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1.
Int J Eat Disord ; 56(9): 1703-1716, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37232007

RESUMO

OBJECTIVE: To examine sex differences in risk factors for anorexia nervosa (AN). METHOD: This population-based study involved 44,743 individuals (6,239 AN cases including 5,818 females and 421 males, and 38,504 controls including 18,818 females and 19,686 males) born in Denmark between May 1981 and December 2009. Follow-up began on the individual's sixth birthday and ended at AN diagnosis, emigration, death, or December 31, 2016, whichever occurred first. Exposures included socioeconomic status (SES), pregnancy, birth, and early childhood factors based on data from Danish registers, and psychiatric and metabolic polygenic risk scores (PRS) based on genetic data. Hazard ratios were estimated using weighted Cox proportional hazards models stratified by sex (assigned at birth), with AN diagnosis as the outcome. RESULTS: The effects of early life exposures and PRS on AN risk were comparable between females and males. Although we observed some differences in the magnitude and direction of effects, there were no significant interactions between sex and SES, pregnancy, birth, or early childhood exposures. The effects of most PRS on AN risk were highly similar between the sexes. We observed significant sex-specific effects of parental psychiatric history and body mass index PRS, though these effects did not survive corrections for multiple comparisons. CONCLUSIONS: Risk factors for AN are comparable between females and males. Collaboration across countries with large registers is needed to further investigate sex-specific effects of genetic, biological, and environmental exposures on AN risk, including exposures in later childhood and adolescence as well as the additive effects of exposures. PUBLIC SIGNIFICANCE: Sex differences in the prevalence and clinical presentation of AN warrant examination of sex-specific risk factors. This population-based study indicates that the effects of polygenic risk and early life exposures on AN risk are comparable between females and males. Collaboration between countries with large registers is needed to further investigate sex-specific AN risk factors and improve early identification of AN.


Assuntos
Anorexia Nervosa , Gravidez , Recém-Nascido , Adolescente , Humanos , Masculino , Feminino , Pré-Escolar , Anorexia Nervosa/epidemiologia , Anorexia Nervosa/genética , Anorexia Nervosa/diagnóstico , Caracteres Sexuais , Fatores de Risco , Pais , Medição de Risco
2.
Front Oncol ; 13: 1105395, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37124531

RESUMO

Background: Diffuse midline glioma (DMG) is an aggressive pediatric central nervous system tumor with strong metastatic potential. As localized treatment of the primary tumor improves, metastatic disease is becoming a more important factor in treatment. We hypothesized that we could model craniospinal irradiation (CSI) through a DMG patient-derived xenograft (PDX) model and that CSI would limit metastatic tumor. Methods: We used a BT245 murine orthotopic DMG PDX model for this work. We developed a protocol and specialized platform to deliver craniospinal irradiation (CSI) (4 Gy x2 days) with a pontine boost (4 Gy x2 days) and compared metastatic disease by pathology, bioluminescence, and MRI to mice treated with focal radiation only (4 Gy x4 days) or no radiation. Results: Mice receiving CSI plus boost showed minimal spinal and brain leptomeningeal metastatic disease by bioluminescence, MRI, and pathology compared to mice receiving radiation to the pons only or no radiation. Conclusion: In a DMG PDX model, CSI+boost minimizes tumor dissemination compared to focal radiation. By expanding effective DMG treatment to the entire neuraxis, CSI has potential as a key component to combination, multimodality treatment for DMG designed to achieve long-term survival once novel therapies definitively demonstrate improved local control.

3.
Diabet Med ; 40(5): e15071, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36807935

RESUMO

AIMS: To summarize and critically appraise evidence regarding the effectiveness of educational and/or behavioural interventions in reducing fear of hypoglycaemia among adults with type 1 diabetes. METHODS: Systematic searches of medical and psychology databases were conducted. Risk-of-bias was assessed using the Joanna Briggs Institute Critical Appraisal Tools. Data were synthesized using random-effects meta-analyses for randomized controlled trials (RCTs) and narrative synthesis for observational studies. RESULTS: Five RCTs (N = 682) and seven observational studies (N = 1519) met the inclusion criteria, reporting on behavioural, structured education and cognitive-behavioural therapy (CBT) interventions. Most studies assessed fear of hypoglycaemia using the Hypoglycaemia Fear Survey Worry (HFS-W) and Behaviour (HFS-B) subscales. Mean fear of hypoglycaemia at baseline was relatively low across studies. Meta-analyses showed a significant effect of interventions on HFS-W (SMD = -0.17, p = 0.032) but not on HFS-B scores (SMD = -0.34, p = 0.113). Across RCTs, Blood Glucose Awareness Training (BGAT) had the largest effect on HFS-W and HFS-B scores, and one CBT-based program was as effective as BGAT in reducing HFS-B scores. Observational studies showed that Dose Adjustment for Normal Eating (DAFNE) was associated with significant fear of hypoglycaemia reductions. CONCLUSIONS: Current evidence suggests that educational and behavioural interventions can reduce fear of hypoglycaemia. However, no study to date has examined these interventions among people with high fear of hypoglycaemia.


Assuntos
Diabetes Mellitus Tipo 1 , Hipoglicemia , Humanos , Adulto , Hipoglicemia/psicologia , Medo/psicologia , Escolaridade , Ansiedade/psicologia , Glicemia
4.
Diabet Med ; 40(4): e15040, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36625417

RESUMO

AIMS: People with type 1 diabetes have a higher risk for cardiovascular disease (CVD). Reduced heart rate variability (HRV) is a clinical marker for CVD. In this observational study using continuous HRV measurement across 26 days, we investigated whether psychological stressors (diabetes distress, depressive symptoms) and glycaemic parameters (hypo- and hyperglycaemic exposure, glycaemic variability and HbA1c ) are associated with lower HRV in people with type 1 diabetes. METHODS: Data from the non-interventional prospective DIA-LINK1 study were analysed. At baseline, depressive symptoms and diabetes distress were assessed. Glucose values and HRV were recorded daily for 26 days using continuous glucose monitoring (CGM) and a wrist-worn health tracker respectively. Multilevel modelling with participant as nesting factor was used to analyse associations between day-to-day HRV and diabetes distress, depressive symptoms and CGM-derived parameters. RESULTS: Data from 149 participants were analysed (age: 38.3 ± 13.1 years, HbA1c : 8.6 ± 1.9%). Participants with elevated diabetes distress had a significantly lower HRV across the 26 days compared to participants without elevated distress (ß = -0.28; p = 0.004). Elevated depressive symptoms were not significantly associated with HRV (ß = -0.18; p = 0.074). Higher daily exposure to hyperglycaemia (ß = -0.44; p = 0.044), higher average exposure to hypoglycaemia (ß = -0.18; p = 0.042) and higher HbA1c (ß = -0.20; p = 0.018) were associated with reduced HRV across the 26 days. Sensitivity analysis with HRV averaged across all days corroborated these results. CONCLUSIONS: Diabetes distress is a clinically meaningful psychosocial stressor that could play a role in the cardiovascular health of people with type 1 diabetes. These findings highlight the need for integrated psychosocial care in diabetes management.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 1 , Humanos , Adulto , Pessoa de Meia-Idade , Frequência Cardíaca/fisiologia , Automonitorização da Glicemia , Estudos Prospectivos , Glicemia/análise
5.
J Diabetes Complications ; 37(11): 108232, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-35927177

RESUMO

AIMS: Research on hypoglycaemia and quality of life (QoL) has focused mostly on severe hypoglycaemia and psychological outcomes, with less known about other aspects of hypoglycaemia (e.g., self-treated episodes) and impacts on other QoL domains (e.g., relationships). Therefore, we examined the impact of all aspects of hypoglycaemia on QoL in adults with type 1 diabetes (T1DM). METHODS: Participants completed an online survey, including assessment of hypoglycaemia-specific QoL (using the 12-item Hypoglycaemia Impact Profile). Mann-Whitney U tests examined differences in hypoglycaemia-specific QoL by hypoglycaemia frequency, severity, and awareness. Hierarchical linear regression examined associations with QoL. RESULTS: Participants were 1028 adults with T1DM (M ± SD age: 47 ± 15 years; diabetes duration: 27 ± 16 years). Severe and self-treated hypoglycaemia and impaired awareness negatively impacted on overall QoL and several QoL domains, including leisure activities, physical health, ability to keep fit/be active, sleep, emotional well-being, spontaneity, independence, work/studies, and dietary freedom. Diabetes distress was most strongly associated with hypoglycaemia-specific QoL, followed by generic emotional well-being, fear of hypoglycaemia, and confidence in managing hypoglycaemia. Hypoglycaemia frequency and awareness were no longer significantly associated with QoL once psychological factors were considered. CONCLUSIONS: Hypoglycaemia negatively impacts on several QoL domains. Psychological factors supersede the effect of hypoglycaemia frequency and awareness in accounting for this negative impact.


Assuntos
Diabetes Mellitus Tipo 1 , Hipoglicemia , Adulto , Humanos , Pessoa de Meia-Idade , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/psicologia , Hipoglicemiantes , Qualidade de Vida , Hipoglicemia/psicologia , Medo/psicologia
6.
Artigo em Inglês | MEDLINE | ID: mdl-35977753

RESUMO

INTRODUCTION: The aim of this study was to determine the psychometric properties of the 12-Item Hypoglycemia Impact Profile (HIP12), a brief measure of the impact of hypoglycemia on quality of life (QoL) among adults with type 1 (T1D) or type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: Adults with T1D (n=1071) or T2D (n=194) participating in the multicountry, online study, 'Your SAY: Hypoglycemia', completed the HIP12. Psychometric analyses were undertaken to determine acceptability, structural validity, internal consistency, convergent/divergent validity, and known-groups validity. RESULTS: Most (98%) participants completed all items on the HIP12. The expected one-factor solution was supported for T1D, T2D, native English speaker, and non-native English speaker groups. Internal consistency was high across all groups (ω=0.91-0.93). Convergent and divergent validity were satisfactory. Known-groups validity was demonstrated for both diabetes types, by frequency of severe hypoglycemia (0 vs ≥1 episode in the past 12 months) and self-treated episodes (<2 vs 2-4 vs ≥5 per week). The measure also discriminated by awareness of hypoglycemia in those with T1D. CONCLUSIONS: The HIP12 is an acceptable, internally consistent, and valid tool for assessing the impact of hypoglycemia on QoL among adults with T1D. The findings in the relatively small sample with T2D are encouraging and warrant replication in a larger sample.


Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Hipoglicemia , Adulto , Humanos , Psicometria , Qualidade de Vida
7.
Pediatr Diabetes ; 23(3): 390-405, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34981624

RESUMO

This systematic review aims to summarize and critically evaluate the current evidence regarding the impact of hypoglycaemia in children and adolescents with type 1 diabetes on parental quality of life. MEDLINE, PsycINFO, CINAHL, and the Cochrane Library were searched. Inclusion criteria were: 1) quantitative design, 2) included parents of children or adolescents with type 1 diabetes, 3) assessment of hypoglycemia in children/adolescents with type 1 diabetes, 4) assessment of parent quality of life (or related domains of life), and 5) analysis of the relationship(s) between the child's hypoglycaemia and parents' quality of life. The data were summarised in accordance with Synthesis Without Meta-Analysis Guidelines. Twelve studies were included, reporting data from 1895 parents across six countries. Ten studies were cross-sectional; two included prospective data. Evidence suggested that greater frequency and severity of hypoglycemia was associated with greater parental fear of hypoglycemia, emotional distress and family burden. Children's hypoglycaemia has a negative impact on the well-being of parents, but there is an absence of evidence regarding the impact on their overall quality of life. Research into the hypoglycaemia-specific quality of life of parents is needed to explore the impact on various areas, such as social and physical dimensions.


Assuntos
Diabetes Mellitus Tipo 1 , Hipoglicemia , Adolescente , Criança , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/psicologia , Humanos , Hipoglicemia/psicologia , Pais/psicologia , Estudos Prospectivos , Qualidade de Vida
8.
Diabet Med ; 39(1): e14727, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34668230

RESUMO

OBJECTIVE: Hypoglycaemic episodes and fear of hypoglycaemia can be burdensome for adults with type 1 diabetes. This study explored support needs relating to hypoglycaemia among adults with type 1 diabetes living in Denmark, Germany, the Netherlands and the United Kingdom. RESEARCH DESIGN AND METHODS: Respondents participated in a web-based qualitative study involving four open-ended questions that asked what they wished other people understood about hypoglycaemia and what other people could do differently to support them with hypoglycaemia. Responses were analyzed using reflexive thematic analysis. RESULTS: Participants were 219 adults with type 1 diabetes (mean ± SD age 39 ± 13 years; mean ± SD diabetes duration 20 ± 14 years). They described unmet needs relating to: (1) Clinical support, involving access to new diabetes technologies, training on hypoglycaemia prevention, personalised care and psychological support; (2) Practical support, involving family and friends better supporting them with hypoglycaemia management and prevention; (3) Education for other people, involving others becoming more informed about hypoglycaemia; and (4) An appreciation of the burden, involving others recognizing the experience and impact of episodes, and the burden of living with the risk of hypoglycaemia. CONCLUSIONS: Adults with type 1 diabetes report several unmet support needs relating to hypoglycaemia. Service delivery should be person-centred and prioritise the individual's support needs. Clinical conversations are needed to identify the individual's support needs and develop tailored support plans. People with diabetes and their family members should be offered hypoglycaemia-specific education and training.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Insulina/administração & dosagem , Internet , Pesquisa Qualitativa , Adolescente , Adulto , Idoso , Diabetes Mellitus Tipo 1/epidemiologia , Família , Feminino , Alemanha/epidemiologia , Humanos , Hipoglicemiantes/administração & dosagem , Masculino , Pessoa de Meia-Idade , Morbidade/tendências , Países Baixos/epidemiologia , Qualidade de Vida , Reino Unido/epidemiologia , Adulto Jovem
9.
Cancers (Basel) ; 13(24)2021 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-34944778

RESUMO

Overexpression of Exportin-1 (XPO1), a key regulator of nuclear-to-cytoplasmic transport, is associated with inferior patient outcomes across a range of adult malignancies. Targeting XPO1 with selinexor has demonstrated promising results in clinical trials, leading to FDA approval of its use for multiple relapsed/refractory cancers. However, XPO1 biology and selinexor sensitivity in childhood cancer is only recently being explored. In this review, we will focus on the differential biology of childhood and adult cancers as it relates to XPO1 and key cargo proteins. We will further explore the current state of pre-clinical and clinical development of XPO1 inhibitors in childhood cancers. Finally, we will outline potentially promising future therapeutic strategies for, as well as potential challenges to, integrating XPO1 inhibition to improve outcomes for children with cancer.

10.
J Neuropathol Exp Neurol ; 80(12): 1099-1107, 2021 12 29.
Artigo em Inglês | MEDLINE | ID: mdl-34850053

RESUMO

Brain tumors are the most common solid tumor in children, and low-grade gliomas (LGGs) are the most common childhood brain tumor. Here, we report on 3 patients with LGG harboring previously unreported or rarely reported RAF fusions: FYCO1-RAF1, CTTNBP2-BRAF, and SLC44A1-BRAF. We hypothesized that these tumors would show molecular similarity to the canonical KIAA1549-BRAF fusion that is the most widely seen alteration in pilocytic astrocytoma (PA), the most common pediatric LGG variant, and that this similarity would include mitogen-activated protein kinase (MAPK) pathway activation. To test our hypothesis, we utilized immunofluorescent imaging and RNA-sequencing in normal brain, KIAA1549-BRAF-harboring tumors, and our 3 tumors with novel fusions. We performed immunofluorescent staining of ERK and phosphorylated ERK (p-ERK), identifying increased p-ERK expression in KIAA1549-BRAF fused PA and the novel fusion samples, indicative of MAPK pathway activation. Geneset enrichment analysis further confirmed upregulated downstream MAPK activation. These results suggest that MAPK activation is the oncogenic mechanism in noncanonical RAF fusion-driven LGG. Similarity in the oncogenic mechanism suggests that LGGs with noncanonical RAF fusions are likely to respond to MEK inhibitors.


Assuntos
Neoplasias Encefálicas/genética , Glioma/genética , Sistema de Sinalização das MAP Quinases/fisiologia , Proteínas de Fusão Oncogênica/genética , Quinases raf/genética , Adolescente , Neoplasias Encefálicas/metabolismo , Criança , Feminino , Glioma/metabolismo , Humanos , Masculino
11.
PLoS One ; 16(12): e0260896, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34855927

RESUMO

OBJECTIVE: To conduct a systematic review to examine associations between hypoglycemia and quality of life (QoL) in children and adolescents with type 1 diabetes. METHODS: Four databases (Medline, Cochrane Library, CINAHL, PsycINFO) were searched systematically in November 2019 and searches were updated in September 2021. Studies were eligible if they included children and/or adolescents with type 1 diabetes, reported on the association between hypoglycemia and QoL (or related outcomes), had a quantitative design, and were published in a peer-reviewed journal after 2000. A protocol was registered the International Prospective Register of Systematic Reviews (PROSPERO; CRD42020154023). Studies were evaluated using the Joanna Briggs Institute's critical appraisal tool. A narrative synthesis was conducted by outcome and hypoglycemia severity. RESULTS: In total, 27 studies met inclusion criteria. No hypoglycemia-specific measures of QoL were identified. Evidence for an association between SH and (domains) of generic and diabetes-specific QoL was too limited to draw conclusions, due to heterogenous definitions and operationalizations of hypoglycemia and outcomes across studies. SH was associated with greater worry about hypoglycemia, but was not clearly associated with diabetes distress, depression, anxiety, disordered eating or posttraumatic stress disorder. Although limited, some evidence suggests that more recent, more frequent, or more severe episodes of hypoglycemia may be associated with adverse outcomes and that the context in which hypoglycemia takes places might be important in relation to its impact. CONCLUSIONS: There is insufficient evidence regarding the impact of hypoglycemia on QoL in children and adolescents with type 1 diabetes at this stage. There is a need for further research to examine this relationship, ideally using hypoglycemia-specific QoL measures.


Assuntos
Diabetes Mellitus Tipo 1/complicações , Hipoglicemia/psicologia , Qualidade de Vida , Estresse Psicológico/etiologia , Adolescente , Criança , Humanos , Hipoglicemia/etiologia , Hipoglicemia/patologia , Estresse Psicológico/patologia
12.
Artigo em Inglês | MEDLINE | ID: mdl-34400465

RESUMO

INTRODUCTION: Achieving glycemic targets and optimizing quality of life (QoL) are important goals of type 1 diabetes care. Hypoglycemia is a common barrier to achieving targets and can be associated with significant distress. However, the impact of hypoglycemia on QoL is not fully understood. The aim of this study was to explore how adults with type 1 diabetes are impacted by hypoglycemia in areas of life that are important to their overall QoL. RESEARCH DESIGN AND METHODS: Participants responded to a web-based qualitative survey involving a novel 'Wheel of Life' activity. Responses were analyzed using reflexive thematic analysis. RESULTS: The final sample included 219 adults with type 1 diabetes from Denmark, Germany, the Netherlands, and the UK. They had a mean±SD age of 39±13 years and diabetes duration of 20±14 years. Participants identified eight areas of life important to their overall QoL, including relationships and social life, work and studies, leisure and physical activity, everyday life, sleep, sex life, physical health, and mental health. Participants reported emotional, behavioral, cognitive, and social impacts of hypoglycemia within domains. Across domains, participants described interruptions, limited participation in activities, exhaustion, fear of hypoglycemia, compensatory strategies to prevent hypoglycemia, and reduced spontaneity. CONCLUSIONS: The findings emphasize the profound impact of hypoglycemia on QoL and diabetes self-care behaviors. Diabetes services should be aware of and address the burden of hypoglycemia to provide person-centered care. Clinicians could ask individuals how hypoglycemia affects important areas of their lives to better understand the personal impact and develop tailored management plans.


Assuntos
Diabetes Mellitus Tipo 1 , Hipoglicemia , Adulto , Glicemia , Diabetes Mellitus Tipo 1/terapia , Humanos , Hipoglicemia/epidemiologia , Pessoa de Meia-Idade , Qualidade de Vida , Inquéritos e Questionários
13.
Diabetes Res Clin Pract ; 174: 108752, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33722700

RESUMO

Hypoglycaemia is a common barrier to optimal glycaemic management and often feared among adults with type 1 diabetes. The aim of this systematic review was to summarize current evidence regarding the impact of hypoglycaemia on quality of life (QoL) and related outcomes. Electronic searches of MEDLINE, PsycINFO, CINAHL, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials were conducted. Peer-reviewed empirical studies investigating the relationship between hypoglycaemia and QoL were eligible for inclusion. Thirty studies met the inclusion criteria. Extracted data was summarized in a narrative synthesis according to Synthesis Without Meta-Analysis guidelines. None of the studies examined the impact of hypoglycaemia on general QoL. There was no association between hypoglycaemia and diabetes-specific QoL in four of the 30 studies. Severe hypoglycaemia was associated with greater fear of hypoglycaemia and diabetes distress, and lower general emotional well-being, but not with depression, anxiety, or health status. Self-treated hypoglycaemia was associated with greater fear of hypoglycaemia. With the exception of fear of hypoglycaemia, this review shows mixed associations between hypoglycaemia and psychological outcomes. Further research is needed to investigate the impact of hypoglycaemia on other domains of QoL.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemia/psicologia , Hipoglicemiantes/efeitos adversos , Qualidade de Vida , Estresse Psicológico/epidemiologia , Diabetes Mellitus Tipo 1/complicações , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/epidemiologia , Hipoglicemiantes/administração & dosagem , Prognóstico , Estresse Psicológico/etiologia
14.
FEBS J ; 288(21): 6127-6141, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33523591

RESUMO

Pediatric high-grade gliomas (pHGG) comprise a deadly, heterogenous category of pediatric gliomas with a clear need for more effective treatment options. Advances in high-throughput molecular techniques have enhanced molecular understanding of these tumors, but outcomes are still poor, and treatments beyond resection and radiation have not yet been clearly established as standard of care. In this review, we first discuss the history of treatment approaches to pHGG to this point. We then review four distinct categories of pHGG, including histone 3-mutant, IDH-mutant, histone 3/IDH-wildtype, and radiation-induced pHGG. We discuss the molecular understanding of each subgroup and targeted treatment options in development. Finally, we look at the development and current status of two novel approaches to pHGG as a whole: localized convection-enhanced chemotherapy delivery and immunotherapy, including checkpoint inhibitors, vaccine therapy, and CAR-T cells. Through this review, we demonstrate the potential for rational, molecularly driven, subtype-specific therapy to be used with other novel approaches in combinations that could meaningfully improve the prognosis in pHGG.


Assuntos
Glioma/terapia , Animais , Criança , Terapia Combinada , Feminino , Glioma/patologia , Histonas/metabolismo , Humanos , Imunoterapia/métodos , Masculino , Prognóstico
15.
Neurooncol Adv ; 2(1): vdaa021, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32642682

RESUMO

BACKGROUND: Hundreds of systemic chemotherapy trials in diffuse intrinsic pontine glioma (DIPG) have not improved survival, potentially due to lack of intratumoral penetration, which has not previously been assessed in humans. METHODS: We used gemcitabine as a model agent to assess DIPG intratumoral pharmacokinetics (PK) using mass spectrometry. RESULTS: In a phase 0 clinical trial of i.v. gemcitabine prior to biopsy in children newly diagnosed with DIPG by MRI, mean concentration in 4 biopsy cores in patient 1 (H3K27M diffuse midline glioma) was 7.65 µM. These compare favorably to levels for patient 2 (mean 3.85 µM, found to have an H3K27-wildtype low-grade glioma on histology), and from a similar study in adult glioblastoma (adjusted mean 3.48 µM). In orthotopic patient-derived xenograft (PDX) models of DIPG and H3K27M-wildtype pediatric glioblastoma, gemcitabine levels and clearance were similar in tumor, pons, and cortex and did not depend on H3K27 mutation status or tumor location. Normalized gemcitabine levels were similar in patient 1 and the DIPG PDX. CONCLUSIONS: These findings, while limited to one agent, provide preliminary evidence for the hypotheses that lack of intratumoral penetration is not why systemic chemotherapy has failed in DIPG, and orthotopic PDX models can adequately model intratumoral PK in human DIPG.

16.
Complement Ther Clin Pract ; 28: 136-145, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28779921

RESUMO

OBJECTIVE: Examining the effectiveness of psychological interventions in treating secondary psychological outcomes of obesity has become prioritized in recent times. The objective of the present study was to compare an eight-week Cognitive-Behavioural Therapy (CBT) and Emotional Freedom Techniques (EFT) intervention program, in the treatment of food cravings and secondary psychological outcomes among overweight or obese adults (N = 83). METHOD: A controlled non-inferiority trial was performed comparing group-delivered CBT to group-delivered EFT. Participants completed the Patient Health Questionnaire at pre- and post-intervention, and at six and 12-months follow-up. RESULTS: The CBT group did not report any significant changes in anxiety scores over time, but the decrease in depression symptoms pre-to post-intervention was significant and this was maintained at 6-and 12-months. Anxiety and depression scores significantly decreased from pre-to post-intervention for the EFT group, and was maintained at 6- and 12-month follow-up. Somatoform scores significantly decreased from pre-intervention to all follow-up points for the CBT group, while the EFT group did not report any significant changes in somatoform symptoms. Results also revealed that EFT is capable of producing reductions in anxiety and depression symptoms, and may be comparable to gold standard approaches such as CBT. CONCLUSION: The current study supports the hypothesis that psychological intervention is beneficial for treating psychological comorbidities of obesity and points to the role mental health issues may play in this area.


Assuntos
Ansiedade/terapia , Terapia Cognitivo-Comportamental , Fissura , Emoções , Obesidade/psicologia , Psicoterapia/métodos , Adulto , Transtornos de Ansiedade , Depressão/terapia , Feminino , Liberdade , Humanos , Masculino , Pessoa de Meia-Idade , Sobrepeso , Psicoterapia de Grupo , Resultado do Tratamento , Adulto Jovem
17.
Cyberpsychol Behav Soc Netw ; 20(3): 142-149, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28263682

RESUMO

Social networking sites (SNSs) provide emerging adults with extreme and unprecedented transparency, exposing them to a plethora of opportunities for social comparison. In light of the growing use of the popular SNS, Instagram, among emerging adults, the purpose of this study was to examine the impact of exposure to social media-based social comparison information on self-esteem. The study recruited 237 participants through social media. The sample was narrowed to young adults aged 18-29 years. The study used a correlational nonexperimental approach to investigate two mediation models proposed in the literature. First, the study investigated the mediating role of social comparison on Instagram in the relationship between intensity of Instagram use and self-esteem. Second, the study examined the mediating role of social comparison in the relationship between self-worth contingent on approval from others and self-esteem. Although the first model was found to be nonsignificant, results observed a significant indirect pathway that confirmed the second model. Thus, social comparison on Instagram mediated the relationship between contingent self-worth and self-esteem. Furthermore, moderation analyses found that self-worth contingent on approval from others moderated the relationship between intensity of Instagram use and social comparison on Instagram. Thus, although Instagram did not directly affect self-esteem, the significant moderation suggested that intensity of Instagram use is influential when the young person's self-worth is contingent on approval from others. Overall, the findings are consistent with previous research and enhance our understanding of the mechanisms that link SNS use to low self-esteem.


Assuntos
Autoimagem , Mídias Sociais , Rede Social , Adolescente , Adulto , Feminino , Humanos , Masculino , Percepção Social , Adulto Jovem
18.
Integr Med (Encinitas) ; 15(2): 27-34, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27330487

RESUMO

CONTEXT: The World Health Organization (WHO) places major depressive disorder (MDD), or depression, as the fourth leading cause of disability worldwide. Some studies have found that cognitive behavioral therapy (CBT) represents the most superior approach in treating mild to severe symptoms. Recent literature has indicated a number of limitations to this therapeutic approach. An approach that has received increasing attention within the literature is the emotional freedom technique (EFT). OBJECTIVE: The current pilot study aimed to evaluate the effectiveness of CBT and EFT in the treatment of depression and comorbid anxiety. DESIGN: The research team designed a pilot study structured as a randomized, controlled trial with 2 intervention arms. SETTING: The study took place at Bond University in Gold Coast, Queensland, Australia. PARTICIPANTS: Participants (n = 10) were local community members who had screened positive for a primary diagnosis of MDD. INTERVENTION: Participants were randomly assigned to an 8-wk CBT or EFT treatment program, the intervention groups. A sample of individuals from the community was assessed for comparative purposes (control group) (n = 57). OUTCOME MEASURES: Pre- and postintervention, all participants were interviewed using the Mini-International Neuropsychiatric Interview (MINI) 6.0, and they completed the following validated questionnaires: (1) the Beck Depression Inventory, second edition (BDI-2) and (2) the Depression, Anxiety, and Stress Scales (DASS-21). RESULTS: Findings revealed that both treatment approaches produced significant reductions in depressive symptoms, with the CBT group reporting a significant reduction postintervention, which was not maintained with time. The EFT group reported a delayed effect involving a significant reduction in symptoms at the 3- and 6-mo follow-ups only. Examination of the individual cases revealed clinically significant improvements in anxiety across both interventions. CONCLUSIONS: Overall, the findings provide evidence to suggest that EFT might be an effective treatment strategy worthy of further investigation.

19.
Explore (NY) ; 12(2): 113-22, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26797227

RESUMO

CONTEXT: In Australia and throughout much of the world, rates of obesity continue to climb as do the prevalence of eating disorders, particularly in adolescents. Psychological consequences of childhood obesity include low self-esteem, depression, body dissatisfaction, and social maladjustment (Young-Hyman et al., 2012). OBJECTIVE AND INTERVENTION: This feasibility study sought to examine the impact of a six-week Emotional Freedom Techniques (EFT) group treatment program upon eating behaviours, self-esteem, compassion, and psychological symptoms. DESIGN: Forty-four students were randomly allocated to either the EFT group or the waitlist control group. RESULTS: Results revealed a delayed effect for both groups at post-intervention, with improved eating habits, self-esteem, and compassion at follow-up. Findings provide preliminary support for EFT as an effective treatment strategy for increasing healthy eating behaviours and improving associated weight-related psychopathology.


Assuntos
Terapia Comportamental/métodos , Emoções , Empatia , Comportamento Alimentar/psicologia , Transtornos da Alimentação e da Ingestão de Alimentos/terapia , Autoimagem , Adolescente , Austrália , Dieta , Ingestão de Alimentos , Estudos de Viabilidade , Transtornos da Alimentação e da Ingestão de Alimentos/psicologia , Feminino , Humanos , Masculino , Terapias Mente-Corpo/métodos , Obesidade Infantil/complicações , Obesidade Infantil/psicologia , Psicoterapia de Grupo
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