims to assess the state of cancer caregiving research in historically underrepresented diverse populations and provide recommendations for future research and policy. RECENT FINDINGS: Research on caregivers of older adults with cancer from diverse backgrounds has primarily been descriptive. Health disparities for historically underrepresented caregivers (LGBTQ + , BIPOC, rural, young adults, youth) exist across several dimensions (e.g., financial, mental, and physical health, and access to caregiver support). Few published studies have closely examined the unique experiences of these caregivers nor provided culturally appropriate tailored interventions. Health equity research within caregiving populations is in its infancy. Priorities for future work should focus on identifying modifiable targets for intervention, changing systems-level processes in acknowledging and supporting caregivers, and creating policies that reduce financial inequities of caregiving.


Assuntos
Cuidadores , Neoplasias , Humanos , Idoso , Adolescente , Neoplasias/terapia
6.
Cancer Med ; 12(7): 8804-8814, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36647557

RESUMO

BACKGROUND: Cancer supportive care interventions often have limited generalizability, goal misalignment, and high costs. We developed and piloted a health coaching intervention, UNC HealthScore, in patients undergoing cancer treatment (ClinicalTrials.gov identifier NCT04923997). We present feasibility, acceptability, and preliminary outcome data. METHODS: HealthScore is a six-month, theory-based, multicomponent intervention delivered through participant-driven coaching sessions. For the pilot study, participants were provided a Fitbit, responded to weekly symptom and physical function digital surveys, and met with a health coach weekly to develop and monitor goals. Coaching notes were discussed in weekly interdisciplinary team meetings and provided back to the treating oncology team. Symptom alerts were monitored and triaged through a study resource nurse to relevant supportive care services. Feasibility was determined based on intervention enrollment and completion. Acceptability was based on satisfaction with coaching and Fitbit-wearing and was informed by semistructured exit interviews. Outcomes evaluated for signs of improvement included several PROMIS (Patient-Reported Outcomes Measurement Information System) measures, including the primary intervention target, physical function. RESULTS: From May 2020 to March 2022, 50 participants completed the single-arm pilot. Feasibility was high: 66% enrolled and 71% completed the full intervention. Participants reported an average of 4.8 and 4.7 (out of 5) on the acceptability of coaching calls and using the Fitbit, respectively. Physical function scores rose 3.1 points (SE = 1.1) from baseline to 3 months, and 4.3 (SE = 1.0) from baseline to 6 months, above established minimal clinically important difference (MCID). Improvements above MCID were also evident in anxiety and depression, and smaller improvements were demonstrated for emotional support, social isolation, cognitive function, symptom burden, and self-efficacy. DISCUSSION: HealthScore shows feasibility, acceptability, and promising preliminary outcomes. Randomized studies are underway to determine the efficacy of preserving physical function in patients with advanced cancer.


Assuntos
Tutoria , Neoplasias , Humanos , Projetos Piloto , Estudos de Viabilidade , Neoplasias/terapia , Promoção da Saúde
7.
Support Care Cancer ; 31(1): 95, 2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36598590

RESUMO

BACKGROUND: Older adults with AML commonly receive a hypomethylating agent (HMA) as first-line therapy. The addition of venetoclax (VEN) to HMAs has been shown to improve remission rates and overall survival. The use of combination therapy (HMA + VEN) requires frequent follow-up, results in longer infusion times, and likely increases caregiver responsibility at home. We describe experiences of informal caregivers (family/friends) providing care to older adults with AML receiving HMA + VEN. METHODS: Fourteen caregivers of older adults with AML receiving HMA + VEN (September 2020 to September 2021) were recruited as part of a control group of an ongoing NIH-funded clinical trial. Semi-structured interviews were conducted to gain initial insight into caregiver experiences at the start of HMA + VEN treatment. Two researchers analyzed the data using thematic content analysis. Data saturation occurred when no new themes were found in subsequent interviews, but all interviews were coded and synthesized. RESULTS: Of the 14 caregivers interviewed, the majority were spouses (n = 10), female (n = 13), and aged 45 to 83 (median age 65). We identified five themes: (1) the impact of an AML diagnosis in older adulthood, (2) care recipient condition changes, (3) perspectives of caregiving roles and tasks, (4) factors influencing caregiving experiences, and (5) support system roles. CONCLUSIONS AND IMPLICATIONS: Caregivers for older adults with AML report a range of experiences navigating health systems, caregiving responsibilities, and resource needs. The risk for caregiver burden and unmet needs should be addressed to improve caregivers' abilities to provide care.


Assuntos
Cuidadores , Leucemia Mieloide Aguda , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Sulfonamidas/uso terapêutico , Ensaios Clínicos como Assunto
8.
Sci Adv ; 7(37): eabf6709, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34516764

RESUMO

Despite recent clinical observations linking the zona incerta (ZI) to anxiety, little is known about whether and how the ZI processes anxiety. Here, we subject mice to anxious experiences and observe an increase in ZI c-fos­labeled neurons and single-cell calcium activity as well as an efficient effect of ZI infusion of diazepam, a classical anxiolytic drug. We further identify that somatostatin (SOM)­, calretinin (CR)­, and vesicular glutamate transporter-2 (Vglut2)­expressing cells display unique electrophysiological profiles; however, they similarly respond to anxiety-provoking stimuli and to diazepam. Optogenetic manipulations reveal that each of these ZI neuronal populations triggers specific anxiety-related behavioral phenotypes. Activation of SOM-expressing neurons induced anxiety, while photoactivation of CR-positive cells and photoinhibition of Vglut2-expressing neurons produce anxiolysis. Furthermore, activation of CR- and Vglut2-positive cells provokes rearing and jumps, respectively. Our findings provide the first experimental evidence that ZI subpopulations encode and modulate different components of anxiety.

9.
Science ; 372(6547): 1205-1209, 2021 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-34112692

RESUMO

Quiescent neural stem cells (NSCs) in the adult mouse ventricular-subventricular zone (V-SVZ) undergo activation to generate neurons and some glia. Here we show that platelet-derived growth factor receptor beta (PDGFRß) is expressed by adult V-SVZ NSCs that generate olfactory bulb interneurons and glia. Selective deletion of PDGFRß in adult V-SVZ NSCs leads to their release from quiescence, uncovering gliogenic domains for different glial cell types. These domains are also recruited upon injury. We identify an intraventricular oligodendrocyte progenitor derived from NSCs inside the brain ventricles that contacts supraependymal axons. Together, our findings reveal that the adult V-SVZ contains spatial domains for gliogenesis, in addition to those for neurogenesis. These gliogenic NSC domains tend to be quiescent under homeostasis and may contribute to brain plasticity.


Assuntos
Células-Tronco Adultas/fisiologia , Ventrículos Cerebrais/fisiologia , Ventrículos Laterais/fisiologia , Células-Tronco Neurais/fisiologia , Neuroglia/fisiologia , Receptor beta de Fator de Crescimento Derivado de Plaquetas/metabolismo , Animais , Astrócitos/citologia , Astrócitos/fisiologia , Axônios/fisiologia , Diferenciação Celular , Divisão Celular , Ventrículos Cerebrais/citologia , Epêndima/citologia , Epêndima/fisiologia , Feminino , Perfilação da Expressão Gênica , Homeostase , Ventrículos Laterais/citologia , Masculino , Camundongos , Neurogênese , Bulbo Olfatório/citologia , Bulbo Olfatório/fisiologia , Oligodendroglia/citologia , Oligodendroglia/fisiologia , Receptor beta de Fator de Crescimento Derivado de Plaquetas/genética
10.
Cell Rep ; 34(11): 108867, 2021 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-33730568

RESUMO

The firing activity of dorso-medial-striatal-cholinergic interneurons (dmCINs) is a neural correlate of classical conditioning. Tonically active, they pause in response to salient stimuli, mediating acquisition of predictive cues/outcome associations. Cortical and thalamic inputs are typical of the rather limited knowledge about underlying circuitry contributing to this function. Here, we dissect the midbrain GABA and glutamate-to-dmCIN pathways and evaluate how they influence conditioned behavior. We report that midbrain neurons discriminate auditory cues and encode the association of a predictive stimulus with a footshock. Furthermore, GABA and glutamate cells form selective monosynaptic contacts onto dmCINs and di-synaptic ones via the parafascicular thalamus. Pathway-specific inhibition of each sub-circuit produces differential impairments of fear-conditioned learning. Finally, Vglut2-expressing cells discriminate between CSs although Vgat-positive neurons associate the predictive cue with the outcome. Overall, these data suggest that each component of the network carries information pertinent to sub-domains of the behavioral strategy.


Assuntos
Condicionamento Clássico , Neurônios GABAérgicos/fisiologia , Glutamatos/metabolismo , Aprendizagem , Área Tegmentar Ventral/fisiologia , Estimulação Acústica , Animais , Colina/metabolismo , Sinais (Psicologia) , Aprendizagem por Discriminação , Eletrochoque , Medo , Feminino , Interneurônios/fisiologia , Masculino , Camundongos Endogâmicos C57BL , Sinapses/fisiologia , Tálamo/fisiologia , Proteína Vesicular 2 de Transporte de Glutamato/metabolismo
11.
J Adv Nurs ; 77(4): 2073-2084, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33460207

RESUMO

AIMS: This protocol directs a study that aims to: (a) describe the caregiver's experience over 8-12 weeks after an index adult patient's allogeneic bone marrow transplant (BMT) for advanced cancer using a case-oriented approach and mixed methods, with qualitative methods in the foreground; and (b) explore networks of relationships among psycho-neurological symptoms, positive psychological states and caregiver health. DESIGN: Case-oriented longitudinal design using multiple data types and analytic approaches. METHODS: Data will be collected from 10-12 caregivers. The sample will be recruited from a large public hospital in the southeastern United States using maximum variation sampling (e.g., caregiver race/ethnicity, relationship to patient, age, education, and number of caregiving roles). Participants will be asked to complete weekly surveys, have their blood drawn bi-weekly and participate in an interview each month during the study period (~100 days). Aim 1 analysis will include directed content analysis and case-oriented visual analysis. Aim 2 analysis will include symptom network estimation of psycho-neurological symptoms, positive psychological states, and caregiver health. Institutional review board approval was obtained August 2018. DISCUSSION: Results will provide an in-depth description of caregivers' experiences in the 100 days after BMT. Findings will inform generation of hypotheses and identification of targets for interventions to improve caregiver's experiences after BMT. IMPACT: This in-depth multi-method longitudinal study to describe caregivers of adult patients receiving an allogeneic BMT is an essential step in understanding caregivers' complex responses to chronic stress and the role of positive psychological states. The results from this study will inform future research on chronic stress processes, intense caregiving, and intervention development.


Assuntos
Cuidadores , Transplante de Células-Tronco Hematopoéticas , Adulto , Transplante de Medula Óssea , Humanos , Estudos Longitudinais , Estresse Psicológico , Inquéritos e Questionários
12.
Nurs Res ; 70(1): 67-71, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32991528

RESUMO

BACKGROUND: Social media platforms are useful for recruiting hard-to-reach populations, such as caregivers of children with cancer, for research. However, there are unique ethical considerations in using social media. OBJECTIVES: The aim of the study was to describe the methods used to recruit hard-to-reach caregivers (parents of children with cancer) for research and related ethical considerations. METHODS: We used The Belmont Report tenets (respect for persons, beneficence, and justice) as a guiding framework to identify issues relevant to social media recruitment of hard-to-reach populations and to describe how we addressed these issues in our study. RESULTS: We engaged leaders of two online communities that offer peer support for caregivers of children with cancer to help with recruitment to our study on financial effect of pediatric cancer. We identified issues in using social media for recruiting hard-to-reach populations in alignment with The Belmont Report, including risk for subject selection bias, privacy rights, protecting identity of participants, data security issues, and access to research. We addressed issues by deliberate study design decisions and engagement with online community advocates. DISCUSSION: Using social media to recruit hard-to-reach populations may be a successful way to engage them in research. Although researchers may remain compliant with the institutional review board of their facilities and are faithful to the tenets of The Belmont Report, unanticipated ethical issues may arise directly or indirectly as a result of using social media. This article identifies these issues and provides suggestions for dealing with them.


Assuntos
Cuidadores/ética , Cuidadores/estatística & dados numéricos , Crianças com Deficiência/estatística & dados numéricos , Neoplasias/enfermagem , Pesquisa em Enfermagem/métodos , Seleção de Pacientes/ética , Mídias Sociais/ética , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Projetos de Pesquisa , Mídias Sociais/estatística & dados numéricos
13.
Aging Cell ; 19(12): e13274, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33174325

RESUMO

Age-associated loss of muscle function is exacerbated by a concomitant reduction in balance, leading to gait abnormalities and falls. Even though balance defects can be mitigated by exercise, the underlying neural mechanisms are unknown. We now have investigated components of the proprioceptive and vestibular systems in specific motor neuron pools in sedentary and trained old mice, respectively. We observed a strong age-linked deterioration in both circuits, with a mitigating effect of exercise on vestibular synapse numbers on motor neurons, closely associated with an improvement in gait and balance in old mice. Our results thus describe how the proprioceptive and vestibular systems are modulated by age and exercise, and how these changes affect their input to motor neurons. These findings not only make a strong case for exercise-based interventions in elderly individuals to improve balance, but could also lead to targeted therapeutic interventions aimed at the respective neuronal circuitry.


Assuntos
Envelhecimento/fisiologia , Esforço Físico/fisiologia , Equilíbrio Postural/fisiologia , Vestíbulo do Labirinto/fisiopatologia , Idoso , Envelhecimento/patologia , Animais , Marcha/fisiologia , Humanos , Coxeadura Animal/fisiopatologia , Coxeadura Animal/prevenção & controle , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios Motores/patologia , Neurônios Motores/fisiologia , Condicionamento Físico Animal , Propriocepção/fisiologia , Vestíbulo do Labirinto/patologia
14.
Int J Nurs Stud ; 103: 103419, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31945603

RESUMO

BACKGROUND: Nurse researchers are increasingly interested in incorporating biological indicators related to chronic stress, or repeated or constant exposure to psychological stressors. Minimally invasive collection methods may improve access to vulnerable populations. OBJECTIVE: To map biological indicators measured through minimally invasive methods investigating biological changes in response to chronic stress. DESIGN, DATA SOURCES, AND METHODS: The paper seeks to answer two questions: What are the characteristics of the minimally-invasive methods used to measure the biological correlates of chronic stress? What are the limitations regarding the use of the minimally-invasive methods and/or biological indicators identified above? Authors completed a scoping review following guidelines from the Joanna Briggs Institute Manual and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for Scoping Reviews. A literature search was completed in PubMed, PsycINFO, and Scopus. 2518 articles were screened and 145 studies were included. Data were extracted using a standardized extraction tool, compiled, and coded. RESULTS: Studies included minimally-invasive methods to measure the hypothalamic-adrenal-pituitary axis (N = 173), immune and inflammatory markers (N = 118), and adult neurogenesis (N = 6). Cortisol was most frequently measured (N = 136), usually in saliva (N = 86). Studies included a variety of limitations for the methods and indicators, including concerns about timing and accuracy of collection, frequency of sampling, and controlling for acute stressors. CONCLUSIONS: Nurse researchers have access to many minimally-invasive methods to measure altered biological processes related to chronic stress. A gap identified by this review is the paucity of minimally-invasive methods for investigating neurogenesis; the measurement of brain derived neurotrophic factor in plasma is a distal proxy and further research is needed to test the response of peripheral levels to psychosocial stress interventions. Additionally, while this scoping review allows nurse researchers to consider possible biological indicators to include in their research, future research is still needed on some of the basic premises of stress research, including agreement on the conceptualization of chronic stress.


Assuntos
Pesquisa em Enfermagem , Pesquisadores , Estresse Psicológico/psicologia , Doença Crônica , Humanos , Hidrocortisona/análise , Saliva/química
15.
Cell Rep ; 27(7): 2184-2198.e4, 2019 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-31091455

RESUMO

Locomotion relies on the activity of basal ganglia networks, where, as the output, the substantia nigra pars reticulata (SNr) integrates incoming signals and relays them to downstream areas. The cellular and circuit substrates of such a complex function remain unclear. We hypothesized that the SNr controls different aspects of locomotion through coordinated cell-type-specific sub-circuits. Using anatomical mapping, single-cell qPCR, and electrophysiological techniques, we identified two SNr sub-populations: the centromedial-thalamo projectors (CMps) and the SN compacta projectors (SNcps), which are genetically targeted based on vesicular transporter for gamma-aminobutyric acid (VGAT) or parvalbumin (PV) expression, respectively. Optogenetic manipulation of these two sub-types across a series of motor tests provided evidence that they govern different aspects of motor behavior. While CMp activity supports the continuity of motor patterns, SNcp modulates the immediate motor drive behind them. Collectively, our data suggest that at least two different sub-circuits arise from the SNr, engage different behavioral motor components, and collaborate to produce correct locomotion.


Assuntos
Locomoção/fisiologia , Neurônios/fisiologia , Substância Negra/citologia , Potenciais de Ação/fisiologia , Animais , Feminino , Núcleos Intralaminares do Tálamo/citologia , Núcleos Intralaminares do Tálamo/metabolismo , Locomoção/genética , Masculino , Camundongos , Inibição Neural/fisiologia , Vias Neurais/metabolismo , Vias Neurais/fisiologia , Optogenética , Parvalbuminas/metabolismo , Substância Negra/fisiologia , Transmissão Sináptica/fisiologia , Ácido gama-Aminobutírico/metabolismo
16.
Nat Commun ; 10(1): 2241, 2019 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-31113944

RESUMO

The red nucleus (RN) is required for limb control, specifically fine motor coordination. There is some evidence for a role of the RN in reaching and grasping, mainly from lesion studies, but results so far have been inconsistent. In addition, the role of RN neurons in such learned motor functions at the level of synaptic transmission has been largely neglected. Here, we show that Vglut2-expressing RN neurons undergo plastic events and encode the optimization of fine movements. RN light-ablation severely impairs reaching and grasping functions while sparing general locomotion. We identify a neuronal population co-expressing Vglut2, PV and C1QL2, which specifically undergoes training-dependent plasticity. Selective chemo-genetic inhibition of these neurons perturbs reaching and grasping skills. Our study highlights the role of the Vglut2-positive rubral population in complex fine motor tasks, with its related plasticity representing an important starting point for the investigation of mechanistic substrates of fine motor coordination training.


Assuntos
Aprendizagem/fisiologia , Atividade Motora/fisiologia , Neurônios/fisiologia , Núcleo Rubro/fisiologia , Animais , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Modelos Animais , Plasticidade Neuronal/fisiologia , Parvalbuminas/metabolismo , Núcleo Rubro/citologia , Transmissão Sináptica/fisiologia , Proteína Vesicular 2 de Transporte de Glutamato/genética , Proteína Vesicular 2 de Transporte de Glutamato/metabolismo
17.
Eur J Oncol Nurs ; 35: 22-32, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30057080

RESUMO

PURPOSE: The study purpose was to map and identify gaps in the recent (∼2011-2017) literature on the costs of illness to parents of children diagnosed with cancer. The costs of illness include direct costs, indirect costs and psychosocial costs. METHODS: A systematic scoping review was conducted. Data sources included PubMed, CINAHL, PsychInfo and EconLit. Studies were eligible for inclusion if they were conducted in high-income countries, published in the English language, and reported parent perspectives on direct costs, indirect costs and/or psychosocial costs due to financial costs. RESULTS: 25 studies were eligible. Most were conducted in Canada, the USA, or Sweden. The studies used a variety of designs, target populations, time frames and sample sizes. Intervention studies were lacking. Across studies fathers were underrepresented. While no study comprehensively measured costs of illness, more studies used rigorous methods and considered psychosocial costs. Financial costs were measured using a micro-costing or general estimates approach. Psychosocial costs were measured using a variety of PRO measures, some of which were investigator developed. The studies provide evidence that financial toxicity occurs in pediatric oncology. CONCLUSIONS: Future studies should comprehensively measure costs using a consistent set of established measures and make efforts to recruit fathers to cost of illness research. Interventions to mitigate financial toxicity are needed.


Assuntos
Efeitos Psicossociais da Doença , Neoplasias/economia , Neoplasias/psicologia , Pais/psicologia , Adulto , Canadá , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Suécia , Estados Unidos
18.
Nat Commun ; 9(1): 1305, 2018 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-29610454

RESUMO

Exosomes are cell-derived nanovesicles (50-150 nm), which mediate intercellular communication, and are candidate therapeutic agents. However, inefficiency of exosomal message transfer, such as mRNA, and lack of methods to create designer exosomes have hampered their development into therapeutic interventions. Here, we report a set of EXOsomal transfer into cells (EXOtic) devices that enable efficient, customizable production of designer exosomes in engineered mammalian cells. These genetically encoded devices in exosome producer cells enhance exosome production, specific mRNA packaging, and delivery of the mRNA into the cytosol of target cells, enabling efficient cell-to-cell communication without the need to concentrate exosomes. Further, engineered producer cells implanted in living mice could consistently deliver cargo mRNA to the brain. Therapeutic catalase mRNA delivery by designer exosomes attenuated neurotoxicity and neuroinflammation in in vitro and in vivo models of Parkinson's disease, indicating the potential usefulness of the EXOtic devices for RNA delivery-based therapeutic applications.


Assuntos
Cérebro/patologia , Sistemas de Liberação de Medicamentos , Exossomos/metabolismo , Doença de Parkinson/terapia , Regiões 3' não Traduzidas , Animais , Encéfalo/metabolismo , Catalase/metabolismo , Comunicação Celular , Linhagem Celular Tumoral , Cérebro/metabolismo , Citosol/metabolismo , Eletroporação , Feminino , Terapia Genética , Células HEK293 , Células HeLa , Humanos , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs , Nanopartículas , RNA Mensageiro/metabolismo , Biologia Sintética
19.
Front Neural Circuits ; 11: 110, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29311846

RESUMO

Data from the World Health Organization (National Institute on Aging, 2011) and the National Institutes of Health (He et al., 2016) predicts that while today the worldwide population over 65 years of age is estimated around 8.5%, this number will reach an astounding 17% by 2050. In this framework, solving current neurodegenerative diseases primarily associated with aging becomes more pressing than ever. In 2017, we celebrate a grim 200th anniversary since the very first description of Parkinson's disease (PD) and its related symptomatology. Two centuries after this debilitating disease was first identified, finding a cure remains a hopeful goal rather than an attainable objective on the horizon. Tireless work has provided insight into the characterization and progression of the disease down to a molecular level. We now know that the main motor deficits associated with PD arise from the almost total loss of dopaminergic cells in the substantia nigra pars compacta. A concomitant loss of cholinergic cells entails a cognitive decline in these patients, and current therapies are only partially effective, often inducing side-effects after a prolonged treatment. This review covers some of the recent developments in the field of Basal Ganglia (BG) function in physiology and pathology, with a particular focus on the two main neuromodulatory systems known to be severely affected in PD, highlighting some of the remaining open question from three main stand points: - Heterogeneity of midbrain dopamine neurons. - Pairing of dopamine (DA) sub-circuits. - Dopamine-Acetylcholine (ACh) interaction. A vast amount of knowledge has been accumulated over the years from experimental conditions, but very little of it is reflected or used at a translational or clinical level. An initiative to implement the knowledge that is emerging from circuit-based approaches to tackle neurodegenerative disorders like PD will certainly be tremendously beneficial.


Assuntos
Acetilcolina/metabolismo , Gânglios da Base/metabolismo , Dopamina/metabolismo , Doença de Parkinson/metabolismo , Animais , Gânglios da Base/patologia , Humanos , Vias Neurais/metabolismo , Vias Neurais/patologia , Doença de Parkinson/patologia
20.
MethodsX ; 3: 326-32, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27222822

RESUMO

Operant behavioral tasks for animals have long been used to probe the function of multiple brain regions (i.e., understanding the role of dopamine in electrical brain stimulation reward [1], or determining the rewarding properties of feeding oriented brain pathways [2]). The recent development of tools and techniques has opened the door to refine the answer to these same questions with a much higher degree of specificity and accuracy, both in biological and spatial-temporal terms [3], [4]. A variety of systems designed to test operant behavior are now commercially available, but have prohibitive costs. Here, we provide a low-cost alternative to a nose poke system for mice. Adapting a freely available sketch for ARDUINO boards, in combination with an in-house built PVC box and inexpensive electronic material we constructed a four-port nose poke system that detects and counts port entries. To verify the applicability and validity of our system we tested the behavior of DAT-CRE transgenic mice injected with an adeno-associated virus to express ChannelRhodopsin 2 in the Ventral tegmental area (VTA) and used the BNC output to drive a blue laser coupled to a fiber implanted above the VTA. Over 6 days, mice perform as it has been reported previously [5] exhibiting a remarkable preference for the port that triggers optogenetic stimulation of VTA dopamine neurons. •We provide a low cost alternative to commercially available nose poke system.•Our custom made apparatus is open source and TTL compatible.•We validate our system with optogenetic self-stimulation of dopamine neurons.

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