RESUMEN
It is a widely held belief that people's choices are less sensitive to changes in value as value increases. For example, the subjective difference between $11 and $12 is believed to be smaller than between $1 and $2. This idea is consistent with applications of the Weber-Fechner Law and divisive normalization to value-based choice and with psychological interpretations of diminishing marginal utility. According to random utility theory in economics, smaller subjective differences predict less accurate choices. Meanwhile, in the context of sequential sampling models in psychology, smaller subjective differences also predict longer response times. Based on these models, we would predict decisions between high-value options to be slower and less accurate. In contrast, some have argued on normative grounds that choices between high-value options should be made with less caution, leading to faster and less accurate choices. Here, we model the dynamics of the choice process across three different choice domains, accounting for both discriminability and response caution. Contrary to predictions, we mostly observe faster and more accurate decisions (i.e., higher drift rates) between high-value options. We also observe that when participants are alerted about incoming high-value decisions, they exert more caution and not less. We rule out several explanations for these results, using tasks with both subjective and objective values. These results cast doubt on the notion that increasing value reduces discriminability.
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Modelos TeóricosRESUMEN
BACKGROUND: Individual- and population-level socioeconomic disadvantages contribute to unequal outcomes among childhood cancer survivors. Reducing health disparities requires understanding experiences of survivors from historically marginalized communities, including those with non-English language preference. PROCEDURE: We partnered with a community-based organization (CBO) serving families of children with cancer in a rural region in California with low socioeconomic status and majority Hispanic/Latino (H/L) residents. We interviewed English- and Spanish-speaking adolescent/young adult (AYA) childhood cancer survivors (≥15 years old, ≥5 years from diagnosis), parents, and CBO staff to evaluate post-treatment needs and impact of CBO support. Data were analyzed qualitatively using applied thematic analysis. Themes were refined through team discussions with our community partners. RESULTS: Twelve AYAs (11 H/L, 11 bilingual), 11 parents (eight H/L, seven non-English preferred), and seven CBO staff (five H/L, five bilingual) participated. AYAs (five female, seven male) were of median (min-max) age 20 (16-32) and 9 (5-19) years post diagnosis; parents (nine female, two male) were age 48 (40-60) and 14 (6-23) years post child's diagnosis. Themes included challenges navigating healthcare, communication barriers among the parent-AYA-clinician triad, and lasting effects of childhood cancer on family dynamics and mental health. Subthemes illustrated that language and rurality may contribute to health disparities. CBO support impacted families by serving as a safety-net, fostering community, and facilitating H/L families' communication. CONCLUSIONS: Childhood cancer has long-lasting effects on families, and those with non-English language preference face additional burdens. Community-based support buffers some of the negative effects of childhood cancer and may reduce disparities.
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Inequidades en Salud , Neoplasias , Adolescente , Adulto , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Familia/psicología , Hispánicos o Latinos/psicología , Neoplasias/terapia , Padres/psicología , Investigación Cualitativa , Poblaciones Vulnerables , Factores Socioeconómicos , Supervivientes de CáncerRESUMEN
This study investigates the resources used by childhood cancer survivors (CCS) to learn about their cancer histories and evaluates if CCS feel these resources prepare them to manage their health needs as young adults. Young adult participants (aged 18-30 years) were diagnosed with cancer at ≤ 10 years and recruited by word of mouth and from social media and/or non-profit organizations and completed semi-structured interviews. A descriptive thematic analysis guided by an essentialist/realist paradigm combined inductive and deductive approaches to identify key themes. Fourteen participants were interviewed, and six key themes were identified: (1) CCS are aware of general cancer history (age at diagnosis, treating hospital, cancer type), (2) CCS are unaware of treatment regimen (medications and duration), (3) CCS want to learn more about their treatment regimens and (4) potential late effects of treatment, (5) CCS use diverse resources to learn about their cancer histories and potential late effects, and (6) survivors' interests to learn about their cancer histories change over time. Limited knowledge of their cancer treatments leaves some CCS unprepared to manage their health needs as young adults or to address potential risk of late effects. CCS recognize their limited knowledge, but the resources available to them fall short of their information needs. Identifying the shortcomings of resources used by CCS provides evidence for how resources need to be improved to meet survivors' cancer education needs.
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Supervivientes de Cáncer , Neoplasias , Humanos , Niño , Adulto Joven , Neoplasias/terapia , SobrevivientesRESUMEN
Chronic myeloid leukemia (CML) is effectively treated with long-term tyrosine kinase inhibitor (TKI) therapy, yet little is known about risks of prolonged TKI exposure in young patients, and long-term effect monitoring is not standardized. We surveyed North American pediatric oncologists (n = 119) to evaluate perceived risk of and surveillance practices for potential toxicities associated with prolonged TKI exposure in children and adolescents/young adults (AYAs) with CML. Survey domains included general and specific risk perceptions and surveillance practices for asymptomatic patients on chronic TKI therapy. We analyzed data descriptively and explored relationships between risk perceptions and surveillance. Risk perceptions varied among oncologists but were similar across six categories (thyroid, cardiac, vascular, metabolic, fertility, psychologic), with less than one-third rating each risk as moderate or high in pediatric and AYA patients. More oncologists perceived moderate or high risk of growth abnormalities in children (62% pediatric, 14% AYA) and financial toxicity in all patients (60% pediatric, 64% AYA). A greater proportion of oncologists with moderate or high perceived risk of thyroid abnormalities reported testing thyroid function compared to those with lower perceived risk; patterns for metabolic risk/lipid tests and cardiac risk/tests were similar. In summary, we found that pediatric oncologists had variable risk perceptions and surveillance practices for potential toxicities associated with prolonged TKI exposure. Standardizing surveillance would help quantify risks and refine recommendations.Supplemental data for this article is available online at https://doi.org/10.1080/08880018.2021.2017085 .
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Enfermedad Injerto contra Huésped , Leucemia Mielógena Crónica BCR-ABL Positiva , Médicos , Adolescente , Niño , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/efectos adversos , Adulto JovenRESUMEN
We used male BTBR mice carrying the Lepob mutation, which are subject to severe and progressive obesity and diabetes beginning at 6 wk of age, to examine the influence of one specific manifestation of sleep apnea, intermittent hypoxia (IH), on male urinary voiding physiology and genitourinary anatomy. A custom device was used to deliver continuous normoxia (control) or IH to wild-type and Lepob/ob (mutant) mice for 2 wk. IH was delivered during the 12-h inactive (light) period in the form of 90 s of 6% O2 followed by 90 s of room air. Continuous room air was delivered during the 12-h active (dark) period. We then evaluated genitourinary anatomy and physiology. As expected for the type 2 diabetes phenotype, mutant mice consumed more food and water, weighed more, and voided more frequently and in larger urine volumes. They also had larger bladder volumes but smaller prostates, seminal vesicles, and urethras than wild-type mice. IH decreased food consumption and increased bladder relative weight independent of genotype and increased urine glucose concentration in mutant mice. When evaluated based on genotype (normoxia + IH), the incidence of pathogenic bacteriuria was greater in mutant mice than in wild-type mice, and among mice exposed to IH, bacteriuria incidence was greater in mutant mice than in wild-type mice. We conclude that IH exposure and type 2 diabetes can act independently and together to modify male mouse urinary function. NEW & NOTEWORTHY Metabolic syndrome and obstructive sleep apnea are common in aging men, and both have been linked to urinary voiding dysfunction. Here, we show that metabolic syndrome and intermittent hypoxia (a manifestation of sleep apnea) have individual and combined influences on voiding function and urogenital anatomy in male mice.
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Diabetes Mellitus Tipo 2/metabolismo , Hipoxia/metabolismo , Síndrome Metabólico/metabolismo , Obesidad/metabolismo , Animales , Diabetes Mellitus Tipo 2/genética , Modelos Animales de Enfermedad , Hipoxia/genética , Resistencia a la Insulina/fisiología , Hígado/metabolismo , Masculino , Síndrome Metabólico/genética , Ratones , Obesidad/genéticaRESUMEN
BACKGROUND: Targeted anticancer therapies such as BCR-ABL tyrosine kinase inhibitors (TKIs) have improved outcomes for chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL). However, little is known about long-term risks of TKIs in children. Exposure-based survivorship guidelines do not include TKIs, thus surveillance practices may be variable. METHODS: We retrospectively examined surveillance for cardiac and endocrine late effects in children receiving TKIs for Ph + leukemias, diagnosed at < 21 years between 2000 and 2018. Frequency of echocardiogram (ECHO), electrocardiogram (EKG), thyroid stimulating hormone (TSH), dual-energy x-ray absorptiometry (DXA), and bone age testing were abstracted. Descriptive statistics were stratified by leukemia type. RESULTS: 66 patients (CML n = 44; Ph + ALL n = 22) met inclusion criteria. Among patients with CML, ≥1 evaluation was done: ECHO (50.0%), EKG (48.8%), TSH (43.9%), DXA (2.6%), bone age (7.4%). Among patients with Ph + ALL, ≥1 evaluation was done: ECHO (86.4%), EKG (68.2%), TSH (59.1%), DXA (63.6%), bone age (44.4%). Over a median 6.3 and 5.7 years of observation, respectively, 2% of patients with CML and 57% with Ph + ALL attended a survivorship clinic. CONCLUSIONS: Despite common exposure to TKIs in survivors of Ph + leukemias, patterns of surveillance for late effects differed in CML and Ph + ALL, with the latter receiving more surveillance likely due to concomitant chemotherapy exposures. Targeted therapies such as TKIs are revolutionizing cancer treatment, but surveillance for late effects and referral to survivorship clinics are variable despite the chronicity of exposure. Evidence based guidelines and longer follow-up are needed.
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Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Cromosoma Filadelfia , Vigilancia de la Población/métodos , Inhibidores de Proteínas Quinasas/efectos adversos , Absorciometría de Fotón/estadística & datos numéricos , Adolescente , Determinación de la Edad por el Esqueleto/estadística & datos numéricos , Supervivientes de Cáncer , Niño , Dasatinib/efectos adversos , Dasatinib/uso terapéutico , Ecocardiografía/estadística & datos numéricos , Electrocardiografía/estadística & datos numéricos , Femenino , Proteínas de Fusión bcr-abl , Humanos , Mesilato de Imatinib/efectos adversos , Mesilato de Imatinib/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Masculino , Terapia Molecular Dirigida/efectos adversos , Inhibidores de Proteínas Quinasas/uso terapéutico , Estudios Retrospectivos , Tirotropina/análisisRESUMEN
PURPOSE: Tumor infiltration by immunosuppressive myeloid cells or tumor-associated macrophages (TAMs) contributes to tumor progression and metastasis. In contrast to their adult counterparts, higher TAM signatures do not correlate with aggressive tumor behavior in pediatric brain tumors. While prominent TAM infiltrates exist before and after radiation, the degree to which irradiated macrophages and microglia support progression or leptomeningeal metastasis remains unclear. Patients with medulloblastoma often present with distant metastases and tumor recurrence is largely incurable, making them prime candidates for the study of novel approaches to prevent neuroaxis dissemination and recurrence. METHODS: Macrophage depletion was achieved using CSF-1 receptor inhibitors (CSF-1Ri), BLZ945 and AFS98, with or without whole brain radiation in a variety of medulloblastoma models, including patient-derived xenografts bearing Group 3 medulloblastoma and a transgenic Sonic Hedgehog (Ptch1+/-, Trp53-/-) medulloblastoma model. RESULTS: Effective reduction of microglia, TAM, and spinal cord macrophage with CSF-1Ri resulted in negligible effects on the rate of local and spinal recurrences or survival following radiation. Results were comparable between medulloblastoma subgroups. While notably few tumor-infiltrating lymphocytes (TILs) were detected, average numbers of CD3+ TILs and FoxP3+ Tregs did not differ between groups following treatment and tumor aggressiveness by Ki67 proliferation index was unaltered. CONCLUSION: In the absence of other microenvironmental influences, medulloblastoma-educated macrophages do not operate as tumor-supportive cells or promote leptomeningeal recurrence in these models. Our data add to a growing body of literature describing a distinct immunophenotype amid the medulloblastoma microenvironment and highlight the importance of appropriate pediatric modeling prior to clinical translation.
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Neoplasias Cerebelosas , Meduloblastoma , Transducción de Señal , Niño , Proteínas Hedgehog , Humanos , Factor Estimulante de Colonias de Macrófagos , Macrófagos , Proteínas Tirosina Quinasas Receptoras , Receptor de Factor Estimulante de Colonias de Macrófagos , Microambiente TumoralRESUMEN
PURPOSE OF REVIEW: Chronic myelogenous leukemia (CML) is rare in children, requiring extrapolation from treatment of adults. In this review, we explore similarities and differences between adult and pediatric CML with a focus on therapeutic advances and emerging clinical questions. RECENT FINDINGS: Pediatric CML is effectively treated with long-term targeted therapy using tyrosine kinase inhibitors (TKIs). Newly diagnosed pediatric patients in chronic phase can now be treated with imatinib, dasatinib, or nilotinib without allogeneic hematopoietic stem cell transplantation. While treatment-free remission is possible in adults in chronic phase with optimal response to therapy, data are currently insufficient to support stopping TKI in pediatrics outside of a clinical trial. Knowledge gaps remain regarding long-term and late effects of TKIs in pediatric CML. Targeted therapy has markedly improved outcomes for pediatric CML, while raising a number of clinical questions, including the possibility of treatment-free remission and long-term health implications of prolonged TKI exposure at a young age.
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Antineoplásicos/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Adolescente , Niño , Dasatinib , Trasplante de Células Madre Hematopoyéticas , Humanos , Mesilato de Imatinib/uso terapéutico , Pirimidinas , Inducción de RemisiónRESUMEN
BACKGROUND: Optimal risk-based survivor health care includes surveillance for late effects and education targeted at reducing or preventing risky health behaviors. Understanding the reasons for a lack of risk-based follow-up care is essential. METHODS: Adult participants from the Childhood Cancer Survivor Study were surveyed about having a cancer-related visit in the past 2 years and the likelihood of having a cancer-related visit in the future. Additional factors thought to be related to the primary outcomes were also assessed. RESULTS: Nine hundred seventy-five survivors completed the survey. Twenty-seven percent (95% confidence interval [CI], 24%-30%) had a cancer-related medical visit in the previous 2 years, and 41% (95% CI, 38%-44%) planned to have such a visit within the next 2 years. The likelihood of having had a cancer-related visit within the last 2 years was higher among survivors assigning greater importance to these visits (relative risk [RR], 1.2; 95% CI, 1.1-1.3), perceiving greater susceptibility to health problems (RR, 1.2; 95% CI, 1.1-1.3), having a moderate to life-threatening chronic health problem related to their cancer (RR, 2.1; 95% CI, 1.7-2.7), seeing a primary care provider for a cancer-related problem (RR, 1.3; 95% CI, 1.0-1.6), having a cancer treatment summary (RR, 1.3; 95% CI, 1.0-1.6), and endorsing greater confidence in physicians' abilities to address questions and concerns (RR, 1.2; 95% CI, 1.0-1.3). CONCLUSIONS: Educational interventions improving awareness of treatment history and susceptibility to cancer-related late effects and corresponding risk-based care are likely to be beneficial for survivors of childhood cancers.
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Supervivientes de Cáncer , Neoplasias/epidemiología , Evaluación de Resultado en la Atención de Salud , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Masculino , Neoplasias/patología , Riesgo , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Biological structures with extreme morphologies are puzzling because they often lack obvious functions and stymie comparisons to homologous or analogous features with more typical shapes. An example of such an extreme morphotype is the uniquely modified vertebral column of the hero shrew Scutisorex, which features numerous accessory intervertebral articulations and massively expanded transverse processes. The function of these vertebral structures is unknown, and it is difficult to meaningfully compare them to vertebrae from animals with known behavioural patterns and spinal adaptations. Here, we use trabecular bone architecture of vertebral centra and quantitative external vertebral morphology to elucidate the forces that may act on the spine of Scutisorex and that of another large shrew with unmodified vertebrae (Crocidura goliath). X-ray micro-computed tomography (µCT) scans of thoracolumbar columns show that Scutisorex thori is structurally intermediate between C. goliath and S. somereni internally and externally, and both Scutisorex species exhibit trabecular bone characteristics indicative of higher in vivo axial compressive loads than C. goliath. Under compressive load, Scutisorex vertebral morphology is adapted to largely restrict bending to the sagittal plane (flexion). Although these findings do not solve the mystery of how Scutisorex uses its byzantine spine in vivo, our work suggests potentially fruitful new avenues of investigation for learning more about the function of this perplexing structure.
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Musarañas/anatomía & histología , Animales , Huesos , Vértebras LumbaresRESUMEN
When making decisions, people tend to choose the option they have looked at more. An unanswered question is how attention influences the choice process: whether it amplifies the subjective value of the looked-at option or instead adds a constant, value-independent bias. To address this, we examined choice data from six eye-tracking studies ( Ns = 39, 44, 44, 36, 20, and 45, respectively) to characterize the interaction between value and gaze in the choice process. We found that the summed values of the options influenced response times in every data set and the gaze-choice correlation in most data sets, in line with an amplifying role of attention in the choice process. Our results suggest that this amplifying effect is more pronounced in tasks using large sets of familiar stimuli, compared with tasks using small sets of learned stimuli.
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Atención/fisiología , Toma de Decisiones/fisiología , Fijación Ocular/fisiología , Percepción Visual/fisiología , Adulto , Medidas del Movimiento Ocular , Humanos , Factores de TiempoRESUMEN
Inflammation is characteristic of most clinical disorders that challenge the neural control of breathing. Since inflammation modulates neuroplasticity, we studied the impact of inflammation caused by prolonged intermittent hypoxia on an important form of respiratory plasticity, acute intermittent hypoxia (three, 5 min hypoxic episodes, 5 min normoxic intervals) induced phrenic long-term facilitation (pLTF). Because chronic intermittent hypoxia elicits neuroinflammation and pLTF is undermined by lipopolysaccharide-induced systemic inflammation, we hypothesized that one night of intermittent hypoxia (IH-1) elicits spinal inflammation, thereby impairing pLTF by a p38 MAP kinase-dependent mechanism. pLTF and spinal inflammation were assessed in anesthetized rats pretreated with IH-1 (2 min hypoxia, 2 min normoxia; 8 h) or sham normoxia and allowed 16 h for recovery. IH-1 (1) transiently increased IL-6 (1.5 ± 0.2-fold; p = 0.02) and inducible nitric oxide synthase (iNOS) (2.4 ± 0.4-fold; p = 0.01) mRNA in cervical spinal homogenates, (2) elicited a sustained increase in IL-1ß mRNA (2.4 ± 0.2-fold; p < 0.001) in isolated cervical spinal microglia, and (3) abolished pLTF (-1 ± 5% vs 56 ± 10% in controls; p < 0.001). pLTF was restored after IH-1 by systemic NSAID administration (ketoprofen; 55 ± 9%; p < 0.001) or spinal p38 MAP kinase inhibition (58 ± 2%; p < 0.001). IH-1 increased phosphorylated (activated) p38 MAP kinase immunofluorescence in identified phrenic motoneurons and adjacent microglia. In conclusion, IH-1 elicits spinal inflammation and impairs pLTF by a spinal p38 MAP kinase-dependent mechanism. By targeting inflammation, we may develop strategies to manipulate respiratory motor plasticity for therapeutic advantage when the respiratory control system is compromised (e.g., sleep apnea, apnea of prematurity, spinal injury, or motor neuron disease).
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Hipoxia/complicaciones , Neuronas Motoras/fisiología , Mielitis/complicaciones , Mielitis/etiología , Plasticidad Neuronal/fisiología , Trastornos Respiratorios/etiología , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Animales , Antiinflamatorios/uso terapéutico , Antígeno CD11b/metabolismo , Citocinas/genética , Citocinas/metabolismo , Modelos Animales de Enfermedad , Regulación de la Expresión Génica/efectos de los fármacos , Cetoprofeno/uso terapéutico , Masculino , Microglía/efectos de los fármacos , Microglía/metabolismo , Neuronas Motoras/efectos de los fármacos , Mielitis/tratamiento farmacológico , Plasticidad Neuronal/efectos de los fármacos , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , Nervio Frénico/fisiopatología , Ratas , Ratas Sprague-Dawley , Factores de Tiempo , VagotomíaRESUMEN
Chronic intermittent hypoxia (CIH) is a hallmark of sleep apnoea, a condition associated with diverse clinical disorders. CIH and sleep apnoea are characterized by increased reactive oxygen species formation, peripheral and CNS inflammation, neuronal death and neurocognitive deficits. Few studies have examined the role of microglia, the resident CNS immune cells, in models of CIH. Thus, little is known concerning their direct contributions to neuropathology or the cellular mechanisms regulating their activities during or following pathological CIH. In this review, we identify gaps in knowledge regarding CIH-induced microglial activation, and propose mechanisms based on data from related models of hypoxia and/or hypoxia-reoxygenation. CIH may directly affect microglia, or may have indirect effects via the periphery or other CNS cells. Peripheral inflammation may indirectly activate microglia via entry of pro-inflammatory molecules into the CNS, and/or activation of vagal afferents that trigger CNS inflammation. CIH-induced release of damage-associated molecular patterns from injured CNS cells may also activate microglia via interactions with pattern recognition receptors expressed on microglia. For example, Toll-like receptors activate mitogen-activated protein kinase/transcription factor pathways required for microglial inflammatory gene expression. Although epigenetic effects from CIH have not yet been studied in microglia, potential epigenetic mechanisms in microglial regulation are discussed, including microRNAs, histone modifications and DNA methylation. Epigenetic effects can occur during CIH, or long after it has ended. A better understanding of CIH effects on microglial activities may be important to reverse CIH-induced neuropathology in patients with sleep disordered breathing.
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Hipoxia/metabolismo , Microglía/metabolismo , Síndromes de la Apnea del Sueño/metabolismo , Animales , Humanos , Hipoxia/etiología , Inflamación/etiología , Inflamación/metabolismo , Sistema de Señalización de MAP Quinasas , Síndromes de la Apnea del Sueño/complicaciones , Receptores Toll-Like/metabolismoRESUMEN
Activation of microglia, CNS resident immune cells, is a pathological hallmark of amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder affecting motor neurons. Despite evidence that microglia contribute to disease progression, the exact role of these cells in ALS pathology remains unknown. We immunomagnetically isolated microglia from different CNS regions of SOD1(G93A) rats at three different points in disease progression: presymptomatic, symptom onset and end-stage. We observed no differences in microglial number or phenotype in presymptomatic rats compared to wild-type controls. Although after disease onset there was no macrophage infiltration, there were significant increases in microglial numbers in the spinal cord, but not cortex. At disease end-stage, microglia were characterized by high expression of galectin-3, osteopontin and VEGF, and concomitant downregulated expression of TNFα, IL-6, BDNF and arginase-1. Flow cytometry revealed the presence of at least two phenotypically distinct microglial populations in the spinal cord. Immunohistochemistry showed that galectin-3/osteopontin positive microglia were restricted to the ventral horns of the spinal cord, regions with severe motor neuron degeneration. End-stage SOD1(G93A) microglia from the cortex, a less affected region, displayed similar gene expression profiles to microglia from wild-type rats, and displayed normal responses to systemic inflammation induced by LPS. On the other hand, end-stage SOD1(G93A) spinal microglia had blunted responses to systemic LPS suggesting that in addition to their phenotypic changes, they may also be functionally impaired. Thus, after disease onset, microglia acquired unique characteristics that do not conform to typical M1 (inflammatory) or M2 (anti-inflammatory) phenotypes. This transformation was observed only in the most affected CNS regions, suggesting that overexpression of mutated hSOD1 is not sufficient to trigger these changes in microglia. These novel observations suggest that microglial regional and phenotypic heterogeneity may be an important consideration when designing new therapeutic strategies targeting microglia and neuroinflammation in ALS.
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Esclerosis Amiotrófica Lateral/inmunología , Corteza Cerebral/inmunología , Microglía/fisiología , Médula Espinal/inmunología , Esclerosis Amiotrófica Lateral/patología , Animales , Arginasa/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Corteza Cerebral/patología , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Galectina 3/metabolismo , Humanos , Interleucina-6/metabolismo , Lipopolisacáridos , Masculino , Microglía/patología , Osteopontina/metabolismo , Fenotipo , Ratas Sprague-Dawley , Ratas Transgénicas , Médula Espinal/patología , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismo , Superóxido Dismutasa-1 , Factor de Necrosis Tumoral alfa/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
BACKGROUND: Cancer survivors experience complex medical and psychosocial challenges after a cancer diagnosis, leading to unmet informational and emotional needs. There is a paucity of cancer survivorship educational resources co-created by survivors and medical professionals. OBJECTIVE: Our aim was to create an educational resource for cancer survivors, caregivers, and medical professionals that would leverage digital storytelling to address survivorship topics. PATIENT INVOLVEMENT: Our content and production team included cancer survivors, clinicians, educators, and design experts. All content was co-created by cancer survivors and medical experts. METHODS: We conducted an environmental scan of existing cancer survivorship educational resources in academic and public domains. Applying human-centered design principles, we incorporated patient perspectives through advisory board meetings and focus groups and identified a podcast as the preferred medium. We selected content and speakers, produced the podcast, and developed a corresponding website. RESULTS: Based on patient recommendations, podcast episodes address mental health, fear of cancer recurrence, relationships, parenting, relating to a new body, care transitions for adult survivors of childhood cancer, disclosing health information, and financial burden of cancer. Podcast guests were invited based on lived or learned experience in these domains. Thirteen guests (survivors, experts) and four hosts (two cancer survivors, two oncologists) co-created 15 podcast episodes. Podcast guests found the storytelling experience to be powerful and therapeutic. DISCUSSION: Digital storytelling is a scalable and accessible educational tool for communicating complex survivorship concepts that can amplify survivors' voices and increase awareness among survivors and clinicians. Co-creation of educational resources for cancer survivorship by survivors and professionals is a feasible and innovative educational strategy. PRACTICAL VALUE: A podcast created by and for cancer survivors in partnership with medical experts highlights opportunities for peer-to-peer digital storytelling to foster community among survivors and caregivers. FUNDING: Podcast production was supported by the Stanford Comprehensive Cancer Center.
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Supervivientes de Cáncer , Neoplasias , Adulto , Humanos , Supervivientes de Cáncer/psicología , Neoplasias/terapia , Neoplasias/psicología , Sobrevivientes/psicología , Supervivencia , ComunicaciónRESUMEN
We compare the effects of burrowing behavior on appendicular bone structure in two Peromyscus (deer mouse) species. P. polionotus creates complex burrows in their territories, while P. eremicus is a non-burrowing nesting mouse. We examined museum specimens' bones of wild-caught mice of the two species and lab-reared P. polionotus not given the opportunity to burrow. Bones were scanned using micro-computed tomography, and cortical and trabecular bone structural properties were quantified. Wild P. polionotus mice had a larger moment of area in the ulnar and tibial cortical bone compared with their lab-reared counterparts, suggesting developmental adaptation to bending resistance. Wild P. polionotus had a larger normalized second moment of area and cross-sectional area in the tibia compared with P. eremicus. Tibial trabecular analysis showed lower trabecular thickness and spacing in wild P. polionotus than in P. eremicus and femoral analysis showed wild P. polionotus had lower thickness than P. eremicus and lower spacing than lab-reared P. polionotus, suggesting adaptation to high loads from digging. Results lay the groundwork for future exploration of the ontogenetic and evolutionary basis of mechanoadaptation in Peromyscus.
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The Stanford Cancer Survivorship Program is a key initiative of Stanford Cancer Institute. The program's mission is to improve the experience and outcomes of patients and family caregivers throughout all phases of the cancer trajectory by advancing survivorship research, clinical care, and education. The four pillars of the program include clinical care delivery with a focus on primary care-survivorship collaboration and expanding specialty services, education and training of healthcare professionals, transdisciplinary patient-oriented research, and community engagement. Cross-cutting areas of expertise include the following: (a) adolescents and young adults (AYAs), (b) mental health and patient self-management, (c) integration of primary care, and (d) postgraduate medical education. The clinical care model includes embedded survivorship clinics within disease groups in outpatient clinics, novel clinics designed to address unmet needs such as sexual health for women, and primary care-based faculty-led survivorship clinics for patients undergoing active cancer care requiring co-management, those who have completed active therapy and those at high risk for cancer due to genetic risk. Educational initiatives developed to date include an online course and medical textbook for primary care clinicians, a lecture series, monthly research team meetings, and rotations for medical trainees. Patient-facing activities include webinars and a podcast series designed to promote awareness, thus expanding the provision of expert-vetted information. Ongoing research focuses on oncofertility and family building after cancer, improving communication for AYAs, changing mindsets to improve quality of life through targeted digital interventions, increasing capacity to care for cancer survivors, and strengthening collaboration with community partners. IMPLICATIONS FOR CANCER SURVIVORS: Stanford's Cancer Survivorship Program includes a robust transdisciplinary and interdisciplinary research, training and clinical platform that is committed to advancing access and improving care for people living with and beyond cancer, through innovation in design and care delivery.
Asunto(s)
Supervivientes de Cáncer , Neoplasias , Adolescente , Adulto Joven , Humanos , Femenino , Calidad de Vida/psicología , Atención a la Salud , Supervivencia , Cuidadores , Neoplasias/terapiaRESUMEN
BACKGROUND: Adult survivors of childhood acute lymphoblastic leukemia (ALL) are at increased cardiovascular risk. Studies of factors including treatment exposures that may modify risk of low cardiorespiratory fitness in this population have been limited. PROCEDURE: To assess cardiorespiratory fitness, maximal oxygen uptake (VO2 max) was measured in 115 ALL survivors (median age, 23.5 years; range 18-37). We compared VO2 max measurements for ALL survivors to those estimated from submaximal testing in a frequency-matched (age, gender, race/ethnicity) 2003-2004 National Health and Nutritional Examination Survey (NHANES) cohort. Multivariable linear regression models were constructed to evaluate the association between therapeutic exposures and outcomes of interest. RESULTS: Compared to NHANES participants, ALL survivors had a substantially lower VO2 max (mean 30.7 vs. 39.9 ml/kg/min; adjusted P < 0.0001). For any given percent total body fat, ALL survivors had an 8.9 ml/kg/min lower VO2 max than NHANES participants. For key treatment exposure groups (cranial radiotherapy [CRT], anthracycline chemotherapy, or neither), ALL survivors had substantially lower VO2 max compared with NHANES participants (all comparisons, P < 0.001). Almost two-thirds (66.7%) of ALL survivors were classified as low cardiorespiratory fitness compared with 26.3% of NHANES participants (adjusted P < 0.0001). In multivariable models including only ALL survivors, treatment exposures were modestly associated with VO2 max. Among females, CRT was associated with low VO2 max (P = 0.02), but anthracycline exposure was not (P = 0.58). In contrast, among males, anthracycline exposure ≥ 100 mg/m(2) was associated with low VO2 max (P = 0.03), but CRT was not (P = 0.54). CONCLUSION: Adult survivors of childhood ALL have substantially lower levels of cardiorespiratory fitness compared with a similarly aged non-cancer population.